WorldWideScience

Sample records for arsenic-induced proliferative diseases

  1. Possible mechanisms for arsenic-induced proliferative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A. [Dartmouth College and Medical School, Hanover, NH (United States)] [and others

    1996-12-31

    Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

  2. Hypereosinophilic syndrome and proliferative diseases.

    Science.gov (United States)

    Ionescu, Marius A; Wang, Li; Janin, Anne

    2009-01-01

    Therapy principles of the last decade and recent advances in the research of polynuclear eosinophil have led to a new approach in the hypereosinophilic syndrome (HES), with important consequences on the development of new and effective therapies. HES is defined by persistent and marked eosinophilia and eosinophil-related organ damage in the absence of any evident cause of hypereosinophilia. Two variants of HES have been characterized, with different prognosis and possible associations with malignant diseases such as myeloid leukemia or T-cell lymphomas. The lymphocytic variant of HES (L-HES) is characterized by the presence of T cell clones, IL-5 expression and possible progression to T-cell lymphoma. Besides steroid therapy, the anti-IL-5 monoclonal antibody mepolizumab is considered as a target therapy for L-HES. The myeloproliferative variant of HES (M-HES) is associated with an increased risk of myeloid leukemia and good response to anti-tyrosine-kinase therapy. The imatinib target is a kinase resulting from an 800-kb deletion on chromosome 4. The fusion gene Fip1-like 1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) has been validated as a marker of response to anti-tyrosine-kinase therapy. Early identification of HES variants is crucial for the rapid introduction of early and appropriately adjusted therapy.

  3. Is proliferative colonic disease presentation changing?

    Institute of Scientific and Technical Information of China (English)

    Vito D Corleto; Cristiano Pagnini; Maria Sofia Cattaruzza; Ermira Zykaj; Emilio Di Giulio; Giovanna Margagnoni; Emanuela Pilozzi

    2012-01-01

    AIM:To compare the site,age and gender of cases of colorectal cancer (CRC) and polyps in a single referral center in Rome,Italy,during two periods.METHODS:CRC data were collected from surgery/pathology registers,and polyp data from colonoscopy reports.Patients who met the criteria for familial adenomatous polyposis,hereditary non-polyposis colorectal cancer syndrome or inflammatory bowel disease were excluded from the study.Overlap of patients between the two groups (cancers and polyps) was carefully avoided.Thex2 statistical test and a regression analysis were performed.RESULTS:Data from a total of 768 patients (352 and 416 patients,respectively,in periods A and B) who underwent surgery for cancer were collected.During the same time periods,a total of 1693 polyps were analyzed from 978 patients with complete colonoscopies (428 polyps from 273 patients during period A and 1265 polyps from 705 patients during period B).A proximal shift in cancer occurred during the latter years for both sexes,but particularly in males.Proximal cancer increased > 3-fold in period B compared to period A in males [odds ratio (OR) 3.31,95%CI:2.00-5.47; P <0.0001).A similar proximal shift was observed for polyps,particularly in males (OR 1.87,95%CI:1.23-2.87;P < 0.0038),but also in females (OR 1.62,95%CI:0.96-2.73; P < 0.07).CONCLUSION:The prevalence of proximal proliferative colonic lesions seems to have increased over the last decade,particularly in males.

  4. First Reported Case of Proliferative Retinopathy in Hemoglobin SE Disease

    Directory of Open Access Journals (Sweden)

    Paul Baciu

    2014-01-01

    Full Text Available We report the first case of proliferative sickle cell retinopathy in a patient with hemoglobin SE (Hb SE disease. Only a few dozen cases of Hb SE disease have been reported previously, and none had evidence of proliferative retinopathy. A 56-year-old African American man presented to our clinic for routine examination and was found to have sea-fan peripheral neovascularization bilaterally without maculopathy. Hemoglobin analysis revealed Hb SE heterozygosity. Sector laser photocoagulation to areas of nonperfusion in both eyes resulted in regression of the peripheral neovascularization over a period of 6 months. Although Hb SE disease is rare, the incidence of Hb SE disease is postulated to rise in the future. Awareness of its potential ocular complications is needed to appropriately refer these patients for screening.

  5. Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan.

    Science.gov (United States)

    Chen, Chien-Jen; Hsu, Lin-I; Wang, Chih-Hao; Shih, Wei-Liang; Hsu, Yi-Hsiang; Tseng, Mei-Ping; Lin, Yu-Chun; Chou, Wei-Ling; Chen, Chia-Yen; Lee, Cheng-Yeh; Wang, Li-Hua; Cheng, Yu-Chin; Chen, Chi-Ling; Chen, Shu-Yuan; Wang, Yuan-Hung; Hsueh, Yu-Mei; Chiou, Hung-Yi; Wu, Meei-Maan

    2005-08-07

    Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress.

  6. Trapping of growth factors by catechins: a possible therapeutical target for prevention of proliferative diseases.

    Science.gov (United States)

    Doss, Michael Xavier; Potta, Shiva Prasad; Hescheler, Jürgen; Sachinidis, Agapios

    2005-05-01

    The prevention of cancer through dietary intervention is currently receiving considerable attention. Several epidemiological studies substantiate that green tea has a protective effect against a variety of malignant proliferative disorders such as lung cancer, breast cancer and prostate cancer. This preventive potential of green tea against cancer is attributed to the biologically active flavonoids called catechins. Epigallocatechin 3-o-gallate, the major catechin found in green tea, mediates diverse physiological and pharmacological actions in bringing about the regression of the tumors and also lowers the risk of nonmalignant cardiovascular proliferative diseases. Much of the current research is being focused on how these catechins specifically bring about the regression of the experimentally induced tumors both in vitro and in vivo. These catechins exert diverse physiological effects against proliferative diseases by several mechanisms, most of which are not completely characterized. This review summarizes the mechanisms by which these catechins play an essential role in regulating the process of carcinogenesis, with a special emphasis on how these catechins antagonize the growth factor-induced proliferative disorders.

  7. Proliferative kidney disease in rainbow trout: time- and temperature-related renal pathology and parasite distribution.

    Science.gov (United States)

    Bettge, Kathrin; Wahli, Thomas; Segner, Helmut; Schmidt-Posthaus, Heike

    2009-01-28

    Proliferative kidney disease is a parasitic infection of salmonid fishes caused by Tetracapsuloides bryosalmonae. The main target organ of the parasite in the fish is the kidney. To investigate the influence of water temperature on the disease in fish, rainbow trout Oncorhynchus mykiss infected with T bryosalmonae were kept at 12 degrees C and 18 degrees C. The number of parasites, the type and degree of lesions in the kidney and the mortality rate was evaluated from infection until full development of disease. While mortality stayed low at 12 degrees C, it reached 77% at 18 degrees C. At 12 degrees C, pathological lesions were dominated by a multifocal proliferative and granulomatous interstitial nephritis. This was accompanied by low numbers of T. bryosalmonae, mainly located in the interstitial lesions. With progression of the disease, small numbers of parasites appeared in the excretory tubuli, and parasite DNA was detected in the urine. Parasite degeneration in the interstitium was observed at late stages of the disease. At 18 degrees C, pathological lesions in kidneys were more severe and more widely distributed, and accompanied by significantly higher parasite numbers. Distribution of parasites in the renal compartments, onset of parasite degeneration and time course of appearance of parasite DNA in urine were not clearly different from the 12 degrees C group. These findings indicate that higher mortality at 18 degrees C compared to 12 degrees C is associated with an enhanced severity of renal pathology and increased parasite numbers.

  8. MicroRNA-214 and MicroRNA-126 Are Potential Biomarkers for Malignant Endothelial Proliferative Diseases

    Directory of Open Access Journals (Sweden)

    Kazuki Heishima

    2015-10-01

    Full Text Available Malignant endothelial proliferative diseases including human angiosarcoma (AS and canine hemangiosarcoma (HSA are serious diseases with a grave prognosis. Establishing liquid biopsy-based biomarkers for screening has definite clinical utility; however, plasma miRNAs up- or down-regulated in these sarcomas have been unclear. For identifying possible diagnostic plasma miRNAs for these sarcomas, we investigated whether plasma miR-214 and miR-126, which miRNAs play important roles in angiogenesis and tumorigenesis, were elevated in malignant endothelial proliferative diseases. For this investigation, human angiosarcoma and canine hemangiosarcoma cell lines and clinical plasma samples of canine hemangiosarcoma were examined by performing miRNA qRT-PCR. We report here that human angiosarcoma and canine hemangiosarcoma cell lines over-secreted miR-214 and miR-126 via microvesicles; in addition, their levels in the plasma samples from canines with hemangiosarcoma were increased. Moreover, the surgical resection of primary tumors decreased the levels of plasma miR-214 and miR-126. Our findings suggest that these malignant endothelial proliferative diseases over-secreted miR-214 and miR-126, thus suggesting that these miRNAs have potential as diagnostic biomarkers for malignant endothelial proliferative diseases in canine and possible in human angiosarcoma.

  9. Proliferative kidney disease in brown trout: infection level, pathology and mortality under field conditions.

    Science.gov (United States)

    Schmidt-Posthaus, Heike; Hirschi, Regula; Schneider, Ernst

    2015-05-21

    Proliferative kidney disease (PKD) is an emerging disease threatening wild salmonid populations. In temperature-controlled aquaria, PKD can cause mortality rates of up to 85% in rainbow trout. So far, no data about PKD-related mortality in wild brown trout Salmo trutta fario are available. The aim of this study was to investigate mortality rates and pathology in brown trout kept in a cage within a natural river habitat known to harbor Tetracapsuloides bryosalmonae. Young-of-the-year (YOY) brown trout, free of T. bryosalmonae, were exposed in the River Wutach, in the northeast of Switzerland, during 3 summer months. Samples of wild brown trout caught by electrofishing near the cage location were examined in parallel. The incidence of PKD in cage-exposed animals (69%) was not significantly different to the disease prevalence of wild fish (82 and 80% in the upstream and downstream locations, respectively). The mortality in cage-exposed animals, however, was as low as 15%. At the termination of the exposure experiment, surviving fish showed histological lesions typical for PKD regression, suggesting that many YOY brown trout survive the initial infection. Our results at the River Wutach suggest that PKD in brown trout does not always result in high mortality under natural conditions.

  10. Arsenic-induced micronuclei formation in mammalian cells and its counteraction by tea.

    Science.gov (United States)

    Sinha, Dona; Roy, Madhumita; Siddiqi, Maqsood; Bhattacharya, Rathin K

    2005-01-01

    The Gangetic plain of West Bengal, India, has been engulfed by a disastrous environmental calamity of arsenic contamination of the ground water. Chronic arsenic toxicity caused by drinking arsenic-contaminated water has been one of the worst health hazards gradually affecting nine districts of West Bengal since the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung disease, gangrene of the toes, neuropathy, and skin cancer are other manifestations. Induction of cancer is frequently associated with DNA damage, changes in ploidy of cells, and non-random chromosome aberrations. Counteraction of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols could be a useful strategy to combat arsenic-induced DNA damage and thereby cancer. A review of the literature showed that it is the antioxidant property of tea polyphenols that affords protection against various types of cancer. The present study was conducted to investigate whether the extracts of green tea and black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate this arsenic-induced genotoxicity. The normal mammalian cell culture derived from male Chinese hamster lung fibroblast cells (V79) was used as the test system to assess the genotoxicity by micronucleus assay. The results showed that both green tea and black tea extracts have equal potential in modulating the arsenic-induced genotoxicity. This effect was perhaps induced by the constituent polyphenols present in green and black tea. In addition, the repair activity of the damaged cells was enhanced when treated with these tea extracts and their polyphenols. Thus, tea and its polyphenols may have a promising role in counteracting the devastating effects of arsenic.

  11. Complex interaction between proliferative kidney disease, water temperature and concurrent nematode infection in brown trout.

    Science.gov (United States)

    Schmidt-Posthaus, Heike; Steiner, Pascale; Müller, Barbara; Casanova-Nakayama, Ayako

    2013-04-29

    Proliferative kidney disease (PKD) is a temperature-dependent disease caused by the myxozoan Tetracapsuloides bryosalmonae. It is an emerging threat to wild brown trout Salmo trutta fario populations in Switzerland. Here we examined (1) how PKD prevalence and pathology in young-of-the-year (YOY) brown trout relate to water temperature, (2) whether wild brown trout can completely recover from T. bryosalmonae-induced renal lesions and eliminate T. bryosalmonae over the winter months, and (3) whether this rate and/or extent of the recovery is influenced by concurrent infection. A longitudinal field study on a wild brown trout cohort was conducted over 16 mo. YOY and age 1+ fish were sampled from 7 different field sites with various temperature regimes, and monitored for infection with T. bryosalmonae and the nematode Raphidascaris acus. T. bryosamonae was detectable in brown trout YOY from all sampling sites, with similar renal pathology, independent of water temperature. During winter months, recovery was mainly influenced by the presence or absence of concurrent infection with R. acus larvae. While brown trout without R. acus regenerated completely, concurrently infected brown trout showed incomplete recovery, with chronic renal lesions and incomplete translocation of T. bryosalmonae from the renal interstitium into the tubular lumen. Water temperature seemed to influence complete excretion of T. bryosalmonae, with spores remaining in trout from summer-warm rivers, but absent in trout from summer-cool rivers. In the following summer months, we found PKD infections in 1+ brown trout from all investigated river sites. The pathological lesions indicated a re-infection rather than a proliferation of remaining T. bryosalmonae. However, disease prevalence in 1+ trout was lower than in YOY.

  12. MicroRNA-181b and microRNA-9 mediate arsenic-induced angiogenesis via NRP1.

    Science.gov (United States)

    Cui, Yi; Han, Zhongji; Hu, Yi; Song, Ge; Hao, Chanjuan; Xia, Hongfei; Ma, Xu

    2012-02-01

    Environmental exposure to inorganic arsenic compounds has been reported to have serious health effects on humans. Recent studies reported that arsenic targets endothelial cells lining blood vessels, and endothelial cell activation or dysfunction, may underlie the pathogenesis of arsenic-induced diseases and developmental toxicity. It has been reported that microRNAs (miRNAs) may act as an angiogenic switch by regulating related genes. The present study was designed to test the hypothesis that arsenite-regulated miRNAs play pivotal roles in arsenic-induced toxicity. Fertilized eggs were injected via the yolk sac with 100  nM sodium arsenite at Hamburger-Hamilton (HH) stages 6, 9, and 12, and harvested at HH stage 18. To identify the individual miRNAs and mRNAs that may regulate the genetic network, the expression profiles of chick embryos were analyzed by microarray analysis. Microarray analyses revealed that the expression of a set of miRNAs changed after arsenite administration, especially miRNA-9, 181b, 124, 10b, and 125b, which exhibited a massive decrease in expression. Integrative analyses of the microarray data revealed that several miRNAs, including miR-9 and miR-181b, might target several key genes involved in arsenic-induced developmental toxicity. A luciferase reporter assay confirmed neuropilin-1 (Nrp1) as a target of mir-9 and mir-181b. Data from the transwell migration assay and the tube-formation assay indicated that miR-9 and mir-181b inhibited the arsenic-induced EA.hy926 cell migration and tube formation by targeting NRP1. Our study demonstrates that the environmental toxin, sodium arsenite, induced angiogenesis by altering the expression of miRNAs and their cognate mRNA targets.

  13. Arsenic Induces p62 Expression to Form a Positive Feedback Loop with Nrf2 in Human Epidermal Keratinocytes: Implications for Preventing Arsenic-Induced Skin Cancer

    Science.gov (United States)

    Shah, Palak; Trinh, Elaine; Qiang, Lei; Xie, Lishi; Hu, Wen-Yang; Prins, Gail S.; Pi, Jingbo; He, Yu-Ying

    2017-01-01

    Exposure to inorganic arsenic in contaminated drinking water poses an environmental public health threat for hundreds of millions of people in the US and around the world. Arsenic is a known carcinogen for skin cancer. However, the mechanism by which arsenic induces skin cancer remains poorly understood. Here, we have shown that arsenic induces p62 expression in an autophagy-independent manner in human HaCaT keratinocytes. In mouse skin, chronic arsenic exposure through drinking water increases p62 protein levels in the epidermis. Nrf2 is required for basal and arsenic-induced p62 up-regulation. p62 knockdown reduces arsenic-induced Nrf2 activity, and induces sustained p21 up-regulation. p62 induction is associated with increased proliferation in mouse epidermis. p62 knockdown had little effect on arsenic-induced apoptosis, while it decreased cell proliferation following arsenic treatment. Our findings indicate that arsenic induces p62 expression to regulate the Nrf2 pathway in human keratinocytes and suggest that targeting p62 may help prevent arsenic-induced skin cancer. PMID:28125038

  14. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Science.gov (United States)

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  15. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism.

    Science.gov (United States)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark; Stachler, Elyse N; Bibby, Kyle J; Stolz, Donna B; Shiva, Sruti; Wang, Zeneng; Hazen, Stanley L; Barchowsky, Aaron; Stolz, John F

    2015-12-15

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes.

  16. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism

    Science.gov (United States)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark; Stachler, Elyse N.; Bibby, Kyle J.; Stolz, Donna B.; Shiva, Sruti; Wang, Zeneng; Hazen, Stanley L.; Barchowsky, Aaron; Stolz, John F.

    2015-01-01

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogeneis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. PMID:26529668

  17. Surgical management of retinal diseases: proliferative diabetic retinopathy and traction retinal detachment.

    Science.gov (United States)

    Cruz-Iñigo, Yousef J; Acabá, Luis A; Berrocal, Maria H

    2014-01-01

    Current indications for pars plana vitrectomy in patients with proliferative diabetic retinopathy (PDR) include vitreous hemorrhage, tractional retinal detachment (TRD), combined tractional and rhegmatogenous retinal detachment (CTRRD), diabetic macular edema associated with posterior hyaloidal traction, and anterior segment neovascularization with media opacities. This chapter will review the indications, surgical objectives, adjunctive pharmacotherapy, microincision surgical techniques, and outcomes of diabetic vitrectomy for PDR, TRD, and CTRRD. With the availability of new microincision vitrectomy technology, wide-angle microscope viewing systems, and pharmacologic agents, vitrectomy can improve visual acuity and achieve long-term anatomic stability in eyes with severe complications from PDR.

  18. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  19. [Proliferative Vitreoretinopathy].

    Science.gov (United States)

    Wiedemann, P; Bringmann, A

    2016-09-01

    Proliferative vitreoretinal retinopathy (PVR) is a very severe complication of vitreoretinal surgery. PVR is characterised by a complex cellular reaction. This corresponds to a vitreoretinal wound healing reaction and leads to tractional retinal detachment fixed by membranes. A rational goal of treatment is the removal of active cells and membranes, particularly the whole vitreous body; this can only be achieved surgically.

  20. Autosomal dominant polycystic kidney disease with diffuse proliferative glomerulonephritis - an unusual association: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Kapoor Vinay

    2010-04-01

    Full Text Available Abstract Introduction Autosomal dominant polycystic kidney disease is an inherited disorder that is characterized by the development and growth of cysts in the kidneys and other organs. Urinary protein excretion is usually less than 1 g/24 hours in autosomal dominant polycystic kidney disease, and an association of nephrotic syndrome with this condition is considered rare. There are only anecdotal case reports of autosomal dominant polycystic kidney disease associated with nephrotic syndrome, with focal segmental glomerulosclerosis being the most commonly reported histopathological diagnosis. Nephrotic-range proteinuria in the presence of autosomal dominant polycystic kidney disease, with or without an accompanying decline in renal function, should be investigated by open renal biopsy to exclude coexisting glomerular disease. To the best of our knowledge, this is the first case of autosomal dominant polycystic kidney disease with histologically proven diffuse proliferative glomerulonephritis presenting with nephrotic-range proteinuria. No other reports of this could be found in a global electronic search of the literature. Case presentation We report the case of a 35-year-old Indo-Aryan man with autosomal dominant polycystic kidney disease associated with nephrotic syndrome and a concomitant decline in his glomerular filtration rate. Open renal biopsy revealed diffuse proliferative glomerulonephritis. An accurate diagnosis enabled us to manage him conservatively with a successful outcome, without the use of corticosteroid which is the standard treatment and the drug most commonly used to treat nephrotic syndrome empirically. Conclusion Despite the reluctance of physicians to carry out a renal biopsy on patients with autosomal dominant polycystic kidney disease, our case supports the idea that renal biopsy is needed in patients with polycystic kidney disease with nephrotic-range proteinuria to make an accurate diagnosis. It also illustrates the

  1. Proliferative activity, lectin-dependent and natural cytotoxicity in blood, lymph node and spleen from patients with Hodgkin's disease.

    Science.gov (United States)

    Bykovskaya, S N; Blochina, N G; Charabadze, M V; Agaphonov, V A; Kupriyanova, T A

    1990-01-01

    Mononuclear cells and T-lymphocytes of the blood, spleen and lymph nodes from 48 patients with Hodgkin disease (HD) and blood donors were tested in assays for lectin-dependent (LD) and natural killer (NK) cytotoxic activity. On average, peripheral blood T cell lectin-dependent cytotoxicity differs from that of the donors. However, cytotoxic activity appears to be dependent on the stage of disease; in the IY stage LD cytotoxicity was decreased 2-fold. The lectin-dependent cytotoxicity was also dependent on the histological type of disease and the lowest level (50% of the control level) was associated with the lymphoid depletion type. The cytotoxic activity of T-lymphocytes from the affected areas of the patients' spleen was more marked than that of the unaffected areas. Spleen cell cytotoxicity showed no other correlations. Cytotoxicity of lymphocytes from the affected lymph nodes was drastically lower than activity of blood and spleen lymphocytes. NK activity of the patients' blood and spleen lymphocytes was twice as low as the control level (healthy donors) and did not correlate with stage and/or histological type of disease. The proliferative activity of lymphocytes from 33 HD patients was tested in vitro using allogeneic mononuclear cells from healthy donors or HD patients and/or PHA as stimulators. The response of patients' lymphocytes to alloantigens appeared to be much less affected than response to polyclonal mitogen. Thus, the results obtained by us demonstrate signs of stimulation of the lymphoid system against a background of general immunosuppression in HD.

  2. Kidney pathology and parasite intensity in rainbow trout Oncorhynchus mykiss surviving proliferative kidney disease: time course and influence of temperature.

    Science.gov (United States)

    Schmidt-Posthaus, Heike; Bettge, Kathrin; Forster, Ursula; Segner, Helmut; Wahli, Thomas

    2012-01-24

    Proliferative kidney disease (PKD) is an endoparasitic disease of salmonids caused by the myxozoan parasite Tetracapsuloides bryosalmonae. We recently described the development of the disease from initial infection until manifestation of clinical disease signs in rainbow trout held at 2 water temperatures, 12 and 18°C. The aim of the present study is to investigate whether (1) infected fish surviving the clinical phase would recover from renal pathological changes, (2) whether they would be able to reduce the parasite load in the kidneys, and (3) whether water temperatures would influence renal recovery and parasite clearance. At 18°C, fish showed a gradual recovery of normal kidney morphology which was associated with a decline in parasite numbers and infection prevalence. Fish kept at 12°C initially showed an enhancement of kidney lesions before recovery of normal kidney morphology took place. The decrease in renal parasite load was retarded compared to 18°C. The results from the present study provide evidence that rainbow trout surviving the clinical phase of PKD are able to (1) fully restore renal structure, and (2) significantly reduce renal parasite loads, although 100% clearance was not achieved within the experimental period of this study. Water temperature influences the rate but not the outcome of the recovery process.

  3. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

    2014-10-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  4. Proliferative multifocal leukoplakia better name that proliferative verrucous leukoplakia

    OpenAIRE

    Aguirre-Urizar Jose M

    2011-01-01

    Abstract In this letter I propose the name "Proliferative Multifocal Leukoplakia" with the goal of reducing under-diagnosis of this disease, improve the early diagnosis, try to make an early therapy and control, and prevent its malignant transformation.

  5. An epidemic model for the interactions between thermal regime of rivers and transmission of Proliferative Kidney Disease in salmonid fish

    Science.gov (United States)

    Carraro, Luca; Bertuzzo, Enrico; Mari, Lorenzo; Gatto, Marino; Strepparava, Nicole; Hartikainen, Hanna; Rinaldo, Andrea

    2015-04-01

    Proliferative kidney disease (PKD) affects salmonid populations in European and North-American rivers. It is caused by the endoparasitic myxozoan Tetracapsuloides bryosalmonae, which exploits freshwater bryozoans (Fredericella sultana) and salmonids as primary and secondary hosts, respectively. Incidence and mortality, which can reach up to 90-100%, are known to be strongly related to water temperature. PKD has been present in brown trout population for a long time but has recently increased rapidly in incidence and severity causing a decline in fish catches in many countries. In addition, environmental changes are feared to cause PKD outbreaks at higher latitude and altitude regions as warmer temperatures promote disease development. This calls for a better comprehension of the interactions between disease dynamics and the thermal regime of rivers, in order to possibly devise strategies for disease management. In this perspective, a spatially explicit model of PKD epidemiology in riverine host metacommunities is proposed. The model aims at summarizing the knowledge on the modes of transmission of the disease and the life-cycle of the parasite, making the connection between temperature and epidemiological parameters explicit. The model accounts for both local population and disease dynamics of bryozoans and fish and hydrodynamic dispersion of the parasite spores and hosts along the river network. The model is time-hybrid, coupling inter-seasonal and intra-seasonal dynamics, the former being described in a continuous time domain, the latter seen as time steps of a discrete time domain. In order to test the model, a case study is conducted in river Wigger (Cantons of Aargau and Lucerne, Switzerland), where data about water temperature, brown trout and bryozoan populations and PKD prevalence are being collected.

  6. Breast cancer risk after diagnosis by screening mammography of nonproliferative or proliferative benign breast disease: a study from a population-based screening program.

    Science.gov (United States)

    Castells, Xavier; Domingo, Laia; Corominas, Josep María; Torá-Rocamora, Isabel; Quintana, María Jesús; Baré, Marisa; Vidal, Carmen; Natal, Carmen; Sánchez, Mar; Saladié, Francina; Ferrer, Joana; Vernet, Mar; Servitja, Sonia; Rodríguez-Arana, Ana; Roman, Marta; Espinàs, Josep Alfons; Sala, María

    2015-01-01

    Benign breast disease increases the risk of breast cancer. This association has scarcely been evaluated in the context of breast cancer screening programs although it is a prevalent finding in mammography screening. We assessed the association of distinct categories of benign breast disease and subsequent risk of breast cancer, as well as the influence of a family history of breast cancer. A retrospective cohort study was conducted in 545,171 women aged 50-69 years biennially screened for breast cancer in Spain. The median of follow-up was 6.1 years. The age-adjusted rate ratio (RR) of breast cancer for women with benign breast disease, histologically classified into nonproliferative and proliferative disease with and without atypia, compared with women without benign breast disease was estimated by Poisson regression analysis. A stratified analysis by family history of breast cancer was performed in a subsample. All tests were two-sided. The age-adjusted RR of breast cancer after diagnosis of benign breast disease was 2.51 (95 % CI: 2.14-2.93) compared with women without benign breast disease. The risk was higher in women with proliferative disease with atypia (RR = 4.56, 95 % CI: 2.06-10.07) followed by those with proliferative disease without atypia (RR = 3.58; 95 % CI = 2.61-4.91). Women with nonproliferative disease and without a family history of breast cancer remained also at increased risk of cancer (OR = 2.23, 95 % CI: 1.86-2.68). An increased risk of breast cancer was observed among screening participants with proliferative or nonproliferative benign breast disease, regardless of a family history of breast cancer. This information may be useful to explore risk-based screening strategies.

  7. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  8. Proliferative kidney disease (PKD) of rainbow trout: temperature- and time-related changes of Tetracapsuloides bryosalmonae DNA in the kidney.

    Science.gov (United States)

    Bettge, K; Segner, H; Burki, R; Schmidt-Posthaus, H; Wahli, T

    2009-05-01

    Proliferative kidney disease (PKD) of salmonids, caused by Tetracapsuloides bryosalmonae, can lead to high mortalities at elevated water temperature. We evaluated the hypothesis that this mortality is caused by increasing parasite intensity. T. bryosalmonae-infected rainbow trout (Oncorhynchus mykiss) were reared at different water temperatures and changes in parasite concentrations in the kidney were compared to cumulative mortalities. Results of parasite quantification by a newly developed real-time PCR agreed with the number of parasites detected by immunohistochemistry, except for very low or very high parasite loads because of heterogenous distribution of the parasites in the kidney. Two experiments were performed, where fish were exposed to temperatures of 12, 14, 16, 18 or 19 degrees C after an initial exposure to an infectious environment at 12-16 degrees C resulting in 100% prevalence of infected fish after 5 to 14 days of exposure. While mortalities differed significantly between all investigated water temperatures, significant differences in final parasite loads were only found between fish kept at 12 degrees C and all other groups. Differences in parasite load between fish kept at 14 degrees C to 19 degrees C were not significant. These findings provide evidence that there is no direct link between parasite intensity and fish mortality.

  9. Protection of arsenic-induced testicular oxidative stress by arjunolic acid.

    Science.gov (United States)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C

    2008-01-01

    Arsenic-induced tissue damage is a major concern to the human population. An impaired antioxidant defense mechanism followed by oxidative stress is the major cause of arsenic-induced toxicity, which can lead to reproductive failure. The present study was carried out to investigate the preventive role of arjunolic acid, a triterpenoid saponin isolated from the bark of Terminalia arjuna, against arsenic-induced testicular damage in mice. Administration of arsenic (in the form of sodium arsenite, NaAsO(2), at a dose of 10 mg/kg body weight) for 2 days significantly decreased the intracellular antioxidant power, the activities of the antioxidant enzymes, as well as the levels of cellular metabolites. In addition, arsenic intoxication enhanced testicular arsenic content, lipid peroxidation, protein carbonylation and the level of glutathione disulfide (GSSG). Exposure to arsenic also caused significant degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes. Pretreatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days could prevent the arsenic-induced testicular oxidative stress and injury to the histological structures of the testes. Arjunolic acid had free radical scavenging activity in a cell-free system and antioxidant power in vivo. In summary, the results suggest that the chemopreventive role of arjunolic acid against arsenic-induced testicular toxicity may be due to its intrinsic antioxidant property.

  10. Biochanin A Ameliorates Arsenic-Induced Hepato- and Hematotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Abdulkadhar Mohamed Jalaludeen

    2016-01-01

    Full Text Available Biochanin A (BCA is a natural organic compound of the phytoestrogenic isoflavone class that has antioxidant and metal chelator properties in the presence of transition metal ions, however, its efficacy in animal models is still obscure. Therefore, the objective of this study was to investigate the protective effects of BCA against arsenic-induced hepatic injury and hematotoxicity in rats. The results suggest that arsenic intoxicated rats showed significantly higher levels of plasma hepatic markers than normal control rats. Furthermore, an increase in lipid peroxidation with depletion of reduced glutathione (GSH and activities of superoxide dismutase (SOD and catalase (CAT occurred in the livers of rats exposed to arsenic. Administration of BCA (20 mg/kg·bw/day and selenium (3 mg/kg·bw/day resulted in a significant reversal of hepatic and oxidative stress markers in arsenic-intoxicated rats. A low dose of BCA (10 mg/kg·bw/day did not show any preventive effect, while a high dose of BCA (40 mg/kg·bw/day partially prevented all hepatotoxicity events. These biochemical perturbations were supported by histopathological observations of the liver. Our results suggest that administration of BCA (20 mg/kg·bw/day attenuated the arsenic hepatotoxicity, a property that could contribute to the therapeutic approaches for chronic liver diseases.

  11. ARSENIC INDUCES SUSTAINED IMPAIRMENT OF SKELETAL MUSCLE AND MUSCLE PROGENITOR CELL ULTRASTRUCTURE AND BIOENERGETICS

    Science.gov (United States)

    Fabrisia, Ambrosio; Elke, Brown; Donna, Stolz; Ricardo, Ferrari; Bret, Goodpaster; Bridget, Deasy; Giovanna, Distefano; Alexandra, Roperti; Amin, Cheikhi; Yesica, Garciafigueroa; Aaron, Barchowsky

    2014-01-01

    Over 4 million individuals in the US, and over 140 million individuals worldwide, are exposed daily to arsenic-contaminated drinking water. Human exposures can range from below the current limit of 10 µg/L to over 1 mg/L, with 100 µg/L promoting disease in a large portion of those exposed. Although increased attention has recently been paid to myopathy following arsenic exposure, the pathogenic mechanisms underlying clinical symptoms remain poorly understood. This study tested the hypothesis that arsenic induces lasting muscle mitochondrial dysfunction and impairs metabolism. When compared to non-exposed controls, mice exposed to drinking water containing 100µg/L arsenite for 5 weeks demonstrated impaired muscle function, mitochondrial myopathy, and altered oxygen consumption that were concomitant with increased mitochondrial fusion gene transcription. There was no difference in levels of inorganic arsenic or its mononomethyl- and dimethyl- metabolites between controls and exposed muscles, confirming that arsenic does not accumulate in muscle. Nevertheless, muscle progenitor cells isolated from exposed mice recapitulated the aberrant myofiber phenotype and were more resistant to oxidative stress, generated more reactive oxygen species, and displayed autophagic mitochondrial morphology, as compared to cells isolated from non-exposed mice. These pathological changes from a possible maladaptive oxidative stress response provide insight into declines in muscle functioning caused by exposure to this common environmental contaminant. PMID:24960579

  12. Biochanin A Ameliorates Arsenic-Induced Hepato- and Hematotoxicity in Rats.

    Science.gov (United States)

    Jalaludeen, Abdulkadhar Mohamed; Ha, Woo Tae; Lee, Ran; Kim, Jin Hoi; Do, Jeong Tae; Park, Chankyu; Heo, Young Tae; Lee, Won Young; Song, Hyuk

    2016-01-09

    Biochanin A (BCA) is a natural organic compound of the phytoestrogenic isoflavone class that has antioxidant and metal chelator properties in the presence of transition metal ions, however, its efficacy in animal models is still obscure. Therefore, the objective of this study was to investigate the protective effects of BCA against arsenic-induced hepatic injury and hematotoxicity in rats. The results suggest that arsenic intoxicated rats showed significantly higher levels of plasma hepatic markers than normal control rats. Furthermore, an increase in lipid peroxidation with depletion of reduced glutathione (GSH) and activities of superoxide dismutase (SOD) and catalase (CAT) occurred in the livers of rats exposed to arsenic. Administration of BCA (20 mg/kg·bw/day) and selenium (3 mg/kg·bw/day) resulted in a significant reversal of hepatic and oxidative stress markers in arsenic-intoxicated rats. A low dose of BCA (10 mg/kg·bw/day) did not show any preventive effect, while a high dose of BCA (40 mg/kg·bw/day) partially prevented all hepatotoxicity events. These biochemical perturbations were supported by histopathological observations of the liver. Our results suggest that administration of BCA (20 mg/kg·bw/day) attenuated the arsenic hepatotoxicity, a property that could contribute to the therapeutic approaches for chronic liver diseases.

  13. First Proliferative Kidney Disease outbreak in Austria, linking to the aetiology of Black Trout Syndrome threatening autochthonous trout populations.

    Science.gov (United States)

    Gorgoglione, Bartolomeo; Kotob, Mohamed H; Unfer, Günter; El-Matbouli, Mansour

    2016-05-01

    Proliferative Kidney Disease (PKD) was diagnosed in juvenile autochthonous brown trout Salmo trutta for the first time in Austria during summer 2014. Cytology showed Tetracapsuloides bryosalmonae sporoblasts, and histology revealed sporogonic (coelozoic) and extrasporogonic (histozoic) stages. Analysis of malacosporean ribosomal small subunit revealed that this strain is closely related to European isolates, although its source is unknown. Infection and high pathogenicity were reproduced upon a pre-restocking test with specific pathogen free (SPF) juvenile trout, resulting in 100% mortality between 28 and 46 d post exposure (dpe), with high ectoparasitosis. Fish showed grade 2 of the Kidney Swelling Index and grade 3 of the PKD histological assessment. T. bryosalmonae enzootic waters were demonstrated in further locations along the River Kamp, with infected bryozoans retrieved up to 6 km upstream of the farm with the PKD outbreak. Fredericella sultana colonies collected from these locations were cultivated in laboratory conditions. Released malacospores successfully induced PKD, and contextually Black Trout Syndrome (BTS), in SPF brown trout. In the absence of co-infections mortality occurred between 59 and 98 dpe, with kidneys enlarged up to 6.74% of total body weight (normal 1.23%). This study confirms the first isolation of a pathogenic myxozoan from an Austrian river tributary of the Danube, where its 2-host life cycle is fully occurring. Its immunosuppressant action could link PKD as a key factor in the multifactorial aetiology of BTS. This T. bryosalmonae isolation provides an impetus to undertake further multi-disciplinary research, aiming to assess the impact of PKD and BTS spreading to central European regions.

  14. Protective effects of Moringa oleifera Lam. leaves against arsenic-induced toxicity in mice

    Institute of Scientific and Technical Information of China (English)

    Afzal Sheikh; Zahangir Alam Saud; Khaled Hossain; Fouzia Yeasmin; Smita Agarwal; Mashiur Rahman; Khairul Islam; Ekhtear Hossain; Shakhawoat Hossain; Md Rezaul Karim; Farjana Nikkon

    2014-01-01

    Objective: To evaluate the protective role of leaves of Moringa oleifera (M. oleifera) Lam. against arsenic-induced toxicity in mice.Methods:non-treated control group while, the second, third, and fourth groups were treated with M.oleifera leaves (50 mg/kg body weight per day), sodium arsenite (10 mg/kg body weight per day) and sodium arsenite plus M. oleifera leaves, respectively. Serum indices related to cardiac, liver and renal functions were analyzed to evaluate the protective effect of Moringa leaves on arsenic-induced effects in mice.Results:Swiss albino male mice were divided into four groups. The first group was used as induced elevation of triglyceride, glucose, urea and the activities of alkaline phospatase, aspartate aminotransferase and alanine aminotransferase in serum. M. oleifera leaves also prevented the arsenic-induced perturbation of serum butyryl cholinesterase activity, total cholesterol and high density lipoprotein cholesterol.Conclusions:The results indicate that the leaves of M. oleifera may be useful in reducing the It revealed that food supplementation of M. oleifera leaves abrogated the arsenic-effects of arsenic-induced toxicity.

  15. IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC INDUCED BLADDER CANCER BY GENE EXPRESSION.

    Science.gov (United States)

    Arsenic is a human carcinogen that induces urinary bladder cancer. Several mechanisms have been proposed for arsenic-induced cancer. Although inorganic arsenic (iAs) does not induce tumors in adult rodents, dimethylarsinic acid (DMA), a major metabolite of iAs, is a rat bladder c...

  16. Therapeutic effects of 0.1% tacrolimus eye drops for refractory allergic ocular diseases with proliferative lesion or corneal involvement

    OpenAIRE

    Fukushima, Atsuki; Ohashi, Yuichi; Ebihara, Nobuyuki; Uchio, Eiichi; Okamoto, Shigeki; Kumagai, Naoki; Shoji, Jun; Takamura,Etsuko; Nakagawa, Yayoi; Namba, Kenichi; Fujishima, Hiroshi; Miyazaki, Dai

    2014-01-01

    Background The objective of this study was to investigate the efficacy of topical 0.1% tacrolimus in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement. Methods This prospective observational study included 1436 patients with refractory allergic conjunctivitis whose condition had responded poorly to conventional antiallergic drugs and/or topical steroids and/or topical cyclosporine. All patients received tacrolimus eye drops twice daily during th...

  17. Therapeutic effects of Moringa oleifera on arsenic-induced toxicity in rats.

    Science.gov (United States)

    Gupta, Richa; Kannan, Gurusamy M; Sharma, Mamta; S Flora, Swaran J

    2005-11-01

    the seed powder of M. oleifera has significant role in protecting animals from arsenic-induced oxidative stress and in the depletion of arsenic concentration. Further studies thus can be recommended for determining the effect of co-administrating seed powder of M. oleifera during chelation therapy with a thiol chelator.

  18. Dissecting chronic lymphocytic leukemia microenvironment signals in patients with unmutated disease: microRNA-22 regulates phosphatase and tensin homolog/AKT/FOXO1 pathway in proliferative leukemic cells.

    Science.gov (United States)

    Palacios, Florencia; Prieto, Daniel; Abreu, Cecilia; Ruiz, Santiago; Morande, Pablo; Fernández-Calero, Tamara; Libisch, Gabriela; Landoni, Ana Inés; Oppezzo, Pablo

    2015-05-01

    Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonal B cells arrested in G0/G1 stages that coexist with proliferative B cells. We identified one of these proliferative subsets in the peripheral blood from patients with unmutated disease (UM). Aiming to characterize the molecular mechanism underlying this proliferative behavior, we performed gene expression analysis of the mRNA and microRNAs in this leukemic subpopulation and compared results with those for the quiescent counterpart. Our results suggest that proliferation of this subset mainly depends on microRNA-22 overexpression, which induces phosphatase and tensin homolog (PTEN) down-regulation and phosphoinositide 3-kinase (PI3K)/AKT pathway activation. These results underline the role of the PI3K/AKT pathway at the origin of this proliferative pool in patients with UM CLL and provide additional rationale for the use of PI3K inhibitors.

  19. Pomegranate protects against arsenic-induced p53-dependent ROS-mediated inflammation and apoptosis in liver cells.

    Science.gov (United States)

    Choudhury, Sreetama; Ghosh, Sayan; Mukherjee, Sudeshna; Gupta, Payal; Bhattacharya, Saurav; Adhikary, Arghya; Chattopadhyay, Sreya

    2016-12-01

    Molecular mechanisms involved in arsenic-induced toxicity are complex and elusive. Liver is one of the most favored organs for arsenic toxicity as methylation of arsenic occurs mostly in the liver. In this study, we have selected a range of environmentally relevant doses of arsenic to examine the basis of arsenic toxicity and the role of pomegranate fruit extract (PFE) in combating it. Male Swiss albino mice exposed to different doses of arsenic presented marked hepatic injury as evident from histological and electron microscopic studies. Increased activities of enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase corroborated extensive liver damage. It was further noted that arsenic exposure initiated reactive oxygen species (ROS)-dependent apoptosis in the hepatocytes involving loss of mitochondrial membrane potential. Arsenic significantly increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB), coupled with increase in phosphorylated Iκ-B, possibly as adaptive cellular survival strategies. Arsenic-induced oxidative DNA damage to liver cells culminated in p53 activation and increased expression of p53 targets like miR-34a and Bax. Pomegranate polyphenols are known to possess remarkable antioxidant properties and are capable of protecting normal cells from various stimuli-induced oxidative stress and toxicities. We explored the protective role of PFE in ameliorating arsenic-induced hepatic damage. PFE was shown to reduce ROS generation in hepatocytes, thereby reducing arsenic-induced Nrf2 activation. PFE also inhibited arsenic-induced NF-κB-inflammatory pathway. Data revealed that PFE reversed arsenic-induced hepatotoxicity and apoptosis by modulating the ROS/Nrf2/p53-miR-34a axis. For the first time, we have mapped the possible signaling pathways associated with arsenic-induced hepatotoxicity and its rescue by pomegranate polyphenols.

  20. Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid

    Energy Technology Data Exchange (ETDEWEB)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C. [Bose Institute, Department of Chemistry, Kolkata, West Bengal (India)

    2008-03-15

    Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO{sub 2} was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO{sub 2} at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO{sub 2} intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property. (orig.)

  1. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity.

  2. Antioxidant and modulatory role of Chlorophytum borivilianum against arsenic induced testicular impairment

    Institute of Scientific and Technical Information of China (English)

    Garima Sharma; Madhu Kumar

    2012-01-01

    Arsenic has a suppressive influence on spermatogenesis and induces impairment in male reproductive system due to oxidative stress.The present study was aimed to test the arsenic induced toxicity and protection by Chlorophytum borivilianum.The effect of sodium arsenite (4 mg/(kg body weight (bw)·day)) via double distilled water without or with C.borivilianum (800 mg/(kg bw·day)) was evaluated in Swiss albino mice for 30 days.The radical scavenging activity of the aqueous C.borivilianum root extract was measured using DPPH (l,l-diphenyl-2-picryl hydrayzyl) radical.Qualitative assessment of various cell types in the testis,sperm count and motility,testicular activity of lipid peroxidation (LPO),reduced glutathione (GSH),acid and alkaline phosphatase,cholesterol and serum testosterone were monitored.Arsenic treatment showed a significant increase in LPO,acid and alkaline phosphatase,cholesterol and decrease in sperm count,sperm motility,GSH and serum testosterone.Combined treatment showed significant decrease in LPO,acid and alkaline phosphatase,cholesterol and elevation in sperm count,sperm motility,GSH and serum testosterone.Testiculat histopathology showed that C.borivilianum had reduced degeneration of germ cell in the seminiferous tubules and loss of sperms induced by arsenic intoxication.The results thus led us to conclude that administration of C.borivilianum root extract is found to be protective against arsenic induced toxicity.

  3. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity.

    Science.gov (United States)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-02

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  4. Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

    Institute of Scientific and Technical Information of China (English)

    LI Shu Gang; GUO Shu Xia; DING Yu Song; NIU Qiang; XU Shang Zhi; PANG Li Juan; MA Ru Lin; JING Ming Xia; FENG Gang Ling; LIU Jia Ming

    2015-01-01

    Objective To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg);ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO+GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

  5. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity

    Science.gov (United States)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-01

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  6. Phytoremedial effect of Withania somnifera against arsenic-induced testicular toxicity in Charles Foster rats

    Directory of Open Access Journals (Sweden)

    Arun Kumar

    2015-06-01

    Full Text Available Objective: The main objective of the current study was to observe the ameliorative effect of Withania somnifera on arsenic-induced testicular toxicity by exploring the crucial parameters such as sperm counts, sperm motility, hormonal assay and lipid peroxidation including histopathology. Materials and Methods: In the present study, arsenic in the form of sodium arsenite was administered orally to male Charles Foster rats for 45 days. Thereafter, ethanolic root extract of Withania somnifera was administered for 30 days to observe its ameliorative effect on male reproductive system. Results: The study revealed that after administration of sodium arsenite, there was a decrease in the sperm counts and sperm motility accompanied by an increased incidence of sperm abnormalities and hormonal imbalance leading to infertility. However, after administration of Withania somnifera, there was significant reversal in the parameters denoting that it not only possesses antioxidant and rejuvenating property but also maintains the cellular integrity of testicular cells leading to normal functioning of it. Conclusion: The study concludes that Withania somnifera possesses phytoremedial effect. It is one of the best antidotes against arsenic-induced reproductive toxicity.

  7. Ameliorative potential of Tephrosia purpurea extract against arsenic induced toxicity in wistar rats

    Directory of Open Access Journals (Sweden)

    Birendra kumar Roy

    2013-05-01

    Full Text Available Aim: The present investigation has been conducted to evaluate the protective activity of Tephrosia purpurea extract (TPE against arsenic induced toxicity. Materials and Methods: For this study, twenty four wistar albino rats were taken. Control group, group – I rats were given sodium arsenite @ 10 mg/kg and group – II rats were treated with TPE @ 500 mg/kg along with sodium arsenite @ 10 mg/kg (daily oral for 28 days. On 29th day animals were slaughtered and various parameters were determined. Serum biomarkers, haematological parameter analysis and histomorphological examination are carried out with estimation of arsenic concentration in tissues. Results: Oral administration of sodium arsenite @ 10 mg/kg for 28 days resulted in a significant decrease in Hb%, TEC and TLC, significant increase of serum glucose, cholesterol, calcium and significant increase in arsenic accumulation in tissues. Histopathological results of intestine revealed haemorrhagic enteritis along with loss of villi. Treatment with Tephrosia purpurea @ 500 mg/kg significantly decreased the elevated glucose, LDH levels, along with significant increase haematological levels towards normal. There was reduced haemorrhagic enteritis and presence of intact villi, as compared to arsenic treated group. But there was no significant difference in serum calcium, serum cholesterol and arsenic concentration in tissues, when compared with arsenic treated group. Conclusion: The study conclude that supplementation of TPE (500 mg/kg daily oral for 28 days has shown protection against arsenic induced toxicity by its protective effect. [Vet World 2013; 6(8.000: 493-496

  8. Immune gene expression profiling of Proliferative Kidney Disease in rainbow trout Oncorhynchus mykiss reveals a dominance of anti-inflammatory, antibody and T helper cell-like activities.

    Science.gov (United States)

    Gorgoglione, Bartolomeo; Wang, Tiehui; Secombes, Christopher J; Holland, Jason W

    2013-07-16

    The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology. Although known to be associated with suppression of some cellular aspects of innate immunity and a prominent lymphocytic hyperplasia, there remains a considerable knowledge gap in our understanding of the underlying immune mechanisms driving PKD pathogenesis. To provide further insights, the expression profiles of a panel of innate/inflammatory and adaptive immune molecules were examined in rainbow trout Oncorhynchus mykiss following a natural exposure to the parasite. Relative to controls, fish with early to advanced stages of kidney pathology exhibited up-regulation of the inflammatory cytokines interleukin (IL)-6 and IL-11, although remaining refractory towards genes indicative of macrophage activity. Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease. Up-regulation of adaptive immune molecules, including cell markers and antibody genes reflect the lymphocytic dominance of this disease and the likely importance of lymphocyte subsets in PKD pathogenesis. Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets. This work, for the first time in the study of fish-myxozoan interactions, suggests that PKD pathogenesis is shaped by an anti-inflammatory phenotype, a profound B cell/antibody response and dysregulated TH cell-like activities. A better understanding of the functional roles of fish immune cells and molecules in PKD pathogenesis may facilitate future development of control measures against this disease.

  9. Proliferative retinopathy predicts nephropathy

    DEFF Research Database (Denmark)

    Karlberg, Charlotte; Falk, Christine; Green, Anders;

    2012-01-01

    We wanted to examine proliferative retinopathy as a marker of incident nephropathy in a 25-year follow-up study of a population-based cohort of Danish type 1 diabetic patients and to examine cross-sectional associations between nephropathy and retinopathy in long-term surviving patients of the same...... photographs at follow-up. Single spot urine was used to evaluate nephropathy at both examinations. Proliferative retinopathy was present in 29 patients (15.8%) at baseline. At follow-up, these patients were more likely to macroalbuminuria (20.7% vs. 6.5%) than patients without proliferative retinopathy...... at baseline. In a multivariate logistic regression adjusted for baseline age, sex, duration of diabetes, smoking, HbA(1,) systolic and diastolic blood pressure, odds ratio of nephropathy (micro- and macroalbuminuria combined) was 2.98 (95% confidence interval 1.18-7.51, p = 0.02) for patients...

  10. Proliferative verrucous leukoplakia: An update.

    Science.gov (United States)

    Munde, Anita; Karle, Ravindra

    2016-01-01

    Proliferative verrucous leukoplakia (PVL) is a rare form of oral leukoplakia, which was first described in 1985 by Hansen et al. Since then, various published case series have presented PVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation, usually higher than 70%. PVL is a long-term progressive condition, which is observed more frequently in elderly women, over 60 years at the time of diagnosis. The buccal mucosa and tongue are the most frequently involved sites. It develops initially as a white plaque of hyperkeratosis that eventually becomes a multifocal disease with confluent, exophytic and proliferative features with a progressive deterioration of the lesions, making it more and more difficult to control. Tobacco use does not seem to have a significant influence on the appearance or progression of PVL and may occur both in smokers and nonsmokers. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa. At present, the etiology of PVL remains unclear as well as its management and diagnosis, which is still retrospective, late and poorly defined, lacking consensus criteria. This short review discusses the clinical and histopathological features, diagnosis, traditional treatment and the current management of the disease.

  11. Effects of Echinacea Purpurea on Wound Healing after Arsenic Induced Skin Necrosis

    Directory of Open Access Journals (Sweden)

    Annahita Rezaie

    2013-11-01

    Full Text Available Background: Evaluation of healing effects of Echinacea extract in Arsenic induced dermal necrosis in rat is the objective of this study. Materials and Methods: In this experimental study 20 male Wistar rats were divided to 2 groups. Dermal necrosis was induced by subcutaneously arsenic injection (4mg/kg for 10 days. In group 2, after arsenic receiving, Echinacea were injected intraperitoneally (400mg/kg. After last day of injection, rats were euthanizes and pathologic samples were collected from dermal ulcers.Results: Histopathologic results revealed necrosis of different dermal layers in arsenic group. There were inflammatory exudates instead of impaired structures. In group 2, there were granulation tissue with high cellularity and new vessels.Conclusion: According to this research findings arsenic can induce dermal necrosis which is a good animal model for dermatologic researches and also Echinacea has healing effects and can protect and limit the Arsenic effects.

  12. Protective effect of arjunolic acid against arsenic-induced oxidative stress in mouse brain.

    Science.gov (United States)

    Sinha, Mahua; Manna, Prasenjit; Sil, Parames C

    2008-02-01

    Arsenic, a notoriously poisonous metalloid, is ubiquitous in the environment, and it affects nearly all organ systems of animals including humans. The present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid against arsenic-induced oxidative damage in murine brain. Sodium arsenite was selected as a source of arsenic for this study. The free-radical-scavenging activity and the in vivo antioxidant power of arjunolic acid were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of sodium arsenite at a dose of 10 mg/kg body weight for 2 days significantly decreased the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase, the level of cellular metabolites, reduced glutathione, total thiols and increased the level of oxidized glutathione. In addition, it enhanced the levels of lipid peroxidation end products and protein carbonyl content. Treatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days prior to arsenic administration almost normalized above indices. Histological findings due to arsenic intoxication and arjunolic acid treatment supported the other biochemical changes in murine brains. Results of 2,2-diphenyl-1-picryl hydrazyl radical scavenging and ferric reducing/antioxidant power assays clearly showed the in vitro radical scavenging as well as the in vivo antioxidant power of arjunolic acid, respectively. The effect of a well-established antioxidant, vitamin C, has been included in the study as a positive control. Combining all, results suggest that arjunolic acid possessed the ability to ameliorate arsenic-induced oxidative insult in murine brain and is probably due to its antioxidant activity.

  13. Ameliorative efficacy of tetrahydrocurcumin against arsenic induced oxidative damage, dyslipidemia and hepatic mitochondrial toxicity in rats.

    Science.gov (United States)

    Muthumani, M; Miltonprabu, S

    2015-06-25

    Arsenic (As) is a well-known human carcinogen and a potent hepatotoxin. Environmental exposure to arsenic imposes a serious health hazard to humans and other animals worldwide. Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, exhibits many of the same physiological and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than the curcumin. It has been reported that THC has antioxidant efficacy attributable to the presence of identical β-diketone of 3rd and 5th substitution in heptane moiety. In the present study, rats were orally treated with arsenic alone (5 mg kg(-1) bw/day) with THC (80 mg kg(-1) bw/day) for 28 days. Hepatotoxicity was measured by the increased activities of serum hepatospecific enzymes, namely aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin along with increased elevation of lipid peroxidative markers, thiobarbituric acid reactive substances. And also elevated levels of serum cholesterol, triglycerides, free fatty acids and phospholipids were observed in arsenic intoxicated rats. These effects of arsenic were coupled with enhanced mitochondrial swelling, inhibition of cytochrome c oxidase, Ca(2+)ATPase and a decrease in mitochondrial calcium content. The toxic effect of arsenic was also indicated by significantly decreased activities of enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase along with non-enzymatic antioxidant such as reduced glutathione. Administration of THC exhibited significant reversal of arsenic induced toxicity in hepatic tissue. All these changes were supported by the reduction of arsenic concentration and histopathological observations of the liver. These results suggest that THC has a protective effect over arsenic induced toxicity in rat.

  14. Epigenome-wide DNA methylation changes with development of arsenic-induced skin lesions in Bangladesh: a case-control follow-up study

    OpenAIRE

    2014-01-01

    Studies have found an association between aberrant DNA methylation and arsenic-induced skin lesions. Yet, little is known about DNA methylation changes over time in people who develop arsenic-induced skin lesions. We sought to investigate epigenome-wide changes of DNA methylation in people who developed arsenic-induced skin lesions in a ten year period. In 2009–2011, we conducted a follow-up study of 900 skin lesion cases and 900 controls and identified 10 people who developed skin lesions si...

  15. Arsenic-induced morphogenic response in roots of arsenic hyperaccumulator fern Pteris vittata.

    Science.gov (United States)

    Forino, Laura Maria Costantina; Ruffini Castiglione, Monica; Bartoli, Giacomo; Balestri, Mirko; Andreucci, Andrea; Tagliasacchi, Anna Maria

    2012-10-15

    On the assumption that arsenic induces stress morphogenetic responses involved in As tolerance and hyperaccumulation in the Pteris vittata fern, we analyzed the root system of young sporophytes grown in 250, 334, and 500 μM As for five days and for 14 days. Anatomical and histological analyses were performed in plants grown for five days to evaluate the number, position, length and differentiation pattern of root hairs. AgNOR staining, employed to study nucleolus behavior in root apices, showed that arsenic influences nucleolar activity (evaluated by nucleolus size, number and absorbance) in the root meristem. In plants treated with 250 and 334 μM As an acropetal shift of root hair development and an increase in hair length and density were observed, linked to an ectopic pattern of differentiation. The opposite trend was recorded in plants treated with 500 μM As. It is worth noting the presence of living border-like cells, not yet observed in ferns, and their increase following As treatments. Analysis and vitality of border-like cells were surveyed after 14 days of treatments. In conclusion As treatments elicited a stress-induced morphogenic response which, by modifying the differentiation pattern, number and length of root hairs, modulating nucleolar activity and interacting with the rhizosphere by inducing border-like cell production, may adjust the rate of root uptake and its metabolic activity.

  16. Arsenic-induced genotoxicity in Nile tilapia (Orechromis niloticus); the role of Spirulina platensis extract.

    Science.gov (United States)

    Sayed, Alaa El-Din H; Elbaghdady, Heba Allah M; Zahran, Eman

    2015-12-01

    Arsenic (As) is one of the most relevant environmental global single substance toxicants that have long been regarded as a carcinogenic and genotoxic potential. In this respect, we evaluated the cytogenetic effect of arsenic exposure in Nile tilapia (Oreochromis niloticus), in terms of erythrocyte alteration, apoptosis, and induction of micronuclei. Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phytoantioxidant, anti-inflammatory, and anti-cancerous properties supplementation. The protective role of Spirulina as supplementary feeds was studied in Nile tilapia (O. niloticus) against arsenic-induced cytogenotoxicity. Four groups were assigned as control group (no SP or As), As group (exposed to water-born As in the form of NaAsO2 at 7 ppm), SP1 (SP at 7.5% + As at the same level of exposure), and SP2 (SP at 10% + As at the same level of exposure). As-treated group had a significant increase in all cytogenetic analyses including erythrocyte alteration, apoptosis, and induction of micronuclei after 2 weeks with continuous increase in response after 3 weeks. The combined treatment of Spirulina at two different concentrations of 7.5 and 10% had significantly declined the induction of erythrocyte alteration, apoptosis, and micronuclei formation induced by arsenic intoxication.

  17. Protective effects of quercetin against arsenic-induced testicular damage in rats.

    Science.gov (United States)

    Baltaci, B B; Uygur, R; Caglar, V; Aktas, C; Aydin, M; Ozen, O A

    2016-12-01

    This study investigated the effect of quercetin on changes in testes due to arsenic exposure. Twenty-seven male rats were divided into three groups: control (10 ml kg(-1)  day(-1) saline), arsenic (10 mg kg(-1)  day(-1) sodium arsenite) and arsenic + quercetin (arsenic + 50 mg kg(-1)  day(-1) quercetin). The rats were sacrificed at the end of 15-day experiment. There was no difference between control group and arsenic group in body weight gain, testicular weight and serum total testosterone level. Quercetin treatment did not cause a significant difference in these parameters. In the arsenic group rats, we determined deterioration in the structure of seminiferous tubules, a decrease in the number of spermatogenic cells, an increase in the number of apoptotic cells, a decrease in the number of PCNA-positive cells, a decrease in SOD, CAT and GSH-Px activities, and an increase in the MDA level in testicular tissue. In all these changes, arsenic+quercetin group showed an improved compared to arsenic group. The amount of arsenic increased in the arsenic group was compared to the control group, and there was no difference between arsenic group and arsenic + quercetin group in the amount of arsenic. In conclusion, quercetin prevented arsenic-induced testicular damage with its anti-apoptotic and antioxidant effects.

  18. Effect of vitamin E supplementation on arsenic induced oxidative stress in goats.

    Science.gov (United States)

    Das, T K; Mani, V; Kaur, H; Kewalramani, N; De, S; Hossain, A; Banerjee, D; Datta, B K

    2012-07-01

    The present study was designed to assess whether supplementation of different levels of vitamin E to long-term arsenic exposed goats affords protection against the oxidative stress caused by the metalloid. Twenty-four crossbred lactating goats were distributed randomly into four groups (control, T(1), T(2) and T(3)) of six in each. The animals in T(1), T(2) and T(3) were given 50 mg/kg DM arsenic daily, while in T(2) and T(3), vitamin E @100 IU and 150 IU/kg DM, respectively, was also supplemented additionally for the period of 12 months. Compared to control, significant (p 63 %), plasma total Ig (22 %) and total antioxidant activity (24 %) was observed in only arsenic treated groups and vitamin E supplementation in both doses produced partial mitigation effect against SOD (23 %, 20 %) and CAT (39 %, 48 %) while complete mitigation against total Ig (16 %, 7 %) and antioxidant activity (10 %, 8 %) was found. Average lymphocyte stimulation index at the end of experiment was (p arsenic exposed groups (1.003 ± 0.01) and significant (p arsenic induced oxidative stress and activities of antioxidant enzymes in goats.

  19. 尿轻链κ、λ及其比值检测在老年B细胞恶性增殖性疾病患者中的应用价值%The applied value of urine light chain κ、λ and κ/λ ratio test in older people with B cell malignant prolif-erative disease

    Institute of Scientific and Technical Information of China (English)

    孙启鑫; 温真真; 朱志刚

    2016-01-01

    Objective To explore the applied value of urine light chainκ、λand κ/λ ratio test in older people with B cell malignant proliferative disease.Methods Young volunteers, general older patients, kidney failure older patients and older patients with B cell malignant proliferative disease were selected and immunoephe-lometry method was applied to detect the level of urine light chainκ、λ and κ/λ ratio.Result The average levels (mg/L)of urine light chain κand λin older patients with kidney failure group(172.00 ±188.10,111.50 ± 109.32)were higher than that in general older patients group(32.72 ±33.60,15.02 ±15.58).In each of the ol-der patients groups,the levels of urine light chainκandλwere higher than that in young volunteers groups(9.30 ±5.80,4.97 ±2.61).The κ/λ ratios of urine light chain in older patients with kidney failure group(1.59 ± 0.4),general older patients group(2.19 ±0.54)and young volunteers group(1.92 ±0.48)were consistent,how-ever,it was significantly abnormal in older patients with B cell malignant proliferative disease group,the ratio was high inκtype(44.8 ±83.17)and low inλtype(0.06 ±0.08).After effective treatment, κ/λ ratio of urine light chain in older patients with B cell malignant proliferative disease tended to normal.Conclusion The level of u-rine light chainκandλis effected by renal function,but not involved the κ/λ ratio.B cell malignant proliferative disease significantly affects theκ/λratio of urine light chain.Constantly monitoring the change ofκ/λratio of u-rine light chain in older peoples with B cell malignant proliferative disease can reflect the proliferative degree of malignant B cell in vivo.%目的 探讨尿轻链κ、λ及其比值检测在老年B细胞恶性增殖性疾病患者中的应用价值.方法 应用免疫比浊法,检测青年对照组、老年普通患者、老年肾衰竭患者以及老年B细胞恶性增殖性疾病患者治疗前后尿轻链κ、λ水平并计算κ/λ比值.

  20. Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

    Science.gov (United States)

    Li, S G; Xu, S Z; Niu, Q; Ding, Y S; Pang, L J; Ma, R L; Jing, M X; Wang, K; Ma, X M; Feng, G L; Liu, J M; Zhang, X F; Xiang, H L; Li, F

    2016-05-01

    This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

  1. Serum Acetyl Cholinesterase as a Biomarker of Arsenic Induced Neurotoxicity in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2005-04-01

    cholinesterase is a candidate biomarker for arsenic-induced neurotoxicity in Sprague-Dawley rats.

  2. Arsenic induces apoptosis by the lysosomal-mitochondrial pathway in INS-1 cells.

    Science.gov (United States)

    Pan, Xiao; Jiang, Liping; Zhong, Laifu; Geng, Chengyan; Jia, Li; Liu, Shuang; Guan, Huai; Yang, Guang; Yao, Xiaofeng; Piao, Fengyuan; Sun, Xiance

    2016-02-01

    Recently, long term arsenic exposure was considered to be associated with an increased risk of diabetes mellitus. While a relation of cause-and-effect between apoptosis of pancreatic β-cells and arsenic exposure, the precise mechanisms of these events remains unclear. The aim of this study was to explore arsenic-induced pancreatic β-cell apoptosis and the mechanisms of through the possible link between lysosomal and the mitochondrial apoptotic pathway. After exposure to 10 μM of arsenic, the reactive oxygen species (ROS) level was significantly increased at 12 h, while the mitochondrial membrane potential was reduced at 24 h and the lysosomal membrane integrity was disrupted at 48 h. A significant increase in protein expression for cytochrome c was also observed using Western blot analysis after exposure to arsenic for 48 h. To further demonstrate that arsenic reduced the lysosomal membrane integrity, cells pretreated with NH4 Cl and exposed to arsenic harbored a lower fluorescence increase than cells that were only exposed to arsenic. In addition, apoptosis was mesured using Hoechst 33342/PI dual staining by microscopy and annexin V-FITC/propidium iodide dual staining by flow cytometry. The results show an increased uptake of the arsenic dose and the cells changed from dark blue to light blue, karyopyknosis, nuclear chromatin condensation, side set or fracture, and a correlation was found between the number of apoptotic cells and arsenic dose. The result of present study suggest that arsenic may induce pancreatic β-cell apoptosis through activation of the lysosome-mitochondrial pathway.

  3. Research Progress on Molecular Mechanisms of Arsenic- induced Oxidative Stress%砷的氧化应激分子机制研究进展

    Institute of Scientific and Technical Information of China (English)

    白彩军; 刘丹; 李冰

    2012-01-01

    砷暴露能够引起多种疾病和病理损伤.目前氧化应激机制是砷毒性的研究热点.砷通过扰乱氧化/抗氧化平衡,从而引起细胞信号通路和转录因子活性、细胞周期和细胞凋亡、线粒体、抗氧化物酶的活性、抗氧化防御系统等方面的改变.本文将就砷的氧化应激分子机制的研究进展进行综述.%Arsenic exposure can cause a variety of diseases and pathological damages. In recent years, oxidative stress mechanism has been considered to be the research focus of arsenic toxicity. Arsenic alters multiple cellular pathways and transcription factor activities, cell cycle and cell apoptosis, mitochondria, antioxidant enzymes activity, and antioxidant defense system by disturbing the pro/antioxidant balance. This review summarizes the molecular mechanism of arsenic- induced oxidative stress.

  4. Characterization of arsenic-induced cytotoxicity in liver with stress in erythrocytes and its reversibility with Pleurotus florida lectin.

    Science.gov (United States)

    Rana, Tanmoy; Bera, Asit Kumar; Bhattacharya, Debasis; Das, Subhashree; Pan, Diganta; Das, Subrata Kumar

    2015-02-01

    Arsenic is one of the most hazardous substances in the environment known to cause toxicity in multiple organs. Cell adhesion, morphological alterations, cell proliferation, terminal deoxyuridine triphosphate nick-end labeling (TUNEL) and caspase-3/CPP32 fluorometric protease assay were important biomarkers to assess apoptosis in cells. This study aimed to evaluate arsenic-induced apoptosis in the hepatocytes of rat and its protective efficacy with coadministration of ascorbic acid (AA) and Pleurotus florida lectin (PFL) individually. Results of the present study also showed that arsenic caused cytotoxicity by elevating morphological alterations, TUNEL-positive nuclei, caspase-3 activity and DNA damage and reducing cell adhesion and cell proliferation in a time-dependent manner. The apoptosis in hepatocytes was reverted to normal value after coadministration of mushroom lectin in arsenic-exposed rat. The study provided significant evidence that PFL has antiapoptotic property against arsenic-induced toxicity. The beneficial effect of PFL was proportional to its duration of exposure. Retard activities of superoxide dismutase and catalase, enhanced lipid peroxidation as well as protein carbonyl in erythrocytes caused by arsenic could also be maintained toward normalcy by supplementation of AA and PFL. These antioxidative effects were exhibited in a time-dependant manner. In rat, treatment with AA and PFL prevented alteration of plasma enzyme activities caused by arsenic. The results concluded that treatment with PFL has significant role in protecting animals from arsenic-induced erythrocytic damage. This finding might be of therapeutic benefit in people suffering from chronic exposure to arsenic from natural sources, a global problem especially relevant to millions of people on the Indian subcontinent.

  5. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  6. [Proliferative vitreoretinopathy: modern view on etiology and pathogenesis].

    Science.gov (United States)

    Artem'eva, O V; Samoĭlov, A N; Zhernakov, S V

    2014-01-01

    Studies on etiology and pathogenesis of proliferative vitreoretinopathy are necessitated by the absence of a unified theory, which would provide a clear understanding of causes and mechanisms of the disease. The results of recent investigations allow to consider proliferative vitreoretinopathy as an uncontrollable plastic process caused by certain changes in the retina aimed at survival of its cells under oxidative stress. This approach enables preclinical indication of the process and development of new therapies.

  7. Protective role of Moringa oleifera (Sajina) seed on arsenic-induced hepatocellular degeneration in female albino rats.

    Science.gov (United States)

    Chattopadhyay, Sandip; Maiti, Smarajit; Maji, Gurupada; Deb, Bimal; Pan, Bappaditya; Ghosh, Debidas

    2011-08-01

    In an attempt to develop new herbal therapy, an aqueous extract of the seed of Moringa oleifera was used to screen the effect on arsenic-induced hepatic toxicity in female rat of Wistar strain. Subchronic exposure to sodium arsenite (0.4 ppm/100 g body weight/day via drinking water for a period of 24 days) significantly increased activities of hepatic and lipid function markers such as alanine transaminase, aspartate transaminase, cholesterol, triglycerides, LDL along with a decrease in total protein and HDL. A notable distortion of hepatocellular histoarchitecture was prominent with a concomitant increase in DNA fragmentation following arsenic exposure. A marked elevation of lipid peroxidation in hepatic tissue was also evident from the hepatic accumulation of malondialdehyde and conjugated dienes along with suppressed activities in the antioxidant enzymes such as superoxide dismutase and catalase. However, co-administration of aqueous seed extract of M. oleifera (500 mg/100 g body weight/day for a period of 24 days) was found to significantly prevent the arsenic-induced alteration of hepatic function markers and lipid profile. Moreover, the degeneration of histoarchitecture of liver found in arsenic-treated rats was protected along with partial but definite prevention against DNA fragmentation induction. Similarly, generation of reactive oxygen species and free radicals were found to be significantly less along with restored activities of antioxidant enzymes in M. oleifera co-administered group with comparison to arsenic alone treatment group. The present investigation offers strong evidence for the hepato-protective and antioxidative efficiencies of M. oleifera seed extract against oxidative stress induced by arsenic.

  8. Chronic proliferative dermatitis in Sharpin null mice: development of an autoinflammatory disease in the absence of B and T lymphocytes and IL4/IL13 signaling.

    Directory of Open Access Journals (Sweden)

    Christopher S Potter

    Full Text Available SHARPIN is a key regulator of NFKB and integrin signaling. Mice lacking Sharpin develop a phenotype known as chronic proliferative dermatitis (CPDM, typified by progressive epidermal hyperplasia, apoptosis of keratinocytes, cutaneous and systemic eosinophilic inflammation, and hypoplasia of secondary lymphoid organs. Rag1(-/- mice, which lack mature B and T cells, were crossed with Sharpin(-/- mice to examine the role of lymphocytes in CDPM. Although inflammation in the lungs, liver, and joints was reduced in these double mutant mice, dermatitis was not reduced in the absence of functional lymphocytes, suggesting that lymphocytes are not primary drivers of the inflammation in the skin. Type 2 cytokine expression is increased in CPDM. In an attempt to reduce this aspect of the phenotype, Il4ra(-/- mice, unresponsive to both IL4 and IL13, were crossed with Sharpin(-/- mice. Double homozygous Sharpin(-/- , Il4ra(-/- mice developed an exacerbated granulocytic dermatitis, acute system inflammation, as well as hepatic necrosis and mineralization. High expression of CHI3L4, normally seen in CPDM skin, was abolished in Sharpin(-/- , Il4ra(-/- double mutant mice indicating the crucial role of IL4 and IL13 in the expression of this protein. Cutaneous eosinophilia persisted in Sharpin(-/- , Il4ra(-/- mice, although expression of Il5 mRNA was reduced and the expression of Ccl11 and Ccl24 was completely abolished. TSLP and IL33 were both increased in the skin of Sharpin(-/- mice and this was maintained in Sharpin(-/- , Il4ra(-/- mice suggesting a role for TSLP and IL33 in the eosinophilic dermatitis in SHARPIN-deficient mice. These studies indicate that cutaneous inflammation in SHARPIN-deficient mice is autoinflammatory in nature developing independently of B and T lymphocytes, while the systemic inflammation seen in CPDM has a strong lymphocyte-dependent component. Both the cutaneous and systemic inflammation is enhanced by loss of IL4 and IL13 signaling

  9. Proliferative periostitis: a case report.

    Science.gov (United States)

    Zand, Vahid; Lotfi, Mehrdad; Vosoughhosseini, Sepideh

    2008-04-01

    Proliferative periostitis of Garré represents a periosteal reaction to the presence of infection or other irritants. This can be odontogenic or nonodontogenic. This is a case report of an odontogenic periostitis resulting from endodontic origin. It was successfully treated by nonsurgical root canal therapy without using antibiotic therapy during the treatment of this case.

  10. A cross sectional study of anemia and iron deficiency as risk factors for arsenic-induced skin lesions in Bangladeshi women

    OpenAIRE

    Kile, Molly L.; Faraj, Joycelyn M.; Ronnenberg, Alayne G.; Quamruzzaman, Quazi; Rahman, Mahmudar; Mostofa, Golam; Afroz, Sakila; Christiani, David C.

    2016-01-01

    Background In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions of people who rely on groundwater as their potable water source. The prevalence of anemia is also high in this region, particularly among women. Moreover, arsenic is known to affect heme synthesis and erythrocytes and the risk of arsenic-induced skin lesions appears to differ by sex. Methods We conducted a case-control study in 147 arsenic-exposed Bangladeshi women to assess the association betwee...

  11. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  12. Comparison of the susceptibility of brown trout (Salmo trutta) and four rainbow trout (Oncorhynchus mykiss) strains to the myxozoan Tetracapsuloides bryosalmonae, the causative agent of proliferative kidney disease (PKD).

    Science.gov (United States)

    Grabner, Daniel S; El-Matbouli, Mansour

    2009-11-12

    Differences in susceptibility to the myxozoan parasite Tetracapsuloides bryosalmonae, the causative agent of proliferative kidney disease (PKD), between four strains of rainbow trout (Oncorhynchus mykiss) and brown trout (Salmo trutta) were evaluated. Fish were exposed to water enzootic for the parasite in the field for 5 days and were subsequently transferred to the laboratory. Relative parasite load was determined after 2, 3 and 4 weeks post-exposure (wpe) by quantitative real-time PCR (qPCR) of kidney samples and number of parasite stages was determined in immunohistochemical stained sections of kidney, liver and spleen tissues. According to qPCR results, the highest amount of parasite DNA per equal amount of host tissue at all time points was measured in brown trout. Two of the rainbow trout strains showed lower relative parasite load than all other groups at the beginning of the experiment, but the parasite multiplied faster in these strains resulting in an equal level of relative parasite load for all rainbow trout strains at 4 wpe. A weak negative correlation of fish size and parasite load was detected. Only in samples of a few fish, single stages of T. bryosalmonae were found in sections stained by immunohistochemistry impeding quantitative evaluation of parasite numbers by this method. The results indicate a differential resistance to T. bryosalmonae between the rainbow trout strains investigated and between rainbow trout and brown trout.

  13. Arsenic-induced mitochondrial oxidative damage is mediated by decreased PGC-1α expression and its downstream targets in rat brain.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-08-25

    The present study was carried out to investigate the molecular mechanism of arsenic-induced mitochondrial oxidative damage and its relation to biogenesis in rat brain. Chronic sodium arsenite (25 ppm, orally) administration for 12 weeks decreased mitochondrial complexes activities and mRNA expression of selective complexes subunits. The expression of mitochondrial biogenesis regulator PGC-1α, and its downstream targets NRF-1, NRF-2 and Tfam were decreased significantly both at mRNA and protein levels suggesting impaired biogenesis following chronic arsenic-exposure. In addition to this, protein expression analysis also revealed activation of Bax and caspase-3, leading to translocation of cytochrome c from mitochondria to cytosol suggesting induction of apoptotic pathway under oxidative stress. This was further confirmed by electron microscopy study which depicted morphological changes in mitochondria in terms of altered nuclear and mitochondrial shape and chromatin condensation in arsenic-treated rats. The immunohistochemical studies showed both nuclear and cytosolic localization of NRF-1 and NRF-2 in arsenic-exposed rat brain further suggesting regulatory role of these transcription factors under arsenic neurotoxicity. The results of present study indicate that arsenic-induced mitochondrial oxidative damage is associated with decreased mitochondrial biogenesis in rat brain that may present as important target to reveal the mechanism for arsenic-induced neurotoxicity.

  14. Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells.

    Science.gov (United States)

    Wang, Lei; Hitron, John Andrew; Wise, James T F; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Xu, Mei; Luo, Jia; Shi, Xianglin

    2015-10-15

    Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development.

  15. [Immunomorphological research on human breast tumors using monoclonal antibodies to intermediate filament proteins. The proliferative epithelial structures in fibrocystic disease (dysplasia) and benign tumors].

    Science.gov (United States)

    Gel'shteĭn, V I; Chipysheva, T A; Ermilova, V D; Litvinova, L V; Bannikov, G A

    1986-01-01

    Proliferating epithelial structures were studied immunomorphologically in 16 cases of fibrocystic disease and benign tumours. Monoclonal antibodies were used to prekeratin (PK) C12, normally specific for the lining epithelium, to prekeratin (PK) E3 and to the protein of intermediate filaments in mesenchymal cells--vimentin, normally specific for myoepithelium. The immunofluorescent analysis of the most common proliferating structures has shown that there are elements with a variable combination of PK C12, PK E3 and vimentin among the proliferating cells. While there are cells similar to normal lining epithelium (PK C12) or myoepithelium (PK E3) and/or vimentin), many cells have no analogues either among normal cells, or among cells from ductal, lobular and tubular tumour forms. Since in the most common forms of breast cancer only cells containing PK C12 were found, the immunofluorescent study with the application of monoclonal antibodies to PK C12, PK E3 and vimentin can be recommended in difficult and dubious cases for the recognition of carcinogenic or dysplastic nature of morphologically similar proliferating structures.

  16. Arsenic induced toxicity in broiler chicks and its alleviation with ascorbic acid: a toxico-patho-biochemical study

    Science.gov (United States)

    Khan, Ahrar; Sharaf, Rabia; Khan, Muhammad Zargham; Saleemi, Muhammad Kashif; Mahmood, Fazal

    2013-01-01

    To find out toxico-pathological effects of arsenic (As) and ameliorating effect of ascorbic acid (Vit C), broilers birds were administered 50 and 250 mg/kg arsenic and Vit C, respectively alone/in combination. As-treated birds exhibited severe signs of toxicity such as dullness, depression, increased thirst, open mouth breathing and watery diarrhea. All these signs were partially ameliorated with the treatment of Vit C. As-treated birds showed a significant decrease in serum total proteins while serum enzymes, urea and creatinine were significantly increased. Alkaline phosphatase and lactate dehydrogenase completely whereas proteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were partial ameliorated in birds treated with As+Vit C as compared to As-treated and control birds. Pale and hemorrhagic liver and swollen kidneys were observed in As-treated birds. Histopathologically, liver exhibited congestion and cytoplasmic vacuolation while in kidneys, condensation of tubular epithelium nuclei, epithelial necrosis, increased urinary spaces, sloughing of tubules from basement membrane and cast deposition were observed in As-treated birds. Pathological lesions were partially ameliorated with the treatment of Vit C. It can be concluded that arsenic induces biochemical and histopathological alterations in broiler birds; however, these toxic effects can be partially attenuated by Vit C.

  17. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    Science.gov (United States)

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-01-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage.

  18. Selenium ameliorates arsenic induced oxidative stress through modulation of antioxidant enzymes and thiols in rice (Oryza sativa L.).

    Science.gov (United States)

    Kumar, Amit; Singh, Rana Pratap; Singh, Pradyumna Kumar; Awasthi, Surabhi; Chakrabarty, Debasis; Trivedi, Prabodh Kumar; Tripathi, Rudra Deo

    2014-09-01

    Arsenic (As) contamination of rice is a major problem for South-East Asia. In the present study, the effect of selenium (Se) on rice (Oryza sativa L.) plants exposed to As was studied in hydroponic culture. Arsenic accumulation, plant growth, thiolic ligands and antioxidative enzyme activities were assayed after single (As and Se) and simultaneous supplementations (As + Se). The results indicated that the presence of Se (25 µM) decreased As accumulation by threefold in roots and twofold in shoots as compared to single As (25 µM) exposed plants. Arsenic induced oxidative stress in roots and shoots was significantly ameliorated by Se supplementation. The observed positive response was found associated with the increased activities of ascorbate peroxidase (APX; EC 1.11.1.11), catalase (CAT; EC 1.11.1.6) and glutathione peroxidase (GPx; EC 1.11.1.9) and induced levels of non-protein thiols (NPTs), glutathione (GSH) and phytochelatins (PCs) in As + Se exposed plants as compared to single As treatment. Selenium supplementation modulated the thiol metabolism enzymes viz., γ-glutamylcysteine synthetase (γ-ECS; EC 6.3.2.2), glutathione-S-transferase (GST; EC 2.5.1.18) and phytochelatin synthase (PCS; EC 2.3.2.15). Gene expression analysis of several metalloid responsive genes (LOX, SOD and MATE) showed upregulation during As stress, however, significant downregulation during As + Se exposure as compared to single As treatment. Gene expressions of enzymes of antioxidant and GSH and PC biosynthetic systems, such as APX, CAT, GPx, γ-ECS and PCS were found to be significantly positively correlated with their enzyme activities. The findings suggested that Se supplementation could be an effective strategy to reduce As accumulation and toxicity in rice plants.

  19. Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic-induced toxicity in mice

    Directory of Open Access Journals (Sweden)

    Guha B

    2003-10-01

    Full Text Available Abstract Background Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols. Methods Mice were divided into different sets of control (both positive and negative and treated series (As-intoxicated, As-intoxicated plus drug-fed. Alanine amino transferase (ALT and aspartate amino transferase (AST activities and reduced glutathione (GSH level in liver and blood were analyzed in the different series of mice at six different fixation intervals. Results Both Arsenicum Album-30 and Arsenicum Album-200 ameliorated arsenic-induced toxicity to a considerable extent as compared to various controls. Conclusions The results lend further support to our earlier views that microdoses of potentized Arsenicum Album are capable of combating arsenic intoxication in mice, and thus are strong candidates for possible use in human subjects in arsenic contaminated areas under medical supervision.

  20. Arsenic induced oxidative stress and the role of antioxidant supplementation during chelation: a review.

    Science.gov (United States)

    Flora, S J S; Bhadauria, Smrati; Kannan, G M; Singh, Nutan

    2007-04-01

    Arsenic is a naturally occurring metalloid, ubiquitously present in the environment in both organic and inorganic forms. Arsenic contamination of groundwater in the West Bengal basin in India is unfolding as one of the worst natural geoenvironmental disaster to date. Chronic exposure of humans to high concentration of arsenic in drinking water is associated with skin lesions, peripheral vascular disease, hypertension, Blackfoot disease and high risk of cancer The underlying mechanism of toxicity includes the interaction with the sulphydryl groups and the generation of reactive oxygen species leading to oxidative stress. Chelation therapy with chelating agents like British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3 dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against arsenic poisoning. The treatment with these chelating agents however is compromised with certain serious drawbacks/side effects. The studies show that supplementation of antioxidants along with a chelating agent prove to be a better treatment regimen. This review attempts to provide the readers with a comprehensive account of recent developments in the research on arsenic poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects.

  1. Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12.

    Science.gov (United States)

    Acharyya, Nirmallya; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit

    2015-11-01

    Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.

  2. Arsenic-induced intensity oscillations in reflection high-energy electron diffraction measurements. [during MBE of GaAs and InAs

    Science.gov (United States)

    Lewis, B. F.; Fernandez, R.; Grunthaner, F. J.; Madhukar, A.

    1986-01-01

    A technique of arsenic-induced RHEED intensity oscillations has been used to accurately measure arsenic incorporation rates as a function of substrate temperature during the homoepitaxial growths of both GaAs and InAs by molecular beam epitaxy (MBE). Measurements were made at growth temperatures from 350 to 650 C and at arsenic fluxes of 0.1 to 10.0 monolayer/s. The method measures only the arsenic actually incorporated into the growing film and does not include the arsenic lost in splitting the arsenic tetramers or lost by evaporation from the sample.

  3. Proliferative verrucous leukoplakia may initially mimic lichenoid reactions.

    Science.gov (United States)

    Lopes, Marcio Ajudarte; Feio, Patricia; Santos-Silva, Alan Roger; Vargas, Pablo Agustin

    2015-10-16

    Proliferative verrucous leukoplakia is an intriguing disease, which occurs particularly in women aged greater than 60 years, is not associated with tobacco and alcohol, and has a high risk of recurrence and malignant transformation. Although it is well known that the typical presentation is characterized by multifocal and verrucous white lesions, there is no description that its initial clinical presentation may simulate a lichenoid reaction.

  4. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Xuefeng, E-mail: xuefengr@buffalo.edu [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Gaile, Daniel P. [Department of Biostatistics, School of Public Health and Health Professions, the State University of New York, Buffalo, NY 14214 (United States); Gong, Zhihong [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Qiu, Wenting [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Ge, Yichen [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Olson, James R. [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195 (United States); Wu, Hongmei, E-mail: hongmeiwwu@hotmail.com [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China)

    2015-03-15

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  5. Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse.

    Science.gov (United States)

    Gupta, Richa; Dubey, D K; Kannan, G M; Flora, S J S

    2007-01-01

    Contamination of ground water by arsenic has become a cause of global public health concern. In West Bengal, India, almost 6 million people are endemically exposed to inorganic arsenic by drinking heavily contaminated groundwater through hand-pumped tube wells. No safe, effective and specific preventive or therapeutic measures for treating arsenic poisoning are available. We recently reported that some of the herbal extracts possess properties effective in reducing arsenic concentration and in restoring some of the toxic effects of arsenic in animal models. Moringa oleifera Lamarack (English: Horseradish-tree, Drumstick-tree, Hindi: Saijan, Sanskrit: Shigru) belongs to the Moringaceae family, is generally known in the developing world as a vegetable, a medicinal plant and a source of vegetable oil. The objective of the present study was to determine whether Moringa oleifera (M. oleifera) seed powder could restore arsenic induced oxidative stress and reduce body arsenic burden. Exposure to arsenic (2.5 mg/kg, intraperitoneally for 6weeks) led to a significant increase in the levels of tissue reactive oxygen species (ROS), metallothionein (MT) and thiobarbituric acid reactive substance (TBARS) which were accompanied by a decrease in the activities in the antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in mice. Arsenic exposed mice also exhibited liver injury as reflected by reduced acid phosphatase (ACP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenic significantly increased the activities of SOD, catalase, GPx with elevation in reduced GSH level in tissues (liver, kidney and brain). These changes were accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver

  6. Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse.

    Science.gov (United States)

    Pachauri, Vidhu; Flora, Sjs

    2015-01-01

    Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

  7. [Proliferative diabetic retinopathy -- therapeutic approach (clinical case)].

    Science.gov (United States)

    Burcea, M; Muşat, Ovidiu; Mahdi, Labib; Gheorghe, Andreea; Spulbar, F; Gobej, I

    2014-01-01

    We present the case of a 54 year old pacient diagnosed with neglected insulin dependent diabetes and proliferative diabetic retinopathy. Surgery was recommended and we practiced posterior vitrectomy, endolaser and heavy silicone oil endotamponade. Post-operative evolution was favorable.

  8. Osteomyelitis with proliferative periostitis: an unusual case.

    Science.gov (United States)

    Tong, Antonio C K; Ng, Irene O L; Yeung, K M Au

    2006-11-01

    Chronic osteomyelitis with subperiosteal new bone formation results from periosteal reaction to chronic inflammatory/infectious stimulation. In the maxillofacial region, it has traditionally been termed Garrè's osteomyelitis with proliferative periostitis and more recently periostitis ossificans. The term Garrè's osteomyelitis has been regarded as a misnomer by many authors in the recent literature. The term chronic osteomyelitis with proliferative periostitis, although cumbersome, is considered to be the most accurate description of the pathology. It usually affects the mandible of young patients secondary to dental infection. Management involves removal of the source of infection and antibiotic treatment. We present an unusual case of chronic osteomyelitis with proliferative periostitis affecting the mandible of a 12-year-old patient. The source of infection was related to the developing lower left third molar, which had apparently no communication with the oral cavity.

  9. Proliferative and necrotising otitis externa in a cat without pinnal involvement: video-otoscopic features.

    Science.gov (United States)

    Borio, Stefano; Massari, Federico; Abramo, Francesca; Colombo, Silvia

    2013-04-01

    Proliferative and necrotising otitis externa is a rare and recently described disease affecting the ear canals and concave pinnae of kittens. This article describes a case of proliferative and necrotising otits externa in a young adult cat. In this case, the lesions did not affected the pinnae, but both ear canals were severely involved. Video-otoscopy revealed a digitally proliferative lesion, growing at 360° all around the ear canals for their entire length, without involvement of the middle ear. Histopathological examination confirmed the diagnosis, and the cat responded completely to a once-daily application of 0.1% tacrolimus ointment diluted in mineral oil in the ear canals. Video-otoscopy findings, not described previously, were very peculiar and may help clinicians to diagnose this rare disease.

  10. Arsenic Induced Inhibition of δ-aminolevulinate Dehydratase Activity in Rat Blood and its Response To Meso 2,3-dimercaptosuccinic Acid and Monoisoamyl DMSA

    Institute of Scientific and Technical Information of China (English)

    SMRATI BHADAURIA; SWARAN J.S.FLORA

    2004-01-01

    Objective The objective of this study was to investigate arsenic induced changes in blood δ-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination. Methods Rat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (Ⅲ) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1, 0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration. Results In vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (Ⅲ and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (Ⅲ) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (Ⅲ), but at two higher concentrations (0.5and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1, 0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value.Conclusions The results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood

  11. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

    Energy Technology Data Exchange (ETDEWEB)

    Samadder, Asmita; Das, Jayeeta; Das, Sreemanti; De, Arnab; Saha, Santu Kumar; Bhattacharyya, Soumya Sundar; Khuda-Bukhsh, Anisur Rahman, E-mail: prof_arkb@yahoo.co.in

    2013-02-15

    Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood–brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenic were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. - Highlights: ► PLGA encapsulated nano

  12. Proliferative histiocytic disorders of canine skin.

    Science.gov (United States)

    Middleton, D J

    1997-06-01

    Proliferative histiocytic disorders of canine skin present a clinical spectrum from the innocuous self-limiting solitary dermal lesion of cutaneous histiocytoma, through the recurrent deep dermal nodules of cutaneous histiocytosis to the generally fatal condition of Bernese Mountain Dogs termed systemic histiocytosis, in which visceral involvement is commonly encountered. Immunocytochemical characterization of the constituent histiocytic cells and accompanying lymphoid infiltrate using canine species specific reagents has elucidated considerably the mechanism by which these conditions exhibit their various biologic behaviours.

  13. Postinfectious diffuse proliferative glomerulonephritis and acute renal failure in an HIV patient.

    Science.gov (United States)

    Enríquez, R; Cabezuelo, J B; Escolano, C; Pérez, M; Amorós, F; Gutiérrez-Rodero, F; Reyes, A

    2004-04-01

    Postinfectious proliferative glomerulonephritis may occur in HIV-infected patients, although it is not a common cause of severe acute renal failure in them. We report a woman with HIV infection, who developed hypocomplementemic acute nephritic syndrome 10 days after an upper respiratory infection. Systemic diseases were excluded. The serum creatinine level increased to 6.6 mg/dl. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis, with mesangial and capillary walls, granular deposits of IgG and C3 by immunofluorescence. She was given corticosteroids with progressive normalization of her renal function. No opportunistic infections have occurred during 1-year follow-up.

  14. Monoclonal gammopathy-associated pauci-immune extracapillary-proliferative glomerulonephritis successfully treated with bortezomib.

    Science.gov (United States)

    Grundmann, Franziska; Witthus, Marco; Göbel, Heike; Kisner, Tuelay; Siewert, Rainer; Benzing, Thomas; Kurschat, Christine E

    2013-06-01

    Extracapillary-proliferative glomerulonephritis is a rare complication of multiple myeloma. Partial remission of kidney involvement with cyclophosphamide therapy has previously been described. We report the case of a 60-year-old male patient diagnosed with rapidly progressive glomerulonephritis associated with IgG kappa monoclonal gammopathy. His kidney biopsy revealed pauci-immune extracapillary-proliferative glomerulonephritis without cryoglobulinaemia. Treatment with the proteasome inhibitor bortezomib induced rapid clinical and histological remission of his kidney disease. The patient's renal function remained stable on bortezomib maintenance therapy. Our findings suggest that bortezomib is a promising therapeutic approach to ameliorate severe kidney damage in monoclonal gammopathy- and myeloma-associated pauci-immune extracapillary-proliferative glomerulonephritis.

  15. Strategic planning ensures surgical success in cases of proliferative vitreoretinopathy.

    Science.gov (United States)

    Lakhanpal, R Ross; Hariprasad, Seenu M

    2015-02-01

    For this Practical Retina column, Dr. Ross Lakhanpal from Baltimore was asked to comment on the current state of thinking and management options for proliferative vitreoretinopathy (PVR) after retinal detachment (RD) surgery.We are all aware that PVR continues to be an important cause of recurrent RD after successful repair. This feared complication has been reported to occur in up to 8% of patients after undergoing RD repair. Despite the historic progress made in managing various vitreoretinal diseases over the past decade, most retina specialists will agree that an unmet need remains in this landscape. Fortunately, advances in various surgical technologies such as instrumentation, lighting, and visualization have improved the outcomes after PVR management.Dr. Lakhanpal discusses causes of PVR, management goals, surgical techniques, and pearls to avoid complications after managing PVR. His experience working in an urban tertiary surgical retina practice enables him to offer insights that will be highly valued by our community.

  16. Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Shafik, Noha M; El Batsh, Maha M

    2016-01-01

    Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p rat group treated with both P. granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

  17. Body linear traits for identifying prolific goats

    Directory of Open Access Journals (Sweden)

    Avijit Haldar

    2014-12-01

    Full Text Available Aim: The present study was conducted on prolific goat breed to identify body linear type traits that might be associated with prolificacy trait in goats. Materials and Methods: Two-stage stratified random sample survey based data were collected from 1427 non-pregnant goats with the history of single, twin and triplet litter sizes (LZ between January 2008 to February 2011 for 3 years in 68 villages located in East and North East India. Data on sixteen body linear traits were analyzed using logistic regression model to do the step-wise selection for identifying the body linear traits that could determine LZ. An average value for each identified body linear trait was determined for classifying the goats into three categories: Goats having the history of single LZ, goats having the history of twin LZ and goats having the history of triplet LZ. Results: The LZ proportions for single, twin and triplet, were 29.50, 59.14 and 11.36%, respectively, with the prolificacy rate of 181.85% in Indian Black Bengal goats. A total of eight body linear traits that could determine LZ in prolific goats were identified. Heart girth (HG measurement (>60.90 cm, paunch girth (PG (>70.22 cm, wither height (WH (>49.75 cm, neck length (>21.45 cm, ear length (>12.80 cm and distance between trochanter major (DTM bones (>12.28 cm, pelvic triangle area (PTA (>572.25 cm2 and clearance at udder (CU (>23.16 cm showed an increase likelihood of multiple LZ when compared to single LZ. Further, HG measurement (>62.29 cm, WH (>50.54 cm, PG (>71.85 cm and ear length (>13.00 cm, neck length (>22.01 cm, PTA (>589.64 cm2, CU (>23.20 cm and DTM bones (>12.47 cm were associated with increased likelihood of triplet LZ, when compared with that of twin LZ. Conclusion: HG measurement was the best discriminating factor, while PG, neck length, DTM bones, CU, PTA, WH and ear length measurements were other important factors that could be used for identifying prolific goats to achieve economic

  18. Clues to prolific productivity among prominent scientists.

    Science.gov (United States)

    Kantha, S S

    1992-10-01

    In a survey based on the biographical sketches, obituary notes and eulogies of notable scientists, eight were identified as belonging to an elite group, having authored more than 1000 research publications, which include books, monographs and patents. They were, in chronological order, Thomas Alva Edison, Paul Karrer, Margaret Mead, Giulio Natta, Hans Selye, Herbert C Brown, Tetsuji Kametani and Carl Djerassi. Among these, Karrer, Natta and Brown were Nobelists in chemistry. Four criteria which can be identified as clues to their prolific productivity are, 1) enthusiasm for compulsive work and eccentric life style, 2) physical and/or environmental handicap, 3) pioneering efforts in a new research field, and 4) selection of research area, predominantly organic chemistry.

  19. Response of arsenic-induced oxidative stress, DNA damage, and metal imbalance to combined administration of DMSA and monoisoamyl-DMSA during chronic arsenic poisoning in rats.

    Science.gov (United States)

    Bhadauria, S; Flora, S J S

    2007-03-01

    -exposed rats compared to that of normal animals. These changes were accompanied by a significant elevation in blood and soft-tissue arsenic concentration. Co-administration of DMSA and MiADMSA at lower dose (0.15 mmol/kg) was most effective not only in reducing arsenic-induced oxidative stress but also in depleting arsenic from blood and soft tissues compared to other treatments. This combination was also able to repair DNA damage caused following arsenic exposure. We thus recommend combined administration of DMSA and MiADMSA for achieving optimum effects of chelation therapy.

  20. Coordination Skills during Vitrectomy in Treatment of Proliferative Diabetic Retinopathy

    Institute of Scientific and Technical Information of China (English)

    Xuehong Chen; Shanshan Luo; Yanchan Liu

    2014-01-01

    Purpose:.To discuss effective nursing and coordination skills for vitrectomy in the treatment of diabetic retinopathy. Methods: Fifty patients (51 eyes) with diabetic retinopathy required vitrectomy were enrolled in this study..Individual nursing service was delivered by strengthening preoperative preparation, providing psychological nursing, and intraopera-tive observation of the severity of diseases by circulating nurses;meticulous nursing was given postoperatively. Results:All 50 patients underwent surgery successfully..Intra-operatively,.patients had stable physical signs..Five patients had postoperative visual acuity0.3..No complicated infection was seen. Conclusion: For patients diagnosed with proliferative diabetic retinopathy requiring vitrectomy,.full preparations should be made and psychological nursing should be delivered preopera-tively, the severity of diseases and clinical reactions should be closely observed intraoperatively,.and proper processing and nursing measures should be taken postoperatively,.which col-lectively enhance surgical success rate,.decrease surgical com-plications,.and attain favorable treatment efficacy.(Eye Science 2014; 29:55-58).

  1. Proliferative Chronic Myelomonocytic Leukemia (CMML) | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available dad de ruxolitinib (INCB018424) en pacientes con leucemia mielomonocítica crónica (LMMC) de tipo mieloprolif...a Ensayo clínico para evaluar la eficacia y la seguridad de ruxolitinib en pacientes con leucemia...investigated Proliferative Chronic Myelomonocytic Leukemia (CMML) leucemia mielom...Chronic Myelomonocytic Leukemia leucemia mielomonocítica crónica E.1.1.2Therapeutic area Diseases [C] - Bloo

  2. Analysis on Pathogenesis of 50 Cases of Bladder Proliferative Lesions

    Institute of Scientific and Technical Information of China (English)

    陈志强; 蓝儒竹; 叶章群; 杨为民

    2003-01-01

    In order to study the pathogenesis, clinical and pathological characteristics of prolifera-tive lesions of the bladder, 50 cases of proliferative lesions of the bladder from 150 patients withcomplaints of frequency, urgency, hematuria and dysuria were subjected to cystoscopic biopsy ofthe suspicious foci in the bladder. In combination with the symptoms, urine routine and urodynam-ics, the relationship of proliferative lesions of the bladder to the inflammation and obstruction of thelower urinary tract was analyzed. Of the 50 cases of proliferative bladder lesions, 44 cases (88%)had lower urinary tract infection and 29 (58%) lower urinary tract obstruction. The patients withlower urinary tract obstruction were all complicated with infection. Three cases were associatedwith transitional cell carcinoma. Malignant cells were detected in 1 case by urinary cytologic exami-nation. Proliferative lesions of the bladder, especially those without other obvious mucosa changesunder cystoscopy, are common histological variants of urothelium in the patients with chronic in-flammation and obstruction of the lower urinary tract. Chronic inflammation and obstruction of thelower urinary tract might be the causes for proliferative lesions of the bladder. It is suggested thatdifferent treatments should be applied according to the scope and histological type of the prolifera-tive lesions.

  3. Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    V V Chernykh

    2015-01-01

    Full Text Available Purpose: The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF] in the vitreous of patients with proliferative diabetic retinopathy (PDR and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR. Materials and Methods : Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1, interleukin-4 (IL-4, IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA were simultaneously measured using enzyme-linked immunoassay. Results : Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05 higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (Π < 0.05 positive correlations were observed between vitreous concentrations of VEGF and IL-17ΐ (r = 0.45, VEGF and IL-8 (r = 0.48, VEGF and IL-4 (r = 0.51, PEDF and IL-17ΐ (r = 0.48, PEDF and IL-8 (r = 0.59, MCP-1 and PEDF (r = 0.72, MCP-1 and IL-8 (r0 = 0.45, IL-4 and IL-17ΐ (r = 0.65, IL-4 and IL-8 (r = 0.71, IL-8 and IL-17ΐ (r = 0.59. Conclusions: Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.

  4. Intravitreal methotrexate infusion for proliferative vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Sadaka A

    2016-09-01

    Full Text Available Ama Sadaka,1 Robert A Sisk,1–3 James M Osher,1,3 Okan Toygar,4 Melinda K Duncan,5 Christopher D Riemann1,3 1Department of Ophthalmology, University of Cincinnati College of Medicine, 2Department of Opthalmology, Cincinnati Children’s Hospital Medical Center, 3Cincinnati Eye Institute, Cincinnati, OH, USA; 4Department of Ophthalmology, Bahcesehir University Medical Faculty, Istanbul, Turkey; 5Department of Biological Sciences, University of Delaware, Newark, DE, USA Purpose: The purpose of this study was to evaluate intravitreal methotrexate infusion (IMI during pars plana vitrectomy (PPV for retinal detachment in patients with high risk for the development of proliferative vitreoretinopathy (PVR.Methods: Patients presenting with severe recurrent PVR with tractional retinal detachment and/or a history of severe ocular inflammation were treated with IMI. Clinical outcomes were determined from a retrospective medical chart review.Results: Twenty-nine eyes presenting with either tractional retinal detachment and recurrent PVR (n=22 or a history of severe inflammation associated with high PVR risk (n=7 received IMI during PPV. Best-corrected visual acuity at 6 months was ≥20/200 in 19 of 29 eyes (66% and remained stable or improved compared with initial presentation in 24 of 29 eyes (83%. At the last follow-up examination, the retinas of 26 of 29 eyes (90% remained attached after IMI while three eyes required another reattachment procedure. Three additional eyes (10% developed recurrent limited PVR without recurrent RD and were observed. No complications attributable to IMI occurred during a mean follow-up of 27 months.Conclusion: Eyes at high risk for PVR development due to a history of prior PVR or intraocular inflammation had a low incidence of PVR following IMI at the time of PPV for RD repair. No significant safety issues from IMI were observed in this series. Keywords: tractional retinal detachment, recurrent retinal detachment, pars

  5. Differential expression of follistatin and FLRG in human breast proliferative disorders

    Directory of Open Access Journals (Sweden)

    Amaral Vania F

    2009-09-01

    Full Text Available Abstract Background Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases. Methods Paraffin embedded specimens of normal breast (NB - n = 8; florid hyperplasia without atypia (FH - n = 17; fibroadenoma (FIB - n = 17; ductal carcinoma in situ (DCIS - n = 10 and infiltrating ductal carcinoma (IDC - n = 15 were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively. Results Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed. Conclusion The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the

  6. Characterisation of the vitreous proteome in proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Wang Hao

    2012-03-01

    Full Text Available Abstract Background Diabetes can lead to serious microvascular complications such as proliferative diabetic retinopathy (PDR, which results in severe vision loss. The diabetes-induced alterations in the vitreous protein composition in diabetic patients with PDR may be responsible for the presence of PDR. The vitreous humour can be utilised in a variety of studies aimed toward the discovery of new targets for the treatment or prevention of PDR and the identification of novel disease mechanisms. The aim of this study was to compare the protein profile of vitreous humour from diabetic patients with PDR with that of vitreous humour from normal human eyes donated for corneal transplant. Results Vitreous humour from type 2 diabetic patients with PDR (n = 10 and from normal human eyes donated for corneal transplant (n = 10 were studied. The comparative proteomic analysis was performed using two-dimensional fluorescence difference gel electrophoresis (2-D DIGE. Differentially produced proteins (abundance ratio > 2 or p Conclusions These data provide an in-depth analysis of the human vitreous proteome and reveal protein alterations that are possibly involved in the pathogenesis of PDR. Further investigation of these special proteins may provide potential new targets for the treatment or the prevention of PDR.

  7. Treatment effects of captopril on non-proliferative diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    WANG Ning; ZHENG Zhi; JIN Hui-yi; XU Xun

    2012-01-01

    Background Diabetic retinopathy (DR) is one of the most common complications of diabetes.Angiotensin-converting enzyme inhibitor is thought to play an important role in preventing and treating retinal diseases in animal models of DR.The aim of the present study was to investigate the role of angiotensin-converting enzyme inhibitor (ACEI,captopril) in the treatment of patients with non-proliferative DR.Methods Three hundred and seventeen type 2 diabetic patients (88.05% of participants) without or with mild to moderate non-proliferative retinopathy were randomly divided into captopril group (n=202) and placebo group (n=115).All subjects received 24-month follow-up.General clinical examinations,including blood pressure and glycated hemoglobin,as well as comprehensive standardized ophthalmic examinations were performed.Color fundus photography and optical coherence tomography (OCT) were used to grade diabetic retinopathy and detect macular edema respectively.Results The levels of blood pressure and glycated hemoglobin in the two groups of patients remained within the normal range during the entire follow-up and no significant difference was found between the initial and last visits,suggesting that ACEI drugs play a protective role on the DR patients independent of its anti-blood pressure role.DR classification showed that 169 eyes (83.66%) remained unchanged and the DR grade of 33 eyes (16.34%) increased in captopril group,while 84 eyes (73.04%) remained unchanged and the grade of 31 eyes (26.96%) increased in placebo group (P=0.024).Captopril treatment improved macular edema in 55.45% eyes,which was significantly higher than the 37.39% improvement in placebo group (P=0.002).No significant difference was found in the visual acuity between the two groups (P=0.271).Conclusion Captopril can improve or delay the development of DR and macular edema,which can be used in the early treatment of DR patients with type 2 diabetic mellitus.

  8. Proliferative glomerulonephritis with monoclonal IgG deposits in a patient with autoimmune hemolytic anemia.

    Science.gov (United States)

    Fujiwara, Takashi; Komatsuda, Atsushi; Ohtani, Hiroshi; Togashi, Masaru; Sawada, Ken-Ichi; Wakui, Hideki

    2013-06-01

    A 25-year-old woman was admitted because of proteinuria. A renal biopsy showed mesangial/endocapillary proliferative glomerulonephritis with IgG2-κ deposits. Electron microscopy showed immune complex-type deposits. She also had Coombs-positive hemolytic anemia, anticardiolipin antibodies, and antinuclear antibodies. Middle-dose steroid therapy led to improvement of proteinuria and hemolytic anemia. Six years later, she developed crescentic glomerulonephritis with IgG2-κ deposits during pregnancy. Middle-dose steroid therapy improved renal dysfunction. This is an exceptional case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a recently described rare dysproteinemia-related glomerulonephritis, associated with autoimmune disease. This case also suggests that crescentic glomerulonephritis can be superimposed on PGNMID.

  9. Proliferative periostitis of Garré: Report of a case.

    Science.gov (United States)

    Jacobson, H L Jay; Baumgartner, J Craig; Marshall, J Gordon; Beeler, William J

    2002-07-01

    Proliferative periostitis of Garré is described as a productive and proliferative inflammatory response of periosteum to infection or other irritation. This can be odontogenic or non-odontogenic in nature. This is a case report of an odontogenic periostitis resulting from periapical inflammation of endodontic origin. It was successfully treated by nonsurgical endodontics. Antibiotic therapy was not used during the treatment of this patient.

  10. Benign Proliferative Breast Lesions and Risk of Cancer

    Directory of Open Access Journals (Sweden)

    Serap Erel

    2010-06-01

    Full Text Available Benign breast lesions (BBL includes a wide variety of histologic entities, which have been broadly classified into non-proliferative lesions, proliferative lesions without atypia, and hyperplasia with atypia. With the increased use of mammography, more benign lesions are being detected, and in order to estimate the risk of breast cancer for specific histologic categories is of great importance to guide clinical management. Women with proliferative lesions without atypia are at slightly increased risk of subsequent breast cancer, whereas women with proliferative lesions with atypia have a higher risk. The risk is 1.5- 2-fold in women with proliferative lesions without atypia, 4-5-fold in women with proliferative lesions with atypia, and 8-10 fold in women with ductal carcinoma in situ. Age at diagnosis of BBL, menopausal status, family history of breast cancer in a first-degree relative, and time since BBL diagnosis on risk of breast cancer are important for risk evaluation. [Archives Medical Review Journal 2010; 19(3.000: 155-167

  11. Proliferative, reparative, and reactive benign bone lesions that may be confused diagnostically with true osseous neoplasms.

    LENUS (Irish Health Repository)

    Wick, Mark R

    2014-01-01

    Diagnostic problems attending intraosseous and parosteal pseudoneoplastic lesions can be radiographic, or histological, or both. Proliferations in this category may contain cellular fibro-osseous or chondro-osseous tissues that are difficult to separate microscopically from those seen in various true neoplasms of the bones. This review considers the clinicopathologic features of fibrous dysplasia, benign fibro-osseous lesions of the jawbones, osteofibrous dysplasia, metaphyseal fibrous defect, giant-cell reparative granuloma, "brown tumor" of hyperparathyroidism, synovial chondrometaplasia, aneurysmal bone cyst, tumefactive chronic osteomyelitis, proliferative Paget disease, and polyvinylpyrrolidone storage disease of bone.

  12. Estrogen signaling in the proliferative endometrium: implications in endometriosis

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Pereira da Costa e Silva

    2016-02-01

    Full Text Available SUMMARY Even though the physiological role of estrogen in the female reproductive cycle and endometrial proliferative phase is well established, the signaling pathways by which estrogen exerts its action in the endometrial tissue are still little known. In this regard, advancements in cell culture techniques and maintenance of endometrial cells in cultures enabled the discovery of new signaling mechanisms activated by estrogen in the normal endometrium and in endometriosis. This review aims to present the recent findings in the genomic and non-genomic estrogen signaling pathways in the proliferative human endometrium specifically associated with the pathogenesis and development of endometriosis.

  13. Proliferative and necrotizing otitis externa in a kitten: successful treatment with intralesional and topical corticosteroid therapy

    Science.gov (United States)

    MOMOTA, Yutaka; YASUDA, Junya; IKEZAWA, Mitsutaka; SASAKI, Jun; KATAYAMA, Masaaki; TANI, Kenji; MIYABE, Masahiro; ONOZAWA, Eri; AZAKAMI, Daigo; ISHIOKA, Katsumi; SAKO, Toshinori

    2016-01-01

    Proliferative and necrotising otitis externa (PNOE) is a very rare disease affecting the ear canals and concave pinnae of kittens. This report describes a 5-month-old cat with PNOE. Histopathological examination confirmed the diagnosis. Treatment was initiated with local injection of methylprednisolone acetate into the lesions. The cat was subsequently treated with clobetasol propionate cream, a potent topical glucocorticoid ointment. The cat showed marked improvement. While topical treatment with tacrolimus, an immunosuppressive agent, is reported to be an effective therapy, to the best of our knowledge, this is the first report to treat PNOE with local corticosteroid therapy. PMID:27570137

  14. Early recurrence of proliferative glomerulonephritis with monoclonal immunoglobulin deposits in a renal allograft

    Directory of Open Access Journals (Sweden)

    Rohit Tewari

    2016-01-01

    Full Text Available Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMIDs is a clinico-pathologic entity, the recurrence of which in the renal allograft has only recently been described. A 55-year-old male presented with rapid deterioration of renal function. Light microscopy showed membranoproliferative glomerulonephritis with kappa light chain restriction and only one sub-class of IgG. He subsequently underwent renal transplant. Two months later, he developed acute graft dysfunction. Renal biopsy showed a recurrence of the disease. Work up for multiple myeloma was positive. Membranoproliferative pattern of injury in the posttransplant setting has a wide range of differential diagnosis, PGNMID being one of them.

  15. Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis

    NARCIS (Netherlands)

    van Tellingen, A.; Voskuyl, A. E.; Vervloet, M. G.; Bijl, M.; de Sevaux, R. G. L.; Berger, S. P.; Derksen, R. H. W. M.; Berden, J. H. M.

    2012-01-01

    Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal fa

  16. Proliferative verrucous leukoplakia; a critical appraisal of the diagnostic criteria

    NARCIS (Netherlands)

    Carrard, V.C.; Brouns, E.R.E.A.; van der Waal, I.

    2013-01-01

    Since its introduction in the literature in 1985, the term proliferative verrucous leukoplakia (PVL) has been the subject of an ongoing discussion with regard to its definition. Widespread or multifocal occurrence of oral leukoplakia is not just synonymous to PVL. In the present treatise the proposa

  17. Reactivity in ELISA with DNA-loaded nucleosomes in patients with proliferative lupus nephritis.

    Science.gov (United States)

    Dieker, Jürgen; Schlumberger, Wolfgang; McHugh, Neil; Hamann, Philip; van der Vlag, Johan; Berden, Jo H

    2015-11-01

    Autoantibodies against nucleosomes are considered a hallmark of systemic lupus erythematosus (SLE). We compared in patients with proliferative lupus nephritis the diagnostic usefulness of a dsDNA-loaded nucleosome ELISA (anti-dsDNA-NcX) with ELISAs in which dsDNA or nucleosomes alone were coated. First, we analysed whether DNA loading on nucleosomes led to masking of epitopes by using defined monoclonal anti-DNA, anti-histone and nucleosome-specific autoantibodies to evaluate the accessibility of nucleosomal epitopes in the anti-dsDNA-NcX ELISA. Second, autoantibody levels were measured in these 3 ELISAs in 100 patients with proliferative lupus nephritis (LN) before immunosuppressive treatment and in 128 non-SLE disease controls. In patients with LN inter-assay comparisons and associations with clinical and serological parameters were analysed. The panel of monoclonal antibodies revealed that all epitopes were equally accessible in the anti-dsDNA-NcX ELISA as in the two other ELISAs. Patients with proliferative lupus nephritis were positive with dsDNA-loaded nucleosomes in 86%, with DNA in 66% and with nucleosomes in 85%. In the non-lupus disease control group these frequencies were 1.6% (2 out of 128) for both the anti-dsDNA-NcX and the anti-dsDNA ELISA and 0% in the anti-nucleosome ELISA. The levels in the anti-dsDNA-NcX ELISA were high in a group of patients with LN that showed absent reactivity in the anti-DNA or low levels in the anti-nucleosome ELISA. Anti-dsDNA-NcX positivity was associated with higher SLEDAI scores within this group. Within nucleosome-based ELISAs, we propose the anti-dsDNA-NcX ELISA as the preferred test system.

  18. An analysis of the growth of the retinal cell population in embryonic chicks yielding proliferative ratios, numbers of proliferative and non-proliferative cells and cell-cycle times for successive generations of cell cycles.

    Science.gov (United States)

    Morris, V B; Cowan, R

    1995-07-01

    Growth curves of the retinal cell population of embryonic chicks were fitted by a branching-process model of cell population growth, thereby estimating the proliferative ratios and mean cell-cycle times of the generations of cell cycles that underlie retinal growth. The proliferative ratio determines the proportion of cells that divides in the next generation, so the numbers of proliferative and non-proliferative cells in each generation of cell cycles were obtained. The mean cell-cycle times determine the times over which the generations are extant. Assuming growth starts from one cell in generation 0, the proliferative cells reach 3.6 x 10(6) and the non-proliferative cells reach 1.1 x 10(6) by generation 23. The next four generations increase the proliferative cell numbers to 13.9 x 10(6) and produce 20.1 x 10(6) non-proliferative cells. In the next five generations in the end phase of growth, non-proliferative cells are produced in large numbers at an average of 13.9 x 10(6) cells per generation as the retinal lineages are completed. The retinal cell population reaches a maximum estimated here at 98.2 x 10(6) cells. The mean cell-cycle time estimates range between 6.8 and 10.1 h in generations before the end phase of growth and between 10.6 and 17.2 h in generations in the end phase. The retinal cell population growth is limited by the depletion of the proliferative cell population that the production of non-proliferative cells entails. The proliferative ratios and the cell-cycle-time distribution parameters are the likely determinants of retinal growth rates. The results are discussed in relation to other results of spatial and temporal patterns of the cessation of cell cycling in the embryonic chick retina.

  19. Imaging findings in children with proliferative disorders following multivisceral transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Hryhorczuk, Anastasia L. [Tufts Medical Center, Department of Radiology, Boston, MA (United States); Kim, Heung Bae [Boston Children' s Hospital, Department of Surgery, Boston, MA (United States); Harris, Marian H.; Vargas, Sara O. [Boston Children' s Hospital, Department of Pathology, Boston, MA (United States); Zurakowski, David [Boston Children' s Hospital, Department of Biostatistics, Boston, MA (United States); Lee, Edward Y. [Boston Children' s Hospital and Harvard Medical School, Departments of Radiology and Medicine, Boston, MA (United States)

    2015-08-15

    Multivisceral transplantation represents an important treatment option for children with intestinal failure. The attendant immunosuppression can lead to a spectrum of cellular proliferations including benign and malignant smooth muscle tumors and lymphoproliferative disorders, many related to cellular dysregulation from Epstein-Barr virus infection. The purpose of this study is to investigate the rates of post-transplantation proliferative disorders among children with multivisceral transplantation and to characterize the imaging and pathological features of these disorders. We identified all consecutive children who underwent multivisceral transplant from August 2004 to October 2011 with at least 27 months of clinical and imaging follow-up. We reviewed medical records to determine the underlying causes of the multivisceral transplant, age at transplantation, onset of neoplasm development, and outcome. Two pediatric radiologists reviewed all imaging studies independently and diagnosis of disease was made by consensus interpretation. Pathological specimens were reviewed for histopathological findings of post-transplantation neoplasm in this pediatric patient population. The study population consisted of 14 consecutive pediatric patients (7 boys and 7 girls; mean age 26 months, range 4-113 months). Of these 14 children, 4 (29%) developed histologically confirmed post-transplant neoplasms at a mean time of 2.4 years after multivisceral transplantation. Types of neoplasms included post-transplant lymphoproliferative disorder (PTLD) in three (21%) and Epstein-Barr-virus-associated smooth muscle tumor in two (14%). (One child developed both neoplasms following transplantation). Both children with smooth muscle tumor associated with Epstein-Barr virus presented with characteristic hypointense solid masses with peripheral rim enhancement on cross-sectional imaging studies. The mortality rate of children who developed post-transplant neoplasms was higher than that of those

  20. Karyopherin alpha2 is essential for rRNA transcription and protein synthesis in proliferative keratinocytes.

    Directory of Open Access Journals (Sweden)

    Noriko Umegaki-Arao

    Full Text Available Karyopherin proteins mediate nucleocytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest KPNA2 expression is induced in tumor cells and is strongly associated with prognosis, although the precise roles and mechanisms of KPNA2 overexpression in proliferative disorders have not been defined. We found that KPNA2 expression is induced in various proliferative disorders of the skin such as psoriasis, Bowen's disease, actinic keratosis, squamous cell carcinoma, Paget's disease, Merkel cell carcinoma, and mycosis fungoides. siRNA-mediated KPNA suppression revealed that KPNA2 is essential for significant suppression of HaCaT proliferation under starvation conditions. Ribosomal RNA transcription and protein synthesis were suppressed by starvation combined with knockdown of KPNA (including KPNA2 expression. KPNA2 localized to the nucleolus and interacted with proteins associated with mRNA processing, ribonucleoprotein complex biogenesis, chromatin modification, and transcription, as demonstrated by tandem affinity purification and mass spectrometry. KPNA2 may be an important promoter of ribosomal RNA and protein synthesis in tumor cells.

  1. Classification of Non-Proliferative Diabetic Retinopathy Based on Segmented Exudates using K-Means Clustering

    Directory of Open Access Journals (Sweden)

    Handayani Tjandrasa

    2014-12-01

    Full Text Available Diabetic retinopathy is a severe complication retinal disease caused by advanced diabetes mellitus. Long suffering of this disease without threatment may cause blindness. Therefore, early detection of diabetic retinopathy is very important to prevent to become proliferative. One indication that a patient has diabetic retinopathy is the existence of hard exudates besides other indications such as microaneurysms and hemorrhages. In this study, the existence of hard exudates is applied to classify the moderate and severe grading of non-proliferative diabetic retinopathy in retinal fundus images. The hard exudates are segmented using K-means clustering. The segmented regions are extracted to obtain a feature vector which consists of the areas, the perimeters, the number of centroids and its standard deviation. Using three different classifiers, i.e. soft margin Support Vector Machine, Multilayer Perceptron, and Radial Basis Function Network, we achieve the accuracy of 89.29%, 91.07%, and 85.71% respectively, for 56 training data and 56 testing data of retinal images.

  2. Improvement in retinal venous oxygen saturation after panretinal photocoagulation is predictive of progression of proliferative diabetic retinopathy

    DEFF Research Database (Denmark)

    Torp, Thomas Lee; Kawasaki, Ryo; Wong, Tien Yin

    We performed a prospective, interventional clinical study on patients with proliferative diabetic retinopathy (PDR) in order to investigate changes in retinal oximetry before and three months after panretinal photocoagulation (PRP) and to correlate this to PDR-activity. Thirty-nine eyes from 34 p...... PRP was independently associated with PDR-activity. This might reflect absence in reduction in vascular endothelial growth factor (VEGF) and could be a potential non-invasive marker of disease activity....

  3. Proliferative periostitis of the mandibular ramus and condyle: a case report

    OpenAIRE

    Seok, Hyun; Kim, Seong-Gon; Song, Ji-Young

    2015-01-01

    Proliferative periostitis is a rare form of osteomyelitis that is characterized by new bone formation with periosteal reaction common causes of proliferative periostitis are dental caries, periodontitis, cysts, and trauma. While proliferative periostitis typically presents as a localized lesion, in this study, we describe an extensive form of proliferative periostitis involving the whole mandibular ramus and condyle. Because the radiographic findings were similar to osteogenic sarcoma, an acc...

  4. Proliferative periostitis of the mandibular ramus and condyle: a case report.

    Science.gov (United States)

    Seok, Hyun; Kim, Seong-Gon; Song, Ji-Young

    2015-08-01

    Proliferative periostitis is a rare form of osteomyelitis that is characterized by new bone formation with periosteal reaction common causes of proliferative periostitis are dental caries, periodontitis, cysts, and trauma. While proliferative periostitis typically presents as a localized lesion, in this study, we describe an extensive form of proliferative periostitis involving the whole mandibular ramus and condyle. Because the radiographic findings were similar to osteogenic sarcoma, an accurate differential diagnosis was important for proper treatment.

  5. Long-term nonprogression and broad HIV-1-specific proliferative T-cell responses

    Directory of Open Access Journals (Sweden)

    Nesrina eImami

    2013-03-01

    Full Text Available Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term nonprogressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilising cure, involving clearance of virus from the host, remains a primary aim, a functional cure may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilised in future strategies designed to improve upon existing therapy. The aim will be to induce long-term nonprogressor or elite controller status in every infected host, through immune-mediated control of viraemia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

  6. Panretinal photocoagulation versus intravitreal injection retreatment pain in high-risk proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Célia Regina Farias de Araújo Lucena

    2013-02-01

    Full Text Available PURPOSE: To compare pain related to intravitreal injection and panretinal photocoagulation in the management of patients with high-risk proliferative diabetic retinopathy. METHODS: Prospective study including patients with high-risk proliferative diabetic retinopathy and no prior laser treatment randomly assigned to receive panretinal photocoagulation (PRP group or panretinal photocoagulation plus intravitreal ranibizumab (PRPplus group. In all patients, panretinal photocoagulation was administered in two sessions (weeks 0 and 2, and intravitreal ranibizumab was administered at the end of the first laser session in the PRPplus group. Retreatment was performed at weeks 16 and 32 if active new vessels were detected at fluorescein angiography. Patients in the PRPplus group received intravitreal ranibizumab and patients in the PRP group received 500-µm additional spots per quadrant of active new vessels. After the end of retreatment, a 100-degree Visual Analog Scale was used for pain score estimation. The patient was asked about the intensity of pain during the whole procedure (retinal photocoagulation session or intravitreal ranibizumab injection. Statistics for pain score comparison were performed using a non-parametric test (Wilcoxon rank sums. RESULTS: Seventeen patients from PRPplus and 14 from PRP group were evaluated for pain scores. There were no significant differences between both groups regarding gender, glycosylated hemoglobin and disease duration. Mean intravitreal injection pain (±SEM was 4.7 ± 2.1 and was significantly lower (p<0.0001 than mean panretinal photocoagulation pain (60.8 ± 7.8. Twelve out of 17 patients from the PRPplus group referred intensity pain score of zero, while the minimal score found in PRP group was found in one patient with 10.5. CONCLUSION: In patients with high-risk proliferative diabetic retinopathy who needed retreatment for persistent new vessels, there was more comfort for the patient when retreatment

  7. Laminins Expression in Children with Mesangial Proliferative Glomerulonephritis

    Institute of Scientific and Technical Information of China (English)

    赵非; 黄松明; 陈荣华; 费莉; 郭梅; 黄文彦

    2003-01-01

    Objective: To investigate the role of laminins in the pathogensis of mesangial praliferalive glomeruonephritis (MsPGN ) in children. Methods: Eighteen renal biopsy specimens of MsPGN and 6 normal kidneys were studied by means of immunohistochemistry and in situ hybridization.Results: ① Protein of α1 chain and γ1 chain of laminin increased around the segments of proliferative mesangium. Increased expression of α2 and βl proteins was found in the segments with mesangial proliferation whereas the β2 chain expression decreased in these areas. ② The mRNA expression of αl,α2,β1 and γ1 increased to different degrees in glomeeruli with mesangial proliferation. But no difference was detected among Mild, Moderate, and Severe MsPGN. Conclusion:①The quantitative and qualitative alterations of laminin chains’ distribution were found in the measngial proliferative glomeruli. The proliferative mesougial cells were the origins of abnormal accumulation and expression of laminins.③ These changes may be the basis of the progresses of MsPGN.

  8. Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis

    Science.gov (United States)

    Caster, Dawn J.; Korte, Erik A.; Merchant, Michael L.; Klein, Jon B.; Wilkey, Daniel W.; Rovin, Brad H.; Birmingham, Dan J.; Harley, John B.; Cobb, Beth L.; Namjou, Bahram; McLeish, Kenneth R.; Powell, David W.

    2015-01-01

    PURPOSE Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN. EXPERIMENTAL DESIGN Human podocyte and glomerular proteins were separated by SDS-PAGE and immunoblotted with sera from SLE patients with and without LN. The regions of those gels corresponding to reactive bands observed with sera from LN patients were analyzed using LC-MS/MS. RESULTS LN reactive bands were seen at approximately 50 kDa in podocyte extracts and between 36-50 kDa in glomerular extracts. Those bands were analyzed by LC-MS/MS and 102 overlapping proteins were identified. Bioinformatic analysis determined that 36 of those proteins were membrane associated, including a protein previously suggested to contribute to glomerulonephritis and LN, annexin A2. By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against annexin A2. CONCLUSION AND CLINICAL RELEVANCE Proteomic approaches identified multiple candidate antigens for autoantibodies in patients with LN. Serum antibodies against annexin A2 were significantly elevated in subjects with proliferative LN, validating those antibodies as potential biomarkers. PMID:25824007

  9. Anti-proliferative activities of sinigrin on carcinogen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Jie, Meng; Cheung, Wan Man; Yu, Vivian; Zhou, Yanling; Tong, Pak Ho; Ho, John W S

    2014-01-01

    Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed. Sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. Rats were orally administered with sinigrin on a daily basis for three months before sacrifice. Sinigrin was found to significantly inhibit the proliferation of liver tumor cells; the number of surface tumors in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and down-regulation of Bcl-2 family members and caspases. Our findings indicated that the liver functions were gradually restored after treatment with sinigrin and that the agent did not cause liver toxicity. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepatocarcinogenesis in rats, and highlight the potential of sinigrin as an anti-cancer agent for liver cancer.

  10. Chronic suppurative osteomyelitis with proliferative periostitis related to a fully impacted third molar germ: a report of two cases

    Science.gov (United States)

    2016-01-01

    In prolonged chronic osteomyelitis, chronic inflammation and low-grade infections can result in new periosteal bone formation. Chronic osteomyelitis with proliferative periostitis (traditionally termed Garré's sclerosing osteomyelitis) mainly affects children and young adults. Here, we present two rare cases of an 11-year-old and a 12-year-old patient with suppurative chronic osteomyelitis with proliferative periostitis without any definitive infection source, such as dental caries or periodontitis. The source of infection was likely to be related to the development of a lower right third molar germ with follicular space widening. Management involved antibiotics and the removal of the third molar germ and surgical debridement. Disease remission and a normal appearance was observed at the six-month follow-up visit. PMID:27595089

  11. Chronic proliferative rhinitis associated with Salmonella enterica subspecies diarizonae serovar 61:k:1, 5, (7) in sheep in Spain.

    Science.gov (United States)

    Lacasta, D; Ferrer, L M; Ramos, J J; Bueso, J P; Borobia, M; Ruiz de Arcaute, M; Figueras, L; González-Sainz, J M; De Las Heras, M

    2012-11-01

    A chronic proliferative rhinitis in sheep associated with Salmonella enterica subspecies diarizonae serovar 61:k:1, 5, (7) is described. Ten adult sheep from eight traditionally managed Rasa Aragonesa flocks located in Aragon (Spain) were studied. Clinical signs began with bilateral thick mucus nasal discharge, wheezing and snoring and progressed to partial or complete obstruction of the nostrils. Necropsy examination revealed swollen ventral nasal turbinates with a roughened mucosal surface partially covered by small polyps. Histopathology revealed chronic proliferative rhinitis with a predominant population of neutrophils that infiltrated the mucosal epithelium. Plasma cells and macrophages were present in the lamina propria. Organisms expressing Salmonella antigen immunohistochemically were detected within epithelial cells. Salmonella enterica subspecies diarizonae serovar 61:k:1, 5, (7) was isolated as a sole microorganism from nasal swabs taken from five animals. The implication of finding this bacterium in various diseases in sheep and its role as a potential zoonosis are discussed.

  12. Chronic suppurative osteomyelitis with proliferative periostitis related to a fully impacted third molar germ: a report of two cases.

    Science.gov (United States)

    Park, Joonhyoung; Myoung, Hoon

    2016-08-01

    In prolonged chronic osteomyelitis, chronic inflammation and low-grade infections can result in new periosteal bone formation. Chronic osteomyelitis with proliferative periostitis (traditionally termed Garré's sclerosing osteomyelitis) mainly affects children and young adults. Here, we present two rare cases of an 11-year-old and a 12-year-old patient with suppurative chronic osteomyelitis with proliferative periostitis without any definitive infection source, such as dental caries or periodontitis. The source of infection was likely to be related to the development of a lower right third molar germ with follicular space widening. Management involved antibiotics and the removal of the third molar germ and surgical debridement. Disease remission and a normal appearance was observed at the six-month follow-up visit.

  13. Recurrent Proliferative Glomerulonephritis With Monoclonal IgG Deposits After a Renal Transplant Which Was Insensitive to Pulse Therapy Remitted by Double Filtration Plasmapheresis.

    Science.gov (United States)

    Wu, Di; Chen, Jin-Song; Cheng, Dong-Rui; Chen, Hao; Li, Xue; Ji, Shu-Ming; Xie, Ke-Nan; Ni, Xue-Feng; Liu, Zhi-Hong; Wen, Ji-Qiu

    2015-10-01

    Proliferative glomerulonephritis with monoclonal IgG deposits manifesting as a nephrotic syndrome recently has been described as a renal disease with the pathological features of mesangial and subendothelial deposits of monoclonal IgG. Eight cases of recurrent proliferative glomerulonephritis with monoclonal IgG deposits after a renal transplant have been reported. Almost all of these patients had a certain remission of proteinuria by steroids alone or with cyclophosphamide, and had further remission through other special treatments (ie, rituximab and plasmapheresis). We present a case of recurrent proliferative glomerulonephritis with monoclonal IgG deposits of the IgG3? subtype after a renal transplant, which was insensitive to pulse intravenous methyl-prednisolone and cyclophosphamide remitted by double filtration plasmapheresis. This case report reveals that recurrent proliferative glomerulo-nephritis with monoclonal IgG deposits may be insensitive to intravenous pulse therapy of methylprednisolone and cyclophosphamide. We advocate double filtration plasmapheresis as an effective treatment of proliferative glomerulo-nephritis with monoclonal IgG deposits on remission of proteinuria.

  14. Effect of focal laser photocoagulation in eyes with mild to moderate non-proliferative diabetic retinopathy

    Science.gov (United States)

    Jeong, Seong Hun; Han, Jung Il; Cho, Sung Won; Lee, Dong Won; Kim, Chul Gu; Lee, Tae Gon; Kim, Jong Woo

    2016-01-01

    AIM To report the effect of focal laser photocoagulation on both the severity of hard exudates (HEs) and the rate of disease progression in eyes with mild to moderate non-proliferative diabetic retinopathy (NPDR). METHODS We retrospectively reviewed the medical records of 33 patients (60 eyes) who had been diagnosed with mild to moderate NPDR between January 2006 and December 2012. The patients were divided into 2 groups: Group A (38 eyes in 20 patients treated using focal laser photocoagulation) and Group B (treated without laser photocoagulation). We also reviewed the best corrected visual acuity measurements, and the fundus photographs taken at both baseline and follow-up visits. RESULTS In Group A, HE severity grade had decreased significantly from baseline to the final visit (Plaser photocoagulation reduced the levels of HEs in eyes with mild to moderate NPDR. However, the treatment was not able to decelerate the progression of DR.

  15. Phenolic composition, antioxidant and anti-proliferative activities of edible and medicinal plants from the Peruvian Amazon

    Directory of Open Access Journals (Sweden)

    Jan Tauchen

    Full Text Available ABSTRACT Among 23 extracts of medicinal and edible plants tested, Mauritia flexuosa L.f., Arecaceae, showed significant antioxidant ability (DPPH and ORAC = 1062.9 and 645.9 ± 51.4 µg TE/mg extract, respectively, while Annona montana Macfad., Annonaceae, demonstrated the most promising anti-proliferative effect (IC50 for Hep-G2 and HT-29 = 2.7 and 9.0 µg/ml, respectively. However, combinatory antioxidant/anti-proliferative effect was only detected in Oenocarpus bataua Mart., Arecaceae (DPPH = 903.8 and ORAC = 1024 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 102.6 and 38.8 µg/ml, respectively and Inga edulis Mart., Fabaceae (DPPH = 337.0 and ORAC = 795.7 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 36.3 and 57.9 µg/ml, respectively. Phenolic content was positively correlated with antioxidant potential, however not with anti-proliferative effect. None of these extracts possessed toxicity towards normal foetal lung cells, suggesting their possible use in development of novel plant-based agents with preventive and/or therapeutic action against oxidative stress-related diseases.

  16. Potentiation of lymphocyte proliferative responses by nickel sulfide

    Science.gov (United States)

    Jaramillo, A.; Sonnenfeld, G.

    1992-01-01

    Crystalline nickel sulfide (NiS) induced a spleen cell proliferation that resembles a mixed lymphocyte reaction (MLR). It depended on cell-cell interaction, induced high levels of interleukin-1 (IL-1) and interleukin-2 (IL-2) and the responding cell subpopulation was composed of CD4+ T lymphocytes. Furthermore, the proliferation was inhibited in a dose-dependent manner by magnesium. Crystalline NiS also increased significantly the spleen cell proliferative response to concanavalin A (Con A) and lipopolysaccharide (LPS) with magnesium potentiating the combined effects of crystalline NiS and mitogens. Interestingly, crystalline NiS did not show any effect on the induction of IL-2 by Con A. The results described herein suggest that crystalline NiS can potentiate both antigenic (MLR) and mitogenic (Con A and LPS) proliferative responses in vitro. Crystalline NiS appears to potentiate these responses by acting in the form of ionic nickel on several intracellular targets for which magnesium ions have different noncompetitive interactions. The effects of magnesium on the potentiating action of crystalline NiS are different depending upon the type of primary stimulatory signal for proliferation (mitogenic or antigenic).

  17. Sequence stratigraphic control on prolific HC reservoir development, Southwest Iran

    Science.gov (United States)

    Lasemi, Y.; Kondroud, K.N.

    2008-01-01

    An important carbonate formation in the Persian Gulf and the onshore oil fields of Southwest Iran is the Lowermost Cretaceous Fahliyan formation. The formation in Darkhowain field consists of unconformity-bounded depositional sequences containing prolific hydrocarbon reservoirs of contrasting origin. Located in the high stand systems tract (HST) of the lower sequence encompassing over 200m of oil column are the most prolific reservoir. Another reservoir is over 80m thick consisting of shallowing-upward cycles that are best developed within the transgressive systems tract of the upper sequence. Vertical facies distribution and their paleobathymetry and geophysical log signatures of the Fahliyan formation in the Darkhowain platform reveal the presence of two unconformity-bounded depositional sequences in Vail et al., Van Wagoner et al., and Sarg. The Fahliyan formation mainly consists of platform carbonates composed of restricted bioclastic lime mudstone to packstone of the platform interior, Lithocodium boundstone or ooid-intraclast-bioclast grainstone of the high energy platform margin and the bioclast packstone to lime mudstone related to the off-platform setting.

  18. Amniocar as a proliferative medium for mesenchymal cells

    Directory of Open Access Journals (Sweden)

    V. V. Chestkov

    2014-01-01

    Full Text Available Objectives. To develop the Amniocar nutrient medium that contains fetal calf serum (FCS and growth factors cocktail for mass cultivation of human fibroblasts. To study proliferative activity of the medium on cultures of HUVEC cells of mesenchymal origin and mesenchymal stromal cells, as well as on cell culture of human amniotic fluid.Materials and methods. Determination of the rate of accumulation of the cellular mass and cell morphology in the course of cultivation of cells of various histogenesis in the Amniocar medium and nutrient medium that contains 10 % of FCS.Results. It has been demonstrated that the Amniocar medium is prevalent as compared to the standard DMEM medium with 10 % of FCS by 2 to 5 times for cultivation of skin fibroblasts, HUVEC, and mesenchymal stem cells. The Amniocar medium increased the quantity of endothelial cells that enter mitosis and maintained the culture of HUVEC cells with prolonged passaging in vitro. Clonal cultivation of human amniotic fluid cells in the Amniocar medium secured development of colonies of both fibroblast and epithelial type.Conclusions. Proliferative Amniocar medium is efficient for mass cultivation of various cells of mesenchymal origin and can be used for diagnostic purposes in medical genetics, oncology, etc.

  19. A Case of Proliferative Retinopathy Complicated with Tuberous Sclerosis Treated by Vitreous Surgery

    Science.gov (United States)

    Nemoto, Emika; Morishita, Seita; Akashi, Mari; Kohmoto, Ryohsuke; Fukumoto, Masanori; Suzuki, Hiroyuki; Kobayashi, Takatoshi; Kida, Teruyo; Sugasawa, Jun; Ikeda, Tsunehiko

    2016-01-01

    We report a case of proliferative retinopathy complicated with retinal hamartoma in a tuberous sclerosis patient. This study involved a 16-year-old female patient who was diagnosed as having tuberous sclerosis at birth. Ophthalmic examination revealed retinal hamartoma surrounding the optic disc in both eyes. Vitreous surgery involving a vitrectomy and resection of the proliferative membranes was performed for proliferative retinopathy in her right eye. Postoperative fundus findings showed improvement and decreased exudative changes. The proliferative and exudative changes appeared to be due to the retinal hamartoma, and vitreous surgery proved effective in this case. PMID:28101046

  20. Early pathogenesis in porcine proliferative enteropathy caused by Lawsonia intracellularis

    DEFF Research Database (Denmark)

    Boutrup, Torsten Snogdal; Boesen, H. T.; Boye, Mette

    2010-01-01

    The intestinal bacterium Lawsonia intracellularis, the cause of proliferative enteropathy (PE) in pigs, is believed to infect mitotically active epithelial cells of the intestinal crypts and then multiply and spread in these cells as they divide. Further spread of infection is thought to occur...... by shedding of bacteria from infected crypts followed by infection of new crypts. The early stages of the pathogenesis of PE, from 0 to 48 hours post-infection (hpi), have not been studied in vivo. In the present study pigs were inoculated with L. intracellularis and killed from 12 hpi to 5 days post...... enterocytes. Furthermore, early invasion of the intestinal connective tissue was observed; with the presence of single bacteria in the lamina propria 12 hpi, and with a further spread of bacteria in the lamina propria observed at 5 dpi, suggesting an active role for the lamina propria in the course...

  1. [Proliferative granulomatous arachnoiditis: an infrequent form of tuberculous myeloradioculopathy].

    Science.gov (United States)

    Amorín Díaz, M; Calleja Puerta, S; Jiménez-Blanco, L; Astudillo, A; Fernández, J M; Lahoz, C H

    2001-01-01

    Proliferative granulomatous arachnoiditis is an infrequent manifestation of central nervous system tuberculosis. The mortality rate is 30%, and there are functional sequels in almost all patients. We present the case of a 22-year-old woman, immunocompetent that suffered form tuberculous radiculo-myelopathy with fatal evolution, which allowed us to confront neuroimaging and neuropathological findings. Although serial MR imaging illustrated evolution of lesions, autopsy revealed more extensive lesions that those observed in neuroimaging studies. The characteristic pathological lesion was an intradural inflammatory exudate with a global medullar necrosis. Even through duration of medical treatment is still discussed, early diagnosis, complete antituberculous drug regimen and prolonged corticosteroid therapy are essential to avoid fatal evolution as occurred in this case.

  2. A case of adult periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome associated with endocapillary proliferative glomerulonephritis.

    Science.gov (United States)

    Cazzato, Massimiliano; Neri, Rossella; Possemato, Niccolo; Puccini, Rodolfo; Bombardieri, Stefano

    2013-03-01

    PFAPA is an acronym for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. This syndrome has been usually described in pediatric patients and it generally resolves spontaneously. The endocapillary proliferative glomerulonephritis (EPG) is a glomerular injury characterized by hypercellularity in glomerular lumen and is caused by post-infectious or autoimmune diseases. In this paper, we describe the case of a 35-year-old man affected by PFAPA and EPG. To our knowledge this association has never been reported in the literature before.

  3. Insulin-sensitizing and Anti-proliferative Effects of Argania spinosa Seed Extracts

    Directory of Open Access Journals (Sweden)

    Samira Samane

    2006-01-01

    Full Text Available Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2, ERK kinase (MEK1/2 and protein kinase B (PKB/Akt signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [3H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases.

  4. Insulin-sensitizing and anti-proliferative effects of Argania spinosa seed extracts.

    Science.gov (United States)

    Samane, Samira; Noël, Josette; Charrouf, Zoubida; Amarouch, Hamid; Haddad, Pierre Selim

    2006-09-01

    Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [(3)H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases.

  5. Automated detection of proliferative retinopathy in clinical practice

    Directory of Open Access Journals (Sweden)

    Audrey Karperien

    2008-03-01

    Full Text Available Audrey Karperien1, Herbert F Jelinek1,2, Jorge JG Leandro3, João VB Soares3, Roberto M Cesar Jr3, Alan Luckie41School of Community Health, Charles Sturt University, Albury, Australia; 2Centre for Research in Complex Systems, Charles Sturt University, Albury, Australia; 3Creative Vision Research Group, Department of Computer Science, IME – University of São Paulo, Brazil; 4Albury Eye Clinic, Albury, AustraliaAbstract: Timely intervention for diabetic retinopathy (DR lessens the possibility of blindness and can save considerable costs to health systems. To ensure that interventions are timely and effective requires methods of screening and monitoring pathological changes, including assessing outcomes. Fractal analysis, one method that has been studied for assessing DR, is potentially relevant in today’s world of telemedicine because it provides objective indices from digital images of complex patterns such as are seen in retinal vasculature, which is affected in DR. We introduce here a protocol to distinguish between nonproliferative (NPDR and proliferative (PDR changes in retinal vasculature using a fractal analysis method known as local connected dimension (Dconn analysis. The major finding is that compared to other fractal analysis methods, Dconn analysis better differentiates NPDR from PDR (p = 0.05. In addition, we are the first to show that fractal analysis can be used to differentiate between NPDR and PDR using automated vessel identification. Overall, our results suggest this protocol can complement existing methods by including an automated and objective measure obtainable at a lower level of expertise that experts can then use in screening for and monitoring DR.Keywords: diabetes, proliferative retinopathy, automated clinical assessment, fractal dimension, complex systems

  6. Characterization and functionality of proliferative human Sertoli cells.

    Science.gov (United States)

    Chui, Kitty; Trivedi, Alpa; Cheng, C Yan; Cherbavaz, Diana B; Dazin, Paul F; Huynh, Ai Lam Thu; Mitchell, James B; Rabinovich, Gabriel A; Noble-Haeusslein, Linda J; John, Constance M

    2011-01-01

    It has long been thought that mammalian Sertoli cells are terminally differentiated and nondividing postpuberty. For most previous in vitro studies immature rodent testes have been the source of Sertoli cells and these have shown little proliferative ability when cultured. We have isolated and characterized Sertoli cells from human cadaveric testes from seven donors ranging from 12 to 36 years of age. The cells proliferated readily in vitro under the optimized conditions used with a doubling time of approximately 4 days. Nuclear 5-ethynyl-2'-deoxyuridine (EdU) incorporation confirmed that dividing cells represented the majority of the population. Classical Sertoli cell ultrastructural features, lipid droplet accumulation, and immunoexpression of GATA-4, Sox9, and the FSH receptor (FSHr) were observed by electron and fluorescence microscopy, respectively. Flow cytometry revealed the expression of GATA-4 and Sox9 by more than 99% of the cells, and abundant expression of a number of markers indicative of multipotent mesenchymal cells. Low detection of endogenous alkaline phosphatase activity after passaging showed that few peritubular myoid cells were present. GATA-4 and SOX9 expression were confirmed by reverse transcription polymerase chain reaction (RT-PCR), along with expression of stem cell factor (SCF), glial cell line-derived neurotrophic factor (GDNF), and bone morphogenic protein 4 (BMP4). Tight junctions were formed by Sertoli cells plated on transwell inserts coated with fibronectin as revealed by increased transepithelial electrical resistance (TER) and polarized secretion of the immunoregulatory protein, galectin-1. These primary Sertoli cell populations could be expanded dramatically in vitro and could be cryopreserved. The results show that functional human Sertoli cells can be propagated in vitro from testicular cells isolated from adult testis. The proliferative human Sertoli cells should have important applications in studying infertility

  7. Proliferative index activity in oral squamous cell carcinoma: indication for postoperative radiotherapy?

    Science.gov (United States)

    Gontarz, M; Wyszyńska-Pawelec, G; Zapała, J; Czopek, J; Lazar, A; Tomaszewska, R

    2014-10-01

    The predictive value of the Ki-67 labelling index and its relationship with radiosensitivity in oral squamous cell carcinoma (SCC) remains controversial. We sought to evaluate whether the expression of Ki-67 antigen found in SCC of the tongue and the floor of the mouth is an indication for postoperative radiotherapy (PORT). The first study group included 34 patients who were treated only with primary surgery, while the second group included 26 patients who underwent primary surgery combined with PORT. The correlation between Ki-67 expression and loco-regional recurrence, as well as the 5-year disease-specific survival, was assessed in the two groups. Cases of high-proliferative tumours showed a significantly higher risk of loco-regional recurrence (P=0.018) and a poorer prognosis (P=0.001) only in the 34 patients treated with surgery alone. In multivariate Cox regression analysis, high Ki-67 expression was an independent predictor of loco-regional recurrence (HR 5.42, P=0.029) and disease-specific survival (HR 9.02, P=0.004). The correlation between Ki-67 expression and the risk of loco-regional recurrence in SCC of the tongue and the floor of the mouth may be useful in the selection of patients at a higher risk of recurrence who would benefit from PORT, despite adequate margins of resection and early stage of the disease.

  8. Antagonistic effect of curcumin on inorganic arsenic-induced acute liver injuries in mice%姜黄素干预对无机砷暴露小鼠急性肝脏损伤的拮抗作用

    Institute of Scientific and Technical Information of China (English)

    王欣; 董丹丹; 邢晓越; 李炜; 李冰

    2012-01-01

    Objective Survey the antagonistic effect of curcumin on inorganic arsenic-induced acute liver injuries. Methods Sixty Kunming female mice were divided into 10 groups, 9 groups were exposed different doses of arsenic (10 mg/L, 50 mg/L and 100 mg/L NaAsO2) contained water by drinking freely for 6 weeks, one group only given water. Different dosages of curcumin (200 mg/kg and 600 mg/kg) were given by gastric perfusion twice a week, then determine the activities of serum ALT and AST, MDA content of liver, GSH content in whole blood and liver, and liver GSH-Px activity. Results Compared with arsenic exposure groups, the risen serum ALT and AST activities of curcumin groups showed significantly decreased (P < 0. 01) , the liver content of MDA was significantly reduced ( P < 0. 01 ) , while the whole blood GSH and liver GSH contents were significantly elevated ( P <0. 01).. Conclusion The results suggested that curcumin has a certain some antagonistic effect on oxidative damage of liver induced by arsenic in mice.%目的 观察姜黄素干预对无机砷暴露所致急性肝脏损伤的拮抗作用.方法 实验小鼠自由饮用不同浓度(10 mg/L、50 mg/L和100 mg/L)亚砷酸钠(NaAsO2)6周,再分别给予姜黄素灌胃干预(200 mg/kg和600 mg/kg,每周2次),分别测定小鼠血清ALT和AST活力,全血和肝脏GSH含量以及肝脏MDA含量.结果 与单纯染毒组小鼠相比,姜黄素干预组血清ALT和AST活力显著下降,全血和肝脏GSH含量显著升高,且肝脏MDA含量显著降低,差异具有统计学意义(P<0.0l).结论 姜黄素干预对无机砷暴露小鼠的急性肝脏毒性和氧化损伤具有一定的拮抗作用.

  9. Identification and characterization of proliferative retinopathy-related long noncoding RNAs

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Rong-Mei; Wang, Xiao-Qun; Yao, Jin [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Shen, Yi; Chen, Sai-Nan [Eye Hospital, Nanjing Medical University, Nanjing (China); Yang, Hong [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Jiang, Qin, E-mail: jqin710@vip.sina.com [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Institute of Integrated Medicine, Nanjing Medical University, Nanjing (China); Yan, Biao, E-mail: yanbiao1982@hotmail.com [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Institute of Integrated Medicine, Nanjing Medical University, Nanjing (China)

    2015-09-25

    Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and vitreoretinal surgery, which can lead to severe vision reduction. Long non-coding RNAs (lncRNAs) play critical roles in many biological processes and disease development. We attempted to determine the role of lncRNAs in the setting of PVR. Microarray analysis revealed that 78 lncRNAs were abnormally expressed in the epiretinal membranes (ERMs) of PVR patients, including 48 up-regulated and 30 down-regulated lncRNA transcripts. We subsequently focus on one lncRNA, MALAT1, and investigated its expression pattern in the biofluid of PVR patients. MALAT1 was significantly up-regulated in the cellular and plasma fraction of peripheral blood in PVR patients. MALAT1 expression was obviously reduced after PVR operation. In vitro experiments revealed the role of MALAT1 in regulating RPE proliferation and migration, which is critical for ERMs formation. This study suggests that lncRNAs are the potential regulators of PVR pathology. MALAT1 is a potential prognostic indicator and a target for the diagnosis and gene therapy for PVR diseases. - Highlights: • 78 lncRNAs are differentially expressed between PVR-ERMs and secondary ERMs. • MALAT1 level is elevated in the ERMs of PVR patients. • Circulating MALAT1 level is up-regulated in PVR patients. • MALAT1 knockdown regulates RPE proliferation and migration.

  10. Subretinal Perfluorocarbon Liquid for Dissection of Proliferative Vitreoretinopathy

    Science.gov (United States)

    Dalma-Weiszhausz, Jose; Franco-Cardenas, Valentina; Dalma, Alejandro

    2012-01-01

    Proliferative vitreoretinopathy (PVR) is a frequent condition following complex retinal detachments or trauma, and subretinal PVR is a common cause of retinal redetachment. Subretinal PVR removal is challenging and may require creating multiple or large retinotomies, making manipulation of the retina difficult and sometimes hazardous. We propose a novel surgical technique that may facilitate subretinal removal of PVR. After peripheral retinotomy of 180 degrees or greater, perfluorocarbon liquid (PFCL) is carefully introduced into the subretinal space as a single bubble which provides space to perform the maneuvers. The PFCL serves as a second hand which folds the retina over, thereby allowing better visualization for safer and easier subretinal PVR removal. PFCL in then removed by direct aspiration as a single bubble while still under balanced salt solution, taking advantage of its high surface tension which prevents leaving bubbles behind. The described technique allows adequate exposure of the subretinal space for proper dissection of difficult-to-reach subretinal PVR. We applied this technique in five patients with chronic retinal detachment, extensive subretinal PVR and poor visual potential. The utilization of subretinal PFCL can assist dissection of subretinal PVR and may be useful in eyes with complicated retinal detachment and poor visual prognosis. PMID:23502847

  11. Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

    Directory of Open Access Journals (Sweden)

    Pei-Rong Wang

    2015-03-01

    Full Text Available Background/Aims: Immunologically and hemodynamically mediated the destruction of glomerular architecture is thought to be the major causes of end-stage renal failure. The purpose of this study is to evaluate the effect of glomerular hypertension on glomerular injury and the progression of glomerular sclerosis after Thy-1 nephritis was induced. Method: Thy-1 nephritis was induced in the stroke-prone spontaneously hypertensive rat strain (SHR-SP (group SP and in age-matched Wistar-Kyoto (WKY (group WKY rats, following unilateral nephrectomy (UNX, and a vehicle was injected alone in UNX SHR-SP as control (group SC. Result: The degree of glomerular damage in response to a single dose of anti-thy-1 antibody, and its functional consequences (eg. proteinuria, diminished GFR are more pronounced in group SP than normotensive group WKY and hypertensive group SC without mesangial cell injury. While normotensive group WKY rats recovered completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on persistent macrophage infiltration, α-SMA expression on day 42-56. In addition, glomerular capillary repair with the GECs was rarely seen in pronouncedly proliferative and sclerostic areas. The incidence of glomerular sclerosis and the level of proteinuria were markedly increased by day 56 in the group SP. Conclusions: Our results demonstrate that glomerular hypertension aggravate glomerular damage and glomerulosclerosis in this model of Thy 1 nephritis.

  12. Dysregulation of T lymphocyte proliferative responses in autoimmunity.

    Directory of Open Access Journals (Sweden)

    Sydney K Elizer

    Full Text Available T cells are critically dependent on cellular proliferation in order to carry out their effector functions. Autoimmune strains are commonly thought to have uncontrolled T cell proliferation; however, in the murine model of autoimmune diabetes, hypo-proliferation of T cells leading to defective AICD was previously uncovered. We now determine whether lupus prone murine strains are similarly hyporesponsive. Upon extensive characterization of T lymphocyte activation, we have observed a common feature of CD4 T cell activation shared among three autoimmune strains-NOD, MRL, and NZBxNZW F1s. When stimulated with a polyclonal mitogen, CD4 T cells demonstrate arrested cell division and diminished dose responsiveness as compared to the non-autoimmune strain C57BL/6, a phenotype we further traced to a reliance on B cell mediated costimulation, which underscores the success of B cell directed immune therapies in preventing T cell mediated tissue injury. In turn, the diminished proliferative capacity of these CD4 T cells lead to a decreased, but activation appropriate, susceptibility to activation induced cell death. A similar decrement in stimulation response was observed in the CD8 compartment of NOD mice; NOD CD8 T cells were distinguished from lupus prone strains by a diminished dose-responsiveness to anti-CD3 mediated stimulation. This distinction may explain the differential pathogenetic pathways activated in diabetes and lupus prone murine strains.

  13. Aquaporin-1 Expression in Proliferative Vitreoretinopathy and in Epiretinal Membranes

    Directory of Open Access Journals (Sweden)

    Elie Motulsky

    2014-01-01

    Full Text Available Purpose. Aquaporin-1 (AQP1 is involved in cell migration and proliferation; therefore, the purpose of the study was to investigate its expression in proliferative vitreoretinopathy (PVR and epiretinal membranes (ERM. Methods. 19 membranes from PVR and ERM were collected following eye surgery. AQP1 mRNA and protein expressions were determined by RT-qPCR and immunofluorescence in the membranes from PVR and ERM. Results. AQP1 mRNA and protein were expressed in both PVR and ERM as shown by RT-qPCR and immunofluorescence. AQP1 protein expression was heterogeneous among and between PVR and ERM and colocalized with alpha-smooth muscle actin (αSMA and with glial fibrillary acidic protein (GFAP. There were a higher percentage of cells coexpressing AQP1 and αSMA than AQP1 and GFAP. GFAP and αSMA did not colocalize. Conclusion. Our data show for the first time AQP1 expression in both PVR and ERM. AQP1 is expressed mostly by the αSMA-positive cells, presumably myofibroblasts, but also by GFAP-positive cells, assumed to be glial cells. These original findings warrant further functional investigations aiming at studying the potential role of AQP1 in cell migration and proliferation occurring during the development of PVR and ERM.

  14. Subretinal Perfluorocarbon Liquid for Dissection of Proliferative Vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Jose Dalma-Weiszhausz

    2012-01-01

    Full Text Available Proliferative vitreoretinopathy (PVR is a frequent condition following complex retinal detachments or trauma, and subretinal PVR is a common cause of retinal redetachment. Subretinal PVR removal is challenging and may require creating multiple or large retinotomies, making manipulation of the retina difficult and sometimes hazardous. We propose a novel surgical technique that may facilitate subretinal removal of PVR. After peripheral retinotomy of 180 degrees or greater, perfluorocarbon liquid (PFCL is carefully introduced into the subretinal space as a single bubble which provides space to perform the maneuvers. The PFCL serves as a second hand which folds the retina over, thereby allowing better visualization for safer and easier subretinal PVR removal. PFCL in then removed by direct aspiration as a single bubble while still under balanced salt solution, taking advantage of its high surface tension which prevents leaving bubbles behind. The described technique allows adequate exposure of the subretinal space for proper dissection of difficult-to-reach subretinal PVR. We applied this technique in five patients with chronic retinal detachment, extensive subretinal PVR and poor visual potential. The utilization of subretinal PFCL can assist dissection of subretinal PVR and may be useful in eyes with complicated retinal detachment and poor visual prognosis.

  15. The rabbit as an infection model for equine proliferative enteropathy.

    Science.gov (United States)

    Sampieri, Francesca; Allen, Andrew L; Pusterla, Nicola; Vannucci, Fabio A; Antonopoulos, Aphroditi J; Ball, Katherine R; Thompson, Julie; Dowling, Patricia M; Hamilton, Don L; Gebhart, Connie J

    2013-04-01

    The objective of this study was to demonstrate the susceptibility of rabbits to Lawsonia intracellularis obtained from a case of clinical equine proliferative enteropathy (EPE). This is a preliminary step toward developing a rabbit infection model for studying pathogenesis and therapy of EPE in horses. Nine does were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were orally inoculated with different doses of cell-cultured L. intracellularis. Controls (Group 3) were sham-inoculated. Feces and blood were collected before the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for collection and evaluation of intestinal samples. Tissues were stained by routine hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L. intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic responses were detected in both infected groups, which maintained high titers through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L. intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14, and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found in Group 3 rabbits. This study describes an EPE rabbit model that simulates natural infection, as typical lesions, immune response, and fecal shedding were present.

  16. Milk production capacity of prolific Priangan sheep: Preweaning performance

    Directory of Open Access Journals (Sweden)

    Bess Tiesnamurti

    2002-12-01

    Full Text Available A study was conducted to investigate the milk production capacity and preweaning performance of the prolific Priangan sheep, at sheep breeding station of the Research Institute for Animal production, Bogor using 126 ewes during three lambing periods in three consecutive years. The milk production was estimated weekly, started at day 7 after lambing date, till lambs were weaned at 90 days of age. The results showed that total milk production was significantly affected (P<0.05 by parity and the number of lambs born with average daily milk production of 519.5 g head-1 day-1. Estimated total milk production was 43.6 kg/lactation (N = 126; SD = 7.8; CV = 19.4%; range = 28.7-53.6 kg. According to the dam parity, the highest milk production was estimated at third parity (40.1 kg head-1 lactation-1, whereas on the basis of litter size, ewes with twin born lamb had the highest production (39.9 kg head-1 lactation-1. The preweaning lamb performance (weaning weight and preweaning daily gain was significantly affected (P<0.05 by ewe parity, sex, litter size and type of birth and weaned, with the average weaning weight of 10.62 kg (N = 208; SD = 3.37; CV = 25.08% and 130.9 + 41.8 g head-1 day-1 (N = 208; SD = 33.5; CV = 31.26%, respectively. Where as lamb birth weight was significantly affected (P<0.05 by ewe parity, sex and the number of lambs bornwith average of 2.39 kg (N = 208; SD = 0.66; CV = 9.8%.

  17. Intravitreal bevacizumab for persistent macular edema with proliferative diabetic retinopathy.

    Science.gov (United States)

    Gulkilik, Gokhan; Taskapili, Muhittin; Kocabora, Selim; Muftuoglu, Gulipek; Demirci, Goktug

    2010-12-01

    To evaluate the effectiveness of an intravitreal bevacizumab injection on retinal neovascularization and diabetic macular edema (DME) refractory to laser photocoagulation therapy. Thirty-four eyes of 22 patients with proliferative diabetic retinopathy and DME refractory to laser photocoagulation therapy received an intravitreal injection of 1.25 mg/0.05 ml of bevazicumab. Changes in mean best-corrected visual acuity (BCVA), central macular thickness (CMT), regression of neovascularization over time, and correlation between BCVA and CMT were evaluated. Follow-up visits were at weeks 1, 2 and 4 and months 3 and 6. Mean BCVA was significantly better than baseline only at week 2 (P = 0.036). Mean CMT decreased significantly from baseline at weeks 1, 2, and 4 (P = 0.001). At months 3 and 6, mean CMT increased, albeit insignificantly (P = 0.804 and P = 1.0). The decrease in fluorescein leakage was moderate in all eyes at the end of week 1. At week 2, there was total resolution of fluorescein leakage in 24 (70.5%) eyes and moderate resolution in 10 (29.5%) eyes. At the end of month 3, the fluorescein leakage was fully resolved in 5 (14.7%) eyes, moderately resolved in 24 (70.5%) eyes, and was similar to baseline in 5 (14.7%) eyes. At month 6, the fluorescein leakage was fully resolved in 3 (8.8%) eyes, moderately resolved in 20 (58.8%) eyes, and was similar to baseline in 11 (32.4%) eyes. A moderate but insignificant negative correlation was found between visual acuity and CMT (P > 0.05). Persistence or recurrence of neovascular tissue after panretinal photocoagulation may be attributed to the production of vascular endothelial growth factor by the residual ischemic retina, which also results in persistent or recurrent DME despite macular grid photocoagulation.

  18. Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Ahmed M Abu El-Asrar

    Full Text Available Neurotrophins (NTs are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF, brain-derived neurotrophic factor (BDNF, neurotrophin-3 (NT-3, and neurotrophin-4 (NT-4 and their receptors TrkA, TrkB, and TrkC in proliferative diabetic retinopathy (PDR. As a comparison, we examined the expression of NTs and their receptors in the retinas of diabetic rats. Vitreous samples from 16 PDR and 15 nondiabetic patients were studied by Western blot analysis and enzyme-linked immunosorbent assay (ELISA. Epiretinal membranes from 17 patients with PDR were studied by immunohistochemistry. Rats were made diabetic with a single high dose of streptozotocin and retinas of rats were examined by Western blot analysis. Western blot analysis revealed a significant increase in the expression of NT-3 and NT-4 and the shedding of receptors TrkA and TrkB in vitreous samples from PDR patients compared to nondiabetic controls, whereas NGF and BDNF and the receptor TrkC were not detected with the use of Western blot analysis and ELISA. In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed NT-3 and the receptors TrkA, TrkB and TrkC in situ, whereas NT-4 was not detected. The expression levels of NT-3 and NT-4 and the receptors TrkA and TrkB, both in intact and solubilized forms, were upregulated in the retinas of diabetic rats, whereas the receptor TrkC was not detected. Co-immunoprecipitation studies revealed binding between NT-3 and the receptors TrkA and TrkB in the retinas of diabetic rats. Our findings in diabetic eyes from humans and rats suggest that the increased expression levels within the NT-3 and NT-4/Trk axis are associated with the progression of PDR.

  19. The rabbit as an infection model for equine proliferative enteropathy

    Science.gov (United States)

    Sampieri, Francesca; Allen, Andrew L.; Pusterla, Nicola; Vannucci, Fabio A.; Antonopoulos, Aphroditi J.; Ball, Katherine R.; Thompson, Julie; Dowling, Patricia M.; Hamilton, Don L.; Gebhart, Connie J.

    2013-01-01

    The objective of this study was to demonstrate the susceptibility of rabbits to Lawsonia intracellularis obtained from a case of clinical equine proliferative enteropathy (EPE). This is a preliminary step toward developing a rabbit infection model for studying pathogenesis and therapy of EPE in horses. Nine does were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were orally inoculated with different doses of cell-cultured L. intracellularis. Controls (Group 3) were sham-inoculated. Feces and blood were collected before the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for collection and evaluation of intestinal samples. Tissues were stained by routine hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L. intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic responses were detected in both infected groups, which maintained high titers through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L. intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14, and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found in Group 3 rabbits. This study describes an EPE rabbit model that simulates natural infection, as typical lesions, immune response, and fecal shedding were present. PMID:24082402

  20. Ameliorative potentials of Syzygium jambolanum extract against arsenic-induced stress in L6 cells in vitro%海南蒲桃提取物对L6细胞砷中毒缓解作用的体外实验

    Institute of Scientific and Technical Information of China (English)

    Asmita Samadder; Jayeeta Das; Sreemanti Das; Raktim Biswas; Anisur Rahman Khuda-Bukhsh

    2012-01-01

    OBJECTIVE:To determine the ameliorative potentials of Syzygium jambolanum (SJ) extract in L6 skeletal muscle cells in regard to arsenic-induced impairment of optimum glucose homeostasis and improper functioning of mitochondria.METHODS:Several study parameters like glucose level and mitochondrial functioning through indexes of pyruvate kinase,glucokinase and mitochondrial membrane potential were assessed.The expression of the relevant marker proteins and mRNAs like glucose transporter 4 (GLUT4),insulin receptor substrate 1 (IRS1),IRS2 and glucokinase for tracking down the signalling cascade were critically analyzed.RESULTS:Introduction of SJ extract could bring about positive modulation of various markers,by acting on GLUT4,thereby bringing about an attenuation of the arsenite-induced toxic conditions in L6 cells.CONCLUSION:Syzygium jambolanum extract has considerable ameliorating potentials against arsenic-induced glucose imbalance and stress and has possibility of therapeutic use in the management of arsenic-induced toxicity including hyperglycemia.%目的:研究海南蒲桃提取物对砷酸盐引起的L6骨骼肌细胞葡萄糖内稳态破坏及线粒体功能异常的缓解作用.方法:通过测量多个指标如丙酮酸激酶活性、葡糖激酶、线粒体膜电位等衡量细胞内葡萄糖水平及线粒体功能,并测量相关标志物的蛋白质及mRNA表达情况,如葡萄糖转运体4、胰岛素受体基质1、胰岛素受体基质2、葡糖激酶等以分析可能有关的信号通路.结果:海南蒲桃提取物能够通过葡萄糖转运体4通路改善砷中毒的L6细胞内诸多标志物的表达,使其正常化,与模型组相比差异有统计学意义.结论:海南蒲桃提取物对细胞砷中毒有明显的缓解作用,未来可考虑将其用于治疗砷中毒相关疾病如高血糖症等.

  1. Angiogenic and Vasculogenic Factors in the Vitreous from Patients with Proliferative Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Ahmed M. Abu El-Asrar

    2013-01-01

    Full Text Available This study was conducted to determine levels of angiogenic and endothelial progenitor cell mobilizing (vasculogenic factors in vitreous fluid from proliferative diabetic retinopathy (PDR patients and correlate their levels with clinical disease activity. Vascular endothelial growth factor (VEGF, soluble vascular endothelial growth factor receptor-2 (sVEGFR-2, stem cell factor (SCF, soluble c-kit (s-kit, endothelial nitric oxide synthase (eNOS, and prostaglandin E2 (PGE2 levels were measured by ELISA in vitreous samples from 34 PDR and 15 nondiabetic patients. eNOS was not detected. VEGF, sVEGFR-2, SCF, and s-kit levels were significantly higher in PDR with active neovascularization compared with quiescent PDR and nondiabetic patients (; 0.007; 0.001; , resp.. In contrast, PGE2 levels were significantly higher in nondiabetic patients compared with PDR patients (. There were significant correlations between levels of sVEGFR-2 versus SCF (, , sVEGFR-2 versus s-kit (, , and SCF versus s-kit (, . Our findings suggest that upregulation of VEGF, sVEGFR-2, SCF, and s-kit supports the contributions of angiogenesis and vasculogenesis in pathogenesis of PDR.

  2. Spontaneous proliferative and neoplastic lesions in thyroid and parathyroid glands of nondomestic felids.

    Science.gov (United States)

    Pope, Jenny P; Steeil, James; Ramsay, Edward C; Reel, Danielle; Newman, Shelley J

    2017-01-01

    Based on microscopic and immunohistochemical characterization, we documented spontaneous proliferative and neoplastic lesions in the thyroid and parathyroid glands of nondomestic felids. Ten animals (4 leopards, 3 tigers, and 3 cougars), all with a previous diagnosis of thyroid neoplasia were identified from the University of Tennessee College of Veterinary Medicine database. The mean age of affected animals was 15.9 y. Twelve neoplasms were identified; 2 animals had 2 concurrent neoplasms. After immunohistochemical characterization using a panel of chromogranin A, thyroglobulin, and calcitonin, 7 of the former thyroid neoplasms were diagnosed as thyroid adenomas, 1 was diagnosed as a thyroid carcinoma, and 4 were diagnosed as parathyroid adenomas. No thyroid medullary neoplasms (C-cell tumors) were diagnosed in the current study. Most of the diagnosed neoplasms were benign (11 of 12), and metastasis was not documented in the single carcinoma. Only 2 animals were suspected to have functional neoplasms (1 thyroid adenoma and 1 parathyroid adenoma), based on associated tissue lesions or serum biochemistry. Other documented lesions in the thyroid and parathyroid glands included thyroid nodular hyperplasia ( n = 7), parathyroid hyperplasia associated with chronic renal disease ( n = 2), a thyroid abscess, and a branchial cyst. Parathyroid adenomas were more commonly diagnosed than expected in comparison with domestic cats. We demonstrated that an immunohistochemistry panel for thyroglobulin, calcitonin, and chromogranin A can be used to differentiate neoplasms of thyroid from parathyroid origin in nondomestic felids.

  3. LYMPHO-PROLIFERATIVE RESPONSES TO VARIOUS FASCIOLA HEPATICA WORM'S ANTIGENS: AN IN VITRO STUDY.

    Science.gov (United States)

    Sharaf, Osama F; Amir, Elamir M; Hawash, Yousry A

    2016-04-01

    Fascioliasis is an important zoonotic disease with approximately 2-4 million people infected worldwide and a further 180 million at risk of infection. F. hepatica can survive within the bile ducts for many years through its ability to suppress the host immunity with Fasciola cathepsin L1 cysteine protease and Glutathione S transferase playing an important role. The aim of the present study is to investigate the in vitro lympho-proliferative responses of hepatic hilar lymphocytes (HLN) of infected sheep in response to different F. hepatica antigens. The suppressive effects of Fasciola excretory/secretory (ES) and tegument (TEG) and their fractions were also investigated. Our results showed that both ES and TEG had significant suppressive effects on lympho-proliferation, up to 74% and 92%, respectively. When these antigens were fractionated, fraction 3 (MW of >10000-30000) of both ES (64%) and TEG (59%) in addition to fraction 4 (MW of ≤ 10000) of TEG (38%) inherited the suppressive effects. Identification of the potential molecule(s) with such suppressive effects on lymphocytes in TEG fraction 4 could reveal vaccine candidates.

  4. Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets.

    Science.gov (United States)

    Bhatti, Adnan Bashir; Usman, Muhammad

    2015-11-06

    The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it.

  5. Antinucleosome antibodies as a potential biomarker for the evaluation of renal pathological activity in patients with proliferative lupus nephritis.

    Science.gov (United States)

    Hung, W T; Chen, Y M; Lan, J L; Chen, H H; Chen, Y H; Chen, D Y; Hsieh, C W; Wen, M C

    2011-11-01

    The objective of this study is to evaluate the correlation between antinucleosome antibodies and renal pathological activity in patients with proliferative lupus nephritis (LN). We evaluated 36 patients with proliferative LN, 14 non-renal lupus patients and 10 healthy volunteers. Lupus activity was assessed using the British Isles Lupus Assessment Group 2004 (BILAG 2004) index, serum anti-double stranded DNA (anti-dsDNA) levels, serum complement levels and daily urinary protein levels. All 36 lupus nephritis patients received renal biopsy. Antinucleosome antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Our results showed that levels of serum antinucleosome antibodies were significantly higher in LN patients (median 90.35 units/ml, interquartile range [IQR] 37.38-135.23) than in non-renal SLE patients (median 5.45 units/ml, IQR 2.6-28.93, p antibodies were positively correlated with BILAG index (Spearman's r = 0.645, p antibodies were negatively correlated with serum levels of C3 (r(s) = -0.400, p antibodies were positively correlated with the histological activity index of LN (r(s) = 0.368, p antibodies and the histological chronicity index. In conclusion, the serum level of antinucleosome antibodies is a potential biomarker for early recognition of renal involvement and evaluation of disease activity in SLE. Our preliminary results suggested that serum levels of antinucleosome antibodies might be a potential biomarker in evaluating pathological activity of LN.

  6. [Nuclear heterogeneity and proliferative capacity of human adipose derived MSC-like cells].

    Science.gov (United States)

    Lavrov, A V; Smirnichina, S A

    2010-01-01

    Adipose derived stem cells (ADSCs) are MSC-like cells which could be easily used for regenerative medicine. Here, the morphology and proliferative capacity of human ADSCs is discribed. ADSCs were analyzed after one month of cultivation at a density of 10 cells/cm2. 21 colonies were counted. Few atypical cells (huge nuclei and cytoplasm) were found in 9 out of 17 colonies analyzed. ANOVA demonstrated that colonies also differed (P = 0.0025) in nuclei dimensions and scatter in the dimensions in each colony. Nuclei dimensions and cell density logarithms correlated in reverse proportion (-0.7; P = 0.002). Thus, ADSCs were heterogeneous and represented two types of cells: small highly proliferative and large low proliferative cells. Cell heterogeneity observed in some colonies might be due to cells registered at different cell cycle phases. Stable and typical morphology, colony-formation capability and high proliferative capacity of cells indicate visceral adipose tissue as a rich source of ADSCs.

  7. The indeterminate cell proliferative disorder: report of a case manifesting as an unusual cutaneous histiocytosis.

    Science.gov (United States)

    Wood, G S; Hu, C H; Beckstead, J H; Turner, R R; Winkelmann, R K

    1985-11-01

    A patient with an unusual, distinctive cutaneous histiocytosis is described. Extensive morphologic, antigenic, and enzymatic studies indicate that this histiocytosis represents a proliferative disorder of cutaneous indeterminate cells. Features that distinguish this disorder from other histiocytoses are discussed.

  8. Anti-proliferative activity of Monensin and its tertiary amide derivatives.

    Science.gov (United States)

    Huczyński, Adam; Klejborowska, Greta; Antoszczak, Michał; Maj, Ewa; Wietrzyk, Joanna

    2015-10-15

    New tertiary amide derivatives of polyether ionophore Monensin A (MON) were synthesised and their anti-proliferative activity against cancer cell lines was studied. Very high activity (IC50=0.09 μM) and selectivity (SI=232) of MON against human biphenotypic myelomonocytic leukemia cell line (MV4-11) was demonstrated. The MON derivatives obtained exhibit interesting anti-proliferative activity, high selectivity index and also are able to break the drug-resistance of cancer cell line.

  9. Monoclonal gammopathy-associated pauci-immune extracapillary-proliferative glomerulonephritis successfully treated with bortezomib

    OpenAIRE

    2013-01-01

    Extracapillary-proliferative glomerulonephritis is a rare complication of multiple myeloma. Partial remission of kidney involvement with cyclophosphamide therapy has previously been described. We report the case of a 60-year-old male patient diagnosed with rapidly progressive glomerulonephritis associated with IgG kappa monoclonal gammopathy. His kidney biopsy revealed pauci-immune extracapillary-proliferative glomerulonephritis without cryoglobulinaemia. Treatment with the proteasome inhibit...

  10. Ibrutinib: another weapon in our arsenal against lympho-proliferative disorders.

    Science.gov (United States)

    Cabras, Maria Giuseppina; Angelucci, Emanuele

    2015-01-01

    In Volume 16, issue 12 of Expert Opinion on Pharmacotherapy, an important article on the new drug ibrutinib was published. This new drug promises to further improve outcome in the treatment of several lympho-proliferative disorders. In this editorial, the most important findings of the article looking particularly to the integration of ibrutinib in current clinical practice will be summarized. Finally this editorial will focus on the next challenges for scientists and physicians in the treatment of lympho-proliferative disorders.

  11. Proliferative activity in oral pyogenic granuloma: A comparative immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Rezvani Gita

    2010-07-01

    Full Text Available Context: Pyogenic granuloma (PG is one of the most common reactive vascular lesions in the oral mucosa, which has been divided into the lobular capillary hemangioma (LCH and the non lobular type (non-LCH as two distinct entities, on the basis of some investigations. Aims: This study aims to compare the proliferative and angiogenic activity of two histological types of PG to determine whether they have two distinct types of biological behavior. Settings and Design: In this retrospective cross-sectional study, immunostaining was performed on 10 cases of each type of PG. Materials and Methods: About 4μm sections were cut from formalin-fixed paraffin-embedded blocks and each specimen was stained with both anti-CD31 and anti-Ki-67 antibodies simultaneously. Labeling index (LI was determined for both types by counting Ki-67 and CD31 positive cells separately and simultaneously in 1000 stromal and luminal cells. Micro vessel count (MVC, the mean number of micro vessels in five areas at Χ200 magnification, was also determined for both groups. Statistical Analysis: The results were statistically compared using the Mann-Whitney U-test. Results: Ki-67 LI in LCH (5.4 ± 2.4 was higher than non-LCH (3.9 ± 3.9. The percentage of CD31 positive cells in LCH (28.5 ± 22 was lower than non-LCH (37.1 ± 20.8 and simultaneously immunostaining for both markers in LCH type (2.4 ± 2.1 was higher than non-LCH (1.2 ± 1. The MVC was approximately 77.35 ± 34.6 and 82.6 ± 42.7 in the lobular areas of LCH and central areas of non-LCH PG, respectively. These differences were not statistically significant. Conclusions: These results demonstrate a higher proliferation activity in endothelial cells of LCH PG than in non-LCH.

  12. Remission of proteinuria indicates good prognosis in patients with diffuse proliferative lupus nephritis.

    Science.gov (United States)

    Koo, H S; Kim, S; Chin, H J

    2016-01-01

    Proteinuria is a well-known risk factor for the progression of renal dysfunction in chronic kidney disease; however, its importance for estimating the prognosis of lupus nephritis requires verification. Korean adult patients with renal biopsy-diagnosed diffuse proliferative lupus nephritis who had undergone three or more consecutive urine protein to creatinine ratio or urine dipstick tests within six months after renal biopsy were enrolled. The cumulative risks, predictors, and outcomes of proteinuric remission and flare were evaluated. This study included 26 men and 167 women with a mean age at renal biopsy of 31.2 ± 9.8 years. Eighty-two (42.5%) patients experienced proteinuric remission during the follow-up period. During a mean follow-up of 157.9 ± 69.5 months, among patients who achieved proteinuric remission, one died, one developed end-stage renal disease (ESRD), and two had composite outcomes; among patients without remission, nine died, 24 developed ESRD, and 30 had composite outcomes. Patients who achieved proteinuric remission had a 0.089-fold risk (95% CI: 0.011-0.736) of mortality, 0.110-fold risk (95% CI: 0.013-0.904) of incident ESRD, and 0.210-fold risk (95% CI: 0.048-0.920) of a composite outcome compared to patients without remission. Among the 82 patients who achieved proteinuric remission, 59 (72.0%) experienced at least one proteinuria flare; however, relapse did not correlate with the incidence of outcomes. In conclusion, proteinuric remission is an independent predictive prognostic marker of good renal survival and mortality, regardless of the interval from biopsy to remission, recurrence of proteinuria after remission, renal function status at remission, or hematuria remission.

  13. Long-term Behavior of Serous Borderline Tumors Subdivided Into Atypical Proliferative Tumors and Noninvasive Low-grade Carcinomas

    DEFF Research Database (Denmark)

    Vang, Russell; Hannibal, Charlotte Gerd; Junge, Jette

    2017-01-01

    Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated...... "atypical proliferative serous tumor (APST)" and a small subset of SBTs with micropapillary architecture that have a poor outcome and are designated "noninvasive low-grade serous carcinoma (niLGSC)". It also has been argued that the difference in behavior between the 2 groups is not due to the subtype...... of the primary tumor but rather the presence of extraovarian disease, specifically invasive implants. According to the terminology of the 2014 WHO Classification, typical SBTs are equivalent to APSTs and SBTs displaying micropapillary architecture are synonymous with niLGSC. In addition, "invasive implants" were...

  14. The differential proliferative ability of satellite cells in Lantang and Landrace pigs.

    Science.gov (United States)

    Wang, Xiu-qi; Yang, Wei-jun; Yang, Zhou; Shu, Gang; Wang, Song-bo; Jiang, Qing-yan; Yuan, Li; Wu, Tong-shan

    2012-01-01

    Here, for the first time, we evaluate the hypothesis that the proliferative abilities of satellite cells (SCs) isolated from Lantang (indigenous Chinese pigs) and Landrace pigs, which differ in muscle characteristics, are different. SCs were isolated from the longissimus dorsi muscle of neonatal Lantang and Landrace pigs. Proliferative ability was estimated by the count and proliferative activity of viable cells using a hemocytometer and MTT assay at different time points after seeding, respectively. Cell cycle information was detected by flow cytometry. Results showed that there was a greater (PLandrace pigs after 72 h of culture. The percentage of cell population in S phase and G(2)/M phases in Lantang pigs were higher (PLandrace pigs. The mRNA abundances of MyoD, Myf5, myogenin and Pax7 in SCs from Lantang pigs were higher (PLandrace pigs. Protein levels of MyoD, myogenin, myostatin, S6K, phosphorylated mTOR and phosphorylated eIF4E were consistent with the corresponding mRNA abundance. Collectively, these findings suggested that SCs in the two breeds present different proliferative abilities, and the proliferative potential of SCs in Lantang pigs is higher than in Landrace pigs.

  15. The development of proliferative verrucous leukoplakia in oral lichen planus. A preliminary study

    Science.gov (United States)

    Llorente-Pendás, Santiago; González-Garcia, Manuel; García-Martín, José-Manuel

    2016-01-01

    Background Was to describe 14 cases of a proliferative verrucous leukoplakia as a clinical evolution of oral lichen planus. Material and Methods The clinical and histopathological characteristics of 14 cases of OLP that progress towards a plaque-like and verrucous form were indicated, with monitoring over a period of six to 24.3 years. Results The female/male ratio was 11/3, (78.6 and 21.4%). The mean age when the first biopsy was undertaken was 56.4 years old. None of the patients smoked during the study. As bilateral reticular was clinically diagnostic criterion, the second most frequent clinical form was the plaque form (n=10; 71.4%), followed by the atrophic (n=6; 42.8%), and erosive forms (n=4; 28.5%). Clinically it spread towards attached gingival mucosa and the hard palate. In the histopathologic study, there were a predominance of hyperkeratosis and verrucous epithelial hyperplasia. Three of the cases progressed to a squamous cell carcinoma, and one patient developed two verrucous carcinoma. Conclusions Further research is needed to demonstrate if proliferative multifocal oral lichen planus and proliferative multifocal oral leukoplakia are the same disorder but have different behaviour of malignancy for reasons of origin. Key words:Oral lichen planus, proliferative verrucous oral leukoplakia, malignant oral lichen planus, multifocal verrucous oral lichen planus, proliferative verrucous oral lichen planus. PMID:27031060

  16. East Indian Sandalwood Oil (EISO) Alleviates Inflammatory and Proliferative Pathologies of Psoriasis

    Science.gov (United States)

    Sharma, Manju; Levenson, Corey; Clements, Ian; Castella, Paul; Gebauer, Kurt; Cox, Michael E.

    2017-01-01

    Psoriasis, a chronic inflammatory skin disease marked by hyper proliferation and aberrant differentiation of keratinocytes, affects 2–3% of the world’s population. Research into the pathogenesis of psoriasis has been hampered by the lack of models that accurately reflect the biology of the psoriatic phenotype. We have previously reported that East Indian Sandalwood oil (EISO) has significant anti-inflammatory properties in skin models and hypothesized that EISO might provide therapeutic benefit to psoriasis patients due to its anti-inflammatory and anti-proliferative properties. Here we present interim results from an on-going proof-of-concept Phase 2 clinical trial in which topically applied EISO is demonstrating to be well tolerated and helpful in alleviating mild to moderate psoriasis symptoms. This led us to evaluate the ability of EISO to affect the psoriatic phenotype using MatTek Corporation reconstituted organotypic psoriatic and normal human skin models. EISO had no impact on the phenotype of the normal skin tissue model, however, EISO treatment of the psoriasis tissue model reverted psoriatic pathology as demonstrated by histologic characterization and expression of keratinocyte proliferation markers, Ki67 and psoriasin. These phenotypic affects correlated with suppressed production of ENA-78, IL-6, IL-8, MCP-1, GM-CSF, and IL-1β. Demonstration of the ability of EISO to abrogate these psoriasis symptoms in well-characterized in vitro psoriatic tissue models, supports the hypothesis that the clinically observed symptom alleviation is due to suppression of intrinsic tissue inflammation reactions in afflicted lesions. This study presents a systematic approach to further study the underlying mechanisms that cause psoriasis, and presents data supporting the potential of EISO as a new ethnobotanical therapeutic concept to help direct and accelerate the development of more effective therapies. PMID:28360856

  17. Cytokine, antibody and proliferative cellular responses elicited by Taenia solium calreticulin upon experimental infection in hamsters.

    Science.gov (United States)

    Mendlovic, Fela; Cruz-Rivera, Mayra; Ávila, Guillermina; Vaughan, Gilberto; Flisser, Ana

    2015-01-01

    Taenia solium causes two diseases in humans, cysticercosis and taeniosis. Tapeworm carriers are the main risk factor for neurocysticercosis. Limited information is available about the immune response elicited by the adult parasite, particularly the induction of Th2 responses, frequently associated to helminth infections. Calreticulin is a ubiquitous, multifunctional protein involved in cellular calcium homeostasis, which has been suggested to play a role in the regulation of immune responses. In this work, we assessed the effect of recombinant T. solium calreticulin (rTsCRT) on the cytokine, humoral and cellular responses upon experimental infection in Syrian Golden hamsters (Mesocricetus auratus). Animals were infected with T. solium cysticerci and euthanized at different times after infection. Specific serum antibodies, proliferative responses in mesenteric lymph nodes and spleen cells, as well as cytokines messenger RNA (mRNA) were analyzed. The results showed that one third of the infected animals elicited anti-rTsCRT IgG antibodies. Interestingly, mesenteric lymph node (MLN) cells from either infected or non-infected animals did not proliferate upon in vitro stimulation with rTsCRT. Additionally, stimulation with a tapeworm crude extract resulted in increased expression of IL-4 and IL-5 mRNA. Upon stimulation, rTsCRT increased the expression levels of IL-10 in spleen and MLN cells from uninfected and infected hamsters. The results showed that rTsCRT favors a Th2-biased immune response characterized by the induction of IL-10 in mucosal and systemic lymphoid organs. Here we provide the first data on the cytokine, antibody and cellular responses to rTsCRT upon in vitro stimulation during taeniasis.

  18. Benign and Malignant Proliferative Fibro-osseous and Osseous Lesions of the Oral Cavity of Dogs.

    Science.gov (United States)

    Soltero-Rivera, M; Engiles, J B; Reiter, A M; Reetz, J; Lewis, J R; Sánchez, M D

    2015-09-01

    Ossifying fibroma (OF) and fibrous dysplasia (FD) are benign, intraosseous, proliferative fibro-osseous lesions (PFOLs) characterized by replacement of normal bone by a fibrous matrix with various degrees of mineralization and ossification. Osteomas are benign tumors composed of mature, well-differentiated bone. Clinical, imaging, and histologic features of 15 initially diagnosed benign PFOLs and osteomas of the canine oral cavity were evaluated. Final diagnoses after reevaluation were as follows: OF (3 cases), FD (4 cases), low-grade osteosarcoma (LG-OSA) (3 cases), and osteoma (5 cases). Histology alone often did not result in a definitive diagnosis for PFOL. OF appeared as a well-circumscribed, radiopaque mass with some degree of bone lysis on imaging. Most lesions of FD showed soft tissue opacity with bone lysis and ill-defined margins. Low-grade OSA appeared as a lytic lesion with a mixed opacity and ill-defined margins. Osteomas were characterized by a mineralized, expansile, well-circumscribed lesion. Although histologic features of PFOLs were typically bland, the lesions diagnosed as LG-OSA had some features of malignancy (eg, bone invasion or a higher mitotic index). Treatment varied widely. Of the 10 dogs with benign PFOL or osteoma with known outcome (10/12), 9 showed either complete response (6/10) or stable disease (3/10) after treatment. Of the 2 dogs with LG-OSA with known outcome, 1 showed complete response after curative intent surgery, but 1 patient had recurrence after partial maxillectomy. Definitive diagnosis of mandibular/maxillary PFOL is challenging via histopathologic examination alone, and accurate diagnosis is best achieved through assimilation of clinical, imaging, and histopathologic features.

  19. Cytokine, antibody and proliferative cellular responses elicited by Taenia solium calreticulin upon experimental infection in hamsters.

    Directory of Open Access Journals (Sweden)

    Fela Mendlovic

    Full Text Available Taenia solium causes two diseases in humans, cysticercosis and taeniosis. Tapeworm carriers are the main risk factor for neurocysticercosis. Limited information is available about the immune response elicited by the adult parasite, particularly the induction of Th2 responses, frequently associated to helminth infections. Calreticulin is a ubiquitous, multifunctional protein involved in cellular calcium homeostasis, which has been suggested to play a role in the regulation of immune responses. In this work, we assessed the effect of recombinant T. solium calreticulin (rTsCRT on the cytokine, humoral and cellular responses upon experimental infection in Syrian Golden hamsters (Mesocricetus auratus. Animals were infected with T. solium cysticerci and euthanized at different times after infection. Specific serum antibodies, proliferative responses in mesenteric lymph nodes and spleen cells, as well as cytokines messenger RNA (mRNA were analyzed. The results showed that one third of the infected animals elicited anti-rTsCRT IgG antibodies. Interestingly, mesenteric lymph node (MLN cells from either infected or non-infected animals did not proliferate upon in vitro stimulation with rTsCRT. Additionally, stimulation with a tapeworm crude extract resulted in increased expression of IL-4 and IL-5 mRNA. Upon stimulation, rTsCRT increased the expression levels of IL-10 in spleen and MLN cells from uninfected and infected hamsters. The results showed that rTsCRT favors a Th2-biased immune response characterized by the induction of IL-10 in mucosal and systemic lymphoid organs. Here we provide the first data on the cytokine, antibody and cellular responses to rTsCRT upon in vitro stimulation during taeniasis.

  20. Notch signaling modulates proliferative vitreoretinopathy via regulating retinal pigment epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Zhang, Jingjing; Yuan, Gongqiang; Dong, Muchen; Zhang, Ting; Hua, Gao; Zhou, Qingjun; Shi, Weiyun

    2016-09-07

    Elevated Notch signaling has been verified in a large range of fibrotic diseases developed in the kidney, liver, and lung, inducing the development of the epithelial-mesenchymal transition (EMT). The aim of this study was to observe the involvement of Notch signaling in the EMT of retinal pigment epithelial (RPE) cells and the pathogenesis of proliferative vitreoretinopathy (PVR). In vitro cultivated human RPE cells (ARPE-19) were treated with 10 ng/mL transforming growth factor (TGF)-β1 for 24, 48, and 72 h. The expression levels of ZO-1, α-SMA, vimentin, Notch1 intracellular domain (NICD1), and Hes-1 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence staining or Western blot. TGF-β1 induced EMT and the activation of Notch signaling in ARPE-19 cells. To examine the effect of Notch inhibition on TGF-β1-induced EMT and PVR formation, ARPE-19 cells were preincubated with γ-secretase inhibitor LY411575 before TGF-β1 treatment. Mouse PVR model was used for in vivo study. ARPE-19 cells were injected intravitreously with or without the LY411575 to examine the effect of Notch inhibition on PVR formation. LY411575 significantly attenuated EMT by inhibiting the Notch signaling activation in vitro. PVR was induced by intravitreal injections of ARPE-19 cells, while LY411575 inhibited mouse PVR formation in vivo. Notch signaling plays a critical role in TGF-β1-induced EMT in vitro and mice PVR model, which provides a novel insight into the pathogenesis of PVR. The specific inhibition of Notch signaling by γ-secretase inhibitor may provide a new approach for the prevention of PVR.

  1. Compression Myelopathy due to Proliferative Changes around C2 Pars Defects without Instability

    Science.gov (United States)

    Kimura, Tetsuya; Tezuka, Fumitake; Abe, Mitsunobu; Yamashita, Kazuta; Takata, Yoichiro; Higashino, Kosaku; Sairyo, Koichi

    2016-01-01

    We report a case with compression myelopathy due to proliferative changes around the C2 pars defects without instability. A 69-year-old man presented with progressive clumsy hands and spastic gait. Plain radiographs showed bilateral spondylolysis (pars defects) at C2 and fusion between C2 and C3 spinous processes. Dynamic views revealed mobility through the pars defects, but there was no apparent instability. Computed tomography showed proliferative changes at the pars defects, which protruded into spinal canal. On magnetic resonance imaging, the spinal cord was compressed and intramedullary high signal change was found. A diagnosis of compression myelopathy due to proliferative changes around the C2 pars defects was made. We performed posterior decompression. Postoperatively, symptoms have been alleviated and images revealed sufficient decompression and no apparent instability. In patients with the cervical spondylolysis, myelopathy caused by instability or slippage have been periodically reported. The present case involving C2 spondylolysis is extremely rare. PMID:27340539

  2. PUF-8, a Pumilio homolog, inhibits the proliferative fate in the Caenorhabditis elegans germline.

    Science.gov (United States)

    Racher, Hilary; Hansen, Dave

    2012-10-01

    Stem cell populations are maintained by keeping a balance between self-renewal (proliferation) and differentiation of dividing stem cells. Within the Caenorhabditis elegans germline, the key regulator maintaining this balance is the canonical Notch signaling pathway, with GLP-1/Notch activity promoting the proliferative fate. We identified the Pumilio homolog, PUF-8, as an inhibitor of the proliferative fate of stem cells in the C. elegans germline. puf-8(0) strongly enhances overproliferation of glp-1(gf) mutants and partially suppresses underproliferation of a weak glp-1(lf) mutant. The germline tumor that is formed in a puf-8(0); glp-1(gf) double mutant is due to a failure of germ cells to enter meiotic prophase. puf-8 likely inhibits the proliferative fate through negatively regulating GLP-1/Notch signaling or by functioning parallel to it.

  3. The altered gravity effect on proliferative system of two-day pea germs

    Science.gov (United States)

    Artemenko, O. A.

    The study of clinorotation effect on proliferative system sensibility of plants is very important for understanding and future investigations of their development characteristics and for examination of cell cycle regulation molecular mechanisms. Determination of two-day pea germ mitotic activity of cells, correlation of mitosis phase and DNA content point to decrease of these parameters under clinorotation during the first 12 hours of the factor influence. Cell cycle stabilization after 12 hours of the experiment show high adaptation capacity of plant proliferative system.

  4. Retrospective study of mycophenolate mofetil treatment in IgA nephropathy with proliferative pathological phenotype

    Institute of Scientific and Technical Information of China (English)

    Liang Yan; Zhang Junjun; Liu Dongwei; Quan Songxia; Xing Guolan; Liu Zhangsuo

    2014-01-01

    Background Mycophenolate mofetil (MMF) and cyclophosphamide (CTX) are widely used in treating various kidney diseases.However,whether they are effective and which one is better for treating IgA nephropathy patients with proliferative pathological phenotype in renal diseases,such as endocapillary proliferation,cellular crescents,and/or capillary loops fibrinoid necrosis is still unknown.We,therefore,initiated a study to compare the effects of MMF and CTX in treating IgA nephropathy with the above pathological lesions.Methods One hundred and nineteen patients with IgA nephropathy who had at least one of the three aforementioned lesions were enrolled.All patients were treated with prednisone; 48 patients received prednisone only (Pred group),40 received MMF and prednisone (MMF + Pred group),and 31 were treated with CTX and prednisone (CTX + Pred group).The median time of follow-up was 30 months (maximum:96 months).The primary endpoint was defined as renal survival.The incidence of remission of proteinuria was the secondary endpoint.Results Serum creatinine in all groups declined significantly at different follow-up times (P=0.002),and the differences among the three groups were significant (P<0.001).At 24 months of follow-up,the decline rates were 12.35%,32.95%,and 24.14% in the Pred,MMF + Pred,and CTX + Pred groups respectively.For urine protein excretion,the decline rates were 49.12% (Pred),73.67% (MMF + Pred),and 63.53% (CTX + Pred) respectively at 24 months of follow-up.The differences among the three groups were not significant (P=0.714).Renal survival (the primary endpoint) was significantly different (P=0.027); however,the sencondary endpoint was similar for all the three groups (P=0.100).Conclusions For IgA nephropathy patients with endocapillary proliferation,cellular crescents,and/or fibrinoid necrosis of capillary loops,prednisone combined with MMF was more effective in lowering the serum creatinine than with CTX.Combined MMF and orednisone

  5. Molecular and hormonal regulation of angiogenesis in proliferative endometrium

    Directory of Open Access Journals (Sweden)

    Yousef Rezaei Chianeh

    2014-02-01

    Full Text Available Angiogenesis is a hallmark of wound healing, the menstrual cycle, cancer, and various ischemic and inflammatory diseases. A rich variety of pro and anti-angiogenic molecules have already been identified. Vascular endothelial growth factor (VEGF is an interesting inducer of angiogenesis and lymphangiogenesis, because it is a highly specific mitogen for endothelial cells. Signal transduction involves binding to tyrosine kinase receptors and results in endothelial cell proliferation, migration, and new vessel formation. In this article, the role of VEGF and other growth factors in the pathology of dysfunctional uterine bleeding is reviewed. We also discuss the role of VEGF expression and interaction with extracellular matrix that lead to possible inhibition or stimulation of Angiogenic factor on endometrium of dysfunctional uterine bleeding patients. [Int J Res Med Sci 2014; 2(1.000: 1-9

  6. A neonate with a unique non-Down syndrome transient proliferative megakaryoblastic disease

    NARCIS (Netherlands)

    E.J.M. Bertrums (Eline); A. Buijs (Arjan); M. van Grotel (Martine); N. Dors (N.); J.D. de Rooij (Johan); V. de Haas (Valerie); S. Hopman (Sanne); M. Jongmans; C.M. Zwaan (Christian Michel); M.M. van den Heuvel-Eibrink (Marry)

    2017-01-01

    markdownabstractTransient myeloproliferative disorder (TMD) is a leukemia type that occurs typically in newborns. In Down syndrome, TMD is referred to as transient abnormal myelopoiesis (TAM).32 Recently, transientness has also been reported in acute myeloid leukemia patients with germline trisomy 2

  7. Influence of pro-angiogenic cytokines on proliferative activity and survival of endothelial cells

    Directory of Open Access Journals (Sweden)

    Solyanik G. I.

    2010-04-01

    Full Text Available Aim. Tumor angiogenesis in contrast to physiological one is characterized by high level of malignant cell production of proangiogenic cytokines, which have different influence on functional activity of endothelial cells. The goal of the study – to carry out a comparative analysis of the influence of a vascular endothelial growth factor (VEGF and an epidermal growth factor (EGF on proliferative activity and survival of endothelial cells upon their confluent and exponential growth. Methods. The proliferative activity of endothelial cells was determined by MTT-test and their viability was detected by the trypane blue exclusion test. Results. It was shown that EGF (irrespectively of the level of serum factors in concentrations higher than 10 ng/ml activated the proliferative activity of confluent endotheliocytes in a concentration-dependent manner by 18–36 % (ð < 0.05 as compared to the control, while this cytokine didn’t affect the endothelial cells in the exponential growth phase. VEGF in wide concentration range didn’t display the mitogenic effect on endotheliocytes in both confluent and exponential growth phases. Furthermore, VEGF in concentrations higher than 100 ng/ml inhibited proliferative activity of confluent endothelial cells by 12 % (ð < 0.05. In case of deficiency of nutrients, EGF and VEGF promoted the survival of endothelial cells, considerably decreasing their death. Conclusions. EGF, in contrast to VEGF, stimulates proliferation and survival of the endothelial cells, whereas VEGF has significant influence only on the survival of the cells

  8. Inhibition of human lymphocyte proliferative response by serum from Plasmodium falciparum infected patients

    DEFF Research Database (Denmark)

    Theander, T G; Svenson, M; Bygbjerg, I C

    1987-01-01

    initiation of treatment suppressed the in vitro lymphocyte proliferative response to both Plasmodium-derived antigens and an unrelated antigen (PPD-tuberculin). The suppressive effect was lost if the serum was incubated at 56 degrees C for 30 min, and the effect was not HLA-restricted since the inhibition...

  9. Reactivity in ELISA with DNA-loaded nucleosomes in patients with proliferative lupus nephritis

    NARCIS (Netherlands)

    Dieker, J.W.; Schlumberger, W.; McHugh, N.; Hamann, P.; Vlag, J. van der; Berden, J.H.M.

    2015-01-01

    Autoantibodies against nucleosomes are considered a hallmark of systemic lupus erythematosus (SLE). We compared in patients with proliferative lupus nephritis the diagnostic usefulness of a dsDNA-loaded nucleosome ELISA (anti-dsDNA-NcX) with ELISAs in which dsDNA or nucleosomes alone were coated. Fi

  10. Epithelial cell proliferative activity of Barrett's esophagus : methodology and correlation with traditional cancer risk markers

    NARCIS (Netherlands)

    Peters, F T; Ganesh, S; Kuipers, E J; de Jager-Krikken, A; Karrenbeld, A; Harms, G; Sluiter, W J; Koudstaal, J; Klinkenberg-Knol, E C; Lamers, C B; Kleibeuker, J H

    1998-01-01

    Barrett's esophagus (BE) is a premalignant condition, due to chronic gastroesophageal reflux. Effective antireflux therapy may diminish cancer risk. To evaluate this option an intermediate marker is needed. We developed a methodology for measurement of epithelial cell proliferative activity of Barre

  11. The Effects of Enhanced Informed Consent in a Pro-Life Pregnancy Counseling Center.

    Science.gov (United States)

    Mardirosian, Kathryn; And Others

    1990-01-01

    Investigated effects of enhanced informed consent condition on attitudes of female clients (n=60) toward a counselor, counseling situation, and decision making in a pro-life pregnancy center. Results suggest enhanced consent did not lead to increased or decreased decisions to abort nor to differential attitudes toward counselor or setting.…

  12. Proliferative cell types in embryonic lineages of the central complex of the grasshopper Schistocerca gregaria.

    Science.gov (United States)

    Boyan, George; Williams, Leslie; Legl, Andrea; Herbert, Zsofia

    2010-08-01

    The central complex of the grasshopper Schistocerca gregaria develops to completion during embryogenesis. A major cellular contribution to the central complex is from the w, x, y, z lineages of the pars intercerebralis, each of which comprises over 100 cells, making them by far the largest in the embryonic protocerebrum. Our focus has been to find a cellular mechanism that allows such a large number of cell progeny to be generated within a restricted period of time. Immunohistochemical visualization of the chromosomes of mitotically active cells has revealed an almost identical linear array of proliferative cells present simultaneously in each w, x, y, z lineage at 50% of embryogenesis. This array is maintained relatively unchanged until almost 70% of embryogenesis, after which mitotic activity declines and then ceases. The array is absent from smaller lineages of the protocerebrum not associated with the central complex. The proliferative cells are located apically to the zone of ganglion mother cells and amongst the progeny of the neuroblast. Comparisons of cell morphology, immunoreactivity (horseradish peroxidase, repo, Prospero), location in lineages and spindle orientation have allowed us to distinguish the proliferative cells in an array from neuroblasts, ganglion mother cells, neuronal progeny and glia. Our data are consistent with the proliferative cells being secondary (amplifying) progenitors and originating from a specific subtype of ganglion mother cell. We propose a model of the way that neuroblasts, ganglion mother cells and secondary progenitors together produce the large cell numbers found in central complex lineages.

  13. Photodynamic therapy for palpebral and conjunctival proliferative vascular tumors: clinical case report.

    Science.gov (United States)

    Sanchez, Carlos Gustavo; Caballero Chávez, Yolanda V; Plazola, Sara

    2009-01-01

    Photodynamic therapy (PDT) has been widely used in ophthalmology for the treatment of diverse pathologies, but no experience has been reported in the handling of patients with palpebral vascular and conjunctive malformations with PDT, we describe the case of one patient with a palpebral proliferative vascular tumor, treated successfully using the PDT as a new treatment alternative.

  14. Prevalence and 25 year incidence of proliferative retinopathy among Danish type 1 diabetic patients

    DEFF Research Database (Denmark)

    Grauslund, J; Green, A; Sjølie, A K

    2009-01-01

    was not associated with baseline duration of diabetes, proteinuria, smoking, body mass index, maculopathy or systolic or diastolic blood pressure. CONCLUSIONS/INTERPRETATION: Retinopathy among long-surviving type 1 diabetic patients is almost universal. Proliferative retinopathy was found in half of these patients...

  15. A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice

    NARCIS (Netherlands)

    HogenEsch, H.; Gijbels, M.J.J.; Offerman, E.; Hooft, J. van; Bekkum, D.W. van; Zurcher, C.

    1993-01-01

    Chronic proliferative dermatitis is a new spontaneous mutation in C57BL/Ka mice. Breeding results suggest an autosomal recessive mode of inheritance. Mutant mice develop skin lesions at the age of 5 to 6 weeks. The lesions occur in the ventral and dorsal skin of the body, whereas ears, footpads, and

  16. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial

    NARCIS (Netherlands)

    Grootscholten, C.; Ligtenberg, G.; Hagen, E. C.; van den Wall Bake, A. W. L.; de Glas-Vos, J. W.; Bijl, M.; Assmann, K. J.; Bruijn, J. A.; van Houwelingen, H. C.; Derksen, R. H. W. M.; Berden, J. H. M.; Weening, J.J.

    2006-01-01

    Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), w

  17. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial.

    NARCIS (Netherlands)

    Grootscholten, C.; Ligtenberg, G.; Hagen, E.C.; Wall Bake, A.W. van den; Glas-Vos, J.W. de; Bijl, M.; Assmann, K.J.M.; Bruijn, J.A.; Weening, J.J.; Houwelingen, H.C. van; Derksen, R.H.W.M.; Berden, J.H.M.

    2006-01-01

    Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), w

  18. Prolific plant regeneration from protoplast-derived tissues of Lotus corniculatus L. (birdsfoot trefoil).

    Science.gov (United States)

    Ahuja, P S; Hadiuzzaman, S; Davey, M R; Cocking, E C

    1983-04-01

    Protoplasts isolated enzymatically from seedling roots, hypocotyls and cotyledons of Lotus corniculatus L. produced callus which underwent prolific shoot regeneration. The rapidity and ease of recovering plants from protoplast-derived tissues makes this forage legume an attractive experimental system for genetic manipulation.

  19. Sustained Inhibition of Proliferative Response After Transient FGF Stimulation Is Mediated by Interleukin 1 Signaling.

    Science.gov (United States)

    Poole, Ashleigh; Kacer, Doreen; Cooper, Emily; Tarantini, Francesca; Prudovsky, Igor

    2016-03-01

    Transient FGF stimulation of various cell types results in FGF memory--a sustained blockage of efficient proliferative response to FGF and other growth factors. FGF memory establishment requires HDAC activity, indicating its epigenetic character. FGF treatment stimulates proinflammatory NFκB signaling, which is also critical for FGF memory formation. The search for FGF-induced mediators of FGF memory revealed that FGF stimulates HDAC-dependent expression of the inflammatory cytokine IL1α. Similarly to FGF, transient cell treatment with recombinant IL1α inhibits the proliferative response to further FGF and EGF stimulation, but does not prevent FGF receptor-mediated signaling. Interestingly, like cells pretreated with FGF1, cells pretreated with IL1α exhibit enhanced restructuring of actin cytoskeleton and increased migration in response to FGF stimulation. IRAP, a specific inhibitor of IL 1 receptor, and a neutralizing anti-IL1α antibody prevent the formation of FGF memory and rescue an efficient proliferative response to FGF restimulation. A similar effect results following treatment with the anti-inflammatory agents aspirin and dexamethasone. Thus, FGF memory is mediated by proinflammatory IL1 signaling. It may play a role in the limitation of proliferative response to tissue damage and prevention of wound-induced hyperplasia.

  20. Proliferative Activity in Libyan Breast Cancer with Comparison to European and Central African Patients

    Directory of Open Access Journals (Sweden)

    Jamela Boder

    2013-01-01

    Full Text Available Background. We evaluated the relation of proliferative indices with clinicopathological features and prognosis in breast cancer (BC of Libyan female patients. The data were compared with corresponding results in Finland and Nigeria. Patients and Methods. Histological samples of breast cancer from 130 patients were retrospectively studied. Mitotic activity index (MAI and standardized mitotic index (SMI were estimated. Results. There were statistically significant correlations between the proliferative indices and most clinicopathological features, with the strongest association observed for histological grade (P=0.01 for SMI and P=0.003 for MAI. The proliferative differences between Libyan, Nigerian, and Finnish population were prominent. The mean values of SMI and MAI in Libyan BC patients were 32.1 mitotic figures per square millimeter and 27.3 mitotic figures per 10 high-power fields, respectively. This is clearly lower than those in Nigeria but much higher than those in Finland. The differences between countries are seen in whole material and are also present in subgroups. The results indicated that mitotic activities can be reliable prognostic indicators in Libyan BCs, as they were among Finnish and Nigerian females. Univariate and multivariate analyses found at cut-offs of 19 and 44 mitosis/mm2 of SMI were the most significant prognostic factors. Conclusions. Proliferative indices with careful estimation of the MAI and SMI could be applied as quantitative criteria for Libyan BC to separate the patients into good, moderate, and bad prognosis groups.

  1. PROLIFERATIVE LESIONS IN SWIMBLADDER OF JAPANESE MEDAKA ORYZIAS LATIPES AND GUPPY POECILIA RETICULATA

    Science.gov (United States)

    Thirteen cases of proliferative lesions of the swimbladder were encountered in Japanese medaka Oryzias latipes and guppy Poecilia reticulata from about 10,000 medaka and 5,000 guppies used in carcinogenicity tests and histologically examined. Two of the four cases from medaka and...

  2. Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population

    Science.gov (United States)

    Gonzalez-Salinas, Roberto; Garcia-Gutierrez, Maria C; Garcia-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul; Soberon-Ventura, Vidal R; Gonzalez, Victoria; Lechuga, Rodrigo; Garcia-Solis, Pablo; Garcia-Gutierrez, David G; Garcia-Solis, Marco Vinicio; Saenz de Viteri, Manuel; Solis-S, Juan C

    2017-01-01

    AIM To assess if the included vascular endothelial growth factor (VEGF) polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus (T2DM). METHODS A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study (ETDRS) standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts. RESULTS In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher's exact test was performed for rs3025021 [OR (95% CI)=0.44(0.08-2.2); P=0.25] and rs2010963 [OR (95% CI)=0.63(0.25-1.6); P=0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows: rs3025021 vs rs3025035: D'=1.0, r2=0.1043, P≤0.0001; rs3025021 vs rs2010963: D'=0.442, r2=0.0446, P=0.149; rs3025035 vs rs2010963: D'=0.505, r2=0.0214, P=0.142. CONCLUSION This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that

  3. Relationship between proliferative activity of bone marrow micrometastasis and plasmatic level of a new cancer marker: lipid associated sialic acid (LASA) in human breast cancer.

    Science.gov (United States)

    Ginsbourg, M; Musset, M; Misset, J L; Mathé, G

    1986-01-01

    The correlation between elevated level of a new plasma cancer marker, Lipid Associated Sialic Acid (LASA) and detection of bone marrow heterotopic epithelial cells by monoclonal antibodies using an immunocytologic technique, associated with the study of the proliferative activity of these heterotopic cells by measurement of their labelling index (LI) was analyzed in 158 samples obtained from 94 breast cancer patients. Six different groups of patients in complete remission of breast cancer, after radical treatment of the primary (minimal residual disease (MRD] were defined, according to the presence with or without proliferative activity of heterotopic cells in the bone marrow or the absence of such cells and to the level, normal or elevated of LASA in the serum of the same patient at the same time. 115 samples (73%) of the patients had an elevated LASA level at the time of the study among which 71 (45%) came from patients in which heterotopic cells were detected in the bone marrow, 32 (20%) of which with proliferative activity (LI+) 39 (25%) without (LI-). In 44 (28%) samples, no heterotopic cells were detected in the B.M. 43 samples (27%) of the patients had a normal LASA level. In 29 (18%) no heterotopic cells could be detected in the B.M. In only 14 could such cells be found, 5 with LI+, 9 with LI-. Both of these cytological and biological parameters can be useful markers of minimal residual disease and help to determine the prognosis and define optimal therapeutic strategy for curable breast cancer. Their prognostic value in predicting relapse awaits further observation with longer follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. The differential proliferative ability of satellite cells in Lantang and Landrace pigs.

    Directory of Open Access Journals (Sweden)

    Xiu-qi Wang

    Full Text Available Here, for the first time, we evaluate the hypothesis that the proliferative abilities of satellite cells (SCs isolated from Lantang (indigenous Chinese pigs and Landrace pigs, which differ in muscle characteristics, are different. SCs were isolated from the longissimus dorsi muscle of neonatal Lantang and Landrace pigs. Proliferative ability was estimated by the count and proliferative activity of viable cells using a hemocytometer and MTT assay at different time points after seeding, respectively. Cell cycle information was detected by flow cytometry. Results showed that there was a greater (P<0.05 number of SCs in Lantang pigs compared with Landrace pigs after 72 h of culture. The percentage of cell population in S phase and G(2/M phases in Lantang pigs were higher (P<0.05, while in G(0/G(1 phase was lower (P<0.05 in comparison with the Landrace pigs. The mRNA abundances of MyoD, Myf5, myogenin and Pax7 in SCs from Lantang pigs were higher (P<0.05, while those of myostatin, Smad3 and genes in the mammalian target of rapamycin (mTOR pathway (with the exception of 4EBP1 were lower (P<0.05 than the Landrace pigs. Protein levels of MyoD, myogenin, myostatin, S6K, phosphorylated mTOR and phosphorylated eIF4E were consistent with the corresponding mRNA abundance. Collectively, these findings suggested that SCs in the two breeds present different proliferative abilities, and the proliferative potential of SCs in Lantang pigs is higher than in Landrace pigs.

  5. Expression of novel genes linked to the androgen-induced, proliferative shutoff in prostate cancer cells.

    Science.gov (United States)

    Geck, P; Szelei, J; Jimenez, J; Lin, T M; Sonnenschein, C; Soto, A M

    1997-01-01

    Androgens control cell numbers in the prostate through three separate pathways: (a) inhibition of cell death, (b) induction of cell proliferation (Step-1) and (c) inhibition of cell proliferation (Step-2, proliferative shutoff). The mechanisms underlying these phenomena are incompletely understood. The human prostate carcinoma LNCaP variants express these pathways as follows: LNCaP-FGC express both steps, LNCaP-LNO expresses Step-2, LNCaP-TAC expresses Step-1, and LNCaP-TJA cells express neither step. These cells facilitated the search for mediators of the androgen-induced proliferative shutoff pathway. Androgen exposure for 24 h or longer induced an irreversible proliferative shutoff in LNCaP-FGC cells. The Wang and Brown approach for identifying differentially expressed mRNAs was used to search for mediators of Step-2. Ten unique inserts were identified and from those ten, three genes were further studied. The basal expression of these genes in shutoff-negative variants was not affected by androgen exposure. They were induced by androgens in shutoff-positive LNCaP variants and the androgen receptor-transfected, shutoff-positive, MCF7-AR1 cells. These genes were induced only in the range of androgen concentrations that elicited the shutoff response. Time course analysis showed that their induction precedes the commitment point by 12-18 h. In addition, they were expressed in the normal prostate during proliferative shutoff. These features suggest that the candidate genes have a role in the regulation cascade for proliferative shutoff.

  6. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi;

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...

  7. Ocular surface changes in type II diabetic patients with proliferative diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Yan; Gao; Yan; Zhang; Yu-Sha; Ru; Xiao-Wu; Wang; Ji-Zhong; Yang; Chun-Hui; Li; Hong-Xing; Wang; Xiao-Rong; Li; Bing; Li

    2015-01-01

    AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy.METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR(NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I test, and corneal fluorescein staining. The non-invasive tear film break-up time(NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy.RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P <0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls(P <0.001).Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover,significant decrease in the corneal epithelial density andmorphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores,and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the

  8. MR findings of bland and proliferative joint effusion in Knee joint

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hak Soo; Joo, Kyung Bin; Yang, Kee Hyuk; Choi, Jung Bin; Kim, Yong Soo; Park, Dong Woo; Park, Choong Ki; Hahm, Chang Kok [College of Medicine, Hanyang University, Seoul (Korea, Republic of)

    2000-05-01

    To determine the MR imaging criteria by which bland and proliferative effusion of the knee may be differentiated. We retrospectively reviewed the MR images of 64 patients (65 cases), in whom T2-weighted sagittal scans revealed anteroposterior distension of the suprapatellar bursa of at least 0.5 cm. The patients were divided into two groups: bland effusion (n=3D36), and proliferative effusion ((n=3D29); pigmented villonodular synovitis (n=3D5), rheumatoid arthritis (n=3D6), septic arthritis (n=3D6), chronic synovitis (n=3D5), gouty arthritis (n=3D3), tuberculous arthritis (n=3D2), and lipoma arborescens (n=3D2)). All conditions were diagnosed on the basis of operative data or clinical criteria. The knee joint space was divided into four compartments: the suprapatellar pouch, central zone, posterior femoral recess, and subpopliteal recess, and the amount and distribution of effusion was then compared between the two groups. The ratios of the width and the length of the lateral recess of the suprapatellar bursa to those of its medial recess were determined, and the findings for the two groups were compared.Abnormality of the intracapular fat pads (prefemoral fat, Hoffa's fat, and quadriceps fat sign) as seen on sagittal scans, is a predictor proliferative effusion, and any such abnormality was evaluated. The synovium was classified as either thin or thick, and as having either a smooth or an irregular margin, as seen on Gadolinium-enhanced T1W1 images. As compared with bland effusion, proliferative effusion involved more prominent joint effusion in the suprapatellar pouch and posterior femoral recess, and in the suprapatellar bursa, the ratio of the width of the lateral recess to that of the medial recess was greater. When comparing the ratio of the length of the lateral recess to that of the medial recess, however, no significant statistical difference was noted. Sensitivity: specificity for proliferative effusion was 58%: 86% on coronal scan and 64%: 93% on

  9. Intracellular expression of the proliferative marker Ki-67 and viral proteins (NS3, NS5A and C in chronic, long lasting hepatitis C virus (HCV infection.

    Directory of Open Access Journals (Sweden)

    Karolina Olejniczak

    2008-01-01

    Full Text Available Hepatitis C virus (HCV continues to represent the main causative agent of the hepatitis, which leads to chronic transformation of the process in 60-80% individuals. It remains unclear how far cellular expression of HCV proteins in vivo may represent an index of progression of the disease and of proliferative activity in the liver in chronic hepatitis C. Aim of the studies included detection and subcellular localization of three HCV proteins (NS3, NS5A and C in liver biopsies from adults (n=19 with chronic, long lasting hepatitis C as related to hepatocyte proliferative activity. The immunocytochemical ABC (avidin biotin-peroxidase complex technique was applied, alone or associated with the ImmunoMax technique. Results of the immunocytochemical tests were compared to histological alterations in liver biopsies, proliferation index and with selected clinical data. A significantly higher expression of NS3 protein was noted, as compared to expressions of NS5A and C proteins. In all the patients, cytoplasmic localization of all proteins dominated over nuclear localization (p0.05. At the level of electron microscopy, protein localization in endoplasmic reticulum (ER membranes, mitochondria, perinuclear region and/or in hepatocyte cell nucleus was observed. No direct relationships could be demonstrated between expressions of HCV proteins and of Ki-67 antigen. No correlations could also be demonstrated between cellular expression of any HCV protein on one hand and grading or staging, alanine transaminase (ALT, serum level of HCV RNA or alpha-fetoprotein (AFP on the other. However, positive correlations were disclosed between proliferative activity of hepatocytes on one hand and patient's age, grading and staging on the other. Advanced hepatic fibrosis correlated also with serum levels of AFP. The studies were supplemented with data on subcellular localization of HCV proteins. Moreover, they indicated that in HCV infection grading and staging

  10. [Kimura's disease: an unrecognized cause of adult-onset nephrotic syndrome with minimal change disease].

    Science.gov (United States)

    Shehwaro, N; Langlois, A-L; Gueutin, V; Debchi, L; Charlotte, F; Rouvier, P; Rottembourg, J; Izzedine, H

    2014-02-01

    Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Kidney disease is thought to be rare in KD. About a case of adult-onset nephrotic syndrome with minimal change disease, we comment Kimura's disease and its associated kidney damage. Kimura disease should be suspected and included in the diagnosis of adult-onset nephrotic syndrome with minimal change disease.

  11. Effects of free amino acids on cytokine secretion and proliferative activity of feline T cells in an in vitro study using the cell line MYA-1.

    Science.gov (United States)

    Paßlack, Nadine; Doherr, Marcus G; Zentek, Jürgen

    2016-10-01

    In vitro studies might be an interesting screening method for targeted in vivo studies in the field of immunonutrition and help to reduce and refine animal studies. As the role of amino acids for immune function of cats has not been evaluated in detail so far, the present study aimed at investigating the effects of eight different amino acids (arginine, leucine, isoleucine, valine, glutamine, lysine, threonine and tryptophan) in six concentrations each (0, 0.25, 0.5, 1, 2 and 8x the cat blood level) on cytokine secretion and proliferative activity of feline T cells (MYA-1) in vitro. The results demonstrated that high doses of arginine increased IL-4, IL-10 and TNF-α secretion of T cells, while increasing concentrations of lysine increased IL-10 secretion and proliferative activity of the T cells. High doses of leucine enhanced GM-CSF and IL-10 secretion, while concentrations of threonine in the cell culture media greater than blood concentration also increased GM-CSF and additionally TNF-α secretion of the cells. The effects of glutamine and isoleucine on T cell function were only small. In conclusion, the present in vitro study could evaluate the immunomodulating potential of specific amino acids for feline T cell function. High doses of arginine, lysine, leucine and threonine had a significant impact on cytokine secretion and proliferative activity of the T cells. Targeted in vivo studies should investigate the clinical relevance of dietary supplementation of those amino acids in healthy and diseased cats as a next step.

  12. In vitro anti-proliferative, anti-bacterial potential and induction of DNA strand break of partially purified Cuscuta reflexa Roxb.

    Directory of Open Access Journals (Sweden)

    Madhulika Bhagat

    2011-01-01

    Full Text Available Cuscuta reflexa is an important medicinal plant, mentioned in Ayurveda, an ancient Indian system of medicine. The plant is selected to evaluate the possibility for novel pharmaceuticals for anticancer and antibiotics drugs. Since most of these drugs had developed resisitance against currently used chemotherapeutics. This study describes the in vitro anti-proliferative, anti-bacterial and single stand DNA break of the holoprasitic plant Cuscuta reflexa. Bioassay-guided fractionation and partial purification of the plant were done and evaluated for antiproliferative activity against human cancer cell lines by SRB assay and single strand DNA break by comet assay. Further antibacterial activity was also performed by agar well diffusion assay. The alcoholic extract, chloroform fraction and partially purified ethylacetate-methanol (1:1 sub-fraction of C. reflexa showed anti-proliferative potential against IMR-32 and 502713 human cancer cell lines. Alcoholic extract exhibited anti-proliferative activity of 74% and 72%, chloroform fraction demonstrated 91% and 95% against neuroblastoma (IMR-32 and colon (502713 cancer cell lines at 100 μg/ml. Single strand DNA break of the chloroform fraction was also demonstrated using comet assay, indicating that possible mode of cell death may be apoptosis. Anti-microbial properties were evaluated against eight species of pathogenic and non-pathogenic microorganisms and maximum zone of inhibition for anti-bacterial activity was found against Staphylococcus aureus (22 mm by alcoholic extract, 21 mm by chloroform fraction and 12 mm by ethylacetate-methanol (1:1 sub-fraction. Minimum inhibitory concentration (MIC of the chloroform fraction was 1500 μg/ml for S. aureus. The plant was found to be equally effective against gram-positive and negative bacteria. Studies are well underway to isolate and identify active compounds from chloroform fraction and ethyl acetate:methanol (1:1 sub-fraction, which can be used as

  13. Analysis of p53 expression and proliferative assessment using PCNA in localized prostate carcinoma

    Directory of Open Access Journals (Sweden)

    Leite K.R.M.

    1999-01-01

    Full Text Available The surgical specimens from 51 men submitted to radical prostatectomy for localized prostate cancer were examined by immunohistochemistry using proliferation cell nuclear antigen (PCNA monoclonal antibody to evaluate the proliferative index (PI. The relationship between PI, biological variables and p53 protein expression was evaluated by immunohistochemistry. PI was low in invasive localized prostate carcinoma (mean, 12.4% and the incidence of PCNA-positive cells was significantly higher in tumors with p53 expression (P = 0.0226. There was no statistical difference in PCNA values when biological parameters such as Gleason score, tumor volume, extraprostatic involvement, seminal vesicle infiltration or lymph node metastasis were considered. We conclude that proliferative activity is usually low in prostate carcinoma but is correlated with p53 immune staining, indicating that p53 is important in cell cycle control in this neoplasm.

  14. A Cellular Automaton Model for Tumor Dormancy: Emergence of a Proliferative Switch

    CERN Document Server

    Chen, Duyu; Torquato, Salvatore

    2014-01-01

    Malignant cancers that lead to fatal outcomes for patients may remain dormant for very long periods of time. Although individual mechanisms such as cellular dormancy, angiogenic dormancy and immunosurveillance have been proposed, a comprehensive understanding of cancer dormancy and the "switch" from a dormant to a proliferative state still needs to be strengthened from both a basic and clinical point of view. Computational modeling enables one to explore a variety of scenarios for possible but realistic microscopic dormancy mechanisms and their predicted outcomes. The aim of this paper is to devise such a predictive computational model of dormancy with an emergent "switch" behavior. Specifically, we generalize a previous cellular automaton (CA) model for proliferative growth of solid tumor that now incorporates a variety of cell-level tumor-host interactions and different mechanisms for tumor dormancy, for example the effects of the immune system. Our new CA rules induce a natural "competition" between the tu...

  15. Acute Hemiparesis in a Child as a Presenting Symptom of Hemispheric Cerebral Proliferative Angiopathy

    Directory of Open Access Journals (Sweden)

    J. J. Gold

    2013-01-01

    Full Text Available A 9-year-old girl with a several-month history of unilateral intermittent headaches presented to the hospital with worsening headaches and unsteadiness. Neurologic exam was positive for a mild right hemiparesis and right homonymous hemianopsia. Noncontrast computed tomography revealed an engorged sagittal and straight sinus with prominent cortical veins concerning an arteriovenous malformation and the patient was admitted to the pediatric intensive care unit. Computed tomography angiogram demonstrated a left hemispheric vascular malformation, without evidence of dural arteriovenous fistula on conventional angiogram consistent with a diagnosis of cerebral proliferative angiopathy. There was no evidence of infarct on magnetic resonance imaging, and the patient’s symptoms were completely resolved within 24 hours. Cerebral proliferative angiopathy is a rare but important vascular malformation distinct from classic arteriovenous malformations that may present with stroke-like symptoms in childhood.

  16. The Frequency of Proliferative Stromal Cells in Adipose Tissue Varies Between Inbred Mouse Strains

    Directory of Open Access Journals (Sweden)

    Mo J

    2009-01-01

    Full Text Available Stromal cells derived from adipose tissue (ASCs can proliferate as undifferentiated cells with a fibroblast-like morphology in cell culture, or can be induced to differentiate into a variety of cell types including, adipipogenic, myogenic, neurogenic, osteogenic, chondrogenic and hepatic cells. There is increasing interest to understand the factors controlling the proliferation of ASCs since these cells might provide a readily available source of autologous stem/progenitor cells for cell therapy applications. To explore potential genetic factors that modify the properties of ASCs, we tried to identify relevant properties of ASCs that differ between inbred mouse strains. Plating cells in a modified colony forming assay indicates that the percentage of high proliferative cells among ASCs differs more than 2-fold between 129x1/svj and C57Bl/6J mice. The identification of genetic factors affecting the proliferative capacity of stem cell populations could improve the efficacy of cell therapy.

  17. [The study of proliferative epithelial activity in cholesteatoma of the middle ear during cytomorphophotometry].

    Science.gov (United States)

    Amador, J M; Esquivias, J J; Ciges, M

    1994-01-01

    Epithelial proliferation in colesteatoma and its influence on the subepithelial inflammatory reaction was studied using morphometry and nuclear photometry of specimens. Twenty specimens of colesteatoma and 15 specimens of skin from the external auditory canal were examined. Nuclear content was greater in the basal cells of colesteatoma epithelium than in the basal cells of external auditory canal epithelium, suggesting increased proliferative activity. This activity was found to be reted to the inflammatory infiltrate of the conjunctive tissue and varied in different specimens.

  18. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells

    OpenAIRE

    Reyhan Akhtar; Mohd Ali; Safrannisa Mahmood; Sankar Nath Sanyal

    2014-01-01

    Background: Silibinin a flavonoid from milk thistle (Silybum marianum) exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml) for 24, 48 or 72 h showed a progressive decline in cell viability. Res...

  19. Retinol induces morphological alterations and proliferative focus formation through free radicalmediated activation of multiple signaling pathways

    Institute of Scientific and Technical Information of China (English)

    Daniel Pens GELAIN; Matheus Augusto de Bittencourt PASQUALI; Fernanda Freitas CAREGNATO; Mauro Antonio Alves CASTRO; José Claudio Fonseca MOREIRA

    2012-01-01

    Aim:Toxicity of retinol (vitamin A)has been previously associated with apoptosis and/or cell malignant transformation.Thus,we investigated the pathways involved in the induction of proliferation,deformation and proliferative focus formation by retinol in cultured Sertoli cells of rats.Methods:Sertoli cells were isolated from immature rats and cultured.The cells were subjected to a 24-h treatment with different concentrations of retinol.Parameters of oxidative stress and cytotoxicity were analyzed.The effects of the p38 inhibitor SB203580(10 μmol/L),the JNK inhibitor SP600125 (10 μmol/L),the Akt inhibitor LY294002 (10 μmol/L),the ERK inhibitor U0126 (10 μmol/L)the pan-PKC inhibitor G(O)6983 (10 μmol/L)and the PKA inhibitor H89 (1 μmol/L)on morphological and proliferative/transformationassociated modifications were studied.Results:Retinol (7 and 14 μmol/L)significantly increases the reactive species production in Sertoli cells,inhibition of p38,JNK,ERK1/2,Akt,and PKA suppressed retinol-induced[3H]dT incorporation into the cells,while PKC inhibition had no effect.ERK1/2 and p38 inhibition also blocked retinol-induced proliferative focus formation in the cells,while Akt and JNK inhibition partially decreased focus formation.ERK1/2 and p38 inhibition hindered transformation-associated deformation in retinol-treated cells,while other treatments had no effect.Conclusion:Our results suggest that activation of multiple kinases is responsible for morphological and proliferative changes associated to malignancy development in Sertoli cells by retinol at the concentrations higher than physiological level.

  20. Japan Turns Pro-Life: Recent Change in Reproductive Health Policy and Controversies over Prenatal Screening

    Directory of Open Access Journals (Sweden)

    Etsuji Okamoto

    2014-02-01

    Full Text Available Japan, known as a pro-choice country in terms of abortion, is currently facing the increase of “selective abortions” thanks to new prenatal screening. Efforts to restrict proliferation of new technology has not been successful and it is likely that Japan will turn pro-life by strictly enforcing the Maternity Protection Act (MPA, which prohibits abortions due to “fetal cause”.

  1. Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

    OpenAIRE

    2011-01-01

    Abstract Background The response of mammalian glial cells to chronic degeneration and trauma is hypothesized to be incompatible with support of neuronal function in the central nervous system (CNS) and retina. To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (p27 or Cdkn1b) in the adult mouse and determined the outcome on retinal structure ...

  2. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery

    DEFF Research Database (Denmark)

    Poulsen, Michael; Oh, Dong-Chan; Clardy, Jon;

    2011-01-01

    Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social...... phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest....

  3. Comparative antitumor and anti-proliferative activities ofHippophae rhamnoidesL. leaves extracts

    Institute of Scientific and Technical Information of China (English)

    Javid Ali; Bashir Ahmad

    2015-01-01

    Objective:To evaluate the antitumor and anti-proliferative activities of methanol, aqueous, acetone, ethyl acetate, ethanol, chloroform andn-hexane extracts ofHippophae rhamnoides leaves. Methods: Antitumor activities were evaluated by using the antitumor potato disc assay by using inoculums (Agrobacterium tumefaciens) with three different concentrations of test samples (10, 100 and 1 000 mg/L). Anti-proliferative activity was evaluated by the given method of methyl thiazolyl tetrazolium assay. The concentrations of the extract ranging from 0.039 to 10 mg/mL were tested against HeLa cells. Results: Highest tumors inhibition activity (60.9% and 55.8%) was shown by methanol and ethanol extracts, with EC50 values of 424.41 and 434.61 mg/L respectively. At 10 mg/mL, The highest cell inhibition 75.61% was observed in methanol extract and the lowest 36.59% were calculated inn-hexane extract. The difference in tumor and cell inhibition (%) may be due to the different concentration of active compounds responsible for antitumor and anti-proliferative activities. All extracts have considerable level of tumor and cell inhibitiory effect in a dose dependent manner. Conclusions:Our finding showed thatHippophae rhamnoidesleaves are a potent natural source of antitumor and antiproliferative agent.

  4. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

    Science.gov (United States)

    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents.

  5. Quinazolinones-Phenylquinoxaline hybrids with unsaturation/saturation linkers as novel anti-proliferative agents.

    Science.gov (United States)

    Palem, Jyothsna Devi; Alugubelli, Gopi Reddy; Bantu, Rajashaker; Nagarapu, Lingaiah; Polepalli, Sowjanya; Jain, S Nishanth; Bathini, Raju; Manga, Vijjulatha

    2016-07-01

    A new series of novel quinazolinones with allylphenyl quinoxaline hybrids 9a-n were efficiently synthesized in good yields by the reaction of 3-allyl-2-methylquinazolin-4(3H)-one (5a-n) with bromophenyl)quinoxaline (8) utilizing Pd catalyzed Heck-cross coupling and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 9a, 9e, 9g and 9h exhibited promising anti-proliferative activity with GI50 values ranging from 0.06 to 0.2μM against four cell lines, while compounds 9e and 9k showed significant activity against HeLa and MIAPACA cell lines and compounds 9b, 9d, 9h and 9j showed selective potency against IMR32 and MDA-MB-231 cell lines. This is the first report on the synthesis and in vitro anti-proliferative evaluation of E-2-(4-substituted)-3-(3-(4-(quinoxalin-2-yl)phenyl)allyl)quinazolin-4(3H)-ones (9a-n). Docking results indicate a sign of good correlation between experimental activity and calculated binding affinity (dock score), suggesting that these compounds could act as promising DNA intercalates.

  6. Anti-proliferative effects of deflazacort on Nb2 cells as quantitated by formazan production.

    Science.gov (United States)

    Adler, R A; Naumann, S A; Mansouri, A; Krieg, R J; Latta, K; Sanders, K M

    1994-01-01

    Prolactin and other lactogenic hormones are mitogenic for the rat T-cell lymphoma line, Nb2. Glucocorticoids have antiproliferative effects on these cells. A limiting feature of experiments utilizing the Nb2 line is their labor-intensive nature. We therefore adapted the commonly used MTT dye proliferation assay for the Nb2 cell line. While rPRL, hPRL, oPRL, hGH, bPL, and to a lesser extent bPRL stimulated the Nb2 cells, hormones without lactogenic activity, rGH and oGH did not. Human serum and rat sera from animals bearing a PRL-secreting tumor stimulated the Nb2 cells in parallel to standards. Glucocorticoids had anti-proliferative effects on Nb2 cells in the presence of half-maximal or maximal PRL doses, as measured by the MTT proliferation assay. It has been claimed that an oxazoline steroid, deflazacort, has anti-inflammatory effects in clinical studies with fewer of the deleterious side-effects common to glucocorticoids. We therefore compared the in vitro anti-proliferative effects of deflazacort with other glucocorticoids. Deflazacort's negative effect on Nb2 cell proliferation was similar to that of cortisol and prednisolone and less than that of dexamethasone. We conclude that the MTT proliferation assay can be used to study both mitogenic and anti-proliferative substances in Nb2 cells. In addition we found that deflazacort acts similarly in vitro to other glucocorticoids.

  7. Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells.

    Science.gov (United States)

    Pandiri, Indira; Chen, Yingqing; Joe, Yeonsoo; Kim, Hyo Jeong; Park, Jeongmin; Chung, Hun Taeg; Park, Jeong Woo

    2016-02-01

    Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay. Breast cancer cells were transfected with siRNA against TTP to inhibit TTP expression or c-Myc and, after metformin treatment, analyzed for cell proliferation by MTS assay. Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner. Importantly, inhibition of TTP abrogated the anti-proliferation effect of metformin. We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation. Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin's anti-proliferative activity in cancer cells.

  8. Comparison of methods for proliferative index analysis for grading pancreatic well-differentiated neuroendocrine tumors.

    Science.gov (United States)

    Goodell, Pamela P; Krasinskas, Alyssa M; Davison, Jon M; Hartman, Douglas J

    2012-04-01

    Assessment of proliferative activity is required for grading well-differentiated pancreatic neuroendocrine tumors. However, a standardized method for obtaining the Ki-67 proliferative index is lacking. This study compared proliferative activity obtained by 3 methods: single-field hot spot (Ki-67 HS) and 10 consecutive field average (Ki-67 CFA) using the Ventana image analysis system (Ventana Medical Systems, Tucson, AZ) and mitotic index (MI). These methods resulted in discrepant grades in 30 (67%) of our 45 cases. With the current Ki-67 cutoff of more than 2% for intermediate-grade tumors, MI, CFA, and HS resulted in specificities of 91%, 94%, and 31%, respectively, for detecting metastasis, with positive predictive values (PPVs) of 25%, 67%, and 31%, respectively. At a higher Ki-67 cutoff of 7.5%, HS analysis resulted in a specificity of 94% and PPV of 71% for predicting metastasis. While single-field HS analysis may be practical and reliable at a higher cutoff, this study emphasizes the variability that can exist when different methods of assessment are used.

  9. uPAR EXPRESSION IN CANINE NORMAL PROSTATE AND WITH PROLIFERATIVE DISORDERS

    Directory of Open Access Journals (Sweden)

    Mariana Rodrigues Faleiro

    2013-06-01

    Full Text Available Prostatic lesions such as prostatic intraepithelial neoplasia (PIN and proliferative inflammatory atrophy (PIA are studied in human and canine species due to their malignance potential. The plasminogen activator (PA system has been suggested to play a central role in cell adhesion, angiogenesis, inflammation, and tumor invasion. The urokinase-type plasminogen activator receptor (uPAR is a component of the PA, with a range of expression in tumor and stromal cells. In this study, uPAR expression in both canine normal prostates and with proliferative disorders (benign prostatic hyperplasia-BPH, proliferative inflammatory atrophy-PIA, prostatic intraepithelial neoplasia-PIN, and carcinoma-PC was evaluated by immunohistochemistry in a tissue microarray (TMA slide to establish the role of this enzyme in extracellular matrix (ECM remodeling and in the processes of tissue invasion. A total of 298 cores and 355 diagnoses were obtained, with 36 (10.1% normal prostates, 46 (13.0% with BPH, 128 (36.1% with PIA, 74 (20.8% with PIN and 71 (20.0% with PC. There is variation in the expression of uPAR in canine prostate according to the lesion, with lower expression in normal tissue and with BPH, and higher expression in tissue with PIA, PIN and PC. The high expression of uPAR in inflammatory and neoplastic microenvironment indicates increased proteolytic activity in canine prostates with PIA, PIN, and PC.

  10. Inhibition of inflammatory and proliferative responses of human keratinocytes exposed to the sesquiterpene lactones dehydrocostuslactone and costunolide.

    Directory of Open Access Journals (Sweden)

    Claudia Scarponi

    Full Text Available The imbalance of the intracellular redox state and, in particular, of the glutathione (GSH/GSH disulfide couple homeostasis, is involved in the pathogenesis of a number of diseases. In many skin diseases, including psoriasis, oxidative stress plays an important role, as demonstrated by the observation that treatments leading to increase of the local levels of oxidant species ameliorate the disease. Recently, dehydrocostuslactone (DCE and costunolide (CS, two terpenes naturally occurring in many plants, have been found to exert various anti-inflammatory and pro-apoptotic effects on different human cell types. These compounds decrease the level of the intracellular GSH by direct interaction with it, and, therefore, can alter cellular redox state. DCE and CS can trigger S-glutathionylation of various substrates, including the transcription factor STAT3 and JAK1/2 proteins. In the present study, we investigated on the potential role of DCE and CS in regulating inflammatory and proliferative responses of human keratinocytes to cytokines. We demonstrated that DCE and CS decreased intracellular GSH levels in human keratinocytes, as well as inhibited STAT3 and STAT1 phosphorylation and activation triggered by IL-22 or IFN-γ, respectively. Consequently, DCE and CS decreased the IL-22- and IFN-γ-induced expression of inflammatory and regulatory genes in keratinocytes, including CCL2, CXCL10, ICAM-1 and SOCS3. DCE and CS also inhibited proliferation and cell-cycle progression-related gene expression, as well as they promoted cell cycle arrest and apoptosis. In parallel, DCE and CS activated the anti-inflammatory EGFR and ERK1/2 molecules in keratinocytes, and, thus, wound healing in an in vitro injury model. In light of our findings, we can hypothesize that the employment of DCE and CS in psoriasis could efficiently counteract the pro-inflammatory effects of IFN-γ and IL-22 on keratinocytes, revert the apoptosis-resistant phenotype, as well as inhibit

  11. 变黑白头翁提取物降低亚砷酸盐对小鼠精细胞的毒性%Dihydroxy-isosteviol methyl ester of Pulsatilla nigricans extract reduces arsenic-induced DNA damage in testis cells of male mice: its toxicity, drug-DNA interaction and signaling cascades

    Institute of Scientific and Technical Information of China (English)

    Asmita Samadder; Jayeeta Das; Sreemanti Das; Durba Das; Arnab De; Kakali Bhadra; Anisur Rahman Khuda-Bukhsh

    2012-01-01

    目的:研究变黑白头翁提取物降低亚砷酸盐对小鼠精细胞毒性的作用.方法:给予实验小鼠亚砷酸钠(20 mg/kg每日),并分别在第30、60、90天对小鼠进行检测.亚砷酸盐中毒小鼠被分为2组,其中一组给予变黑白头翁提取物(35 mg/kg),另一组给予85%乙醇.通过检测小鼠精细胞凋亡标志蛋白CYP1A1、p53及caspase 3的活性,确定细胞及DNA的损伤情况,并测定睾丸毒性标志物的水平.通过圆二色光谱仪及熔化温度数据检测变黑白头翁提取物与DNA的相互作用情况.结果:亚砷酸盐中毒小鼠的所有细胞凋亡标志蛋白及睾丸毒性标志物的水平均有所上升,而经变黑白头翁提取物治疗的小鼠上述各项指标均降低或恢复至正常水平.变黑白头翁提取物与DNA相互作用,引起了DNA结构和构象的变化.结论:变黑白头翁提取物可作为砷中毒引起的生殖功能损害的治疗药物给予研究和开发.%OBJECTIVE:To evaluate the ameliorative efficacy of dihydroxy-isosteviol methyl ester (DIME) of Pulsatilla nigricans extract in arsenic-induced DNA damage in testis cells of mice.METHODS:The mice were treated with sodium arsenite (SA) solution intragastrically at a dose of 20 mg/kg per day and examined at 30,60,and 90 dafter treatment.We divided SA-intoxicated mice into two sub-groups:one fed with DIME at a dose of 35 mg/kg and the other with 85% alcohol.We analyzed the expressions of apoptotic signal proteins like CYP1A1,p53 and caspase 3,ascertained the level of cellular and DNA damage and estimated the level of testicular-toxicity biomarkers.We studied the interaction of DIME with calf thymus DNA as target through circular dichroism spectra and melting temperature profiles.RESULTS:We observed an elevation in all apoptotic and toxicity biomarkers leading to cellular and DNA damage in the SA-intoxicated mice which showed significant inhibition or reversal on administration of DIME.Results also showed that

  12. Feline corneal disease.

    Science.gov (United States)

    Moore, Phillip Anthony

    2005-05-01

    The cornea is naturally transparent. Anything that interferes with the cornea's stromal architecture, contributes to blood vessel migration, increases corneal pigmentation, or predisposes to corneal edema, disrupts the corneas transparency and indicates corneal disease. The color, location, and shape and pattern of a corneal lesion can help in determining the underlying cause for the disease. Corneal disease is typically divided into congenital or acquired disorders. Congenital disorders, such as corneal dermoids are rare in cats, whereas acquired corneal disease associated with nonulcerative or ulcerative keratitis is common. Primary ocular disease, such as tear film instability, adenexal disease (medial canthal entropion, lagophthalmus, eyelid agenesis), and herpes keratitis are associated with the majority of acquired corneal disease in cats. Proliferative/eosinophilic keratitis, acute bullous keratopathy, and Florida keratopathy are common feline nonulcerative disorders. Nonprogressive ulcerative disease in cats, such as chronic corneal epithelial defects and corneal sequestration are more common than progressive corneal ulcerations.

  13. Human immune compartment comparisons: Optimization of proliferative assays for blood and gut T lymphocytes.

    Science.gov (United States)

    Dock, Jeffrey; Hultin, Lance; Hultin, Patricia; Elliot, Julie; Yang, Otto O; Anton, Peter A; Jamieson, Beth D; Effros, Rita B

    2017-03-21

    The accumulation of peripheral blood late-differentiated memory CD8 T cells with features of replicative (cellular) senescence, including inability to proliferate in vitro, has been extensively studied. Importantly, the abundance of these cells is directly correlated with increased morbidity and mortality in older persons. Of note, peripheral blood contains only 2% of the total body lymphocyte population. By contrast, the gut-associated lymphoid tissue (GALT) is the most extensive lymphoid organ, housing up to 60% of total body lymphocytes, but has never been assessed with respect to senescence profiles. We report here the development of a method for measuring and comparing proliferative capacity of peripheral blood and gut colorectal mucosa-derived CD8 T cells. The protocol involves a 5-day culture of mononuclear leukocyte populations, from blood and gut colorectal mucosa respectively, labeled with 5-(and 6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) and 5-bromo-2'-deoxyuridine (BrdU) and stimulated with anti-CD2/3/28-linked microbeads. Variables tested and optimized as part of the protocol development include: mode of T cell stimulation, CFSE concentration, inclusion of a second proliferation marker, BrdU, culture duration, initial culture concentration, and inclusion of autologous irradiated feeder cells. Moving forward, this protocol demonstrates a significant advance in the ability of researchers to study compartment-specific differences of in vitro proliferative dynamics of CD8 T cells, as an indicator of replicative senescence and immunological aging. The study's two main novel contributions are (1) Optimization and adaptation of standard proliferative dynamics blood T cell protocols for T cells within the mucosal immune system. (2) Introduction of the novel technique of combining CFSE and BrdU staining to do so.

  14. The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Esther J Kuiper

    Full Text Available BACKGROUND: In proliferative diabetic retinopathy (PDR, vascular endothelial growth factor (VEGF and connective tissue growth factor (CTGF cause blindness by neovascularization and subsequent fibrosis, but their relative contribution to both processes is unknown. We hypothesize that the balance between levels of pro-angiogenic VEGF and pro-fibrotic CTGF regulates angiogenesis, the angio-fibrotic switch, and the resulting fibrosis and scarring. METHODS/PRINCIPAL FINDINGS: VEGF and CTGF were measured by ELISA in 68 vitreous samples of patients with proliferative DR (PDR, N = 32, macular hole (N = 13 or macular pucker (N = 23 and were related to clinical data, including degree of intra-ocular neovascularization and fibrosis. In addition, clinical cases of PDR (n = 4 were studied before and after pan-retinal photocoagulation and intra-vitreal injections with bevacizumab, an antibody against VEGF. Neovascularization and fibrosis in various degrees occurred almost exclusively in PDR patients. In PDR patients, vitreous CTGF levels were significantly associated with degree of fibrosis and with VEGF levels, but not with neovascularization, whereas VEGF levels were associated only with neovascularization. The ratio of CTGF and VEGF was the strongest predictor of degree of fibrosis. As predicted by these findings, patients with PDR demonstrated a temporary increase in intra-ocular fibrosis after anti-VEGF treatment or laser treatment. CONCLUSIONS/SIGNIFICANCE: CTGF is primarily a pro-fibrotic factor in the eye, and a shift in the balance between CTGF and VEGF is associated with the switch from angiogenesis to fibrosis in proliferative retinopathy.

  15. A Convenient and Efficient Method to Enrich and Maintain Highly Proliferative Human Fetal Liver Stem Cells.

    Science.gov (United States)

    Guo, Xuan; Wang, Shu; Dou, Ya-ling; Guo, Xiang-fei; Chen, Zhao-li; Wang, Xin-wei; Shen, Zhi-qiang; Qiu, Zhi-gang; Jin, Min; Li, Jun-wen

    2015-06-01

    Pluripotent human hepatic stem cells have broad research and clinical applications, which are, however, restricted by both limited resources and technical difficulties with respect to isolation of stem cells from the adult or fetal liver. In this study, we developed a convenient and efficient method involving a two-step in situ collagenase perfusion, gravity sedimentation, and Percoll density gradient centrifugation to enrich and maintain highly proliferative human fetal liver stem cells (hFLSCs). Using this method, the isolated hFLSCs entered into the exponential growth phase within 10 days and maintained sufficient proliferative activity to permit subculture for at least 20 passages without differentiation. Immunocytochemistry, immunofluorescence, and flow cytometry results showed that these cells expressed stem cell markers, such as c-kit, CD44, epithelial cell adhesion molecule (EpCAM), oval cell marker-6 (OV-6), epithelial marker cytokeratin 18 (CK18), biliary ductal marker CK19, and alpha-fetoprotein (AFP). Gene expression analysis showed that these cells had stable mRNA expression of c-Kit, EpCAM, neural cell adhesion molecule (NCAM), CK19, CK18, AFP, and claudin 3 (CLDN-3) throughout each passage while maintaining low levels of ALB, but with complete absence of cytochrome P450 3A4 (C3A4), phosphoenolpyruvate carboxykinase (PEPCK), telomeric repeat binding factor (TRF), and connexin 26 (CX26) expression. When grown in appropriate medium, these isolated liver stem cells could differentiate into hepatocytes, cholangiocytes, osteoblasts, adipocytes, or endothelial cells. Thus, we have demonstrated a more economical and efficient method to isolate hFLSCs than magnetic-activated cell sorting (MACS). This novel approach may provide an excellent tool to isolate highly proliferative hFLSCs for tissue engineering and regenerative therapies.

  16. Proliferative verrucous leukoplakia: recognition and differentiation from conventional leukoplakia and mimics.

    Science.gov (United States)

    Gillenwater, Ann M; Vigneswaran, Nadarajah; Fatani, Hanadi; Saintigny, Pierre; El-Naggar, Adel K

    2014-11-01

    The majority of conventional leukoplakia remains constant and only a subset progress to high-grade dysplasia or invasive carcinoma. A less recognized form known as proliferative verrucous leukoplakia (PVL) represents a unique progressive and elusive variant. Identifying patients with this form can only be achieved through the keen clinical observation of the temporal gross and histologic progression in individual patients with squamous cell carcinoma. The difficulty in the early diagnosis of PVL stems from the overlapping clinical and pathologic features with conventional multifocal leukoplakia with dysplasia. We present the current view on the clinicopathologic and biological characteristics of PVL and discuss their diagnosis, differential diagnosis, and management.

  17. Proliferative verrucous leukoplakia (PVL): a review of an elusive pathologic entity!

    Science.gov (United States)

    Gillenwater, Ann M; Vigneswaran, Nadarajah; Fatani, Hanadi; Saintigny, Pierre; El-Naggar, Adel K

    2013-11-01

    Proliferative verrucous leukoplakia (PVL) is a rare less recognized form of oral leukoplakia. Patients with this condition represent a unique clinically and pathologically progressive characteristic from conventional leukoplakia. Because of the lack of defined pathologic lesions, identifying patients with the early diagnosis of PVL is challenging. This is largely due to the overlapping clinical and pathologic early features with conventional multifocal leukoplakia with dysplasia. The diagnosis can only be achieved through the keen clinical observation of the temporal progression in individual patients to verrucous and/or conventional squamous carcinoma. We present a brief view of the clinicopathologic and biological characteristics of PVL and discuss diagnosis, differential diagnosis, and management.

  18. Embryonic viability, parental care and the pro-life thesis: a defence of Bovens.

    Science.gov (United States)

    Surovell, Jonathan

    2014-04-01

    On the basis of three empirical assumptions about the rhythm method and the viability of embryos, Bovens concludes that the pro-life position regarding empbryos implies that it is prima facie wrong to use the rhythm method. Pruss objects to Bovens's philosophical presuppositions and Kennedy to his empirical premises. This essay defends two revised versions of Bovens's argument. These arguments revise Bovens's empirical assumptions in response to Kennedy and, in response to Pruss, supplement Bovens's argument with what I call 'the principle of parental care'.

  19. Evaluation of a novel enzyme-linked immunosorbent assay for serological diagnosis of porcine proliferative enteropathy

    DEFF Research Database (Denmark)

    Boesen, Henriette Toft; Jensen, Tim Kåre; Møller, Kristian;

    2005-01-01

    A specific enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to the porcine pathogen Lawsonia intracellularis was developed and evaluated using sera from naive, naturally infected as well as experimentally infected pigs. On the basis of 37 serum samples collected from experime...... was a specific and sensitive method for detecting specific antibodies, and may be a good alternative to the existing serological tests for L intracellularis. It may be usable for diagnosis of proliferative enteropathy and for determination of a herd's epidemiologic status....

  20. Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Torp, Thomas Lee; Lundberg, Kristian;

    Title of abstract: Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy Design of study: Three months prospective, interventional clinical study. Purpose: The retinal vascular tree can be measured non-invasively and summarized...... diagnosed patients with PDR were included. At baseline, all patients received standard PRP treatment by a navigated laser (NAVILAS®, OD-OS GmbH, Berlin, Germany). Wide-field fundus fluorescein angiography (Optomap, Optos PLC., Dunfermline, Scotland, UK) was performed at BL to verify diagnosis of PDR...

  1. Evaluating for Vitreous Surgery Used in Proliferative Vitreoretinopathy Grede D_3

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    Proliferative vitreoretinopathy (PVR) is one of the main failure causes of retinal detachment repair. In this paper, 25 cases of vitreous surgery used in the PVR D3 are analyzed. The diagnosis of PVR depended on the classification of the America Retina Society Terminology Committee. Vitrectomy and peeling were carried out in all of the patients. Intraocular tamponade included silicone oil and gas tamponade. Follow-up is more than 3 months. The anatomic successful rate was 68% and 11 cases arrived 20/400...

  2. Proliferative Effect of sTRAIL on Mouse Pancreatic Beta Cells

    Directory of Open Access Journals (Sweden)

    Sevim Kahraman

    2014-09-01

    Full Text Available Beta cell loss/impairment of function appears as a significant problem in both type 1 and type 2 diabetes. TRAIL (TNF-related apoptosis-inducing ligand was recently correlated with both types of diabetes with a proposed protective effect. TRAIL was also shown to promote survival and proliferation in different cells such as vascular smooth muscle cells and human vascular endothelial cells. Recently, TRAIL was claimed to protect pancreatic beta cells against cytokine-related harm. We hypothesized a proliferative effect for TRAIL on beta cells, and used Min6 mouse pancreatic beta cell line to test our hypothesis.

  3. Evaluation of anti-proliferative and anti-inflammatory activities of Pelagia noctiluca venom in Lipopolysaccharide/Interferon-γ stimulated RAW264.7 macrophages.

    Science.gov (United States)

    Ayed, Yosra; Sghaier, Rabiaa Manel; Laouini, Dhafer; Bacha, Hassen

    2016-12-01

    Components of Pelagia noctiluca (P. noctiluca) venom were evaluated for their anticancer and nitric Oxide (NO) inhibition activities. Three fractions, out of four, obtained by gel filtration on Sephadex G75 of P. noctiluca venom revealed an important selective anti-proliferative activity on several cell lines such as human bladder carcinoma (RT112), human glioblastoma (U87), and human myelogenous leukemia (K562) but not on mitogen-stimulated peripheral blood mononuclear cells. Interestingly, P. noctiluca components showed an important dose-dependent anti-inflammatory activity, through inhibition of NO production via transcriptional regulation of Inducible NO Synthase (iNOS), in IFN-γ/LPS stimulated RAW 264.7 macrophages. These data strongly suggest that P. noctiluca venom could be used as a natural inhibitor of cancer cell lines and a potent anti-inflammatory agent for the treatment of anti-inflammatory diseases.

  4. Immunohistochemical Estimates of Angiogenesis, Proliferative Activity, p53 Expression, and Multiple Drug Resistance Have No Prognostic Impact in Osteosarcoma: A Comparative Clinicopathological Investigation

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Jensen, Kenneth; Vaeth, Michael;

    2008-01-01

    regarding angiogenesis (CD34), proliferative activity (MIB-1), and the expression of p53 and MDR (P-glycoprotein (Pgp); clones JSB-1, C494, and MRK16). Quantitative and semiquantitative scores of immunoreactive cells were analyzed statistically along with retrospectively obtained clinicopathologic variables...... (P = .64) and p53 (P > .32), whereas the MIB-1 index was reduced in the post-chemotherapy specimens (P = .02). The overall, disease-specific survival was 47%, increasing to 54% in patients receiving pre-operative chemotherapy. Statistical analyses showed prognostic impact exclusively by patient age...... and type of osteosarcoma. Discussion. The studied series of patients documented already prior to the chemotherapy era, a rather excellent survival and estimates of angiogenesis, proliferation, p53, and Pgp expressions, did not demonstrate sufficient power to serve as predictors of treatment response...

  5. Dashed line relaxing retinotomy in the management of retinal detachment with anterior proliferative vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Tsen CL

    2015-04-01

    Full Text Available Chui-Lien Tsen,1 Yu-Harn Horng,1 Shwu-Jiuan Sheu1,2 1Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2School of Medicine, National Yang-Ming University, Taipei, Taiwan Background: We describe the anatomical and functional outcomes of eyes that underwent a modified technique of relaxing retinotomy, dashed line relaxing retinotomy, in the management of retinal detachment with anterior proliferative vitreoretinopathy.Methods: We retrospectively reviewed 54 consecutive eyes in 52 patients who received pars plana vitrectomy with relaxing retinotomy during retinal detachment repair. Perfluorocarbon liquid (PFCL was used as a standard procedure to stabilize the retina during retinotomy to prevent slippage or inversion of the posterior flap. If PFCL was not available due to economic reasons, dashed line relaxing retinotomy was performed instead. Best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure measurement, lens status, and fundus examination were analyzed. We excluded patients who were followed up <4 months.Results: Regarding anatomical success rates and visual outcomes, we found no significant differences between patients treated with intraoperative PFCL and those treated with dashed line relaxing retinotomy without PFCL.Conclusion: Compared to the simple and efficient PFCL-assisted relaxing retinotomy, dashed relaxing retinotomy is not the first choice when PFCL is available. Based on our results, this modified technique may offer an alternative in patients with anterior proliferative vitreoretinopathy for whom PFCL is not available. Keywords: perfluorocarbon liquid, PFCL 

  6. Evidence of Anti-Proliferative Activities in Blue Mussel (Mytilus edulis By-Products

    Directory of Open Access Journals (Sweden)

    Marie-Elise Carbonneau

    2013-03-01

    Full Text Available Shellfish waste components contain significant levels of high quality protein and are therefore a potential source for biofunctional high-value peptides. The feasibility of applying a pilot scale enzymatic hydrolysis process to whole Mytilus edulis and, by fractionation, recover hydrolysates presenting a biological activity of interest, was evaluated. Fractions were tested on four immortalized cancerous cell lines: A549, BT549, HCT15 and PC3. The 50 kDa fraction, enriched in peptides, presented anti-proliferative activity with all cell lines and results suggest a bioactive molecule synergy within the fraction. At a protein concentration of 44 µg/mL, the 50 kDa fraction induced a mortality of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines. At the low protein concentration of only 11 µg/mL the 50 kDa fraction still entails a cell mortality of 76% for A549 and 87% for PC3 cell lines. The 50 kDa fraction contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis and the lowest levels detected of taurine and methionine and highest levels of threonine, proline and glycine amino acids. The enzymatic hydrolysis process suggests that Mytilus edulis by-products should be viewed as high-valued products with strong potential as anti-proliferative agent and promising active ingredients in functional foods.

  7. Cyclin D3 is selectively required for proliferative expansion of germinal center B cells.

    Science.gov (United States)

    Cato, Matthew H; Chintalapati, Suresh K; Yau, Irene W; Omori, Sidne A; Rickert, Robert C

    2011-01-01

    The generation of robust T-cell-dependent humoral immune responses requires the formation and expansion of germinal center structures within the follicular regions of the secondary lymphoid tissues. B-cell proliferation in the germinal center drives ongoing antigen-dependent selection and the generation of high-affinity class-switched plasma and memory B cells. However, the mechanisms regulating B-cell proliferation within this microenvironment are largely unknown. Here, we report that cyclin D3 is uniquely required for germinal center progression. Ccnd3(-/-) mice exhibit a B-cell-intrinsic defect in germinal center maturation and fail to generate an affinity-matured IgG response. We determined that the defect resulted from failed proliferative expansion of GL7(+) IgD(-) PNA(+) B cells. Mechanistically, sustained expression of cyclin D3 was found to be regulated at the level of protein stability and controlled by glycogen synthase kinase 3 in a cyclic AMP-protein kinase A-dependent manner. The specific defect in proliferative expansion of GL7(+) IgD(-) PNA(+) B cells in Ccnd3(-/-) mice defines an underappreciated step in germinal center progression and solidifies a role for cyclin D3 in the immune response, and as a potential therapeutic target for germinal center-derived B-cell malignancies.

  8. Diffusion-Weighted MRI Reflects Proliferative Activity in Primary CNS Lymphoma

    Science.gov (United States)

    Meyer, Jonas; Gawlitza, Matthias; Frydrychowicz, Clara; Müller, Wolf; Preuss, Matthias; Bure, Lionel; Quäschling, Ulf; Hoffmann, Karl-Titus; Surov, Alexey

    2016-01-01

    Purpose To investigate if apparent diffusion coefficient (ADC) values within primary central nervous system lymphoma correlate with cellularity and proliferative activity in corresponding histological samples. Materials and Methods Echo-planar diffusion-weighted magnetic resonance images obtained from 21 patients with primary central nervous system lymphoma were reviewed retrospectively. Regions of interest were drawn on ADC maps corresponding to the contrast enhancing parts of the tumors. Biopsies from all 21 patients were histologically analyzed. Nuclei count, total nuclei area and average nuclei area were measured. The proliferation index was estimated as Ki-67 positive nuclei divided by total number of nuclei. Correlations of ADC values and histopathologic parameters were determined statistically. Results Ki-67 staining revealed a statistically significant correlation with ADCmin (r = -0.454, p = 0.038), ADCmean (r = -0.546, p = 0.010) and ADCmax (r = -0.515, p = 0.017). Furthermore, ADCmean correlated in a statistically significant manner with total nucleic area (r = -0.500, p = 0.021). Conclusion Low ADCmin, ADCmean and ADCmax values reflect a high proliferative activity of primary cental nervous system lymphoma. Low ADCmean values—in concordance with several previously published studies—indicate an increased cellularity within the tumor. PMID:27571268

  9. Anal malignant proliferative trichilemmoma: report of a rare case with review of literature.

    Science.gov (United States)

    Cui, Ang; Mei, Zubing; Cui, Long

    2015-01-01

    Trichilemmoma is a rare type of benign cutaneous neoplasm, which derives from outer sheath of hair follicle. It barely develops malignant progression and has rarely been reported in anal cancer. In this article, we report a case of a 73-year-old woman who presented to the outer-patient department with complaints of a ruptured and longstanding anal phyma. All the appearances were atypical. Blood routine examination showed that neutrophilic granulocyte percentage was elevated and suggest it was a simple inflammation response. No evidence of malignancy was detected upon the laboratory examinations. Then we performed an abscess incision drainage for the patient. A few days later, the biopsy pathological report suggested the specimen is a malignant proliferative trichilemmoma. We decided to perform a wide local excision instead of an extended radical operation in order to preserve anus. After the surgery, we chose not to give chemoradio-treatment for fear of side effects and complications. Careful follow-up indicates that peri-anal malignant proliferative trichilemmoma may have a good prognosis and our treatment is a good choice for the patients with this tumor. Because of the low occurrence rate of anal cancer, especially malignant trichilemmoma, any clinical manifestation and experience are valuable. On one hand, our case may help to take the consideration of the diagnosis of malignant trichilemmoma in case of longtime-suffered peri-anal mass, on the other hand it propose a different treatment method from other anal cancers for clinical doctors.

  10. Comparison of combined and sequential surgery for proliferative diabetic retinopathy: a single surgeon study.

    Directory of Open Access Journals (Sweden)

    Ye Yang

    Full Text Available PURPOSE: To compare the results of combined and consecutive surgeries to treat proliferative diabetic retinopathy and cataract. METHODS: Retrospective comparative study. Forty-one patients with proliferative diabetic retinopathy (PDR were enrolled. Twenty-nine eyes for the combined surgery group and twelve eyes for the sequential group were included. All surgeries were performed by one surgeon. Phacoemulsification was performed using a clear cornea incision. The vitrectomy was performed using a 20-gauge vitreous cutter. RESULTS: The best corrected visual acuity (BCVA and intra- and post-operative complications were the main outcome measures. In the combined surgery group, the BCVA increased in 18 (62.1% eyes, while eight (27.6% eyes remained stable and three (10.3% eyes decreased. Postoperative complications included fibrinous exudation in nine eyes, macular edema in three eyes and vitreous hemorrhage in three eyes. In the sequential surgery group, the BCVA increased in seven (58.3% eyes, remained the same in four (33.3% eyes and was reduced in one (8.3% eye. Postoperative complications included macular edema in two eyes, neovascular glaucoma in two eyes and vitreous hemorrhage in one eye. CONCLUSIONS: Both combined and sequential surgeries are safe and effective for treating PDR and cataracts. The combined surgery had a higher incidence of fibrinous exudation.

  11. Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

    Directory of Open Access Journals (Sweden)

    Fero Matthew

    2011-10-01

    Full Text Available Abstract Background The response of mammalian glial cells to chronic degeneration and trauma is hypothesized to be incompatible with support of neuronal function in the central nervous system (CNS and retina. To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (p27 or Cdkn1b in the adult mouse and determined the outcome on retinal structure and function. Results p27-deficient Müller glia reentered the cell cycle, underwent aberrant migration, and enhanced their expression of intermediate filament proteins, all of which are characteristics of Müller glia in a reactive state. Surprisingly, neuroglial interactions, retinal electrophysiology, and visual acuity were normal. Conclusion The benign outcome of proliferative reactive Müller gliosis suggests that reactive glia display context-dependent, graded and dynamic phenotypes and that reactivity in itself is not necessarily detrimental to neuronal function.

  12. Proliferative Diabetic Retinopathy Surgery against the Background of Prior Retinal Laser Coagulation

    Directory of Open Access Journals (Sweden)

    Fazilat Bakhritdinova, PhD, ScD¹

    2013-03-01

    Full Text Available The study has been performed to compare the immediate and long-term outcomes of Vitreoretinal Surgery (VS on patients with Proliferative Diabetic Retinopathy (PDR in relation to Prior Retinal Laser Coagulation (PLC. The study included 56 patients (71 eyes with diabetes mellitus (type 2 - 52/93%, men – 39/75% complicated with proliferative diabetic retinopathy (PDR, requiring VS. Of these, 33 eyes (no PLC underwent primary vitrectomy, while the remaining 38 eyes (PLC had undergone panretinal laser coagulation over the past five years. In our study, PLC significantly contributed to the preservation of improved functional retinal status, despite the development of complications, which is an indication for VS. The PLC patients exhibited early recovery and a higher visual acuity throughout the observation period. Thus, the study revealed that in the case of prior VS, laser photocoagulation of the retina helps preserve the visual acuity, both at the time of and during the first year after surgery, reduces surgery duration and decreases the need to tamponade the vitreous cavity with silicone oil. Besides, PLC of the retina is accompanied by a significantly lower incidence of intra- and post-operational hemorrhage and reduces the need for repeated vitreoretinal procedures. The present study presents further arguments in favor of early retinal laser photocoagulation on patients with diabetes mellitus complicated by PDR.

  13. Anti-proliferative activity of Fumaria vaillantii extracts on different cancer cell lines

    Directory of Open Access Journals (Sweden)

    Fatemeh Haji Abbas Tabrizi

    2016-01-01

    Full Text Available Plant-derived natural products are known to have cancer chemo-preventive and chemo-therapeutic properties. Plant extracts or their active constituents are used as folk medicine in traditional therapies by 80% of the world population. The aim of the present study was to determine the anti-proliferative potential of Fumaria vaillantii extracts on three different cancer cell lines including malignant melanoma SKMEL-3, human breast adenocarcinoma MCF-7 and human myelogenous leukemia K562 as well as human gingival fibroblast (HGF as normal cell line. Anti-proliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, flowcytometry and annexin methods. Total phenolics and flavonoids were determined by Folin-Ciocalteu and aluminum chloride methods. Chloroform fraction had the lowest IC 50 value at 72 h (0.1 μg/ml in MCF-7 cells. Flowcytometry and annexin-V analysis indicated that the chloroform fraction induced necrosis in MCF-7 cells. In addition, the colorimetric methods showed that the methanolic fraction possessed the highest amount of total phenolics (33.03 ± 0.75 mg/g of dry powder and flavonoids (10.5 ± 2.0 mg/g of dry powder.The collective data demonstrated that F. vaillantii chloroform fraction may contain effective compounds with chemo-therapeutic potential act through an apoptotic independent pathway.

  14. Anti-proliferative effect of chalcone derivatives through inactivation of NF-κB in human cancer cells.

    Science.gov (United States)

    Venkateswararao, Eeda; Sharma, Vinay K; Yun, Jieun; Kim, Youngsoo; Jung, Sang-Hun

    2014-07-01

    To investigate the anti-proliferative effect of NF-κB inhibitor, a series of analogs of (E)-1-(2-hydroxy-6-(isopentyloxy)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (5a) were prepared and evaluated for their NF-κB inhibition and anti-proliferative activity against various human cancer cell lines. Compounds (E)-1-(2-(3,3-dimethylbutoxy)-6-hydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (5e) and (E)-4-(3-(2-(3,3-dimethylbutoxy)-6-hydroxyphenyl)-3-oxoprop-1-enyl)benzenesulfonamide (5p) showed good NF-κB inhibition as well as potent anti-proliferative activity. SAR studies showed that all the compounds with potent or moderate NF-κB inhibition displayed good anti-proliferative activity. All the analogs (5b-r) maintained a good correlation between their NF-κB inhibition and anti-proliferative activity though the extent is not directly proportional to each other.

  15. [Proliferative activity parameters and their correlation with genetic damage of blood lymphocytes during cultivation under the conditions of cytokinetic block].

    Science.gov (United States)

    Ingel', F I; Iurchenko, V V; Gus'kov, A S; Krivtsova, E K; Iurtseva, N A

    2006-01-01

    The subjects of the study were 15 volunteers aged 22 to 25 years, who underwent 25 air ionization sessions. The effects of genome instability were evaluated, and correlations between indicators of genome damage (lesions of micronuclei and nucleoplasmatic bridges) and parameters of proliferative and replicative activity (mitotic index, proliferative pool, the fraction of rapidly dividing cells, and replication index) of blood lymphocytes in the culture were studied. In order to establish the associations between the parameters, the parallel cultures were exposed to 0.07 mM of the standard mutagen MNNG during 5 hours. The study showed that the course of air ionization did not induce the micronuclei and nucleoplasmatic bridges in binuclear cells, but increased proliferative cell activity. This effect was accompanied by an increase in the fraction of rapidly dividing cells among all the dividing cells, and an increase in the dispersion of all proliferation parameters. MNNG induced a constant level of micronuclei in binuclear cells during the whole course, but not before the beginning of air ionization. The changes in the parameter "the fraction of dividing cells" (proliferative pool) were the most prominent manifestation of the suppression of proliferation by MNNG. MNNG loading inhibited the formation of binuclear cells most of all. The results demonstrate a non-random character of the correlation between the level of micronuclei in binuclear cells and proliferative activity parameters during cell cultivation under the conditions of cytokinetic block.

  16. In-feed macrolide Leucomycin (Leucomag 30% PR for prevention of proliferative enteropathy in experimentally infected pigs

    Directory of Open Access Journals (Sweden)

    Silvia de Araújo França

    Full Text Available The aim of this study was to evaluate the efficacy of orally administered leucomycin at 90 and 180ppm for the prevention of porcine proliferative enteropathy (PPE in experimentally infected pigs. A total of 90 commercial five-week-old pigs were randomly assigned to receive leucomycin in feeding at 90 (T2, 180ppm (T3, or untreated (T1. All animals in the treated groups received medicated feed for 14 days starting one day before inoculation. Each pig was inoculated intragastrically with approximately 4.5x10(9 Lawsonia intracellularis in the form of porcine intestinal mucosal homogenate. Body weight, feed consumption and clinic signs were evaluated throughout the study. Necropsies and gross evaluation of intestines were performed in all animals on day 23 post-inoculation (pi or at death, and ileum samples were collected for immunohistochemistry (IHC for L. intracellularis. Clinical presentation of the disease was more evident in the non-medicated group (T1 than in the medicated ones (T2, T3 between days 16 and 21pi. Average daily gain, average daily feed consumption and feed conversion efficiency were better in groups treated with either dose of leucomycin. The total intestine lesion length per group (T1, T2 and T3 was 869, 473 and 331cm, respectively. The majority of the animals (84.4% were positive for L. intracellularis antigen in ileum sections stained by IHC. Under the conditions of this study, leucomycin administered in feed at 90 and 180ppm for 14 days was effective in improving performance of pigs inoculated with intestinal homogenate containing L. intracellularis.

  17. The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women.

    Science.gov (United States)

    Huh, Sung Jin; Oh, Hannah; Peterson, Michael A; Almendro, Vanessa; Hu, Rong; Bowden, Michaela; Lis, Rosina L; Cotter, Maura B; Loda, Massimo; Barry, William T; Polyak, Kornelia; Tamimi, Rulla M

    2016-04-01

    The frequency and proliferative activity of tissue-specific stem and progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast cancer risk and the frequency of mammary epithelial cells expressing p27, estrogen receptor (ER), and Ki67 in normal breast tissue. We performed a nested case-control study of 302 women (69 breast cancer cases, 233 controls) who had been initially diagnosed with benign breast disease according to the Nurses' Health Studies. Immunofluorescence for p27, ER, and Ki67 was performed on tissue microarrays constructed from benign biopsies containing normal mammary epithelium and scored by computational image analysis. We found that the frequency of Ki67(+) cells was positively associated with breast cancer risk among premenopausal women [OR = 10.1, 95% confidence interval (CI) = 2.12-48.0]. Conversely, the frequency of ER(+) or p27(+) cells was inversely, but not significantly, associated with subsequent breast cancer risk (ER(+): OR = 0.70, 95% CI, 0.33-1.50; p27(+): OR = 0.89, 95% CI, 0.45-1.75). Notably, high Ki67(+)/low p27(+) and high Ki67(+)/low ER(+) cell frequencies were significantly associated with a 5-fold higher risk of breast cancer compared with low Ki67(+)/low p27(+) and low Ki67(+)/low ER(+) cell frequencies, respectively, among premenopausal women (Ki67(hi)/p27(lo): OR = 5.08, 95% CI, 1.43-18.1; Ki67(hi)/ER(lo): OR = 4.68, 95% CI, 1.63-13.5). Taken together, our data suggest that the fraction of actively cycling cells in normal breast tissue may represent a marker for breast cancer risk assessment, which may therefore impact the frequency of screening procedures in at-risk women. Cancer Res; 76(7); 1926-34. ©2016 AACR.

  18. Proliferative hypothalamic neurospheres express NPY, AGRP, POMC, CART and Orexin-A and differentiate to functional neurons.

    Directory of Open Access Journals (Sweden)

    Lígia Sousa-Ferreira

    Full Text Available Some pathological conditions with feeding pattern alterations, including obesity and Huntington disease (HD are associated with hypothalamic dysfunction and neuronal cell death. Additionally, the hypothalamus is a neurogenic region with the constitutive capacity to generate new cells of neuronal lineage, in adult rodents. The aim of the present work was to evaluate the expression of feeding-related neuropeptides in hypothalamic progenitor cells and their capacity to differentiate to functional neurons which have been described to be affected by hypothalamic dysfunction. Our study shows that hypothalamic progenitor cells from rat embryos grow as floating neurospheres and express the feeding-related neuropeptides Neuropeptide Y (NPY, Agouti-related Protein (AGRP, Pro-OpioMelanocortin (POMC, Cocaine-and-Amphetamine Responsive Transcript (CART and Orexin-A/Hypocretin-1. Moreover the relative mRNA expression of NPY and POMC increases during the expansion of hypothalamic neurospheres in proliferative conditions.Mature neurons were obtained from the differentiation of hypothalamic progenitor cells including NPY, AGRP, POMC, CART and Orexin-A positive neurons. Furthermore the relative mRNA expression of NPY, CART and Orexin-A increases after the differentiation of hypothalamic neurospheres. Similarly to the adult hypothalamic neurons the neurospheres-derived neurons express the glutamate transporter EAAT3. The orexigenic and anorexigenic phenotype of these neurons was identified by functional response to ghrelin and leptin hormones, respectively. This work demonstrates the presence of appetite-related neuropeptides in hypothalamic progenitor cells and neurons obtained from the differentiation of hypothalamic neurospheres, including the neuronal phenotypes that have been described by others as being affected by hypothalamic neurodegeneration. These in vitro models can be used to study hypothalamic progenitor cells aiming a therapeutic intervention to

  19. To report a case of unilateral proliferative retinopathy following noncerebral malaria with Plasmodium falciparum in Southern India

    Directory of Open Access Journals (Sweden)

    Aditya Verma

    2015-01-01

    Full Text Available The retinopathy in association with malaria fever described so far includes retinal hemorrhages, vessel changes, retinal discoloration/whitening and papilledema. Malaria retinopathy has been mostly described in severe cases, associated with Plasmodium falciparum, correlating the patho-physiology of retinal and cerebral manifestations. We report an unusual case of proliferative retinopathy as a manifestation of malaria fever, caused by P. falciparum with no cerebral involvement. The patient had features of unilateral retinal vascular occlusion with proliferative changes and vitreous hemorrhage. To the best of our knowledge, such a case has never been reported so far in the literature. This report highlights the possible occurrence of severe proliferative changes associated with malaria fever, which if diagnosed early can prevent possible blindness.

  20. ROLE OF THE MORPHOMETRIC PARAMETERS OF INTRATUMORAL MICROVESSELS AND THE PROLIFERATIVE ACTIVITY OF TUMOR CELLS IN RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. A. Gorban

    2014-08-01

    Full Text Available Tumor cell proliferation and angiogenesis are essential factors for tumor growth, progression, and metastasis.Objective: to assess the relationship between the values of proliferative activity and the morphometric parameters of intratumoral microvessels in metastatic and localized carcinomas of the kidney.Materials and methods. Surgical specimens taken from 54 patients (32 men and 22 women aged 26 to 69 years (mean age 55 ± 1.5 years with the verified diagnosis of clear-cell renal cell carcinoma (RCC were studied.Conclusion. Proliferative activity and angioarchitectonics are an important biological characteristic of a tumor of unequal clinical value in RCC. Metastatic carcinoma has a higher proliferative activity and a low tumor vascularization than those of localized carcinoma.

  1. Specific detection of Lawsonia intracellularis in porcine proliferative enteropathy inferred from fluorescent rRNA in situ hybridization

    DEFF Research Database (Denmark)

    Boye, Mette; Jensen, Tim Kåre; Møller, Kristian;

    1998-01-01

    of the probe was determined by simultaneous comparison with indirect immunofluorescence assay for detection of L. intracellularis in formalin-fixed tissue samples from 15 pigs affected by porcine proliferative enteropathy. We used 10 tissue samples from pigs without proliferative mucosal changes as negative...... controls. The results showed that the oligonucleotide probe is specific for L. intracellularis and that fluorescent in situ hybridization targeting ribosomal RNA is a suitable and fast method for specific detection and histological recognition of L. intracellularis in formalin-fixed tissue.......Fluorescent in situ hybridization targeting 16S ribosomal RNA was used for specific detection of the obligate intracellular bacterium Lawsonia intracellularis in enterocytes from pigs affected by proliferative enteropathy. A specific oligonucleotide probe was designed and the specificity...

  2. THE EXPRESSION OF p16 AND CYCLIN D1 IN PROLIFERATIVE ENDOMETRIUM AND ENDOMETRIAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To studythe role of p16 and cyclin in the genesis and development of endometrial car-cinoma. Methods 12 cases of normal endometrium, 22 cases of proliferative endometrium and 41 cases of endome- trial carcinoma were detected for the expression of p16 and cyclin D1 by means of immunohistochemical S-P. Results In normal endometrium p16 was expressed while cyclm D1was almost negative in the proliferative phase, but both of them were negative in the secretory phase. Among the groups of the simple and compound hyperplasia, the atypical hyperplasia and the endometrial carcinoma,the expression of p16 showed a descending tendency, while the expression of cyclin showed an ascending tendency. In endometrial carcinomas the expression of p16 was significantly lower than that of normal endometrium and proliferative endometrium (P<0. 01 ,P<0.05). However, the expression of cy- clin in proliferate endometrium and endometrial carcinoma was significantly higher than that in normal endometri- un (P<0. 05,P<0. 01). The overexpression of cyclin D1 in the atypical hyperplasia group was obviously different from that in the simple and compound hyperplasia group (P<0.01). In endometrial carcinoma,the expression of p16 was decreasing with the descending of cell differentiate degree, on the opposite, the expression of cyclin was in-creased and there existed a negative correlation between them. It was also observed that the overexpression of cyclin was significant different between and ( P <0. 01 ). Conclusion p1 6 is a negative regulating factor of cell cycle in endometrial carcinoma, while cyclin is a positive one. Both of them are important in the genesis and devel-opment of endometrial carcinoma. The Iow expression of p1 6 and the overexpression of cyclin are related with the malicious biological behaviors of endometrial carcinoma and maybe play an important role in the judgement of prog- nosis. Overexpression of cyclin may be an earlier molecular event in the genesis of

  3. Association between faecal load of lawsonia intracellularis and pathological findings of proliferative enteropathy in pigs with diarrhoea

    DEFF Research Database (Denmark)

    Pedersen, Ken Steen; Ståhl, Marie; Guedes, Roberto Maurício Carvalho;

    2012-01-01

    (median excretion: 5.92 log10 bacteria/g faeces) compared to pigs without gross lesions of proliferative enteropathy (median excretion: correlation coefficient between the measureable PE lesions and L. intracellularis excretion was 0.50 (P....001). A significantly increasing trend in Lawsonia intracellularis excretion level for increasing proliferative enteropathy histopathology and immunohistochemistry scores was demonstrated (Pcorrelation coefficient between the histopathology scores and L. intracellularis excretion was 0.......67 (Pcorrelation coefficient between the IHC scores and L. intracellularis excretion was 0.77 (P

  4. Low expression of angiotensinogen and dipeptidyl peptidase 1 in saliva of patients with proliferative verrucous leukoplakia

    Science.gov (United States)

    Flores, Isadora Luana; Santos-Silva, Alan Roger; Coletta, Ricardo Della; Leme, Adriana Franco Paes; Lopes, Marcio Ajudarte

    2016-01-01

    AIM To elucidate the profile of the salivary proteome. METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia (PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach, followed by analyses of variance and logistic regression tests. RESULTS A total of two hundred and eighty-three proteins were confidently identified in saliva. By combining two low abundance proteins from the PVL group, angiotensinogen (AGT) and dipeptidyl peptidase 1 (DPP1), a model for group differentiation was built with a concordance index of 94.2%, identifying both proteins as potential etiologic biomarkers for PVL. CONCLUSION This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL. PMID:27900324

  5. [The origin of papillary neovascularization in patients with proliferative diabetic retinopathy].

    Science.gov (United States)

    Sdobnikova, S V; Mazurina, N K

    2004-01-01

    The case study covers examinations of 63 patients with diabetes mellitus (DM), type 1, and with proliferative diabetic retinopathy (PDR). According to the results of fluorescence angiography, the patients were shared between 3 groups: Group 1--early contrasting of papillary vascular neoplasms; Group 2--late contrasting; and Group 3--mixed contrasting. We explained the available differences by that the vascular neoplasms of the optic nerve disk (OND) originate from 2 main blood supply basins, i.e. choroidal and retinal ones. They reflect, with respect to the above stated, the hemodynamic properties of the choroidal mycocirculation, which is characterized by a higher hemodynamic load and a higher intravascular pressure, or the retinal hemomicrocirculation. The pathological signs of diabetic retinopathy in the choroidal system may fail to correlate with changes in the retinal vascular system itself. Therefore, the findings of fluorescence angiography do not always represent the genuine scope of pathological manifestations occurring in the hemomicrocirculation system in case of PDR.

  6. Detection of Glutamate and γ-aminobutyric Acid in Vitreous of Patients with Proliferative Diabetic Retinopathy

    Institute of Scientific and Technical Information of China (English)

    Juan Deng; De-Zheng Wu; Rulong Gao

    2000-01-01

    Purpose: To study the levels of glutamate and γ-aminobutyric acid (GABA) in vitreous of patients with proliferative diabetic retinopathy(PDR) and to investigate their roles in retinal ischemia.Method: Vitreous samples were collected from 25 patients (27 eyes) with PDR and 14patients ( 14 eyes) with idiopathic macular hole. Glutamate and GABA detection were performed by high-performance liquid chromatography (HPLC).Results: Patients with PDR had significantly higher concentrations of glutamate and GABA than the control group. The glutamate level has a significantly positive correlation with GABA level.Conclusion: Detection of glutamate and GABA in vitreous provides biochemical support for the mechanism and treatment of ischemic retinal damage in patients with PDR.

  7. Nonproliferative and Proliferative Lesions of the Rat and Mouse Skeletal Tissues (Bones, Joints, and Teeth)

    Science.gov (United States)

    Fossey, Stacey; Vahle, John; Long, Philip; Schelling, Scott; Ernst, Heinrich; Boyce, Rogely Waite; Jolette, Jacquelin; Bolon, Brad; Bendele, Alison; Rinke, Matthias; Healy, Laura; High, Wanda; Roth, Daniel Robert; Boyle, Michael; Leininger, Joel

    2016-01-01

    The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is an initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the skeletal tissues and teeth of laboratory rats and mice, with color photomicrographs illustrating examples of many common lesions. The standardized nomenclature presented in this document is also available on the internet (http://www.goreni.org/). Sources of material were databases from government, academic and industrial laboratories throughout the world. PMID:27621538

  8. Proliferative ameloblastomatous calcifying cystic odontogenic tumor of the mandible: A rare histological variant

    Directory of Open Access Journals (Sweden)

    Kamala Rawson

    2015-01-01

    Full Text Available Calcifying cystic odontogenic tumor (CCOT is an extremely rare clinical entity. It was considered as a cyst until 2005, when World Health Organization included it among the odontogenic tumors. It presents as a slow-growing, painless swelling of the jaw. Radiographically, it may be seen as a unilocular or multilocular radiolucency. Here, we present a case of a proliferative ameloblastomatous type of CCOT of the left mandible. Conventional radiography and cone beam computed tomography were performed, in which the lesion was found to be unicystic without any sign of calcification. The lesion was also associated with an impacted 37 tooth, which was displaced to the inferior border of the mandible.

  9. New ursane triterpenoids from Salvia urmiensis Bunge: Absolute configuration and anti-proliferative activity.

    Science.gov (United States)

    Farimani, Mahdi Moridi; Bahadori, Mir Babak; Koulaei, Sheyda Ahmadi; Salehi, Peyman; Ebrahimi, Samad Nejad; Khavasi, Hamid Reza; Hamburger, Matthias

    2015-10-01

    Two new triterpenoids, urmiensolide B (1) and urmiensic acid (2), with rare carbon skeletons together with three known compounds were isolated from the aerial parts of Salvia urmiensis Bunge, an endemic species of Iran. The structures were established by a combination of 1D and 2D NMR, and HRESIMS, and in the case of 2 and 3, their structures were confirmed by single-crystal X-ray analysis. The absolute configuration of 2 was established by electronic circular dichroism (ECD) spectra. The new compounds were evaluated for their anti-proliferative activities against A549 and MCF-7 human cancer cell lines. Compounds 1 and 2 showed IC50 values of 2.8 and 1.6 μM against MCF-7 cells, respectively.

  10. Mitochondrial localization of the low level p53 protein in proliferative cells

    Energy Technology Data Exchange (ETDEWEB)

    Ferecatu, Ioana; Bergeaud, Marie; Rodriguez-Enfedaque, Aida; Le Floch, Nathalie [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Oliver, Lisa [INSERM U601, Universite de Nantes, Faculte de Medecine, Nantes Cedex (France); Rincheval, Vincent; Renaud, Flore [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Vallette, Francois M. [INSERM U601, Universite de Nantes, Faculte de Medecine, Nantes Cedex (France); Mignotte, Bernard [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Vayssiere, Jean-Luc, E-mail: jean-luc.vayssiere@uvsq.fr [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France)

    2009-10-02

    p53 protein plays a central role in suppressing tumorigenesis by inducing cell cycle arrest or apoptosis through transcription-dependent and -independent mechanisms. Emerging publications suggest that following stress, a fraction of p53 translocates to mitochondria to induce cytochrome c release and apoptosis. However, the localization of p53 under unstressed conditions remains largely unexplored. Here we show that p53 is localized at mitochondria in absence of apoptotic stimuli, when cells are proliferating, localization observed in various cell types (rodent and human). This is also supported by acellular assays in which p53 bind strongly to mitochondria isolated from rat liver. Furthermore, the mitochondria subfractionation study and the alkaline treatment of the mitochondrial p53 revealed that the majority of mitochondrial p53 is present in the membranous compartments. Finally, we identified VDAC, a protein of the mitochondrial outer-membrane, as a putative partner of p53 in unstressed/proliferative cells.

  11. [Immunohistochemical description of proliferative activity and apoptosis of lung squamous cell carcinoma (literature review)].

    Science.gov (United States)

    Филенко, Борис Н; Ройко, Наталия В; Степанчук, Алла П; Проскурня, Сергей А

    2016-01-01

    The analysis of the publications are describe immunohistochemical study of proliferative activity and apoptosis of lung squamous cell carcinoma. Established that the imbalance between proliferation and cell death is a key process in the development of tumors. However, the value of tumor markers in histogenesis and morfogenesis of tumors and forecast their occurrence is not studied enough. Despite the significant amount of scientific literature devoted to this issue, has not yet established a clear link expression of immunohistochemical markers of proliferation and apoptosis with the degree of differentiation of squamous cell lung cancer. Analysis of the literature shows that the morphology of this histogenetics type lung cancer at the cellular, subcellular structural and functional levels are controversial and require detailed investigation.

  12. Suppression of angiogenic activity of sera from diabetic patients with non-proliferative retinopathy by compounds of herbal origin and sulindac sulfone.

    Science.gov (United States)

    Skopinski, Piotr; Szaflik, Jerzy; Duda-Król, Barbara; Nartowska, Jadwiga; Sommer, Ewa; Chorostowska-Wynimko, Joanna; Demkow, Urszula; Skopinska-Rózewska, Ewa

    2004-10-01

    Angiogenesis, the process of new blood vessel formation, is the key event in the mechanism of several pathological processes including diabetic retinopathy. The physiological control of angiogenesis depends on the balance between stimulatory and inhibitory factors. Therefore, a number of anti-angiogenic approaches has been developed, many of them based on the inhibition of the functional activity of pro-angiogenic factors. The aim of the present study was to compare the anti-angiogenic effectiveness of sulindac sulfone and some herbal compounds in the serum-induced angiogenesis test performed in Balb/c mice. Pooled sera from 35 patients with diabetes type 2 and retinopathy were used as pro-angiogenic stimuli. The strongest inhibitory effect was observed for the sulindac sulfone and ursolic acid in the highest concentration of 200 micro g/ml, as well as for the low-dosage concomitant treatment with 2 micro g/ml of epigallocatechin gallate (EGCG, green tea flavanol), ursolic acid (plant-derived triterpenoid), sulindac sulfone and convalamaroside (steroidal saponin). Combination treatment was significantly more effective than monotherapy with medium (20 micro g/ml) or lowest doses of tested compounds. The present study is the first to demonstrate the potent anti-angiogenic effect of the combination therapy comprising of plant-derived extracts and sulindac sulfone, as tested in the in vivo angiogenesis experimental model with sera of non-proliferative diabetic retinopathy patients used as the pro-angiogenic stimuli. We think that it might be the first step toward application of some of these compounds, in the future, in preventive anti-angiogenic therapy of these patients, as well, as in the treatment of later, proliferative stage of this disease.

  13. Fulminant proliferative diabetic retinopathy in the non-photocoagulated eye following acute renal failure.

    Science.gov (United States)

    Jang, Liuna; Herbort, Carl P

    2016-12-01

    Management of diabetic retinopathy should follow more strict and aggressive rules in patients at risk for severe acute renal impairment. Such patients should be identified and possibly prophylactically laser treated to avoid the severe consequences demonstrated in this case report. A 34-year-old type 2 diabetes patient with a stabilized diabetic retinopathy developed acute and severe retinal decompensation within weeks after acute renal failure complicated his chronic stable renal impairment. Fluorescein angiographic and optical coherence tomographic illustrations of the rapid evolution of the retinal condition are presented. The patient had previously been treated with panretinal photocoagulation in his left eye. After 8 years of regular 6-monthly checked stability, he developed rapid-onset proliferative diabetic retinopathy and macular edema in his right eye within 3 months of his last ocular check-up. Fluorescein angiography showed neovessels and major ischemic areas. Emergency panretinal photocoagulation and a sub-Tenon's injection were necessary to achieve control of the situation with regression of neovessels and complete regression of macular edema. This case shows that it is imperative for nephrologists to be well informed about a patient's ocular situation in order to give timely information to the ophthalmologist who can intervene to protect the retina in case of renal failure. On the other hand, the ophthalmologist should be familiar with the renal function of his patient with renal impairment so that he can decide to perform prophylactic retinal panphotocoagulation that should be imperatively considered even without strict indications in patients with renal impairment at risk for further deterioration of renal function, in order to prevent such explosive ischemic and proliferative retinopathy putting vision at risk.

  14. Serum MiRNA Biomarkers serve as a Fingerprint for Proliferative Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Shao Qing

    2014-11-01

    Full Text Available Background: Diabetic retinopathy (DR is a retinopathy resulting from diabetes mellitus (DM which was classified into non-proliferative DR (NPDR and proliferative DR (PDR. Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR. Methods: In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR. Results: Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%. Conclusions: These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.

  15. Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy.

    Science.gov (United States)

    Rey-Funes, Manuel; Larrayoz, Ignacio M; Fernández, Juan C; Contartese, Daniela S; Rolón, Federico; Inserra, Pablo I F; Martínez-Murillo, Ricardo; López-Costa, Juan J; Dorfman, Verónica B; Martínez, Alfredo; Loidl, César F

    2016-06-01

    Perinatal asphyxia induces retinal lesions, generating ischemic proliferative retinopathy, which may result in blindness. Previously, we showed that the nitrergic system was involved in the physiopathology of perinatal asphyxia. Here we analyze the application of methylene blue, a well-known soluble guanylate cyclase inhibitor, as a therapeutic strategy to prevent retinopathy. Male rats (n = 28 per group) were treated in different ways: 1) control group comprised born-to-term animals; 2) methylene blue group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery; 3) perinatal asphyxia (PA) group comprised rats exposed to perinatal asphyxia (20 min at 37°C); and 4) methylene blue-PA group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery, and then the pups were subjected to PA as above. For molecular studies, mRNA was obtained at different times after asphyxia, and tissue was collected at 30 days for morphological and biochemical analysis. Perinatal asphyxia produced significant gliosis, angiogenesis, and thickening of the inner retina. Methylene blue treatment reduced these parameters. Perinatal asphyxia resulted in a significant elevation of the nitrergic system as shown by NO synthase (NOS) activity assays, Western blotting, and (immuno)histochemistry for the neuronal isoform of NOS and NADPH-diaphorase activity. All these parameters were also normalized by the treatment. In addition, methylene blue induced the upregulation of the anti-angiogenic peptide, pigment epithelium-derived factor. Application of methylene blue reduced morphological and biochemical parameters of retinopathy. This finding suggests the use of methylene blue as a new treatment to prevent or decrease retinal damage in the context of ischemic proliferative retinopathy.

  16. Histomorphometrical and proliferative aspects of placenta and uterus of the collared peccary (Tayassu tajacu).

    Science.gov (United States)

    Santos, T C; Tonarelli, C; Teixeira, F A; Oliveira, M F; Maria, D; Reginato, P; Kfoury, J R; Oliveira, C A L; Lourenço, D A L; Miglino, M A

    2012-06-01

    The histomorphometric and proliferative characteristics of the collared peccary (Tayassu tajacu) placenta and uterus were analyzed. The material was examined by standard histological techniques and histochemistry (PAS, Perls and Alcian Blue pH 0.5 and 2.5%) and the cellular proliferation by AgNORs and flow cytometry. All the analyzed morphometric variables differed between pregnant and non-pregnant uteri in the luteal phase using the Dunnet test. Height and gland diameter of uterine glands increased linearly during pregnancy, with an intense positive PAS and Perls reaction in all stages. The cells with more than seven AgNORs per nuclei and the cells in the G2M cell cycle phase in the maternal tissue also increased after 70 days of pregnancy. The uteroplacental ridges had a linear increase in size with two distinct areas, base and top, with uterine epithelium and trophoblastic cells changing their morphology following the placental ridge development. Flow cytometry analysis showed the percentage of cells in each cell cycle phase with a quadratic behavior for stages G2/M in the maternal tissue, suggesting an increase in proliferative capacity of maternal tissue after 65 days of pregnancy. The same quadratic effect was observed in the G0/G1 phase in both maternal and fetal tissues. Cells in apoptosis showed cubic behavior in both tissues. The morphometric and cellular dynamic aspects observed in this study have not been previously described and they extend our knowledge of functions relating to maternal-fetal dynamics in this species.

  17. Hes4 controls proliferative properties of neural stem cells during retinal ontogenesis.

    Science.gov (United States)

    El Yakoubi, Warif; Borday, Caroline; Hamdache, Johanna; Parain, Karine; Tran, Hong Thi; Vleminckx, Kris; Perron, Muriel; Locker, Morgane

    2012-12-01

    The retina of fish and amphibian contains genuine neural stem cells located at the most peripheral edge of the ciliary marginal zone (CMZ). However, their cell-of-origin as well as the mechanisms that sustain their maintenance during development are presently unknown. We identified Hes4 (previously named XHairy2), a gene encoding a bHLH-O transcriptional repressor, as a stem cell-specific marker of the Xenopus CMZ that is positively regulated by the canonical Wnt pathway and negatively by Hedgehog signaling. We found that during retinogenesis, Hes4 labels a small territory, located first at the pigmented epithelium (RPE)/neural retina (NR) border and later in the retinal margin, that likely gives rise to adult retinal stem cells. We next addressed whether Hes4 might impart this cell subpopulation with retinal stem cell features: inhibited RPE or NR differentiation programs, continuous proliferation, and slow cell cycle speed. We could indeed show that Hes4 overexpression cell autonomously prevents retinal precursor cells from commitment toward retinal fates and maintains them in a proliferative state. Besides, our data highlight for the first time that Hes4 may also constitute a crucial regulator of cell cycle kinetics. Hes4 gain of function indeed significantly slows down cell division, mainly through the lengthening of G1 phase. As a whole, we propose that Hes4 maintains particular stemness features in a cellular cohort dedicated to constitute the adult retinal stem cell pool, by keeping it in an undifferentiated and slowly proliferative state along embryonic retinogenesis.

  18. ARTEMIS stabilizes the genome and modulates proliferative responses in multipotent mesenchymal cells

    Directory of Open Access Journals (Sweden)

    Tompkins Kathleen

    2010-10-01

    Full Text Available Abstract Background Unrepaired DNA double-stranded breaks (DSBs cause chromosomal rearrangements, loss of genetic information, neoplastic transformation or cell death. The nonhomologous end joining (NHEJ pathway, catalyzing sequence-independent direct rejoining of DSBs, is a crucial mechanism for repairing both stochastically occurring and developmentally programmed DSBs. In lymphocytes, NHEJ is critical for both development and genome stability. NHEJ defects lead to severe combined immunodeficiency (SCID and lymphoid cancer predisposition in both mice and humans. While NHEJ has been thoroughly investigated in lymphocytes, the importance of NHEJ in other cell types, especially with regard to tumor suppression, is less well documented. We previously reported evidence that the NHEJ pathway functions to suppress a range of nonlymphoid tumor types, including various classes of sarcomas, by unknown mechanisms. Results Here we investigate roles for the NHEJ factor ARTEMIS in multipotent mesenchymal stem/progenitor cells (MSCs, as putative sarcomagenic cells of origin. We demonstrate a key role for ARTEMIS in sarcoma suppression in a sensitized mouse tumor model. In this context, we found that ARTEMIS deficiency led to chromosomal damage but, paradoxically, enhanced resistance and proliferative potential in primary MSCs subjected to various stresses. Gene expression analysis revealed abnormally regulated stress response, cell proliferation, and signal transduction pathways in ARTEMIS-defective MSCs. Finally, we identified candidate regulatory genes that may, in part, mediate a stress-resistant, hyperproliferative phenotype in preneoplastic ARTEMIS-deficient MSCs. Conclusions Our discoveries suggest that Art prevents genome damage and restrains proliferation in MSCs exposed to various stress stimuli. We propose that deficiency leads to a preneoplastic state in primary MSCs and is associated with aberrant proliferative control and cellular stress

  19. Sumoylation is tumor-suppressive and confers proliferative quiescence to hematopoietic progenitors in Drosophila melanogaster larvae

    Directory of Open Access Journals (Sweden)

    Marta E. Kalamarz

    2011-12-01

    How cell-intrinsic regulation of the cell cycle and the extrinsic influence of the niche converge to provide proliferative quiescence, safeguard tissue integrity, and provide avenues to stop stem cells from giving rise to tumors is a major challenge in gene therapy and tissue engineering. We explore this question in sumoylation-deficient mutants of Drosophila. In wild type third instar larval lymph glands, a group of hematopoietic stem/progenitor cells acquires quiescence; a multicellular niche supports their undifferentiated state. However, how proliferative quiescence is instilled in this population is not understood. We show that Ubc9 protein is nuclear in this population. Loss of the SUMO-activating E1 enzyme, Aos1/Uba2, the conjugating E2 enzyme, Ubc9, or the E3 SUMO ligase, PIAS, results in a failure of progenitors to quiesce; progenitors become hyperplastic, misdifferentiate, and develop into microtumors that eventually detach from the dorsal vessel. Significantly, dysplasia and lethality of Ubc9 mutants are rescued when Ubc9wt is provided specifically in the progenitor populations, but not when it is provided in the niche or in the differentiated cortex. While normal progenitors express high levels of the Drosophila cyclin-dependent kinase inhibitor p21 homolog, Dacapo, the corresponding overgrown mutant population exhibits a marked reduction in Dacapo. Forced expression of either Dacapo or human p21 in progenitors shrinks this population. The selective expression of either protein in mutant progenitor cells, but not in other hematopoietic populations, limits overgrowth, blocks tumorogenesis, and restores organ integrity. We discuss an essential and complex role for sumoylation in preserving the hematopoietic progenitor states for stress response and in the context of normal development of the fly.

  20. Induction of IgA and sustained deficiency of cell proliferative response in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Yalena Amador-Ca(n)izares; Liz Alvarez-Lajonchere; Ivis Guerra; Ingrid Rodnguez-Alonso; Gillian Martínez-Donato; Julián Triana; Eddy E González-Horta; Angel Pérez; Santiago Due(n)as-Carrera

    2008-01-01

    AIM: In the present study, antibody and peripheral blood mononuclear cells (PBMC) proliferative responses against hepatitis C virus (HCV) antigens were evaluated in HCV chronically infected patients. METHODS: Paired serum and PBMC samples were taken six months apart from 34 individuals, either treated or not, and tested by enzyme-linked immunosorbent assay (ELISA) and carboxyfluorescein succinimidyl ester staining.RESULTS: Over 70% of the patients showed specific IgG and IgM against capsid, E1 and NS3, while HVR-1 was recognized by half of the patients. An increase in the levels of the anti-capsid IgM (P = 0.027) and IgG (P=0.0006) was observed in six-month samples, compared to baseline. Similarly, a significantly higher percent of patients had detectable IgA reactivity to capsid (P=0.017) and NS3 (P=0.005) after six months, compared to baseline. Particularly, IgA against structural antigens positively correlated with hepatic damage (P=0.036). IgG subclasses evaluation against capsid and NS3 revealed a positive recognition mediated by IgG1 in more than 80% of the individuals. On the contrary, less than 30% of the patients showed a positive proliferative response either of CD4+ or CD8+ T cells, being the capsid poorly recognized. CONCLUSION: These results confirm that while the cellular immune response is narrow and weak, a broad and vigorous humoral response occurs in HCV chronic infection. The observed correlation between IgA and hepatic damage may have diagnostic significance, although it warrants further confirmation.

  1. Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Hikichi T

    2011-05-01

    Full Text Available Taiichi Hikichi1, Naohiro Tateda2, Toshiaki Miura31Department of Ophthalmology, Ohtsuka Eye Hospital, Sapporo; 2Asahikawa National College of Technology, Asahikawa; 3Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, JapanBackground: The purpose of this study was to evaluate the dynamics of plasma melatonin secretion in patients with type 2 diabetes mellitus and diabetic retinopathy.Methods: Plasma melatonin levels were measured by high-performance liquid chromatography in 56 patients. Patients were divided into a diabetic group (30 patients and a nondiabetic group (26 patients. The diabetic group was divided further into a proliferative diabetic retinopathy (PDR group (n = 14 and a nonproliferative diabetic retinopathy (NPDR group (n = 16. Plasma melatonin levels obtained at midnight and 3 am were compared between the groups.Results: Nighttime melatonin levels were significantly lower in the diabetic group than in the nondiabetic group (P < 0.03 and lower in the PDR group than in the nondiabetic and NPDR groups (P < 0.01 and P < 0.03, respectively, but no significant difference was found between the nondiabetic and NPDR groups. The daytime melatonin level did not significantly differ between the nondiabetic and diabetic groups or between the nondiabetic, NPDR, and PDR groups.Conclusion: The nighttime melatonin level is altered in patients with diabetes and PDR but not in diabetic patients without PDR. Although patients with PDR may have various dysfunctions that affect melatonin secretion more severely, advanced dysfunction of retinal light perception may cause altered melatonin secretion. Alteration of melatonin secretion may accelerate further occurrence of complications in diabetic patients.Keywords: circadian rhythm, diabetes, proliferative diabetic retinopathy, melatonin

  2. Hyper-activation of Notch3 amplifies the proliferative potential of rhabdomyosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Maria De Salvo

    Full Text Available Rhabdomyosarcoma (RMS is a pediatric myogenic-derived soft tissue sarcoma that includes two major histopathological subtypes: embryonal and alveolar. The majority of alveolar RMS expresses PAX3-FOXO1 fusion oncoprotein, associated with the worst prognosis. RMS cells show myogenic markers expression but are unable to terminally differentiate. The Notch signaling pathway is a master player during myogenesis, with Notch1 activation sustaining myoblast expansion and Notch3 activation inhibiting myoblast fusion and differentiation. Accordingly, Notch1 signaling is up-regulated and activated in embryonal RMS samples and supports the proliferation of tumor cells. However, it is unable to control their differentiation properties. We previously reported that Notch3 is activated in RMS cell lines, of both alveolar and embryonal subtype, and acts by inhibiting differentiation. Moreover, Notch3 depletion reduces PAX3-FOXO1 alveolar RMS tumor growth in vivo. However, whether Notch3 activation also sustains the proliferation of RMS cells remained unclear. To address this question, we forced the expression of the activated form of Notch3, Notch3IC, in the RH30 and RH41 PAX3-FOXO1-positive alveolar and in the RD embryonal RMS cell lines and studied the proliferation of these cells. We show that, in all three cell lines tested, Notch3IC over-expression stimulates in vitro cell proliferation and prevents the effects of pharmacological Notch inhibition. Furthermore, Notch3IC further increases RH30 cell growth in vivo. Interestingly, knockdown of Notch canonical ligands JAG1 or DLL1 in RMS cell lines decreases Notch3 activity and reduces cell proliferation. Finally, the expression of Notch3IC and its target gene HES1 correlates with that of the proliferative marker Ki67 in a small cohort of primary PAX-FOXO1 alveolar RMS samples. These results strongly suggest that high levels of Notch3 activation increase the proliferative potential of RMS cells.

  3. Telomere shortening reduces Alzheimer's disease amyloid pathology in mice

    NARCIS (Netherlands)

    Rolyan, Harshvardhan; Scheffold, Annika; Heinrich, Annette; Begus-Nahrmann, Yvonne; Langkopf, Britta Heike; Hoelter, Sabine M.; Vogt-Weisenhorn, Daniela M.; Liss, Birgit; Wurst, Wolfgang; Lie, Dieter Chichung; Thal, Dietmar Rudolf; Biber, Knut; Rudolph, Karl Lenhard

    2011-01-01

    Alzheimer's disease is a neurodegenerative disorder of the elderly and advancing age is the major risk factor for Alzheimer's disease development. Telomere shortening represents one of the molecular causes of ageing that limits the proliferative capacity of cells, including neural stem cells. Studie

  4. Proliferative effect of whey from cows' milk obtained at two different stages of pregnancy measured in MCF-7 cells.

    Science.gov (United States)

    Nielsen, Tina S; Andersen, Charlotte; Sejrsen, Kris; Purup, Stig

    2012-02-01

    Dietary estrogens may play a role in the etiology of hormone-dependent cancers like breast cancer. Cow's milk contains various endogenous estrogens and feed derived phytoestrogens that potentially contribute to an estrogenic effect of milk in consumers, and therefore we evaluated the effect of milk (whey) in a proliferation assay with estrogen-sensitive MCF-7 human breast cancer cells. Milk samples were obtained from 22 cows representing different stages of pregnancy (first and second half) and whey was produced from the milk. 0·1, 0·25 or 0·5% whey was included in the cell culture medium and after 6 days of treatment cell proliferation was assessed by a colorimetric method with a fluorometer. Whey induced significant (Pwhey at all concentrations tested. There was no difference in the proliferative effect of whey depending on the stage of pregnancy from which the milk was obtained. We did not observe anti-proliferative effects when whey was tested in the presence of 10 pm estradiol in the medium. In conclusion, these results indicate that whey, irrespective of the pregnancy stage from which the milk was obtained induced a significant proliferative response in MCF-7 cells and no anti-proliferative effect, which may be caused, at least in part, by estrogens present in milk. The implications of our findings in relation to for example breast cancer will have to be studied further in other model systems preferentially in vivo.

  5. Proteomics of the human endometrial glandular epithelium and stroma from the proliferative and secretory phases of the menstrual cycle.

    Science.gov (United States)

    Hood, Brian L; Liu, Baoquan; Alkhas, Addie; Shoji, Yutaka; Challa, Rusheeswar; Wang, Guisong; Ferguson, Susan; Oliver, Julie; Mitchell, Dave; Bateman, Nicholas W; Zahn, Christopher M; Hamilton, Chad A; Payson, Mark; Lessey, Bruce; Fazleabas, Asgerally T; Maxwell, G Larry; Conrads, Thomas P; Risinger, John I

    2015-04-01

    Despite its importance in reproductive biology and women's health, a detailed molecular-level understanding of the human endometrium is lacking. Indeed, no comprehensive studies have been undertaken to elucidate the important protein expression differences between the endometrial glandular epithelium and surrounding stroma during the proliferative and midsecretory phases of the menstrual cycle. We utilized laser microdissection to harvest epithelial cells and stromal compartments from proliferative and secretory premenopausal endometrial tissue and performed a global, quantitative mass spectrometry-based proteomics analysis. This analysis identified 1224 total proteins from epithelial cells, among which 318 were differentially abundant between the proliferative and secretory phases (q glandular cells in the secretory phase, was confirmed to be elevated in midsecretory-phase baboon uterine lavage samples and also observed to have an N-linked glycosylated form that was not observed in the proliferative phase. This study provides a detailed view into the global proteomic alterations of the epithelial cells and stromal compartments of the cycling premenopausal endometrium. These proteomic alterations during endometrial remodeling provide a basis for numerous follow-up investigations on the function of these differentially regulated proteins and their role in reproductive biology and endometrial pathologies.

  6. Exonuclease 1 is essential for maintaining genomic stability and the proliferative capacity of neural but not hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Junling Zhang

    2014-01-01

    Full Text Available Exonuclease 1 (Exo1 has been implicated in the regulation of DNA damage responses in stem cells with dysfunctional telomeres. However, it is unclear whether Exo1-mediated DNA maintenance pathways play a role in the maintenance of genomic stability and the self-renewal of tissue stem cells in mice with functional telomeres. Here, we analyzed the proliferative capacity of neural stem cells (NSCs and hematopoietic stem cells (HSCs from Exo1−/− mice. Our study shows that Exo1 deficiency impairs the maintenance of genomic stability and proliferative capacity in NSCs but not HSCs. In line with these results, we detected a decrease in proliferation and an up-regulation of p21 expression levels in Exo1-deficient NSCs but not Exo1-deficient HSCs. Our data provide experimental evidence that Exo1 deficiency has a differential impact on the homeostasis and proliferative capacity of tissue stem cells in the brain and bone marrow, suggesting that different tissue stem cells utilize distinct mechanisms for maintaining their genomic stability. Our current study provides important insight into the role of Exo1-mediated DNA maintenance pathways in the maintenance of genomic stability and the proliferative capacity of tissue stem cells.

  7. The role of optical coherence tomography in the diagnosis and treatment selection for proliferative diabetic retinopathy complicated by vitreomacular traction

    Directory of Open Access Journals (Sweden)

    M. I. Kerimov

    2014-07-01

    Full Text Available Purpose: Identification of proliferative diabetic retinopathy complicated by vitreomacular traction syndrome and performance evaluation of 23 gauge (G pars plana vitrectomy using a spectral optical tomography (OCT.Material and methods: 18 eyes of 15 patients underwent 23 G pars plana vitrectomy for complications of proliferative diabetic retinopathy in 2009‑2012. Vitreomacular interface examination was performed by OCT with Spectral Cirrus HD (Carl Zeiss Meditec, Germany. Follow-up was 6 months to 3 years.Results: Mean visual acuity in operated eyes was 1,34±0,30 in LogMAR units, after surgery improved to 0,75±0,34. OCT showed normalization of macular anatomy with reduction of macular thickness.Conclusion: OCT remains a valuable tool as for anatomical localization of vitreomacular interface pathology, as well for surgical planning and changes after surgery in patients with proliferative diabetic retinopathy complicated by vitreomacular traction syndrome. 23 G vitrectomy allows to obtain satisfactory anatomical and functional results in different types of vitreomacular traction in patients with proliferative diabetic retinopathy.

  8. The role of optical coherence tomography in the diagnosis and treatment selection for proliferative diabetic retinopathy complicated by vitreomacular traction

    Directory of Open Access Journals (Sweden)

    M. I. Kerimov

    2013-01-01

    Full Text Available Purpose: Identification of proliferative diabetic retinopathy complicated by vitreomacular traction syndrome and performance evaluation of 23 gauge (G pars plana vitrectomy using a spectral optical tomography (OCT.Material and methods: 18 eyes of 15 patients underwent 23 G pars plana vitrectomy for complications of proliferative diabetic retinopathy in 2009‑2012. Vitreomacular interface examination was performed by OCT with Spectral Cirrus HD (Carl Zeiss Meditec, Germany. Follow-up was 6 months to 3 years.Results: Mean visual acuity in operated eyes was 1,34±0,30 in LogMAR units, after surgery improved to 0,75±0,34. OCT showed normalization of macular anatomy with reduction of macular thickness.Conclusion: OCT remains a valuable tool as for anatomical localization of vitreomacular interface pathology, as well for surgical planning and changes after surgery in patients with proliferative diabetic retinopathy complicated by vitreomacular traction syndrome. 23 G vitrectomy allows to obtain satisfactory anatomical and functional results in different types of vitreomacular traction in patients with proliferative diabetic retinopathy.

  9. Evaluation of viability and proliferative activity of human urothelial cells cultured onto xenogenic tissue-engineered extracellular matrices.

    LENUS (Irish Health Repository)

    Davis, Niall F

    2011-04-01

    To evaluate the viability and proliferative activity of human urothelial cells (HUCs) cultured on tissue-engineered extracellular matrix scaffolds and to assess the potential of extracellular matrixes to support the growth of HUCs in their expected in vivo urine environment.

  10. Effect of Enterococcus faecium EF 55 on morphometry and proliferative activity of intestinal mucosa in broilers infected with Salmonella Enteritidis

    Directory of Open Access Journals (Sweden)

    Ševčíková Zuzana

    2016-09-01

    Full Text Available Introduction: The present study aimed to investigate the effect of Enterococcus faecium EF55 on chickens, as well as its influence on proliferative activity of epithelial intestinal cells after infection with Salmonella enterica serovar Enteritidis phage type 4 (SE PT4. Moreover, the length and area of duodenal and jejunal villi of the birds were examined.

  11. Studies into the mechanism of arsenic-induced neurotoxicity

    NARCIS (Netherlands)

    Vahidnia, Ali

    2008-01-01

    Arsenic (As) is a notoriously poisonous metalloid with known hazardous effects to human health. The project described in this thesis was aimed at elucidating the probable mechanism of As-induced neurotoxicity in vivo and in vitro. The animal studies in this thesis were designed to answer questions a

  12. Pathology review of proliferative lesions of the exocrine pancreas in two chronic feeding studies in rats with ammonium perfluorooctanoate

    Directory of Open Access Journals (Sweden)

    Jessica M. Caverly Rae

    2014-01-01

    Full Text Available Two chronic dietary studies, conducted years apart, with ammonium perfluorooctanoate (APFO in Sprague Dawley rats have been previously reported. Although both included male 300 ppm dietary dose groups, only the later study, conducted in 1990–1992 by Biegel et al., reported an increase in proliferative lesions (hyperplasia and adenoma of the acinar pancreas. An assessment of the significance of the differences between both studies requires careful consideration of: the diagnostic criteria for proliferative acinar cell lesions of the rat pancreas (for example, the diagnosis of pancreatic acinar cell hyperplasia versus adenoma is based on the two-dimensional size of the lesion rather than distinct morphological differences; the basis for those criteria in light of their relevance to biological behavior; and the potential diagnostic variability between individual pathologists for difficult-to-classify lesions. A pathology peer review of male exocrine pancreatic tissues from the earlier study, conducted in 1981–1983 by Butenhoff et al., was undertaken. This review identified an increase in acinar cell hyperplasia but not adenoma or carcinoma in the earlier study. Both studies observed a proliferative response in the acinar pancreas which was more pronounced in the study by Biegel et al. Definitive reasons for the greater incidence of proliferative lesions in the later study were not identified, but some possible explanations are presented herein. The relevance of this finding to human risk assessment, in the face of differences in the biological behavior of human and rat pancreatic proliferative lesions and the proposed mechanism of formation of these lesions, are questionable.

  13. Immunochemical expression of proliferative cell nuclear antigen in aging cultured astrocytes

    Directory of Open Access Journals (Sweden)

    M. C. Vanzani

    2003-08-01

    Full Text Available Cell differentiation degree and mitotic activity were sequentially assessed by immunoperoxidase labeling of glial fibrillary acidic protein (GFAP and proliferative cell nuclear antigen (PCNA, respectively, in rat brain cultured astrocytes maintained up to 60 days in vitro (DIV of first subculture, or weekly passaged until their 12th subculture. Cell count was performed through a 0.01 mm2 section reticule and morphometric analysis with a stereological grid. The number of double immunoreactive cells peaked by 2 DIV to achieve its lowest value at 60 DIV. At 24 hs of cell seeding of successive passages, such values peaked by the 6th subculture to gradually decrease thereafter. Increasing cell hypertrophy was found during the long-term first subculture but not after passaging. At the end of the observation period, doubly immunolabeled astrocytes were still recorded, thus evidencing retention of proliferative potential despite aging.El grado de diferenciación celular y la actividad mitótica fueron secuencialmente determinados mediante marcación por inmunoperoxidasa de la proteína gliofibrilar ácida (GFAP y del antígeno nuclear de proliferación celular (PCNA, respectivamente, en cultivos astrocitarios obtenidos de encéfalo de rata y mantenidos hasta 60 días in vitro (DIV de su primer subcultivo, o mediante pasajes semanales hasta el 12do subcultivo. El conteo celular se realizó mediante una retícula de 0.01-mm2 de sección y el análisis morfométrico con una grilla estereológica. El número de células doblemente inmunorreactivas alcanzó valores máximos a los 2 DIV para descender a los menores a los 60 DIV. A las 24 hs de sembrado celular de los sucesivos pasajes, esos valores ascendieron hacia el 6to subcultivo para luego declinar. En cuanto a la hipertrofia celular, se observó en todo el curso del primer subcultivo, pero no durante los posteriores pasajes. Al final del período de observación, todavía se continuaban detectando

  14. Proliferative vitreo-retinal disorders: experimental models in vivo and in vitro.

    Science.gov (United States)

    Martini, B

    1992-01-01

    The aim of the present thesis was to develop, refine, and assess experimental models for the study of proliferative vitreo-retinal disorders. An intravitreal injection of a colloidal solution of microparticles was used in the primate eye to produce pathologic changes including intraocular cell invasion, cell proliferation, neovascularization, collagen synthesis, and tractional retinal detachment. In a separate primate model for laser-induced subretinal neovascularization, the origin and the occurrence of macrophages was evaluated. Examinations were performed using ophthalmoscopy, slit-lamp microscopy, light microscopy, and transmission electron microscopy. Cell cultures were employed to study the effects of vitreous humor and macrophages on the proliferation of cultured retinal pigment epithelial (RPE) cells and cultured fibroblasts using a Coulter counter. Morphologic changes were documented by phase micrography. A quantitative estimation of the extracellular matrix deposition of fibrous proteins by macrophage-modulated RPE cells as well as by vitreous-modulated RPE cells was done using enzymatic digestion and radioactive labeling techniques. A qualitative analysis of the types of collagen that was deposited in the extracellular matrices by vitreous modulated cultures was also made using indirect immunofluorescence. Using a newly developed RPE cell specific monoclonal antibody, the avidin-biotin-peroxidase labeling technique was finally employed to test the phenotypic epitope expression of macrophage-modulated and non-modulated RPE cells. A new experimental in vivo model for pathologic changes that characterize proliferative vitreo-retinal disorders was developed in the primate eye. In the model for laser-induced subretinal neovascularization, macrophages were shown to be principally recruited from the systemic circulation. Using cell cultures, it was found that both macrophage-conditioned medium and vitreous humor, separately or combined, exert mitogenic effects

  15. 增生性糖尿病视网膜病变和增生性玻璃体视网膜病变患者玻璃体中TGF-β2的表达及意义%Expression of transforming growth factor-β2 in the vitreous body of patients with proliferative diabetic retinopathy and proliferative vitreoretinopathy

    Institute of Scientific and Technical Information of China (English)

    高军; 王雪; 颜华

    2013-01-01

    目的 通过定量测定增生性玻璃体视网膜疾病患者玻璃体中转化生长因子β2(TGF-β2)含量,探讨TGF-β2在增生性玻璃体视网膜疾病发生发展过程中的作用.方法 实验研究.收集行玻璃体切除手术61例(61眼)增生性玻璃体视网膜疾病患者玻璃体标本,其中增生性糖尿病视网膜病变(PDR)组37例(37眼)、增生性玻璃体视网膜病变(PVR)组24例(24眼),正常对照组8例(8眼)采用酶联免疫吸附测定法(ELISA)定量检测PDR患者、PVR患者和正常对照组玻璃体TGF-β2含量.结果 PDR组、PVR组及正常对照组玻璃体TGF-β2含量分别为(22.71 ±2.32) ng/ml,(21.28± 1.79) ng/ml,(19.00±0.62)ng/ml,PDR组、PVR组玻璃体TGF-β2含量均高于正常对照组,差异有统计学意义(F=7.756,P<0.01).PDR组玻璃体TGF-β2含量高于PVR组,差异有统计学意义(P<0.05).PDR组TGF-β2含量Ⅵ期高于Ⅴ期,差异有统计学意义(P<0.01).PVR组TGF-β2含量D级高于C级,差异有统计学意义(P<0.01).PDR组TGF-β2含量与眼病史呈正相关(r=0.705,P<0.01).PVR组TGF-β2含量与眼病史呈正相关(r=0.934,P<0.01).结论 TGF-β2可能在增生性玻璃体视网膜疾病的发生发展中起到重要作用.%Objective To observe the expression of transforming growth factor-β2 (TGF-β2) in the vitreous body of patients with proliferative vitreoretinal diseases; to investigate the role of TGF-β2in the pathogenesis of proliferative vitreoretinal diseases.Methods In an experimental study,vitreous specimens were obtained during vitrectomy from 61 patients (61 eyes) with proliferative vitreoretinal diseases.The vitreous specimens were obtained from 37 eyes with proliferative diabetic retinopathy (PDR) and 24 eyes with proliferative vitreoretinopathy (PVR).Eight vitreous fluid samples were obtained from a normal control group.The concentrations of TGF-β2 in the vitreous body were detected by enzyme-linked immunosorbent assay (ELISA).Results The concentrations

  16. Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants

    Science.gov (United States)

    Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G; Vang, Russell; Cope, Leslie; Junge, Jette; Kjaer, Susanne K; Kurman, Robert J; Shih, Ie-Ming

    2014-01-01

    There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced-stage disease identified from a nation-wide tumour registry in Denmark. Mutational analysis for hotspots in KRAS and BRAF was successful in 55 APSTs and demonstrated KRAS mutations in 34 (61.8%) and BRAF mutations in eight (14.5%). Mutational analysis was successful in 56 peritoneal implants and revealed KRAS mutations in 34 (60.7%) and BRAF mutations in seven (12.5%). Mutational analysis could not be performed in two primary tumours and in nine implants, either because DNA amplification failed or because there was insufficient tissue for mutational analysis. For these specimens we performed VE1 immunohistochemistry, which was shown to be a specific and sensitive surrogate marker for a V600E BRAF mutation. VE1 staining was positive in one of two APSTs and seven of nine implants. Thus, among 63 implants for which mutation status was known (either by direct mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST–implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST–implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11 SBT/APST–implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST–implant (non-invasive and invasive) pairs (p < 0.00001). This study provides cogent evidence that the vast majority of peritoneal implants, non-invasive and invasive, harbour the identical KRAS or BRAF mutations that are present in the associated SBT/APST, supporting the view that peritoneal implants are derived from the primary ovarian tumour. PMID:24307542

  17. Hand-Schüller-Christian disease

    Directory of Open Access Journals (Sweden)

    Deepak Bhargava

    2012-01-01

    Full Text Available Langerhan cell histiocytosis, formerly known as histiocytosis X, traditionally denotes a group of diseases that stem from proliferative reticuloendothelial disturbances.The etiology and pathogenesis of the disease remain debatable. In this paper we report a case of Langerhan cell histiocytosis in a 3 1 / 2 -year-old child who reported to the department of oral pathology with gingival enlargements. The radiological features and histopathological features are also discussed.

  18. The c-Myc Transactivation Domain Is a Direct Modulator of Apoptotic versus Proliferative Signals

    Science.gov (United States)

    Chang, David W.; Claassen, Gisela F.; Hann, Stephen R.; Cole, Michael D.

    2000-01-01

    We have assayed the oncogenic, proliferative, and apoptotic activities of the frequent mutations that occur in the c-myc gene in Burkitt's lymphomas. Some alleles have a modest (50 to 60%) increase in transforming activity; however, the most frequent Burkitt's lymphoma allele (T58I) had an unexpected substantial decrease in transforming activity (85%). All alleles restored the proliferation function of c-Myc in cells that grow slowly due to a c-myc knockout. There was discordance for some alleles between apoptotic and oncogenic activities, but only the T58A allele had elevated transforming activity with a concomitant reduced apoptotic potential. We discovered a novel missense mutation, MycS71F, that had a very low apoptotic activity compared to wild-type Myc, yet this mutation has never been found in lymphomas, suggesting that there is no strong selection for antiapoptotic c-Myc alleles. MycS71F also induced very low levels of cytochrome c release from mitochondria, suggesting a mechanism of action for this mutation. Phosphopeptide mapping provided a biochemical basis for the dramatically different biological activities of the transformation-defective T58I and transformation-enhanced T58A c-Myc alleles. Furthermore, the antiapoptotic survival factor insulin-like growth factor 1 was found to suppress phosphorylation of T58, suggesting that the c-Myc transactivation domain is a direct target of survival signals. PMID:10825194

  19. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells

    Directory of Open Access Journals (Sweden)

    Reyhan Akhtar

    2014-02-01

    Full Text Available Background: Silibinin a flavonoid from milk thistle (Silybum marianum exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml for 24, 48 or 72 h showed a progressive decline in cell viability. Results: Loss of cell viability was time dependent and optimum inhibition of cell growth (78% was observed at 72 h. Under inverted microscope, the dead cells were seen as cell aggregates. IC50 (silibinin concentration killing 50% cells values were 180, 110 and 40μg/ml at 24, 48 and 72 h respectively. Conclusion: These findings re-enforce the anticancer potential of silibinin, as reported earlier for various other cancer cell lines (Ramasamy and Agarwal (2008, Cancer Letters, 269: 352-62.

  20. Biocatalytically Oligomerized Epicatechin with Potent and Specific Anti-proliferative Activity for Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ramaswamy Nagarajan

    2008-11-01

    Full Text Available Catechins, naturally occurring flavonoids derived from wine and green tea, are known to exhibit multiple health benefits. Epigallocatechin gallate (EGCG is one of the most widely investigated catechins, but its efficacy in cancer therapy is still inconsistent and limited. The poor stability of EGCG has contributed to the disparity in the reported anti-cancer activity and other beneficial properties. Here we report an innovative enzymatic strategy for the oligomerization of catechins (specifically epicatechin that yields stable, water-soluble oligomerized epicatechins with enhanced and highly specific anti-proliferative activity for human breast cancer cells. This one-pot oxidative oligomerization is carried out in ambient conditions using Horseradish Peroxidase (HRP as a catalyst yielding water-soluble oligo(epicatechins. The oligomerized epicatechins obtained exhibit excellent growth inhibitory effects against human breast cancer cells with greater specificity towards growth-inhibiting cancer cells as opposed to normal cells, achieving a high therapeutic differential. Our studies indicate that water-soluble oligomeric epicatechins surpass EGCG in stability, selectivity and efficacy at lower doses.

  1. Cucumarioside A2-2 causes changes in the morphology and proliferative activity in mouse spleen.

    Science.gov (United States)

    Pislyagin, E A; Manzhulo, I V; Dmitrenok, P S; Aminin, D L

    2016-05-01

    The immunomodulatory effect of triterpene glycoside cucumarioside A2-2 (CA2-2), isolated from the Far Eastern sea cucumber Cucumaria japonica, on the mouse spleen was investigated in comparison with lipopolysaccharide (LPS). It has been shown that the intraperitoneal (i.p.) glycoside administration did not influence on splenic weights, while the statistically significant increase in splenic weight was observed after LPS administration. Changes in the ratio of red to white pulp after CA2-2 or LPS administration were observed. The proportion of splenic white pulp after glycoside or LPS administration increased by up to 34% and 36%, respectively. A detailed study of the distribution of the РСNA (Proliferating Cell Nuclear Antigen) marker showed that the proliferative activity in the white pulp under CA2-2 and LPS influence increased 2.07 and 2.24 times, respectively. The localization of PCNA-positive nuclei in the white pulp region, as well as their dimensional characteristics, suggests that a large proportion of the proliferating cell population consisted of B cells. The mass spectrometry profiles of spleen peptide/protein homogenate were obtained using the MALDI-TOF-MS (Matrix -Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry) approach. It was found that i.p. stimulation of animals with CA2-2 or LPS leads to marked changes in the intensity of revealed characteristic peaks of peptides/proteins after exposure to immunostimulants.

  2. Two new diterpene derivatives from Euphorbia lunulata Bge and their anti-proliferative activities.

    Science.gov (United States)

    Liu, Chao; Liao, Zhi-xin; Liu, Shi-jun; Qu, Yan-bo; Wang, Heng-shan

    2014-07-01

    A new ent-abietane-type diterpene lactone (1) and a new jatrophane-type diterpenoid (2), together with twelve known compounds including three diterpenes (3-5), five triterpenes (6-10) and four sterides (11-14) were isolated from the ethanol extract of the whole plant of Euphorbia lunulata Bge. The structure of compounds 1 and 2 was elucidated on the basis of 1D and 2D NMR spectra and the HR-ESI-MS data. The structure of compound 2 was further analyzed by an X-ray crystallographic study. The in vitro anti-proliferative activities against MCF-7 and NCI-H460 cell lines for compounds 1-5 (diterpene) were evaluated. The results showed marked activity for compound 1 against the two cell lines with the IC50 values 19.5 (NCI-H460) and 18.6 (MCF-7) μM, while for cis-platinum (a positive cytotoxic control agent) 29.7 (NCI-H460) and 27.7 (MCF-7) μM. Compounds 2-5 exhibited moderate cytotoxic activities for the two cell lines with the IC50 values ranging from 32.1 to 58.2 μM.

  3. The adult macaque spinal cord central canal zone contains proliferative cells and closely resembles the human.

    Science.gov (United States)

    Alfaro-Cervello, Clara; Cebrian-Silla, Arantxa; Soriano-Navarro, Mario; Garcia-Tarraga, Patricia; Matías-Guiu, Jorge; Gomez-Pinedo, Ulises; Molina Aguilar, Pilar; Alvarez-Buylla, Arturo; Luquin, Maria-Rosario; Garcia-Verdugo, Jose Manuel

    2014-06-01

    The persistence of proliferative cells, which could correspond to progenitor populations or potential cells of origin for tumors, has been extensively studied in the adult mammalian forebrain, including human and nonhuman primates. Proliferating cells have been found along the entire ventricular system, including around the central canal, of rodents, but little is known about the primate spinal cord. Here we describe the central canal cellular composition of the Old World primate Macaca fascicularis via scanning and transmission electron microscopy and immunohistochemistry and identify central canal proliferating cells with Ki67 and newly generated cells with bromodeoxyuridine incorporation 3 months after the injection. The central canal is composed of uniciliated, biciliated, and multiciliated ependymal cells, astrocytes, and neurons. Multiciliated ependymal cells show morphological characteristics similar to multiciliated ependymal cells from the lateral ventricles, and uniciliated and biciliated ependymal cells display cilia with large, star-shaped basal bodies, similar to the Ecc cells described for the rodent central canal. Here we show that ependymal cells with one or two cilia, but not multiciliated ependymal cells, proliferate and give rise to new ependymal cells that presumably remain in the macaque central canal. We found that the infant and adult human spinal cord contains ependymal cell types that resemble those present in the macaque. Interestingly, a wide hypocellular layer formed by bundles of intermediate filaments surrounded the central canal both in the monkey and in the human, being more prominent in the stenosed adult human central canal.

  4. Effect of Lipo-prostaglandin E1on Mesangial Proliferative Glomerulonephritis in Rats

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The antinephritic effect of lipo-prostaglandin E1, prostaglandin E1 incorporated in lipid microspheres was investigated using an experimental model of mesangial proliferative glomerulonephritis (MsPGN). Twenty-two female rats were randomly divided into nephritic group (N, n= 6),lipo-prostaglandin E1 treated group (NL, n = 8) and control group (C, n = 6). Lipo-prostaglandin E1 was given intravenously at 40 μg · kg-1 · d-1 from the 6th week to the 8th week. Twenty-four h urinary protein contents and blood creatinine (Cr) were determined and the pathological changes were observed in the experiment. The expression of proliferating cell nuclear antigen (PCNA), extracellular matrix (fibronectin, FN; collagen type Ⅳ, Col Ⅳ) and transforming growth factor β1(TGFβ1) was detected by using immunohistochemistry. The results showed that lipo-prostaglandin E1 significantly inhibited the glomerular histopathological changes as well as the elevation of plasma Cr (P<0.05). The overexpression of PCNA, FN, Col Ⅳ and TGFβ1 were also obviously inhibited in group NL as compared with the group N (P<0.01). It was suggested that lipo-prostaglandin E1could improve renal function, inhibit the proliferation of glomerular cells and reduce the deposition of extracellular matrix, which may be related to the down-regulation of the TGFβ1 expression.

  5. Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Shu-Ling; Wu; Dong-Mei; Zhan; Shu-Hong; Xi; Xiang-Lian; He

    2014-01-01

    AIM:To investigate the role of tissue plasminogen activator(t-PA) and plasminogen activator inhibitor(PAI)in proliferative diabetic retinopathy(PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor(VEGF) expressions.METHODS:A total of 36 vitreous samples were collected from 36 patients with PDR(PDR group), and 17 vitreous samples from 17 patients with idiopathic macular hole were used as control. The concentrations of t-PA, PAI and VEGF in samples were determined by ELISA method. The correlations among t-PA, PAI and VEGF expressions were discussed.RESULTS:The concentrations of t-PA, PAI and VEGF in the PDR group were significantly higher than those in the control group(P <0.001). The t-PA and PAI expressions were highly correlated with the VEGF expression(P <0.001).CONCLUSION:In addition to VEGF, a variety of bioactive substances, such as t-PA and PAI, are involved in the pathogenesis involved in the angiogenesis of PDR.VEGF can activate t-PA expression, resulting in collagen tissue degradation and angiogenesis. VEGF may also activate the mechanism for endogenous anti-neovascularization.

  6. Detection of benign proliferative lesions on vocal cords with voice handicap index.

    Science.gov (United States)

    Huang, Xuekun; Zhang, Gehua; Liu, Xiujin; Wang, Tao; Zhu, Ling

    2012-10-01

    The aim of this study was to investigate the significance and practical applicability of the voice handicap index (VHI) in the diagnosis of benign proliferative lesions of the vocal cords (BLVCs). The detection of VHI included the calculation of functional (F), physical (P) and emotional (E) domains, and the score of each domain and total score (TVH). The VHI was scored in patients with BLVCs and healthy controls. Eighty-four patients with BLVCs and 27 healthy controls were enrolled in the present study. The F, P, E and TVH scores were 10.40±7.84, 19.88±8.81, 9.39±8.49 and 39.37±21.83, respectively, in the BLVC group and 0.78±0.97, 0.85±1.06, 0.26±0.72 and 1.89±2.31, respectively, in the control group. A significant difference was found between the two groups (PVHI score in BLVC patients (P>0.05). There was no marked difference in the VHI score between voice-consuming and non-voice consuming occupations (P>0.05) or between males and females (P>0.05). In BLVC patients, VHI may subjectively express the voice handicap, while daily duration of speech, course of BLVC, occupation and gender have no impact on VHI.

  7. Characterization of highly proliferative secondary tumor clusters along host blood vessels in malignant glioma.

    Science.gov (United States)

    Wang, Ting-Chung; Cheng, Chun-Yu; Yang, Wei-Hsun; Chen, Wen-Cheng; Chang, Pey-Jium

    2015-11-01

    The aim of the present study was to investigate the extensive invasion of tumor cells into normal brain tissue, a life‑threatening feature of malignant gliomas. How invasive tumor cells migrate into normal brain tissue and form a secondary tumor structure remains to be elucidated. In the present study, the morphological and phenotypic changes of glioma cells during invasion in a C6 glioma model were investigated. C6 glioma cells were stereotactically injected into the right putamen region of adult Sprague‑Dawley rats. The brain tissue sections were then subjected to hematoxylin and eosin, immunohistochemical or immunofluorescent staining. High magnification views of the tissue sections revealed that C6 cells formed tumor spheroids following implantation and marked invasion was observed shortly after spheroid formation. In the later stages of invasion, certain tumor cells invaded the perivascular space and formed small tumor clusters. These small tumor clusters exhibited certain common features, including tumor cell multilayers surrounding an arteriole, which occurred up to several millimeters away from the primary tumor mass; a high proliferation rate; and similar gene expression profiles to the primary tumor. In conclusion, the present study revealed that invading tumor cells are capable of forming highly proliferative cell clusters along arterioles near the tumor margin, which may be a possible cause of the recurrence of malignant glioma.

  8. Anti-Proliferative Effect of Rosmarinus officinalis L. Extract on Human Melanoma A375 Cells.

    Science.gov (United States)

    Cattaneo, Lucia; Cicconi, Rosella; Mignogna, Giuseppina; Giorgi, Alessandra; Mattei, Maurizio; Graziani, Giulia; Ferracane, Rosalia; Grosso, Alessandro; Aducci, Patrizia; Schininà, M Eugenia; Marra, Mauro

    2015-01-01

    Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed.

  9. Molecular characterisation of Atlantic salmon paramyxovirus (ASPV): A novel paramyxovirus associated with proliferative gill inflammation

    Science.gov (United States)

    Falk, K.; Batts, W.N.; Kvellestad, A.; Kurath, G.; Wiik-Nielsen, J.; Winton, J.R.

    2008-01-01

    Atlantic salmon paramyxovirus (ASPV) was isolated in 1995 from gills of farmed Atlantic salmon suffering from proliferative gill inflammation. The complete genome sequence of ASPV was determined, revealing a genome 16,968 nucleotides in length consisting of six non-overlapping genes coding for the nucleo- (N), phospho- (P), matrix- (M), fusion- (F), haemagglutinin-neuraminidase- (HN) and large polymerase (L) proteins in the order 3???-N-P-M-F-HN-L-5???. The various conserved features related to virus replication found in most paramyxoviruses were also found in ASPV. These include: conserved and complementary leader and trailer sequences, tri-nucleotide intergenic regions and highly conserved transcription start and stop signal sequences. The P gene expression strategy of ASPV was like that of the respiro-, morbilli- and henipaviruses, which express the P and C proteins from the primary transcript and edit a portion of the mRNA to encode V and W proteins. Sequence similarities among various features related to virus replication, pairwise comparisons of all deduced ASPV protein sequences with homologous regions from other members of the family Paramyxoviridae, and phylogenetic analyses of these amino acid sequences suggested that ASPV was a novel member of the sub-family Paramyxovirinae, most closely related to the respiroviruses. ?? 2008 Elsevier B.V. All rights reserved.

  10. Identification of proliferative progenitors associated with prominent postnatal growth of the pons

    Science.gov (United States)

    Lindquist, Robert A.; Guinto, Cristina D.; Rodas-Rodriguez, Jose L.; Fuentealba, Luis C.; Tate, Matthew C.; Rowitch, David H.; Alvarez-Buylla, Arturo

    2016-01-01

    The pons controls crucial sensorimotor and autonomic functions. In humans, it grows sixfold postnatally and is a site of paediatric gliomas; however, the mechanisms of pontine growth remain poorly understood. We show that the murine pons quadruples in volume postnatally; growth is fastest during postnatal days 0–4 (P0–P4), preceding most myelination. We identify three postnatal proliferative compartments: ventricular, midline and parenchymal. We find no evidence of postnatal neurogenesis in the pons, but each progenitor compartment produces new astroglia and oligodendroglia; the latter expand 10- to 18-fold postnatally, and are derived mostly from the parenchyma. Nearly all parenchymal progenitors at P4 are Sox2+Olig2+, but by P8 a Sox2− subpopulation emerges, suggesting a lineage progression from Sox2+ ‘early' to Sox2− ‘late' oligodendrocyte progenitor. Fate mapping reveals that >90% of adult oligodendrocytes derive from P2–P3 Sox2+ progenitors. These results demonstrate the importance of postnatal Sox2+Olig2+ progenitors in pontine growth and oligodendrogenesis. PMID:27188978

  11. The effects of acute heat stress on proliferative and apoptotic processes in the rat adrenal cortex

    Directory of Open Access Journals (Sweden)

    Petrović-Kosanović Dragana

    2013-01-01

    Full Text Available Hyperthermia can cause significant structural and functional reorganization of tissues and organs. The proliferative and apoptotic processes of rat adrenal cortex were analyzed by light and electron microscopy after an acute exposure to high ambient temperature. Animals were divided in two groups. The first group consisted of intact controls. The rats from the second group were exposed to a high ambient temperature of 38°C for 60 min. Mitotic chromosomes and the largest number of immunoreactive nuclei for the Ki-67 were observed in the zona reticularis (ZR of the control animals. The relative number of mitoses after heat stress showed a significant decrease in the zona glomerulosa (ZG; 66.8%, zona fasciculata (ZF; 27.8% and ZR (86.7% (for all zones p<0.05, while in the whole adrenal cortex the after-treatment decrease was 61.9% (p<0.05 compared to the controls. Under heat stress numerous apoptotic nuclei were seen at the light and ultrastructural levels in all the zones of the adrenal cortex. Such dynamics of mitosis/apoptosis events seriously affect adrenal cortex morphology. [Projekat Ministarstva nauke Republike Srbije, br. 173023 i br. 173009

  12. Anti-proliferative activities of terpenoids isolated from Alisma orientalis and their structure-activity relationships.

    Science.gov (United States)

    Xu, Wen; Li, Ting; Qiu, Jian-Fang; Wu, Shui-Sheng; Huang, Ming-Qing; Lin, Li-Gen; Zhang, Qing-Wen; Chen, Xiu-Ping; Lu, Jin-Jian

    2015-01-01

    This study aimed to isolate terpenoids from Alisma orientalis (Sam.) Juzep. and elucidate their antiproliferative activities, as well as structure-activity relationships. Fourteen protostane-type triterpenoids were isolated from the rhizome of A. orientalis. Among these triterpenoids, alisol A (1), alisol A 24-acetate (2), alisol B (3), alisol B 23-acetate (4), and alisol G (8) presented inhibitory effects on cancer cell lines tested. Compounds 3 and 4 showed the highest potential; IC50 values for HepG2, MDA-MB-231, and MCF-7 cells were 16.28, 14.47, and 6.66 μM for 3 and 18.01, 15.97, and 13.56 μM for 4, respectively. Based on these results, we concluded that the degree of C-16 oxidation and the double bond between C-13 and C-17 may be significant in anti-proliferative activities. Further study showed that 3 and 4 effectively induced apoptosis, as confirmed by flow cytometry. Increased intracellular calcium concentration and endoplasmic reticulum stress were detected after treatment with 4 in HepG2 cells. Although compounds 1 and 2 induced minimal apoptosis, they evidently delayed the G2/M phase in HepG2 cells. Further study showed that 1-4 also enhanced LC3II expression, indicating autophagy is occured.

  13. The Anti-Proliferative Effect of Inhibitor of Telomerase on Cultured Retinal Pigment Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to provide a new method for treating proliferative vitreoretinopathy (PVR), the effects of anti-proliferation and apoptosis induction of inhibitors of telomerase and heat shock protein 90 (Hsp90) on the cultured retinal pigment epithelial (RPE) cells were investigated. The rate of apoptosis cells was measured by using TUNEL on the cultured RPE cells, the co-cultured RPE cells with inhibitor of telomerase (camptothecin) or the co-cultured RPE cells with inhibitor of Hsp90 (geldanamycin). The cell proliferation status was measured in the above three groups by using MTT method. The rate of apoptosis in the RPE cells co-cultured with camptothecin or geldanamycin was increased remarkably (P<0.05). MTT showed the rate of growth inhibition was 8.4 %, 32.3 % and 72.3 % at the concentrations of camptothecin 1 μmol/L, 5 μmol/L, 10 μmol/L, respectively, and 6.5 %, 30.9 %, 71.9 % at the concentrations of geldanamycin 1 μmol/L, 5 μmol/L, 10 μmol/L, respectively. It was concluded that telomerase and Hsp90 can promote the proliferation of the cultured RPE cells, while the inhibitor of them can induce apoptosis and inhibit the growth of the RPE cells.

  14. Medulloblastoma: evaluation of proliferative index by monoclonal antibody Mib-1, its prognostic correlation and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Ferrari Antonio Fernandes

    2003-01-01

    Full Text Available In the past few years, the monoclonal antibody MIB-1 has been used by researchers in order to retrospectively study paraffin imbibed tumor fragments. The medulloblastoma is the most common malignant central nervous system tumor in childhood. The objectives were: determination of the mean Mib-1 LI value from these patients, as well as the prognostic value of the method.This retrospective study represents an analysis of the cellular proliferation index of posterior fossa medulloblastomas collected from 22 patients at A.C. Camargo Hospital, from January 1990 to December 1999. The histopathological diagnosis was confirmed by H&E and proliferative index (LI was achived with Mib-1 which detects proliferating cells during G1, G2, S and M phases.The results demostrated that the mean Mib-1 was 30,1%, and ranged from 5,2% to 62,0%.In conclusion, this method has prognostic value, has to be used as routine for patients harboring medulloblastomas and the ones who have PI greater than the mean value found in this study, should be treated aggressively.

  15. Lymphocytic proliferative response to outer-membrane proteins isolated from Salmonella.

    Science.gov (United States)

    González, C R; Isibasi, A; Ortiz-Navarrete, V; Paniagua, J; García, J A; Blanco, F; Kumate, J

    1993-01-01

    Porins isolated from Salmonella typhi have been demonstrated to protect against the challenge with this bacteria in mice. The mechanism has not been clarified, but could be associated with activation of both humoral and cellular immunity. In order to evaluate the induction of specific T cell responses, the lymphocytic proliferation to porins isolated from Salmonella typhimurium, Salmonella typhi and Escherichia coli was examined by 3H-thymidine incorporation assay in mice immunized with three different antigens: acetone-killed S. typhimurium, its porins, or outer-membrane proteins (OMPs) isolated from S. typhi. Higher proliferative responses were observed in mice immunized with porins and OMPs compared with those which received the acetone-killed bacteria. Although cross-reactivity was observed between porins, they were not mitogenic. Moreover, porins were able to activate T lymphocytes isolated from mice immunized with S. typhi OMPs. These results suggest that T cell activation, through the release of lymphokines, may play a role in the induction of protective immunity with porins.

  16. Microglia from neurogenic and non-neurogenic regions display differential proliferative potential and neuroblast support

    Directory of Open Access Journals (Sweden)

    Gregory Paul Marshall

    2014-07-01

    Full Text Available Microglia isolated from the neurogenic subependymal zone (SEZ and hippocampus (HC are capable of massive in vitro population expansion that is not possible with microglia isolated from non-neurogenic regions. We asked if this regional heterogeneity in microglial proliferative capacity is cell intrinsic, or is conferred by interaction with respective neurogenic or non-neurogenic niches. By combining SEZ and cerebral cortex (CTX primary tissue dissociates to generate heterospatial cultures, we find that exposure to the SEZ environment does not enhance CTX microglia expansion; however, the CTX environment exerts a suppressive effect on SEZ microglia expansion. Furthermore, addition of purified donor SEZ microglia to either CTX- or SEZ-derived cultures suppresses the expansion of host microglia, while the addition of donor CTX microglia enhances the over-all microglia yield. These data suggest that SEZ and CTX microglia possess intrinsic, spatially restricted characteristics that are independent of their in vitro environment, and that they represent unique and functionally distinct populations. Finally, we determined that the repeated supplementation of neurogenic SEZ cultures with expanded SEZ microglia allows for sustained levels of inducible neurogenesis, provided that the ratio of microglia to total cells remains within a fairly narrow range.

  17. Chitin and chitosan from the Norway lobster by-products: Antimicrobial and anti-proliferative activities.

    Science.gov (United States)

    Sayari, Nadhem; Sila, Assaâd; Abdelmalek, Baha Eddine; Abdallah, Rihab Ben; Ellouz-Chaabouni, Semia; Bougatef, Ali; Balti, Rafik

    2016-06-01

    Chitin was recovered through enzymatic deproteinization of the Norway lobster (Nephrops norvegicus) processing by-products. The obtained chitin was characterized and converted into chitosan by N-deacetylation, the acid-soluble form of chitin. Chitosan samples were then characterized by Fourier transform infrared spectroscopy (FTIR) and 13 Cross polarization magic angle spinning nuclear magnetic resonance (CP/MAS)-NMR spectroscopy. The antimicrobial activity and anti-proliferative capacity of chitosan were evaluated. Antimicrobial activity assays indicated that prepared chitosan exhibited marked inhibitory activity against the bacterial and fungal strains tested. Further, cytotoxic effects of chitosan samples on human colon carcinoma cells HCT116 was evaluated using the MTT assay. Chitosan showed the antiproliferative capacity against the colon-cancer-cell HCT116 in a dose dependent manner with IC50 of 4.6mg/ml. Indeed, HCT116 cell proliferation was significantly inhibited (p<0.05) between 13.5 and 67.5% at 0.5-6mg/mL of chitosan after 24h of cell treatment. The chitosan showed high antitumor activity which seemed to be dependent on its characteristics such as acetylation degree.

  18. Proteome analysis of proliferative response of bystander cells adjacent to cells exposed to ionizing radiation.

    Science.gov (United States)

    Gerashchenko, Bogdan I; Yamagata, Akira; Oofusa, Ken; Yoshizato, Katsutoshi; de Toledo, Sonia M; Howell, Roger W

    2007-06-01

    Recently (Cytometry 2003, 56A, 71-80), we reported that direct cell-to-cell contact is required for stimulating proliferation of bystander rat liver cells (WB-F344) cocultured with irradiated cells, and neither functional gap junction intercellular communication nor long-range extracellular factors appear to be involved in this proliferative bystander response (PBR). The molecular basis for this response is unknown. Confluent monolayers of WB-F344 cells were exposed to 5-Gray (Gy) of gamma-rays. Irradiated cells were mixed with unirradiated cells and co-cultured for 24 h. Cells were harvested and protein expression was examined using 2-DE. Protein expression was also determined in cultures of unirradiated and 5-Gy irradiated cells. Proteins were identified by MS. Nucleophosmin (NPM)-1, a multifunctional nucleolar protein, was more highly expressed in bystander cells than in either unirradiated or 5-Gy irradiated cells. Enolase-alpha, a glycolytic enzyme, was present in acidic and basic variants in unirradiated cells. In bystander and 5-Gy irradiated cells, the basic variant was weakly expressed, whereas the acidic variant was overwhelmingly present. These data indicate that the presence of irradiated cells can affect NPM-1 and enolase-alpha in adjacent bystander cells. These proteins appear to participate in molecular events related to the PBR and suggest that this response may involve cellular defense, proliferation, and metabolism.

  19. Small Interfering RNA Targeted to ASPP2 Promotes Progression of Experimental Proliferative Vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Xiao-Li Chen

    2016-01-01

    Full Text Available Background. Epithelial-mesenchymal transition (EMT of retinal pigment epithelium (RPE is vital in proliferative vitreoretinopathy (PVR development. Apoptosis-stimulating proteins of p53 (ASPP2 have recently been reported to participate in EMT. However, the role of ASPP2 in PVR pathogenesis has not been identified. Methods. Immunohistochemistry was used to investigate the expression of ASPP2 in epiretinal membranes of PVR patients. ARPE-19 cells were transfected with ASPP2-siRNA, followed with measurement of cell cytotoxicity, proliferation, and migration ability. EMT markers and related inflammatory and fibrosis cytokines were measured by western blot or flow cytometry. Additionally, PVR rat models were induced by intravitreal injection of ARPE-19 cells transfected with ASPP2-siRNA and evaluated accordingly. Results. Immunofluorescence analysis revealed less intense expression of ASPP2 in PVR membranes. ASPP2 knockdown facilitated the proliferation and migration of RPE cells and enhanced the expression of mesenchymal markers such as alpha smooth muscle actin, fibronectin, and ZEB1. Meanwhile, ASPP2-siRNA increased EMT-related and inflammatory cytokines, including TGF-β, CTGF, VEGF, TNF-α, and interleukins. PVR severities were more pronounced in the rat models with ASPP2-siRNA treatment. Conclusions. ASPP2 knockdown promoted EMT of ARPE-19 cells in vitro and exacerbated the progression of experimental PVR in vivo, possibly via inflammatory and fibrosis cytokines.

  20. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery.

    Directory of Open Access Journals (Sweden)

    Michael Poulsen

    Full Text Available Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest.

  1. Management of severe proliferative vitreo-retinopathy with perfluorocarbon liquids and silicone oil.

    Science.gov (United States)

    Wu, W C; Kuo, S L; Chen, J Y

    1999-10-01

    12 patients of retinal detachment with advanced proliferative vitreoretinopathy were managed with intraoperative perfluoro-N-octane and postoperative silicone oil injection from March 1994 to June 1996 in Kaohsiung Medical University Hospital. The combined intraoprative procedures included posterior vitrectomy (12 eyes), membrane peeling (12 eyes), lower peripheral iridectomy (8 eyes), endo-photocoagulation (8 eyes), retinotomy (8 eyes), and retinal fixation with tack (1 eye). After a minimum of 10 months of follow up, the retina was successfully reattached in 10 (84%) of the 12 eyes, 5 of these eyes had stable tractional detachments on the anterior part of the scleral buckle. Seven patients (58.3%) regained vision of 5/200 or better. The rate of improvement by listing best corrected visual acuity after operation was 75%. We think that the ability to readily remove additional pre-retinal fibrous tissue after the retina was flattened with perfluorocarbon liquids allowed the surgeon to perform a further complete membrane dissection. It can therefore improve the success rate of surgery and hence decrease the rate of complications that was previously thought to be caused by sillicone oil.

  2. Anti-proliferative and antioxidative activities of Thai noni/Yor (Morinda citrifolia Linn.) leaf extract.

    Science.gov (United States)

    Thani, Wasina; Vallisuta, Omboon; Siripong, Pongpan; Ruangwises, Nongluck

    2010-03-01

    In this study the leaves of the Thai noni/Yor, (Morinda citrifolia Linn.) were extracted by several methods and evaluated against human cancer cell lines: KB (human epidermoid carcinoma), HeLa (human cervical carcinoma), MCF-7 (human breast carcinoma) and HepG2 (human hepatocellular carcinoma) cell lines as well as a Vero (African green monkey kidney) cell line, employing the MTT colorimetric method, comparing it to damnacanthal, rutin, and scopoletin. The dichloromethane extract of the fresh leaf showed a better inhibitory effect against KB and HeLa cells with IC50 values of 21.67 and 68.50 microg/ml, respectively. The dichloromethane extract of dried leaves revealed cytotoxicity against the KB cell line with an IC50 value of 39.00 microg/ml. Other extracts, as well as rutin and scopoletin, showed reduced anti-proliferative effects on all cancer cell lines (IC50 103 to over 600 microg/ml). Interestingly, the damnacanthal had potent cytotoxicity against all cancer cell lines and Vero cell lines. These results suggest Thai noni extracts may be safer than the pure compounds, due to their higher safety ratios, which is a good indicator for possible cancer treatment. Several non-aqueous extracts from the leaves showed antioxidant properties, giving IC50 values of 0.20-0.35 mg/ml. It can be concluded the leaves of M. citrifolia may have benefit as a food supplement for chemoprevention against epidermoid and cervical cancers.

  3. White kidney bean lectin exerts anti-proliferative and apoptotic effects on cancer cells.

    Science.gov (United States)

    Chan, Yau Sang; Xia, Lixin; Ng, Tzi Bun

    2016-04-01

    A 60-kDa glucosamine binding lectin, white kidney bean lectin (WKBL), was purified from Phaseolus vulgaris cv. white kidney beans, by application of anion exchange chromatography on Q-Sepharose, affinity chromatography on Affi-gel blue gel, and FPLC-size exclusion on Superdex 75. The anti-proliferative activity of WKBL on HONE1 cells and HepG2 cells was stronger than the activity on MCF7 cells and WRL68 cells (IC50 values for a 48-h treatment with WKBL on HONE1 cells: 18.8 μM; HepG2 cells: 19.7 μM; MCF7 cells: 26.9 μM; and WRL68 cells: >80 μM). The activity could be reduced by addition of glucosamine, which occupies the binding sites of WKBL, indicating that carbohydrate binding is crucial for the activity. Annexin V-FITC and PI staining, JC-1 staining and Hoechst 33342 staining revealed that apoptosis was induced on WKBL-treated HONE1 cells and HepG2 cells, but not as obviously on MCF7 cells. Cell cycle analysis also showed a slight cell cycle arrest on HONE1 cells after WKBL treatment. Western blotting suggested that WKBL induced apoptosis of HONE1 cells occurred through the extrinsic apoptosis pathway, with detection of increased level of active caspase 3, 8 and 9.

  4. Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells

    Science.gov (United States)

    Hansberg-Pastor, Valeria

    2017-01-01

    Progesterone-induced blocking factor (PIBF) is a progesterone (P4) regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P4 and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas. PIBF mRNA expression was upregulated by P4 (10 nM) from 12 to 24 h. Glioblastoma cells expressed two PIBF isoforms, 90 and 57 kDa. The content of the shorter isoform was increased by P4 at 24 h, while progesterone receptor antagonist RU486 (10 μM) blocked this effect. PIBF (100 ng/mL) increased the number of U87 cells on days 4 and 5 of treatment and induced cell proliferation on day 4. Wound-healing assays showed that PIBF increased the migration of U87 (12–48 h) and U251 (24 and 48 h) cells. Transwell invasion assays showed that PIBF augmented the number of invasive cells in both cell lines at 24 h. These data suggest that PIBF promotes proliferation, migration, and invasion of human glioblastoma cells. PMID:28168193

  5. Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

    OpenAIRE

    Watson Cheryl S; Jeng Yow-Jiun

    2009-01-01

    Abstract Background Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH3/B6/F10, originally subcloned from GH3 cells based on its ability to express high l...

  6. Detection of serum antibodies cross-reacting with Mycobacterium avium subspecies paratuberculosis and beta-cell antigen zinc transporter 8 homologous peptides in patients with high-risk proliferative diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Antonio Pinna

    Full Text Available PURPOSE: MAP3865c, a Mycobacterium avium subspecies paratuberculosis (MAP cell membrane protein, has a relevant sequence homology with zinc transporter 8 (ZnT8, a beta-cell membrane protein involved in Zn++ transportation. Recently, antibodies recognizing MAP3865c epitopes have been shown to cross-react with ZnT8 in type 1 diabetes patients. The purpose of this study was to detect antibodies against MAP3865c peptides in patients with high-risk proliferative diabetic retinopathy and speculate on whether they may somehow be involved in the pathogenesis of this severe retinal disorder. METHODS: Blood samples were obtained from 62 type 1 and 80 type 2 diabetes patients with high-risk proliferative diabetic retinopathy and 81 healthy controls. Antibodies against 6 highly immunogenic MAP3865c peptides were detected by indirect ELISA. RESULTS: Type 1 diabetes patients had significantly higher rates of positive antibodies than controls. Conversely, no statistically significant differences were found between type 2 diabetes patients and controls. After categorization of type 1 diabetes patients into two groups, one with positive, the other with negative antibodies, we found that they had similar mean visual acuity (∼ 0.6 and identical rates of vitreous hemorrhage (28.6%. Conversely, Hashimoto's thyroiditis prevalence was 4/13 (30.7% in the positive antibody group and 1/49 (2% in the negative antibody group, a statistically significant difference (P = 0.016. CONCLUSIONS: This study confirmed that type 1 diabetes patients have significantly higher rates of positive antibodies against MAP/ZnT8 peptides, but failed to find a correlation between the presence of these antibodies and the severity degree of high-risk proliferative diabetic retinopathy. The significantly higher prevalence of Hashimoto's disease among type 1 diabetes patients with positive antibodies might suggest a possible common environmental trigger for these conditions.

  7. Anti-proliferative and mutagenic activities of aqueous and methanol extracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae).

    Science.gov (United States)

    Er, Hui Meng; Cheng, En-Hsiang; Radhakrishnan, Ammu Kutty

    2007-09-25

    The anti-proliferative effects of the aqueous and methanol extracts of leaves of Pereskia bleo (Kunth) DC (Cactaceae) against a mouse mammary cancer cell line (4T1) and a normal mouse fibroblast cell line (NIH/3T3) were evaluated under an optimal (in culture medium containing 10% foetal bovine serum (FBS)) and a sub-optimal (in culture medium containing 0.5% FBS) conditions. Under the optimal condition, the aqueous extract showed a significant (pCactaceae) do not have appreciable anti-proliferative effect on the 4T1 and NIH/3T3 cells as the EC(50) values obtained are greater than 50 microg/mL when tested under optimal culture condition. Moreover, the aqueous extract may form mutagenic compound(s) upon the metabolisation by liver enzymes.

  8. Separation and purification and in vitro anti-proliferative activity of leukemia cell K562 of Galium aparine L. petroleum

    Directory of Open Access Journals (Sweden)

    Guoqing Shi

    2016-05-01

    Full Text Available To explore material basis of in vitro anti-proliferative activity of leukemia cell K562 of petroleum ether phase of product resulting from Galium aparine L. 60% ethanol extraction, the experiment adopts column chromatography combined with thin layer preparation, isolates and purifies petroleum ether, conducts structural identification of obtained single compound and applies MTT method for viability assay of in vitro anti-proliferative activity of leukemia cell K562. Experimental results show that G. aparine L. petroleum ether contains mainly β-sitosterol, daucosterol and dibutyl phthalate and other substances. Under experimental conditions, the three could inhibit the proliferation of leukemia cell K562 with dose-effect and time-effect relationship, of which dibutyl phthalate has strongest activity. Dibutyl phthalate with excellent activity, β-sitosterol with rich content and moderate effect should be the main contributor to its biological activity.

  9. 17β-Estradiol Suppresses Cytotoxicity and Proliferative Capacity of Murine Splenic NK1.1+ Cells

    Institute of Scientific and Technical Information of China (English)

    Sha Hao; Pengfei Li; Junli Zhao; Yali Hu; Yayi Hou

    2008-01-01

    In order to clarify the effects of 17β-estradiol(E2)on natural killer(NK)cells and the possibly regulatory mechanisms,we obtained highly purified and viable NK cells from C57BL/6J mouse spleen by a magnetic cell sorter(MACS).These cells were treated with E2 and then their cytotoxicity and proliferative capacity were examined.To further investigate the mechanisms on the effect of E2 on NK cells,expressions of activationassociated markers(CD69,CD122)and inhibitory receptors(CD94,Ly49),and intracellular cytokine production Were analyzed.At last,we performed the cDNA microarray to explore the possible involved genes.We found that E2 could suppress NK cell cytotoxicity and proliferative capacity in vitro.E2 reduced NK cell cytotoxicity and proliferative capacity,which may be through influencing the phenotypes and cytokine expression of NK cells, mainly involving CD94 and IFN-γ.Furthermore,regulation of Stat4,Fyn,Sh2d1a,Eat2,Cd244,Irf1,Runx1,Irf7, Irf5,Esrra and Nr5a1 genes may be related to the cytotoxicity,proliferation and cytokine production of E2-mediated purified NK cells.

  10. 17beta-estradiol suppresses cytotoxicity and proliferative capacity of murine splenic NK1.1+ cells.

    Science.gov (United States)

    Hao, Sha; Li, Pengfei; Zhao, Junli; Hu, Yali; Hou, Yayi

    2008-10-01

    In order to clarify the effects of 17beta-estradiol (E2) on natural killer (NK) cells and the possibly regulatory mechanisms, we obtained highly purified and viable NK cells from C57BL/6J mouse spleen by a magnetic cell sorter (MACS). These cells were treated with E2 and then their cytotoxicity and proliferative capacity were examined. To further investigate the mechanisms on the effect of E2 on NK cells, expressions of activation-associated markers (CD69, CD122) and inhibitory receptors (CD94, Ly49), and intracellular cytokine production were analyzed. At last, we performed the cDNA microarray to explore the possible involved genes. We found that E2 could suppress NK cell cytotoxicity and proliferative capacity in vitro. E2 reduced NK cell cytotoxicity and proliferative capacity, which may be through influencing the phenotypes and cytokine expression of NK cells, mainly involving CD94 and IFN-gamma. Furthermore, regulation of Stat4, Fyn, Sh2d1a, Eat2, Cd244, Irf1, Runx1, Irf7, Irf5, Esrra and Nr5a1 genes may be related to the cytotoxicity, proliferation and cytokine production of E2-mediated purified NK cells.

  11. Rational design, synthesis and anti-proliferative evaluation of novel 1,4-benzoxazine-[1,2,3]triazole hybrids.

    Science.gov (United States)

    Bollu, Rajitha; Palem, Jyothsna Devi; Bantu, Rajashaker; Guguloth, Vijayacharan; Nagarapu, Lingaiah; Polepalli, Sowjanya; Jain, Nishant

    2015-01-07

    A series of novel 1,2,3-triazole-1,4-benzoxazine hybrids 5a-n were efficiently synthesized employing click chemistry approach and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 5n and 5g exhibited promising anti-proliferative activity with GI50 values ranging from 1.2 to 2.5 μM and 0.1-1.1 μM respectively against all cell lines, like HeLa, MDA-MB-231, MIAPACA and IMR32, while compound 5l showed significant activity against MDA-MB-231 and IMR32 with GI50 values ranging from 1.1 and 1.4 μM. This is the first report on the synthesis and in vitro anti-proliferative evaluation of 1,2,3-triazole-1,4-benzoxazine hybrids.

  12. Cell output, cell cycle duration and neuronal specification: a model of integrated mechanisms of the neocortical proliferative process

    Science.gov (United States)

    Caviness, V. S. Jr; Goto, T.; Tarui, T.; Takahashi, T.; Bhide, P. G.; Nowakowski, R. S.

    2003-01-01

    The neurons of the neocortex are generated over a 6 day neuronogenetic interval that comprises 11 cell cycles. During these 11 cell cycles, the length of cell cycle increases and the proportion of cells that exits (Q) versus re-enters (P) the cell cycle changes systematically. At the same time, the fate of the neurons produced at each of the 11 cell cycles appears to be specified at least in terms of their laminar destination. As a first step towards determining the causal interrelationships of the proliferative process with the process of laminar specification, we present a two-pronged approach. This consists of (i) a mathematical model that integrates the output of the proliferative process with the laminar fate of the output and predicts the effects of induced changes in Q and P during the neuronogenetic interval on the developing and mature cortex and (ii) an experimental system that allows the manipulation of Q and P in vivo. Here we show that the predictions of the model and the results of the experiments agree. The results indicate that events affecting the output of the proliferative population affect both the number of neurons produced and their specification with regard to their laminar fate.

  13. Increased Stiffness in Aged Skeletal Muscle Impairs Muscle Progenitor Cell Proliferative Activity.

    Directory of Open Access Journals (Sweden)

    Grégory Lacraz

    Full Text Available Skeletal muscle aging is associated with a decreased regenerative potential due to the loss of function of endogenous stem cells or myogenic progenitor cells (MPCs. Aged skeletal muscle is characterized by the deposition of extracellular matrix (ECM, which in turn influences the biomechanical properties of myofibers by increasing their stiffness. Since the stiffness of the MPC microenvironment directly impacts MPC function, we hypothesized that the increase in muscle stiffness that occurs with aging impairs the behavior of MPCs, ultimately leading to a decrease in regenerative potential.We showed that freshly isolated individual myofibers from aged mouse muscles contain fewer MPCs overall than myofibers from adult muscles, with fewer quiescent MPCs and more proliferative and differentiating MPCs. We observed alterations in cultured MPC behavior in aged animals, where the proliferation and differentiation of MPCs were lower and higher, respectively. These alterations were not linked to the intrinsic properties of aged myofibers, as shown by the similar values for the cumulative population-doubling values and fusion indexes. However, atomic force microscopy (AFM indentation experiments revealed a nearly 4-fold increase in the stiffness of the MPC microenvironment. We further showed that the increase in stiffness is associated with alterations to muscle ECM, including the accumulation of collagen, which was correlated with higher hydroxyproline and advanced glycation end-product content. Lastly, we recapitulated the impaired MPC behavior observed in aging using a hydrogel substrate that mimics the stiffness of myofibers.These findings provide novel evidence that the low regenerative potential of aged skeletal muscle is independent of intrinsic MPC properties but is related to the increase in the stiffness of the MPC microenvironment.

  14. Evaluation of cell proliferative activity after irradiation using immunohistochemical approach and flow cytometry

    Energy Technology Data Exchange (ETDEWEB)

    Tamada, Takashi (Okayama Univ. (Japan). School of Medicine)

    1992-06-01

    To evaluate a proliferative activity of post-irradiated malignant cells, we studied the kinetics of HeLa cells using immunohistochemical approach and flow cytometry. HeLa cells were stained with two proliferation-associated monoclonal antibodies, Ki-67 and anti-DNA polymerase {alpha} antibody. Nucleoli of non-irradiated cells were granularly stained with Ki-67. After irradiation, only the center of nuclei was diffusely stained with Ki-67. One hundred forty-four hours after low-dose irradiation, the staining patterns became the same as the control. On the other hand, after high-dose irradiation, the center of nuclei was weakly stained. DNA polymerase {alpha} was diffusely labelled with nuclei of the control. It was located around the border of nuclei of low-dose irradiated cells like a ring. But after high-dose irradiation, it was granularly distributed in the periphery of nuclei. FITC conjugated Ki-67/PI two parameter analysis was done by a single laser flow cytometer. Twenty-four hours after irradiation, DNA-histograms showed the accumulation to G{sub 2}/M phase and the increase of DNA content of G{sub 2}/M cells, as exposure dose was increased. Two parameter analysis showed the increase of FITC uptake of G{sub 2}/M phase as dose increased. These changes of flow cytometry were remarkably observed after 24 hours' incubation. It was shown that the difference of Ki-67 antigen and DNA polymerase {alpha} appearance depended on the irradiation dose. These findings suggest that immunohistochemical staining with Ki-67 or anti-DNA polymerase {alpha} antibody and flow cytometry using Ki-67 are available to evaluate cell damages after irradiation. (author).

  15. Expression and localisation of BDNF, NT4 and TrkB in proliferative vitreoretinopathy.

    Science.gov (United States)

    Ghazi-Nouri, Seyed M S; Ellis, James S; Moss, Stephen; Limb, G Astrid; Charteris, David G

    2008-05-01

    Exogenous brain derived neurotrophic factor (BDNF) is known to rescue ganglion cell death after optic nerve injury. Its mechanism of action is believed to be indirect via glial cells in the retina. In this study we investigated the changes in expression and localisation of BDNF, neurotrophin-4 (NT4) and their common receptor (TrkB) in retinectomy sections of patients with proliferative vitreoretinopathy (PVR). Nine full-thickness retinectomy specimens obtained at retinal reattachment surgery for PVR were fixed in 4% paraformaldehyde immediately after excision and compared to similarly processed normal donor retinas (4 eyes). Agarose-embedded sections (100 microm thick) were double labelled for immunohistochemistry by confocal microscopy, with antibodies against BDNF, NT4, TrkB, rod opsin, glial fibrillary acidic protein (GFAP), cellular retinaldehyde binding protein (CRALBP) and Brn3. This study demonstrates expression of NT4 by ganglion cells and shows expression of BDNF and NT4 in the outer photoreceptor segments is downregulated during PVR, whilst NT4 is markedly upregulated throughout the retina during this condition. The findings here suggest that NT4 may play a neural protective role during the development of PVR. It also shows that upregulation of NT4 in PVR is localised to Müller glial cells, indicating either over-expression of this factor by Müller cells or that Müller cells internalise NT4 for trafficking across the retina. TrkB expression was not observed in PVR retina. The observations that Müller glia demonstrate upregulation of NT4 suggests that retinal injury may lead to activation of this neurotrophin by Müller cells as part of their neuroprotective functions.

  16. Can the combination of localized "proliferative therapy" with "minor ozonated autohemotherapy" restore the natural healing process?

    Science.gov (United States)

    Gracer, R I; Bocci, V

    2005-01-01

    Regenerative injection therapy (RIT), also known as proliferative therapy, has been used for over 30 years in the USA in patients with spinal and peripheral joint and ligamentous pathologies. It involves the injection of mildly irritating medications onto ligaments and tendons, most commonly at origins and insertions. These injections cause a mild inflammatory response which "turns on" the normal healing process and results in the regeneration of these structures. At the same time they strengthen and become less sensitive to pain through a combination of neurolysis of small nerve fibers (C-fibers) and increased stability of the underlying structures. Oxygen/ozone therapy is a well established complementary therapy practiced in many European countries. The ozone dissolves in body fluids and immediately reacts with biomolecules generating messengers responsible for biological and therapeutic activities. This results in an anti inflammatory response, which also results in a similar trophic reaction to that of RIT. It is logical to expect that combining these two modalities would result in enhanced healing and therefore improved clinical outcomes. Oxygen/ozone therapy, accomplished by autohemotherapy (AHT), is performed by either administering ozonated blood intravenously (Major AHT) or via intramuscular route (Minor AHT). These procedures result in stimulation of the immune and healing systems. Our concept is that the local injection of this activated blood injected directly to the ligamentous areas that are also being treated with RIT will act as a direct stimulation to the healing process. In addition, combining this with intravenous major AHT should stimulate the immune system to augment and support this process. RIT and oxygen/ozone therapy have been extensively studied separately. We propose a study of lumbosacral ligamentous pain to explore this therapeutic combination. We hope that this paper will stimulate general interest in this area of medicine and result

  17. Identification of a novel, alpha2-fucosylation-dependent uptake system in highly proliferative cells.

    Science.gov (United States)

    Aldi, Silvia; Capone, Antonietta; Giovampaola, Cinzia Della; Ermini, Leonardo; Pianigiani, Elisa; Mariotti, Giancarlo; Rosati, Floriana

    2015-02-01

    In this paper we describe a new structure present in highly proliferative cells and absent in cells with normal growth potential. We used cultured bovine venular endothelial cells (CVEC) as examples of high proliferation, and dermal fibroblasts of a primary culture as examples of normal proliferation. The structure, consisting of tubules radiating from the nuclear region to the tips of cell protrusions, was revealed by its strong positivity to the fucose-binding lectin from Lotus (LTL) that prefers glycans with alpha-1,2-linked fucose. Another fucose-binding lectin that prefers glycans with alpha-1,6-linked fucose was instead found to localize glycans exclusively in Golgi complexes. LTL binding sites were also found at the surface of CVEC in a restricted region close to the nucleus. The role of alpha-1,2-linked fucose in forming or maintaining the tubules was confirmed by the fact that down-regulation of the fucosyltransferases FUT1 and FUT2 resulted in disappearance of the tubular structure. LTL also proved able to penetrate the cells through the tubular structures up to the nuclear region and to inhibit proliferation. Endostatin was also found to massively penetrate the cells in the tubular structures in control cells but not in FUT1/2 depleted cells. In cells of a first passage primary culture of dermal fibroblasts the tubular LTL-positive structure was absent as well as the LTL-positive sites at the external surface, and both fucose-binding lectins were found to exclusively localize glycans in Golgi complexes. Tubules were again found progressively in fibroblasts derived from repeated passages, where faster growing cells predominate. Disappearance of LTL-positivity in Golgi complexes paralleled appearance of LTL-positive tubules. The role of Golgi complexes in forming the tubules is discussed.

  18. Characterisation of human non-proliferative diabetic retinopathy using the fractal analysis

    Institute of Scientific and Technical Information of China (English)

    Stefan; Tǎlu; Dan; Mihai; Cǎlugǎru; Carmen; Alina; Lupascu

    2015-01-01

    · AIM: To investigate and quantify changes in the branching patterns of the retina vascular network in diabetes using the fractal analysis method.·METHODS: This was a clinic-based prospective study of 172 participants managed at the Ophthalmological Clinic of Cluj-Napoca, Romania, between January 2012 and December 2013. A set of 172 segmented and skeletonized human retinal images, corresponding to both normal(24 images) and pathological(148 images)states of the retina were examined. An automatic unsupervised method for retinal vessel segmentation was applied before fractal analysis. The fractal analyses of the retinal digital images were performed using the fractal analysis software Image J. Statistical analyses were performed for these groups using Microsoft Office Excel2003 and Graph Pad In Stat software.·RESULTS: It was found that subtle changes in the vascular network geometry of the human retina are influenced by diabetic retinopathy(DR) and can be estimated using the fractal geometry. The average of fractal dimensions D for the normal images(segmented and skeletonized versions) is slightly lower than the corresponding values of mild non-proliferative DR(NPDR) images(segmented and skeletonized versions).The average of fractal dimensions D for the normal images(segmented and skeletonized versions) is higher than the corresponding values of moderate NPDR images(segmented and skeletonized versions). The lowestvalues were found for the corresponding values of severe NPDR images(segmented and skeletonized versions).· CONCLUSION: The fractal analysis of fundus photographs may be used for a more complete understanding of the early and basic pathophysiological mechanisms of diabetes. The architecture of the retinal microvasculature in diabetes can be quantitative quantified by means of the fractal dimension.Microvascular abnormalities on retinal imaging may elucidate early mechanistic pathways for microvascular complications and distinguish patients with DR from

  19. Diagnostic accuracy of fiberoptic ductoscopy plus in vivo iodine staining for intraductal proliferative lesions

    Institute of Scientific and Technical Information of China (English)

    FENG Xin-zhi; SONG Ying-hua; ZHANG Feng-xia; JIANG Chuan-wu; MEI Hong; ZHAO Bin

    2013-01-01

    Background lodine staining during endoscopy has been successfully used to detect early carcinomatous and precancerous lesions in the esophagus,cervix,and oral cavity.The objective of this study was to determine the diagnostic accuracy of fiberoptic ductoscopy (FDS) plus in vivo iodine staining for intraductal proliferative lesions of the breast.Methods We performed periodic acid-Schiff (PAS) and in vitro iodine staining on 52 and 64 specimens of benign mammary hyperplasia,respectively,and 57 and 53 specimens of ductal carcinoma in situ (DCIS),respectively.Next,FDS was performed on 177 recurrent nipple discharge patients who were randomly divided into two groups.One group was iodine-staining group in which 92 patients were randomly selected to undergo iodine staining during FDS,and the remaining 85 were assigned to the control group.Biopsy specimens of suspicious lesions were obtained and subjected to histopathological examination.Results Following PAS staining,benign mammary hyperplasia lesions were positively stained,while negligible PAS positivity was observed in the DCIS lesions (P <0.05).Following in vitro iodine staining,benign mammary hyperplasia specimens appeared dark brown,whereas DCIS samples appeared significantly lighter or unstained.Compared with the pathological examination results,FDS with iodine staining showed an agreement rate in the diagnosis of ductal intraepithelial neoplasia (DIN),sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,and Youden index of 97.82%,98.83%,83.33%,5.93,0.014,and 0.8216,respectively; the corresponding values for FDS without iodine staining were 88.24%,89.16%,50.00%,1.78,0.217,and 0.3916,respectively.Conclusion FDS with iodine staining was superior to conventional FDS for the diagnosis of DIN and is valuable for breast cancer prevention.

  20. Unexpected recovery from longterm renal failure in severe diffuse proliferative lupus nephritis

    Directory of Open Access Journals (Sweden)

    Ross Sophia

    2012-08-01

    Full Text Available Abstract Background Severe renal manifestation of systemic lupus erythematosus (SLE is not uncommon and is associated with an indeterminate prognosis. Complete remission can be obtained, however, at least in the young when chronic lesions are absent and adequate anti-inflammatory therapy is immediately initiated. Case presentation We report the unusual case of a 12-year-old girl who presented with severe oliguric renal failure, macrohematuria and skin rash. Renal biopsy revealed the diagnosis of severe diffuse proliferative glomerulonephritis (GN with cellular crescents in 15 out of 18 glomeruli and full-house pattern in immunofluorescence indicating lupus nephritis IVB according to WHO, IV-G(A according to ISN/RPS classification. The serological parameters confirmed the diagnosis of SLE and the patient was immediately treated with methylprednisolone, cyclophosphamide and immunoadsorption. Initially, despite rapid amelioration of her general condition, no substantial improvement of renal function could be achieved and the patient needed hemodialysis treatment for 12 weeks. Unexpectedly, in the further follow-up at first diuresis increased and thereafter also creatinine levels substantially declined so that hemodialysis could be discontinued. Today, 6 years after the initial presentation, the patient has normal renal function and a SLEDAI score of 0 under a continuous immunosuppressive therapy with Mycophenolate mofetil (MMF and low dose steroid. Conclusion Despite the severity of the initial renal injury and the unfavourable renal prognosis the kidney apparently has a tremendous capacity to recover in young patients when the damage is acute and adequate anti-inflammatory therapy is initiated without delay.

  1. Effect of different fixative solutions on eyes with experimental proliferative vitreoretinopathy.

    Science.gov (United States)

    Nassar, Khaled; Lüke, Julia; Lüke, Matthias; Kamal, Mahmoud; Soliman, Mahmoud M; Grisanti, Salvatore; Grisanti, Swaantje

    2015-04-01

    The aim of this study was to evaluate the use of different fixatives on the reliability of histopathological changes in a rabbit model of proliferative vitreoretinopathy (PVR). Twenty eyes from 10 rabbits were divided into four groups. The right eyes were used in two experimental groups (each n = 5), and the left, in two control groups (each n = 5). Using a newly developed scleral incision marker, an oblique scleral incision was standardized in the experimental groups, followed by intravitreal injection of 0.4 ml autologous blood and the left for wound repair for four weeks. Eyes were enucleated at four weeks. The groups differed in the type of used fixative solution (formaldehyde 4% vs. 1% buffered formaldehyde and 1.25% glutaraldehyde). The eyes were evaluated for the development of fibrosis, retinal detachment (RD), and processed for histopathology. Fibrous ingrowth of a variable degree was present in the experimental groups originating from the trauma site. Experimental eyes fixed with formaldehyde 4% had RD extension that was greater than that fixed in formaldehyde/glutaraldehyde mixture; however, the difference did not reach statistical significance (P = 0.15). This difference was not fully explained by the fibrosis which developed. In addition, in control groups, formaldehyde 4% induced a fixative-dependent retinal separation that was absent in eyes fixed with formaldehyde/glutaraldehyde mixture (P = 0.03). In conclusion, a mixture of buffered formaldehyde 1% and glutaraldehyde 1.25% combined with standardized scleral incision resulted in consistent pathological changes. A reliable PVR model is a condition sine qua non to evaluate antifibrotic treatment strategies.

  2. Apparent mesonephric duct (rete anlage) origin for cysts and proliferative epithelial lesions in the mouse ovary.

    Science.gov (United States)

    Long, Gerald G

    2002-01-01

    Ovaries and adjacent parovarian (mesovarial) tissues of CD-1 mice of various ages were examined to characterize cystic and proliferative epithelial lesions of the ovary and parovarian tissues. Ovaries and adjacent tissues from 6 mice each at approximately 3 and 8 months of age were processed for light microscopy and step-sections (50-micron intervals) of the entire tissue were examined. Tissues were collected from 40 mice each at 16 through 24 months of age and 3 step sections per mouse were examined. Mesonephric duct remnants were found in all mice at 3 and 8 months. Ducts were usually in the mesovarial adipose tissue and near or within the ovarian hilus and were often loosely associated with smooth muscle of the mesovarial ligament. The epithelium of the ducts varied from low cuboidal to columnar, occasional individual cells were ciliated, and small papillary configurations of epithelium were occasionally present. Ducts were dilated (> 1 mm) more often in mice at 8 months compared to 3 months, and some were continuous with cystic spaces within the ovaries. As mice aged (16-24 months), dilation and cystic change in ducts and associated compression of ovarian tissue away from the ovarian hilus became common. The epithelium of dilated ducts was generally flattened, but foci of cuboidal to columnar epithelium and/or occasional ciliated cells were present. Many ducts contained foci of hyperplastic and/or hypertrophic epithelium, and papillary projections of epithelium were occasionally found. Some of the latter lesions were consistent with a diagnosis of papillary cystadenoma. Hyperplasia of associated fibromuscular stroma was limited to a few apparently extraovarian ducts. The results of this study indicate that remnant mesonephric ductular structures are common in and adjacent to the ovaries of CD-1 mice. As mice age, these ducts become dilated and, in some, the epithelium becomes hyperplastic and/or hyperptrophic. These mesonephric duct remnants appear to be a

  3. Unicentric Castleman’s disease

    Directory of Open Access Journals (Sweden)

    Zaheda Kausar

    2014-07-01

    Full Text Available Castleman’s disease (CD is a rare benign lympho-proliferative disorder characterized by non-neoplastic lymphnode hypertrophy. Its etiology is unknown. It has been found in association with Ka-posi’s sarcoma, necessitating investigation for HIV. CD can be unicentric (localized, multicentric or mixed. We present a case of 13 years old male who presented with cervical lymphadenopathy, intermittent fever and weight loss in whom histopathological examination of a lymph node led to diagnosis of this rare condition hyaline vascular type of unicentric Castleman’s disease.

  4. Stimulative Effects of Low Intensity He-Ne Laser Irradiation on the Proliferative Potential and Cell-Cycle Progression of Myoblasts in Culture

    Directory of Open Access Journals (Sweden)

    Cui-Ping Zhang

    2014-01-01

    Full Text Available Low intensity laser irradiation (LILI was found to promote the regeneration of skeletal muscle in vivo but the cellular mechanisms are not fully understood. Myoblasts, normally quiescent and inactivated in adult skeletal muscle, are a type of myogenic progenitor cells and considered as the major candidates responsible for muscle regeneration. The aim of the present study was to study the effect of LILI on the growth potential and cell-cycle progression of the cultured myoblasts. Primary myoblasts isolated from rat hind legs were cultured in nutrient-deficient medium for 36 hours and then irradiated by helium-neon laser at a certain energy density. Immunohistochemical and flow cytometric analysis revealed that laser irradiation could increase the expression of cellular proliferation marker and the amount of cell subpopulations in the proliferative phase as compared with the nonirradiated control group. Meanwhile, the expressions of cell-cycle regulatory proteins in the laser-treated myoblasts were markedly upregulated as compared to the unirradiated cells, indicating that LILI could promote the reentry of quiescent myoblasts into the cell division cycle. These results suggest that LILI at certain fluences could promote their proliferation, thus contributing to the skeletal muscle regeneration following trauma and myopathic diseases.

  5. Müller glia as an important source of cytokines and inflammatory factors present in the gliotic retina during proliferative vitreoretinopathy.

    Science.gov (United States)

    Eastlake, K; Banerjee, P J; Angbohang, A; Charteris, D G; Khaw, P T; Limb, G A

    2016-04-01

    Retinal gliosis is characterized by biochemical and physiological changes that often lead to Müller glia proliferation and hypertrophy and is a feature of many neuro-degenerative and inflammatory diseases such as proliferative vitreoretinopathy (PVR). Although Müller glia are known to release inflammatory factors and cytokines, it is not clear whether cytokine production by these cells mirrors the pattern of factors present in the gliotic retina. Lysates from normal cadaveric retina and gliotic retinal specimens from patients undergoing retinectomy for treatment of PVR, the Müller cell line MIO-M1 and four human Müller glial cell preparations isolated from normal retina were examined for their expression of cytokines and inflammatory factors using semi-quantitative dot blot antibody arrays and quantitative arrays. Comparative analysis of the expression of inflammatory factors showed that in comparison with normal retina, gliotic retina exhibited greater than twofold increase in 24/102 factors examined by semiquantitative arrays, and a significant increase in 19 out of 27 factors assessed by quantitative methods (P retina, suggesting that targeting the production of inflammatory factors by Müller glia may constitute a valid approach to prevent neural damage during retinal gliosis and this merits further investigations.

  6. Signal Intensities in Preoperative MRI Do Not Reflect Proliferative Activity in Meningioma

    Directory of Open Access Journals (Sweden)

    Stefan Schob

    2016-08-01

    representing proliferative activity.

  7. Activation of neural progenitor cells in human eyes with proliferative vitreoretinopathy.

    Science.gov (United States)

    Johnsen, Erik O; Frøen, Rebecca C; Albert, Réka; Omdal, Bente K; Sarang, Zsolt; Berta, András; Nicolaissen, Bjørn; Petrovski, Goran; Moe, Morten C

    2012-05-01

    In addition to the ability for self-renewal and functional differentiation, neural stem/progenitor cells (NSCs) can respond to CNS injuries by targeted migration. In lower vertebrates, retinal injury is known to activate NSCs in the ciliary marginal zone (CMZ). Cells expressing markers of NSCs are also present in the ciliary body epithelium (CE) and in Müller glia in the peripheral retina (PR) of the adult human eye. However, these cells seem to be quiescent in the adult human eye and recent reports have shown that CE cells have limited properties of NSCs. In order to further clarify whether NSCs exist in the adult human eye, we tested whether NSC-like cells could be activated in eyes with proliferative vitreoretinopathy (PVR). The PR and CE were studied for NSC-associated markers in human enucleated control eyes and eyes with confirmed PVR, as well as in a mouse model of PVR. Furthermore, cells isolated from vitreous samples obtained during vitrectomies for retinal detachment were directly fixed or cultured in a stem cell-promoting medium and compared to cells cultured from the post-mortem retina and CE. In situ characterization of the normal eyes revealed robust expression of markers present in NSCs (Nestin, Sox2, Pax6) only around peripheral cysts of the proximal pars plana region and the PR, the latter population also staining for the glial marker GFAP. Although there were higher numbers of dividing cells in the CE of PVR eyes than in controls, we did not detect NSC-associated markers in the CE except around the proximal pars plana cysts. In the mice PVR eyes, Nestin activation was also found in the CE. In human PVR eyes, proliferation of both non-glial and glial cells co-staining NSC-associated markers was evident around the ora serrata region. Spheres formed in 7/10 vitreous samples from patients with PVR compared to 2/15 samples from patients with no known PVR, and expressed glial - and NSC-associated markers both after direct fixation and repetitive

  8. Anti-inflammatory and anti-proliferative activities of the wild edible cruciferous: Diplotaxis simplex.

    Science.gov (United States)

    Jdir, Hamida; Khemakham, Bassem; Najjaa, Hanen; Chakroun, Mouna; Jridi, Mourad; Ben Arfa, Abdelkarim; Ben Ali, Yassine; Zouari, Nacim

    2016-10-01

    Context The present study deals with new biological properties of the wild edible Diplotaxis simplex (Viv.) Spreng (Brassicaceae). Objectives The current study evaluates the antioxidant, the anti-inflammatory and the anti-cancer properties of ethyl acetate and ethanol extracts from D. simplex flowers. Materials and methods The anti-proliferative activity of the extracts (10-70 μg/mL) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) against human colon cancer cell line Caco-2. The anti-inflammatory potential was evaluated by the inhibitory effect of the extracts (1.5-7.5 mg/mL) on phospholipase A2 activity as well as on carrageenan-induced paw oedema in mice. Extracts (200 mg/kg) or indomethacin (50 mg/kg) as positive control were injected intraperitoneally for albino mice prior to the induction of the oedema by carrageenan. Antioxidant activities were investigated using various complementary methods. Results Flower extracts contained a high level of polyphenolics (17.10-52.70 mg GAE/g) and flavonoids (74.20-100.60 mg QE/g), which correlate with its appreciable antioxidant potential in β-carotene peroxidation (IC50 value: 12.50-27.10 μg/mL), DPPH(•) radical-scavenging (IC50 value: 0.20-0.40 mg/mL), Fe(3+ )reducing (EC50 value: 0.10-0.14 mg/mL) and Fe(2+ )chelating (IC50 value: 0.20-0.60 mg/mL) assays. These extracts were effective in inhibiting cancer cell growth (IC50 value: 62.0-63.25 μg/mL). Besides, the ethyl acetate extract inhibited phospholipase A2 activity (IC50 value: 2.97 mg/mL) and reduced the paw oedema in mice (from 0.38 ± 0.01 to 0.24 ± 0.01 cm), 4 h post-carrageenan challenge. Conclusion These data suggest that D. simplex may be useful as a candidate in the treatment of inflammation and the colon cancer.

  9. Panretinal photocoagulation versus panretinal photocoagulation plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy

    Science.gov (United States)

    Zhou, Ai-Yi; Zhou, Chen-Jing; Yao, Jing; Quan, Yan-Long; Ren, Bai-Chao; Wang, Jian-Ming

    2016-01-01

    AIM To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab (IVB) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study criteria. METHODS The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP (PRP group) or PRP plus intravitreal injection of 1.25 mg of bevacizumab (PRP-Plus group). Patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), intraocular pressure (IOP), and new vessel size in fluorescein angiography (FA) and optical coherence tomography for the assessment of central subfield macular thickness (CSMT) at baseline and at weeks 12 (±2), 16 (±2), 24 (±2) and 48 (±2). Main outcome measures also included vitreous clear-up time and neovascularization on the disc (NVD) regression time. Adverse events associated with intravitreal injection were investigated. RESULTS Thirty consecutive patients (n=36 eyes) completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations (NVs), BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group (P<0.05). Patients received an average of 1.3 injections (range: 1-2). Ten eyes (27.8%) underwent 2 injections. Two eyes had ocular

  10. Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2009-09-01

    Full Text Available Abstract Background Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH3/B6/F10, originally subcloned from GH3 cells based on its ability to express high levels of the membrane estrogen receptor-α. Methods We measured the proliferative effects of these phytoestrogens using crystal violet staining, the activation of several mitogen-activated protein kinases (MAPKs and their downstream targets via a quantitative plate immunoassay, and caspase enzymatic activities. Results Four phytoestrogens (coumestrol, daidzein, genistein, and trans-resveratrol were studied over wide concentration ranges. Except trans-resveratrol, all phytoestrogens increased GH3/B6/F10 cell proliferation at some concentration relevant to dietary levels. All four phytoestrogens attenuated the proliferative effects of estradiol when administered simultaneously. All phytoestrogens elicited MAPK and downstream target activations, but with time course patterns that often differed from that of estradiol and each other. Using selective antagonists, we determined that MAPKs play a role in the ability of these phytoestrogens to elicit these responses. In addition, except for trans-resveratrol, a serum removal-induced extrinsic apoptotic pathway was blocked by these phytoestrogens. Conclusion Phytoestrogens can block physiological estrogen-induced tumor cell growth in vitro and can also stimulate growth at high dietary concentrations in the absence of endogenous estrogens; these actions are correlated with slightly different signaling response patterns. Consumption of these compounds should be considered in strategies to control endocrine tumor cell

  11. GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Tao; Meng, Lingjun [Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030 (United States); Tsai, Robert Y.L., E-mail: rtsai@ibt.tamhsc.edu [Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030 (United States)

    2011-10-22

    Highlights: {yields} Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. {yields} Cell type-dependent synergy between MPA and anti-proliferative agents. {yields} The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. {yields} The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

  12. The Germinative Epithelium of Sheep Vibrissae and Wool Follicles has Extensive Proliferative Potential but is Dependent on the Dermal Papilla

    Science.gov (United States)

    Rufaut, Nicholas W; Goldthorpe, Nicole T; Craven, Anthony J; Wallace, Olivia AM; Wildermoth, Janet E; Nixon, Allan J

    2012-01-01

    Aim: To investigate the growth potential of keratinocytes derived from the germinative epithelium (GE) of ovine hair follicles. Stem cells from the outer root sheath (ORS) of hair follicles migrate to the GE in the lower follicle where they proliferate and differentiate to form the hair fiber. It has been suggested that the GE comprises transit-amplifying cells and that the duration of anagen is determined by their limited proliferative potential. However, we show here that keratinocytes derived from the GE of ovine follicles grow extensively in vitro, arguing against this hypothesis. Materials and Methods: Primary cultures of keratinocytes were initiated from microdissected GE tissue from ovine vibrissae and wool follicles. Clonal lines of keratinocytes were derived by limiting dilution. Their growth potential was determined by exhaustive serial passaging. Expression of differentiation markers was evaluated by real-time polymerase chain reaction. Results: Initiation of these cultures required that interaction between the GE and dermal papilla was maintained. However, the keratinocytes could subsequently be cloned and were grown as pure cell populations for 26-52 cell doublings. This proliferative potential is several orders of magnitude greater than required to maintain a single anagen phase. The keratinocytes were indistinguishable from ORS keratinocytes from the same follicles, expressing K14 while undifferentiated, and upregulating the epidermal and inner root sheath markers, loricrin and KRT27 on differentiation. Thus, these cells initially depend on papilla-derived signals to grow, but can revert to an ORS-like phenotype in vitro. Their extensive proliferative capacity shows that the GE is not an exclusively transit-amplifying cell population. PMID:23180913

  13. Proliferative effect of whey from cows' milk varying in phyto-oestrogens in human breast and prostate cancer cells.

    Science.gov (United States)

    Nielsen, Tina S; Höjer, Annika; Gustavsson, Anne-Maj; Hansen-Møller, Jens; Purup, Stig

    2012-05-01

    Intake of dietary phyto-oestrogens has received a great deal of attention owing to their potential influence on hormone-sensitive cancers such as breast and prostate cancer. Cows' milk contains phyto-oestrogens and the content varies according to the composition of the feed and the type and amount of legumes used. In this study we evaluated the proliferative effect of milk (whey) with different phyto-oestrogen content in human breast (MCF-7) and prostate cancer cells (PC-3). Milk was obtained from cows fed either a birdsfoot trefoil-timothy silage based ration (B1) or two different red clover silage based diets (R1 and R2) resulting in total phyto-oestrogen contents of 403, 1659 and 1434 ng/ml for the B1, R1 and R2 diets, respectively. Whey was produced from the milk and added to cell culture medium in concentrations up to 10% for MCF-7 cells and 5% for PC-3 cells. Cell proliferation was measured fluorometrically after 7 d for MCF-7 cells and 5 d for PC-3 cells. There was no significant difference in the proliferative effect of whey from the different dietary treatments at any of the whey concentrations tested. An anti-proliferative effect (Pwhey was seen when tested in the presence of 10 pM oestradiol in the medium. This effect was independent of dietary treatment of cows. Whey induced a significant (Pmilk decreased PC-3 cell proliferation, and therefore the stimulatory effect of whey in PC-3 cells is believed to be mediated by other bioactives than equol. In conclusion, our results suggest that using whey in these proliferation assays, it was not possible to discriminate between milk with high or low levels of phyto-oestrogens.

  14. Matrix proteins from smoke-exposed fibroblasts are pro-proliferative

    NARCIS (Netherlands)

    Krimmer, David I.; Burgess, Janette K.; Wooi, Teh K.; Black, Judith L.; Oliver, Brian G. G.

    2012-01-01

    Airway remodeling decreases lung function in chronic obstructive pulmonary disease (COPD). Extracellular matrix (ECM) deposition is increased in remodeled airways and drives cellular processes of proliferation, migration, and inflammation. We investigated the role of cigarette smoke in altering the

  15. Ki-67 immunoreactivity in meningiomas--determination of the proliferative potential of meningiomas using the monoclonal antibody Ki-67

    DEFF Research Database (Denmark)

    Madsen, C; Schrøder, H D

    1997-01-01

    The proliferative potential of 66 human intracranial meningiomas (15 benign, 15 atypical, 15 recurrent, 13 bone-invasive, and 8 brain-invasive) was investigated by means of immunohisto-chemistry using the monoclonal antibody Ki-67. This antibody recognizes a nuclear antigen present in human cells...... during all active phases of the cell cycle, but absent in the resting phase. The purpose of this retrospective study was to estimate the Ki-67-labelling index (L.I.) and see if this index could help discriminate between the different groups of meningiomas. Our results demonstrated that L.I. could...

  16. Effect of laser photocoagulation and bevacizumab intravitreal in proliferative diabetic retinopathy: review on biomarkers of oxidative stress

    Directory of Open Access Journals (Sweden)

    Andi A. Victor

    2014-06-01

    Full Text Available Background: This study was aimed to compare the effect of laser photocoagulation (LF, intravitreal bevacizumab (IVB and combined treatments on biomarkers of oxidative stress such as aldehhyde dehidrogenase (ALDH, malondialdehyde (MDA level, superoxide dismutase (SOD activities, and vitreal vascular endothelial growth factor (VEGF on proliferative diabetic retinopathy (DR patients.Methods: In this single blind randomized clinical trial, 72 eyes from 69 cases of proliferative DR in Cipto Mangunkusumo Hospital between February 2011 - June 2013 were randomized into 4 groups : 1 control (n = 18; 2 LF pre-vitrectomy (n = 18; 3 IVB pre-vitrectomy (n = 18; and 4 combined IVB and LF pre-vitrectomy (n = 18. One-way ANOVA was used to compare oxidative stress parameters in the four groups.Results: There were no statistically significant differences in the average plasma ALDH activity (0.034 ± 0.02; 0.027 ± 0.02; 0.025 ± 0.02; 0.031 ± 0.11 IU/mg protein; p = 0.66, vitreal MDA level (1.661 ± 1.21; 1.557 ± 1.32; 1.717 ± 1.54; 1.501 ± 1.09 nmol/mL; p = 0.96 and SOD activity (0.403 ± 0.50; 0.210 ± 0.18; 0.399 ± 0.49; 0.273 ± 0.32 U/mL; p = 0.38 among these four groups, respectively. However, the VEGF vitreal level (pg/mL showed a statistically significant difference (0.356 ± 0.60; 0.393 ± 0.45; 0.150 ± 0.24; 0.069 ± 0.13; p = 0.05. The VEGF level in combination group was five times lower than the control group (p = 0.05.Conclusion: Combined treatments of DR by IVB and LF were correlated with lower vitreal MDA and plasma VEGF level, but did not have any effect on plasma ALDH and vitreal SOD in proliferative DR. Combined treatments with IVB and LF are recommended for the management of proliferative DR patients.  

  17. Proliferative responses of blood mononuclear cells (BMNC) in a cohort of elderly humans: role of lymphocyte phenotype and cytokine production

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.;

    2000-01-01

    -old humans and in 91 young controls. Decreased proliferation was associated with a reduced number of true naive CD4(+) cells (CD62L(+)CD45RO(-)). Furthermore, a low IL-2-stimulated proliferation was correlated with a decreased PHA response in the elderly cohort, whereas reciprocal interactions of IL-10......- and IL-2-producing cells were of importance in both elderly and young subjects. Accordingly, a minimum of true naive CD4(+) cells was required for a normal proliferative response to PHA, perhaps by providing sufficient IL-2 which is critical for growth of naive as well as memory cells....

  18. Insulin Promotes Proliferative Vitality and Invasive Capability of Pancreatic Cancer Cells via Hypoxia-inducible Factor 1α Pathway

    Institute of Scientific and Technical Information of China (English)

    汪理; 周伟; 勾善淼; 王统玲; 刘涛; 王春友

    2010-01-01

    This study examined whether insulin-stimulated hypoxia-inducible factor 1α(HIF-1α) expression plays a crucial role in promoting the proliferative vitality and invasive capability in human pancreatic cancer cells.PANC-1 cells were divided into three groups:Control group,insulin group and insulin+YC-1(a pharmacological inhibitor of HIF-1α) group in terms of different treatments.Cells in the insulin group or insulin+YC-1 group were treated with insulin(0.1,1,10 and 100 nmol/L) alone or combined with 3-(5'-hydr...

  19. Evaluation of lincomycin in drinking water for treatment of induced porcine proliferative enteropathy using a Swine challenge model.

    Science.gov (United States)

    Bradford, James R; Winkelman, Nathan L; Moreira, Frederico P; Elfring, Gregory D

    2004-01-01

    A single-location, challenge-model study was conducted to evaluate the effectiveness of lincomycin against porcine proliferative enteropathy when administered through the drinking water at 125 and 250 mg/gallon. The primary variables of interest were pig removal rate, diarrhea scores, demeanor scores, and abdominal appearance scores. Ancillary performance variables examined included average daily feed intake, average daily gain, and feed per gain. After a 3-day acclimation period, pigs were challenged on 2 consecutive days with a mucosal homogenate containing a total dose of 1.4 x 10(9) cells of Lawsonia intracellularis. Five days later, when porcine proliferative enteropathy was well established, drinking water medicated with 125 mg (L125) or 250 mg (L250) lincomycin/gallon was provided to two groups of pigs for 10 days. Pigs were observed for 13 days following the treatment period. A third group of pigs served as controls and received unmedicated drinking water throughout the study. The L250 group experienced a significantly lower (P < .05) pig removal rate than the control group over the 23-day observation period. Additionally, for every primary variable, the L250 group experienced a significantly decreased (P < .01) number of abnormal days compared with the control group. The L125 group showed a significant reduction (P < .05) in abnormal demeanor and abnormal abdominal appearance scores compared with controls.

  20. [Atmospheric electromagnetic field oscillations and the nature of the proliferative process in the focus of acute inflammation].

    Science.gov (United States)

    Kasenov, K U; Brimov, D Zh

    1992-01-01

    Experiments were conducted on 300 rats kept in a warm room (16-18 degrees C) in the cold season of a year to study the influence of a signal effect of atmospheric processes, namely changes in of atmospheric electricity parameters, on the early proliferative reactions in a focus of acute inflammation. The results of 50 experiments on which a geomagnetic storm was superimposed were excluded form the analysis subsequently. Inflammation was modelled by implanting a 3 x 4-mm piece of a cover glass under the skin. Following 48 hours the number of hematogenic and histiogenic cells superimposed on one surface of the implanted glass was counted. These were fibroblasts, macrophages, polynuclear and giant cells. An analysis showed that frosty weather, the existence and direction of a wind, atmospheric-electrical processes preceding the passage of meteorological fronts influenced the nature of proliferative responses. The authors revealed the efficacy of electromagnetic screening of the animals, which mitigated the effect of the atmospheric electromagnetic waves.

  1. Content of endoplasmic reticulum and Golgi complex membranes positively correlates with the proliferative status of brain cells.

    Science.gov (United States)

    Silvestre, David C; Maccioni, Hugo J F; Caputto, Beatriz L

    2009-03-01

    Although the molecular and cellular basis of particular events that lead to the biogenesis of membranes in eukaryotic cells has been described in detail, understanding of the intrinsic complexity of the pleiotropic response by which a cell adjusts the overall activity of its endomembrane system to accomplish these requirements is limited. Here we carried out an immunocytochemical and biochemical examination of the content and quality of the endoplasmic reticulum (ER) and Golgi apparatus membranes in two in vivo situations characterized by a phase of active cell proliferation followed by a phase of declination in proliferation (rat brain tissue at early and late developmental stages) or by permanent active proliferation (gliomas and their most malignant manifestation, glioblastomas multiforme). It was found that, in highly proliferative phases of brain development (early embryo brain cells), the content of ER and Golgi apparatus membranes, measured as total lipid phosphorous content, is higher than in adult brain cells. In addition, the concentration of protein markers of ER and Golgi is also higher in early embryo brain cells and in human glioblastoma multiforme cells than in adult rat brain or in nonpathological human brain cells. Results suggest that the amount of endomembranes and the concentration of constituent functional proteins diminish as cells decline in their proliferative activity.

  2. Anti-proliferative Effects of Androctonus amoreuxi Scorpion and Cerastes cerastes Snake Venoms on Human Prostate Cancer Cells

    Science.gov (United States)

    Akef, Hassan; Kotb, Nahla; Abo-Elmatty, Dina; Salem, Sayed

    2017-01-01

    The present study evaluated the effects of Androctonus amoreuxi scorpion venom, Cerastes cerastes snake venom and their mixture on prostate cancer cells (PC3). An MTT assay was used to determine the anti-proliferative effect of the venoms, while quantitative real time PCR was used to evaluate the expression of apoptosis-related genes (Bax and Bcl-2). Furthermore, colorimetric assays were used to measure the levels of malondialdehyde (MDA) and antioxidant enzymes. Our results show that the venoms significantly reduced PC3 cell viability in a dose-dependent manner. On the other hand, these venoms significantly decreased Bcl-2 gene expression. Additionally, C. cerastes venom significantly reduced Bax gene expression, while A. amoreuxi venom and a mixture of A. amoreuxi & C. cerastes venoms did not alter Bax expression. Consequently, these venoms significantly increased the Bax/Bcl-2 ratio and the oxidative stress biomarker MDA. Furthermore, these venoms also increased the activity levels of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. Overall, the venoms have cytotoxic and anti-proliferative effects on PC3 cells. PMID:28382285

  3. Classifications for Proliferative Vitreoretinopathy (PVR: An Analysis of Their Use in Publications over the Last 15 Years

    Directory of Open Access Journals (Sweden)

    Salvatore Di Lauro

    2016-01-01

    Full Text Available Purpose. To evaluate the current and suitable use of current proliferative vitreoretinopathy (PVR classifications in clinical publications related to treatment. Methods. A PubMed search was undertaken using the term “proliferative vitreoretinopathy therapy”. Outcome parameters were the reported PVR classification and PVR grades. The way the classifications were used in comparison to the original description was analyzed. Classification errors were also included. It was also noted whether classifications were used for comparison before and after pharmacological or surgical treatment. Results. 138 papers were included. 35 of them (25.4% presented no classification reference or did not use any one. 103 publications (74.6% used a standardized classification. The updated Retina Society Classification, the first Retina Society Classification, and the Silicone Study Classification were cited in 56.3%, 33.9%, and 3.8% papers, respectively. Furthermore, 3 authors (2.9% used modified-customized classifications and 4 (3.8% classification errors were identified. When the updated Retina Society Classification was used, only 10.4% of authors used a full C grade description. Finally, only 2 authors reported PVR grade before and after treatment. Conclusions. Our findings suggest that current classifications are of limited value in clinical practice due to the inconsistent and limited use and that it may be of benefit to produce a revised classification.

  4. Isolation of lignans from Schisandra chinensis with anti-proliferative activity in human colorectal carcinoma: Structure-activity relationships.

    Science.gov (United States)

    Gnabre, John; Unlu, Irem; Chang, Tso-Cheng; Lisseck, Paul; Bourne, Bryan; Scolnik, Ryan; Jacobsen, Neil E; Bates, Robert; Huang, Ru Chih

    2010-10-15

    Separate benzocyclooctadiene lignans were isolated from the berries of Schisandra chinensis in milligram quantities on analytical reverse phase (RP) HPLC by an automated repeat-injection method and shown to have anti-proliferative activity against human colorectal cancer cells. Structures of the compounds were determined by a combination of NMR and mass spectrometry. Stereospecific NMR assignments for gomisin-N and deoxyschisandrin, gave more complete and accurate data than previously reported, based on 600MHz 2D HSQC, DQF-COSY and HMBC data. Comparison of coupling constants and HMBC crosspeak intensities with calculated and X-ray crystal structures confirmed their stereochemistry and conformation. Analysis of structure-activity relationships revealed the importance of key structural determinants. The S-biphenyl configuration of gomisin N, the most active lignan, correlated with increased anti-proliferative activity, while the presence of a hydroxyl group at the C7 position reduced or abolished this activity. Increased activity was also observed when a methylenedioxy group was present between C12 and C13. The percent yield of the most active compounds relative to the starting plant materials was 0.0156% for deoxyschisandrin and 0.0173% for gomisin N. The results of these studies indicate that automated repeat-injection method of analytical HPLC may provide a superior alternative to the standard semi-preparative HPLC techniques for separation of complex mixtures.

  5. Transitory FGF treatment results in the long-lasting suppression of the proliferative response to repeated FGF stimulation.

    Science.gov (United States)

    Poole, Ashleigh; Knowland, Nicholas; Cooper, Emily; Cole, Rebecca; Wang, Hongchuan; Booth, Lucas; Kacer, Doreen; Tarantini, Francesca; Friesel, Robert; Prudovsky, Igor

    2014-05-01

    FGF applied as a single growth factor to quiescent mouse fibroblasts induces a round of DNA replication, however continuous stimulation results in arrest in the G1 phase of the next cell cycle. We hypothesized that FGF stimulation induces the establishment of cell memory, which prevents the proliferative response to repeated or continuous FGF application. When a 2-5 days quiescence period was introduced between primary and repeated FGF treatments, fibroblasts failed to efficiently replicate in response to secondary FGF application. The establishment of "FGF memory" during the first FGF stimulation did not require DNA synthesis, but was dependent on the activity of FGF receptors, MEK, p38 MAPK and NFκB signaling, and protein synthesis. While secondary stimulation resulted in strongly decreased replication rate, we did not observe any attenuation of morphological changes, Erk1/2 phosphorylation and cyclin D1 induction. However, secondary FGF stimulation failed to induce the expression of cyclin A, which is critical for the progression from G1 to S phase. Treatment of cells with a broad range histone deacetylase inhibitor during the primary FGF stimulation rescued the proliferative response to the secondary FGF treatment suggesting that the establishment of "FGF memory" may be based on epigenetic changes. We suggest that "FGF memory" can prevent the hyperplastic response to cell damage and inflammation, which are associated with an enhanced FGF production and secretion. "FGF memory" may present a natural obstacle to the efficient application of recombinant FGFs for the treatment of ulcers, ischemias, and wounds.

  6. A proliferative probiotic Bifidobacterium strain in the gut ameliorates progression of metabolic disorders via microbiota modulation and acetate elevation

    Science.gov (United States)

    Aoki, Ryo; Kamikado, Kohei; Suda, Wataru; Takii, Hiroshi; Mikami, Yumiko; Suganuma, Natsuki; Hattori, Masahira; Koga, Yasuhiro

    2017-01-01

    The gut microbiota is an important contributor to the worldwide prevalence of metabolic syndrome (MS), which includes obesity and diabetes. The anti-MS effects exerted by Bifidobacterium animalis ssp. lactis GCL2505 (BlaG), a highly proliferative Bifidobacterium strain in the gut, and B. longum ssp. longum JCM1217T (BloJ) were comparatively examined. BlaG treatment reduced visceral fat accumulation and improved glucose tolerance, whereas BloJ had no effect on these parameters. Gut microbial analysis revealed that BlaG exerted stronger effects on the overall bacterial structure of the gut microbiota than BloJ, including enrichment of the genus Bifidobacterium. The levels of acetate and glucagon-like peptide-1 were increased by BlaG treatment in both the gut and plasma, but not by BloJ treatment. Correlation analysis suggested that the elevation of gut acetate levels by BlaG treatment plays a pivotal role in the BlaG-induced anti-MS effects. These findings indicated that BlaG, a highly viable and proliferative probiotic, improves metabolic disorders by modulating gut microbiota, which results in the elevation of SCFAs, especially acetate. PMID:28252037

  7. Extranodal manifestation of Rosai-Dorfman disease with bilateral ocular involvement

    Directory of Open Access Journals (Sweden)

    Chayanika Kala

    2011-01-01

    Full Text Available Rosai-Dorfman disease, that is, sinus histiocytosis with massive lymphadenopathy is a benign systemic proliferative disorder of histiocytes. The typical clinical presentation of the disease includes bilateral painless massive lymphadenopathy, fever and polyclonal hypergammaglobulinemia. Extranodal involvement is present in only a few cases and skin lesions are the most common form of extranodal disease. However, purely cutaneous Rosai-Dorfman disease is uncommon. In this study, we describe a 10-year-old child presenting with bilateral ocular involvement.

  8. Age-dependent alterations of the hippocampal cell composition and proliferative potential in the hAβPPSwInd-J20 mouse.

    Science.gov (United States)

    Fu, YuHong; Rusznák, Zoltán; Kwok, John B J; Kim, Woojin Scott; Paxinos, George

    2014-01-01

    The J20 mouse expresses human mutant amyloid-β protein precursor (hAβPPSwInd) and is an established transgenic model of Alzheimer's disease (AD). From the age of 5 months, amyloid-β (Aβ) deposits appear in the hippocampus with concomitant increase of AD-associated features. Although changes occurring after the appearance of Aβ deposits have been extensively studied, very little is known about alterations that occur prior to 5 months. The present study aimed to identify changes in the cellular composition and proliferative potential of the J20 hippocampus using 1-18-month-old mice. Neuronal, non-neuronal, Ki-67+, and TUNEL+ cell numbers were counted with the isotropic fractionator method. Age-dependent changes of the expression of microglia-, astrocyte-, and neurogenesis-specific markers were sought in the entire hippocampus. Several transgene-associated changes were revealed before the appearance of Aβ deposits. The number of proliferating cells decreased whereas the number of microglia clusters increased as early as 4 weeks of age. The neurogenesis was also impaired in the dentate gyrus of 7-11-week-old J20 mice. A statistically significant negative correlation was found between the number of proliferating cells and age in both populations, but the time course of the age-dependence was steeper in wild-type than in J20 mice. Negative age-dependence was noted when the number of cells committed to apoptosis was examined. Our results indicate that overexpression of mutant hAβPP initiates a cascade of pathologic events well before the appearance of visible Aβ plaques. Accordingly, early signs of AD include reduced cell proliferation, impaired neurogenesis, and increased activity of microglia in the hippocampus.

  9. Unicentric Castleman’s Disease Masquerading Pancreatic Neoplasm

    Directory of Open Access Journals (Sweden)

    Saurabh Jain

    2012-01-01

    Full Text Available Castleman’s disease is a rare nonclonal proliferative disorder of the lymph nodes with an unknown etiology. Common locations of Castleman’s disease are mediastinum, neck, axilla, and abdomen. Castleman’s disease of a peripancreatic location masquerading as pancreatic neoplasm is an even rarer entity. On search of published data, we came across about 17 cases published on peripancreatic Castleman’s disease until now. Here we are reporting a case of retropancreatic Castleman's disease masquerading as retroperitoneal neoplasm in a 46-year-old male patient.

  10. Furanodiene presents synergistic anti-proliferative activity with paclitaxel via altering cell cycle and integrin signaling in 95-D lung cancer cells.

    Science.gov (United States)

    Xu, Wen-Shan; Dang, Yuan-Ye; Chen, Xiu-Ping; Lu, Jin-Jian; Wang, Yi-Tao

    2014-02-01

    Furanodiene (FUR) is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents anti-proliferative activities in several cancer cell lines. Recently, we found that the combined treatment of FUR with paclitaxel (TAX) showed synergetic anti-proliferative activities in 95-D lung cancer cells. Herein, we showed that FUR reduced the cell numbers distributed in mitosis phase induced by TAX while increased those in G1 phase. The protein levels of cyclin D1, cyclin B1, CDK6 and c-Myc were all down-regulated in the group of combined treatment. The dramatically down-regulated expression of integrin β4, focal adhesion kinase and paxillin might partially contribute to the synergic effect. Though FUR alone obviously induced endoplasmic reticulum stress, this signaling pathway may not contribute to the synergetic anti-proliferative effect as the protein expression of CHOP and BIP was similar in FUR alone and combined treatment group.

  11. Evaluation of the proliferative activity of immunocompetent cells in the jejunal and iliac lymph nodes of prepubertal female wild boars diagnosed with mixed mycotoxicosis

    Directory of Open Access Journals (Sweden)

    Zielonka Łukasz

    2015-06-01

    Full Text Available The study evaluated the proliferative activity of immunocompetent cells in the jejunal and iliac lymph nodes of prepubertal female wild boars exposed to deoxynivalenol and zearalenone in naturally contaminated feed. The evaluation was performed with the use of the MTT assay and 2 mitogens: lipopolysaccharide (LPS and concanavalin A. Intensified proliferative processes in T and B lymphocytes were revealed. The mitogenic activity of LPS was more expressed in the lymphocytes of both iliac and jejunal lymph nodes in comparison with the control group. Proliferative activity was higher in iliac lymph nodes than in jejunal lymph nodes. A reverse trend was observed in the percentage of live cells, which was higher in jejunal lymph nodes during the evaluation of lymphocyte proliferation.

  12. Automatic detection Non-proliferative Diabetic Retinopathy using image processing techniques

    Directory of Open Access Journals (Sweden)

    RajuS. Maher

    2016-01-01

    Full Text Available Diabetes is a chronic disease that is reaching epidemic proportions worldwide. There are currently more than 190 million people with diabetes worldwide. The World Health Organization (WHO estimates that this will rise to 221 million by the year 2010, largely due to population growth, ageing, urbanization and a sedentary lifestyle. Diabetes is currently the fourth main cause of death in most developed countries. In Singapore, the prevalence of diabetes in our population is 8.2% according to the 2004 National Health Survey. This is expected to grow as our population age. Diabetic Retinopathy, if not well managed and controlled, can progress steadily to devastating complications like blindness. At present, various analyses on complicated interaction between hereditary and environmental factors are being undertaken regarding the onset of diabetes. The development of diabetic complication has become a major concern regarding the prognosis of diabetic patients. Diabetes Retinopathy is one of the most common diseases that people get affected by over the years. By doing this paper, we hope to detect the stages of Diabetic Retinopathy as early as possible so as to prevent and cure more Singaporeans from falling prey to this disease.

  13. Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

    Science.gov (United States)

    Bayala, Bagora; Bassole, Imaël Henri Nestor; Gnoula, Charlemagne; Nebie, Roger; Yonli, Albert; Morel, Laurent; Figueredo, Gilles; Nikiema, Jean-Baptiste; Lobaccaro, Jean-Marc A; Simpore, Jacques

    2014-01-01

    This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78%) and β-caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor (12.730%), α-pinene (6.87%) and trans α-bergamotene (5.32%) for Ocimum americanum; β-caryophyllene (21%), α-pinene (20.11%), sabinene (10.26%), β-pinene (9.22%) and α-phellandrene (7.03%) for Hyptis spicigera; p-cymene (25.27%), β-caryophyllene (12.70%), thymol (11.88), γ-terpinene (9.17%) and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum conyzoides; eucalyptol (59.55%), α-pinene (9.17%) and limonene (8.76%) for Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene (8.40%), β-bisabolene (7.83%) and β-sesquiphellandrène (5.34%) for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides

  14. Chemical Composition, Antioxidant, Anti-Inflammatory and Anti-Proliferative Activities of Essential Oils of Plants from Burkina Faso

    Science.gov (United States)

    Bayala, Bagora; Bassole, Imaël Henri Nestor; Gnoula, Charlemagne; Nebie, Roger; Yonli, Albert; Morel, Laurent; Figueredo, Gilles; Nikiema, Jean-Baptiste; Lobaccaro, Jean-Marc A.; Simpore, Jacques

    2014-01-01

    This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography–mass spectrometry and gas chromatography–flame ionization detector. Major constituents were α-terpineol (59.78%) and β-caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor (12.730%), α-pinene (6.87%) and trans α-bergamotene (5.32%) for Ocimum americanum; β-caryophyllene (21%), α-pinene (20.11%), sabinene (10.26%), β-pinene (9.22%) and α-phellandrene (7.03%) for Hyptis spicigera; p-cymene (25.27%), β-caryophyllene (12.70%), thymol (11.88), γ-terpinene (9.17%) and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum conyzoides; eucalyptol (59.55%), α-pinene (9.17%) and limonene (8.76%) for Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene (8.40%), β-bisabolene (7.83%) and β-sesquiphellandrène (5.34%) for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides

  15. Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression

    Directory of Open Access Journals (Sweden)

    Hanamura Ichiro

    2006-10-01

    Full Text Available Abstract Background A high proliferative capacity of tumor cells usually is associated with shortened patient survival. Disruption of the RB pathway, which is critically involved in regulating the G1 to S cell cycle transition, is a frequent target of oncogenic events that are thought to contribute to increased proliferation during tumor progression. Previously, we determined that p18INK4c, an essential gene for normal plasma cell differentiation, was bi-allelically deleted in five of sixteen multiple myeloma (MM cell lines. The present study was undertaken to investigate a possible role of p18INK4c in increased proliferation of myeloma tumors as they progress. Results Thirteen of 40 (33% human myeloma cell lines do not express normal p18INK4c, with bi-allelic deletion of p18 in twelve, and expression of a mutated p18 fragment in one. Bi-allelic deletion of p18, which appears to be a late progression event, has a prevalence of about 2% in 261 multiple myeloma (MM tumors, but the prevalence is 6 to10% in the 50 tumors with a high expression-based proliferation index. Paradoxically, 24 of 40 (60% MM cell lines, and 30 of 50 (60% MM tumors with a high proliferation index express an increased level of p18 RNA compared to normal bone marrow plasma cells, whereas this occurs in only five of the 151 (3% MM tumors with a low proliferation index. Tumor progression is often accompanied by increased p18 expression and an increased proliferation index. Retroviral-mediated expression of exogenous p18 results in marked growth inhibition in three MM cell lines that express little or no endogenous p18, but has no effect in another MM cell line that already expresses a high level of p18. Conclusion Paradoxically, although loss of p18 appears to contribute to increased proliferation of nearly 10% of MM tumors, most MM cell lines and proliferative MM tumors have increased expression of p18. Apart from a small fraction of cell lines and tumors that have inactivated

  16. Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

    Directory of Open Access Journals (Sweden)

    Bagora Bayala

    Full Text Available This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78% and β-caryophyllene (10.54% for Ocimum basilicum; 1, 8-cineol (31.22%, camphor (12.730%, α-pinene (6.87% and trans α-bergamotene (5.32% for Ocimum americanum; β-caryophyllene (21%, α-pinene (20.11%, sabinene (10.26%, β-pinene (9.22% and α-phellandrene (7.03% for Hyptis spicigera; p-cymene (25.27%, β-caryophyllene (12.70%, thymol (11.88, γ-terpinene (9.17% and thymyle acetate (7.64% for Lippia multiflora; precocene (82.10%for Ageratum conyzoides; eucalyptol (59.55%, α-pinene (9.17% and limonene (8.76% for Eucalyptus camaldulensis; arcurcumene (16.67%, camphene (12.70%, zingiberene (8.40%, β-bisabolene (7.83% and β-sesquiphellandrène (5.34% for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides showed the

  17. Mitogenic and anti-proliferative activity of a lectin from the tubers of Voodoo lily (Sauromatum venosum).

    Science.gov (United States)

    Singh Bains, Jagmohan; Singh, Jatinder; Kamboj, Sukhdev Singh; Nijjar, Kamaljeet Kaur; Agrewala, Javed N; Kumar, Vinod; Kumar, Ashok; Saxena, A K

    2005-05-25

    A new lectin with the potent mitogenic and in vitro anti-proliferative activity was isolated from the tubers of a wild monocotyledonous plant Sauromatum venosum (Schott), from the family Araceae, by affinity chromatography on the asialofetuin linked amino-activated silica beads. The apparent native molecular mass of S. venosum lectin (SVL), as determined by gel filtration chromatography, was 54 kDa. In HPLC, size exclusion and cation exchange chromatography, SVL gave a single peak and also a single band of 13.5 kDa in SDS-PAGE, pH 8.3, under reducing and non-reducing conditions, indicating that the lectin is composed of four identical subunits. S. venosum lectin agglutinated rabbit, rat, sheep and guinea pig erythrocytes but reacted with goat erythrocytes after the neuraminidase treatment. However, SVL was unable to agglutinate human ABO blood group erythrocytes even after treatment with neuraminidase. SVL was inhibited by N-acetyl-D-Lactosamine (LacNAc), which is an important marker in various carcinomas and a complex desialylated glycoprotein, asialofetuin. The amino acid composition showed that lectin contained a high amount of aspartic acid and glycine but totally devoid of cysteine. However, trace amounts of methionine was present. The lectin showed a potent mitogenic response towards BALB/c splenocytes and human lymphocytes. As the mitogenic stimulation was more than that of Con A, a standard well-known plant mitogen and the response of this lectin was almost double than that of Con A. This lectin is endowed with proliferation of T cells as revealed by IL-2 bioassay but showed no production of immunoglobulins thus indicating the non-stimulation of B cells. SVL significantly inhibited the proliferation of murine cancer cell-lines, i.e., WEHI-279 to 84.6%, J774 to 81%, P388D1 to 74% and A-20 to 47%. In addition, the in vitro anti-proliferative activity of SVL was also evaluated against nine human cancer cell lines representing different organs and tissues

  18. Proliferative activity (MIB-1 index) is an independent prognostic parameter in patients with high-grade soft tissue sarcomas of subtypes other than malignant fibrous histiocytomas

    DEFF Research Database (Denmark)

    Jensen, V; Sørensen, Flemming Brandt; Bentzen, S M;

    1998-01-01

    AIMS: To evaluate the prognostic value of tumour proliferative activity, p53 accumulation and bcl-2 expression in a retrospective series of 216 patients with soft tissue sarcomas (STS). METHODS AND RESULTS: The immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tissue....... The proliferative activity was assessed by use of the monoclonal antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. The percentage of proliferating cells (the MIB-1 index) ranged between 1% and 85% (median 12%). A significant increase in mean MIB-1 index was seen with increasing...

  19. Effects of breed and zeranol implantation on serum insulin, somatomedin-like activity and fibroblast proliferative activity.

    Science.gov (United States)

    Wangsness, P J; Olsen, R F; Martin, R J

    1981-01-01

    Twenty-eight Suffolk-sired (Sx) and 28 Finnsheep-sired (Fx) lambs were implanted with either 0 or 12 mg zeranol. Zeranol significantly increased average daily gain over that of controls. Serum taken at biweekly intervals for 6 weeks was assayed for insulin, somatomedin-like activity (Sm) and fibroblast proliferative activity (FPA). Insulin appeared to increase with time, but there were no consistent time changes for FPA or Sm. Serum insulin concentration was higher (P less than .05) in implanted lambs than in controls (33.4 vs 25.6 microU/ml). Unlike insulin, serum Sm and FPA were not affected by zeranol implantation, and, thus, these serum factors appeared not to be involved in zeranol-stimulated growth. Sm was higher in the faster growing Sx lambs than in the slower growing Fx lambs. Thus, serum Sm activity may be involved in normal regulation of growth.

  20. INTENSITY OF APOPTOTIC AND PROLIFERATIVE EVENTS IN LYMPHOCYTES UNDER DYSLIPIDEMIC CONDITIONS AT EARLY STAGES OF CHRONIC BRAIN ISCHEMIA

    Directory of Open Access Journals (Sweden)

    A. V. Zurochka

    2014-01-01

    Full Text Available Incidence of different types of dislipoproteinemias (DLPs and a balance between apoptosis andproliferation of lymphocytes were studied in males exhibiting initial manifestations of cerebral blood flowinsufficiency (ICBI. In general, high intensity of lymphocyte activation was revealed in patients with ICBI,with amplified proliferative potential demonstrable in this group. We have also shown a trend to increasednumbers of T and B lymphocytes expressing antiapoptogenic bcl-2 protein. The changes in apoptosis and cellproliferation intensity were more pronounced in IIA and IIB types of DLP. In these groups, unidirectionalchanges of FasR expression were observed. However, the parameters reflecting readiness to apoptosis werechanged multidirectionally. Cholesterol and oxysterols transported to the cells under excessive dyslipidemiamay influence activities of transcription factor genes (bcl-2, Fas-regulatory gene (TDAG51, thus, probably,causing an imbalance between cellular proliferation and apoptosis.

  1. STUDY ON PERIPHERAL BLOOD MONONUCLEAR CELL(PBMC) PROLIFERATIVE RESPONSES TO DIFFERENT HCV ANTIGENS IN PATIENTS WITH HEPATITIS C

    Institute of Scientific and Technical Information of China (English)

    窦骏; 刘克洲; 陈智; 沃建尔; 何南祥; 徐陈槐; 章明太; 王信子

    1999-01-01

    To explore the cellular immune function in patients with hepatitis C and study the HCV pathogenic mechanism and immune protection effect against HCV infection in host. PBMC proliferative responses in vitro to HCV synthetic peptides (Cp9, Ns4) and recombinant HCV proteins (C,E1 ,E2 ,NS3) were evaluated in 21 patients with chronic hepatitis C and 3 patients with acute hepatitis C. Phenotypic characteristics of proliferating cells in PBMC were detected by FACS after PBMC were stimulated with HCV antigens. Results showed that lymphoproliferative responses of PBMC from patients with hepatitis C to synthetic peptides (Cp9, NS4) and rccombinant proteins (C,E1 ,E2 and NS3) were detected and its stimulation index(SI) were 1.69±0.51, 1. 61±0.54, 1. 68±0.58,1. 49±0.44, 1.44±0.44 and 1. 33±0. 33 respectively. Two out of three patients with acute hepatitis C had efficient lymphoproliferative response to HCV antigens (SI≥2. 1) and their serum HCV-RNA were seroconversion and serum ALT values were returned to normal when studied. Phenotype analysis showed that phenotypic characteristics of proliferating cells was CD4+ lymphocytes and CD8+ lymphocytes proliferative responses was less than that of CD4+ lymphocytes. The results indicate that PBMC from patients with hepatitis C exist proliferative responses to different HCV antigens. CD4+ lymphocytes proliferative response is greater than that of CD8+ lymphocytes. The efficient lymphoproliferative responses to HCV antigens in patients with acute hepatitis C suggests that the patients possibly have a good clinical prognosis.%为探讨丙型肝炎(HC)病人细胞免疫功能和丙型肝炎病毒(HCV)的致病机制及机体对其免疫保护作用,收集24例HC病人(急性3例,慢性21例),用3H-TdR掺入法研究病人外周血单个核细胞(PBMC)对不同HCV抗原增殖反应,并用流式细胞仪(FACS)检测了PBMC中CD4+、CD8+淋巴细胞亚群在HCV抗原刺激后的变化.结果:HC病人PBMC对HCV合成肽CP9,NS

  2. Stathmin 1 is involved in the highly proliferative phenotype of high-risk myelodysplastic syndromes and acute leukemia cells.

    Science.gov (United States)

    Machado-Neto, João Agostinho; de Melo Campos, Paula; Favaro, Patricia; Lazarini, Mariana; Lorand-Metze, Irene; Costa, Fernando Ferreira; Olalla Saad, Sara Teresinha; Traina, Fabiola

    2014-02-01

    Stathmin 1 is an important cytoplasmic microtubule-destabilizing protein that plays critical roles in proliferation and accurate chromosome segregation through regulation of microtubule dynamics. High levels of Stathmin 1 expression have been reported in leukemia and solid tumors. However, Stathmin 1 has not been studied in myelodysplastic syndrome cells. We, herein, report that significantly higher Stathmin 1 levels were observed in proliferating hematopoietic cells, in high-risk MDS and acute leukemia cells. In addition, Stathmin 1 silencing in U937 and Namalwa leukemia cells reduced cell proliferation and clonogenicity. Our data suggest that Stathmin 1 expression may be related to the highly proliferative phenotype of hematopoietic cells and add new insights into the participation of Stathmin 1 in hematological malignancies.

  3. Exercise but not prostanoids enhance levels of vascular endothelial growth factor and other proliferative agents in human skeletal muscle interstitium

    DEFF Research Database (Denmark)

    Höffner, Lotte; Nielsen, Jens Jung; Langberg, Henning;

    2003-01-01

    young males. The subjects performed one-legged knee extensions (20 W). The concentration of VEGF in the 960 kDa dialysate was greater (P ...In the present study we examined whether exercise and prostanoids have an effect on the muscle interstitial concentration of vascular endothelial growth factor (VEGF) and on the proliferative effect of muscle interstitial fluid. Dialysate from resting and exercising human skeletal muscle, obtained...... either during control conditions or during cyclooxygenase inhibition, was examined for its content of VEGF and for its effect on endothelial cell proliferation. Microdialysis probes with high (960 kDa) and low (5 kDa) molecular-mass cut-off membranes were placed in the vastus lateralis muscle of healthy...

  4. Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.

    Science.gov (United States)

    Lobb, Karen L; Hipskind, Philip A; Aikins, James A; Alvarez, Enrique; Cheung, Yiu-Yin; Considine, Eileen L; De Dios, Alfonso; Durst, Gregory L; Ferritto, Rafael; Grossman, Cora Sue; Giera, Deborah D; Hollister, Beth A; Huang, Zhongping; Iversen, Philip W; Law, Kevin L; Li, Tiechao; Lin, Ho-Shen; Lopez, Beatriz; Lopez, Jose E; Cabrejas, Luisa M Martin; McCann, Denis J; Molero, Victoriano; Reilly, John E; Richett, Michael E; Shih, Chuan; Teicher, Beverly; Wikel, James H; White, Wesley T; Mader, Mary M

    2004-10-21

    Two closely related diaryl acylsulfonamides were recently reported as potent antitumor agents against a broad spectrum of human tumor xenografts (colon, lung, breast, ovary, and prostate) in nude mice. Especially intriguing was their activity against colorectal cancer xenografts. In this paper, rapid parallel synthesis along with traditional medicinal chemistry techniques were used to quickly delineate the structure-activity relationships of the substitution patterns in both phenyl rings of the acylsufonamide anti-proliferative scaffold. Although the molecular target of the compounds remains unclear, we determined that the vascular endothelial growth factor-dependent human umbilical vein endothelial cells assay in combination with a soft agar disk diffusion assay allowed for optimization of potency in the series. The pharmacokinetic properties and in vivo activity in an HCT116 xenograft model are reported for representative compounds.

  5. Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents.

    Science.gov (United States)

    Eldehna, Wagdy M; Almahli, Hadia; Al-Ansary, Ghada H; Ghabbour, Hazem A; Aly, Mohamed H; Ismael, Omnia E; Al-Dhfyan, Abdullah; Abdel-Aziz, Hatem A

    2017-12-01

    Treatment of patients with triple-negative breast cancer (TNBC) is challenging due to the absence of well- defined molecular targets and the heterogeneity of such disease. In our endeavor to develop potent isatin-based anti-proliferative agents, we utilized the hybrid-pharmacophore approach to synthesize three series of novel isatin-based hybrids 5a-h, 10a-h and 13a-c, with the prime goal of developing potent anti-proliferative agents toward TNBC MDA-MB-231 cell line. In particular, compounds 5e and 10g were the most active hybrids against MDA-MB-231 cells (IC50 = 12.35 ± 0.12 and 12.00 ± 0.13 μM), with 2.37- and 2.44-fold increased activity than 5-fluorouracil (5-FU) (IC50 = 29.38 ± 1.24 μM). Compounds 5e and 10g induced the intrinsic apoptotic mitochondrial pathway in MDA-MB-231; evidenced by the reduced expression of the anti-apoptotic protein Bcl-2, the enhanced expression of the pro-apoptotic protein Bax and the up-regulated active caspase-9 and caspase-3 levels. Furthermore, 10g showed significant increase in the percent of annexin V-FITC positive apoptotic cells from 3.88 to 31.21% (8.4 folds compared to control).

  6. Relationship of serum somatomedin-like activity and fibroblast proliferative activity with age and growth in the rat.

    Science.gov (United States)

    Olsen, R F; Wangsness, P J; Patton, W H; Martin, R J

    1980-03-01

    An assay for fibroblast proliferative activity (FPA) using human lung fibroblasts, WI-38, was described. The assay was responsive to varying rat serum levels and was not influenced by direct growth hormone (GH) addition. The relationship of serum growth factors to age and body weight was examined in the rat. In study 1, serum was obtained from lean Zucker rats at 3, 5, 7, 9, 11 and 30 wk of age. Six samples were taken at each age and serum samples were analyzed for somatomedin-like activity (Sm) and fibroblast proliferative activity (FPA). Serum Sm was not different at any of the sampling ages. FPA was low at 3 wk, but was higher and constant from 5 wk to 30 wk. In study 2, 73 lean Zucker rats (7 wk of age) were maintained on laboratory chow and water ad libitum for 4 wk, and then serum was obtained by decapitation. The rats were ranked according to each of four different criteria: average daily gain (ADG) for the duration of the study, ADG for the fourth week, total body protein and total body fat. Serum Sm, FPA and insulin concentrations on the top 10 and bottom 10 rats of each ranking were compared. Neither FPA nor insulin was significantly different for any ranking. Serum Sm was significantly higher in the top 10 rats ranked by ADG for the duration of the study. Sm was not significantly different in rats ranked by body weight, total body protein or total body fat. The data suggest that serum somatomedin-like activity (Sm) may be important in the earlier stages of growth in rats.

  7. Potential Anti-proliferative and Immunomodulatory Effects of Marine Microalgal Exopolysaccharide on Various Human Cancer Cells and Lymphocytes In Vitro.

    Science.gov (United States)

    Park, Geon-Tae; Go, Ryeo-Eun; Lee, Hae-Miru; Lee, Geum-A; Kim, Cho-Won; Seo, Jeong-Woo; Hong, Won-Kyung; Choi, Kyung-Chul; Hwang, Kyung-A

    2017-02-04

    Marine microalgal exopolysaccharides (EPSs) have drawn great attention due to their biotechnological potentials such as anti-viral, anti-oxidant, anti-lipidemic, anti-proliferative, and immunomodulatory activities, etc. In the present study, the EPS derived from microalgae Thraustochytriidae sp.-derived mutant GA was investigated for its anti-proliferation and immunomodulation. Anti-cancer efficacy of the microalgal EPS was examined for the alterations in cell proliferation and cell cycle-related gene expression that occur in three types of human cancer cell lines, BG-1 ovarian, MCF-7 breast, and SW-620 colon cancer cell lines, by its treatment. Alterations in immunoreactivity by the microalgal EPS were examined by measuring its influence on the growth of T and B lymphocytes and cytokine production of T cells. In cell viability assay, the microalgal EPS inhibited cancer cell growth at the lowest concentration of 10(-11) dilution and in a dose-responsive manner within the range of dilution of 10(-11)~10(-3). In addition, the protein expression of cell cycle progression genes such as cyclin D1 and E in these cancer cell lines was significantly reduced by the microalgal EPS in a dose- and a time-dependant manner. In cell proliferation assay using T and B cells, the microalgal EPS induced B cell proliferation even at the lowest dilution of 10(-11), but not T cells. In cytokine assay, the microalgal EPS decreased the formation of IL-6 and INF-γ at 10(-3) dilution compared to the control and had no significant effects on TNF-α. Collectively, these findings suggest that the EPS derived from microalgae Thraustochytriidae sp. GA has an anti-proliferative activity against cancer cells and an immunomodulatory effect by having an influence on B cell proliferation and cytokine secretion of T cells.

  8. Oncogenic Role of Skp2 and p27Kip1 in Intraductal Proliferative Lesions of the Breast

    Institute of Scientific and Technical Information of China (English)

    Yan Lv; Yun Niu; Xiu-min Ding; Xu-qi Xiao

    2012-01-01

    Objective To investigate whether the connection of p27Kip1 to S-phase kinase-associated protein 2 (Skp2) plays an oncogenic role in intraductal proliferative lesions of the breast.Methods Here we investigated the mechanism involved in association of Skp2's degradation of p27Kip1 With the breast carcinogenesis by immunohistochemical method through detection of Skp2 and p27Kip1 protein levels in 120 paraffin-embedded tissues of intraductal proliferative lesions including usual ductal hyperplasia (UDH,n=30),atypical ductal hyperplasia (n=30),flat epithelial atypia (FEA,n=30),and ductal carcinoma in situ (DCIS,n=30).Moreover,the expression status of Skp2 and p27Kip1 in 30 cases of the normal breast paraffin-embedded tissues were explored.Results The DCIS group was with the highest Skp2 level and the lowest p27Kip1 level,and the UDH group was with the lowest Skp2 level and the highest p27Kip1 level.Both Skp2 and p27Kip1 levels in the DCIS group were significantly different from those in the UDH group (all P<0.01).The levels of Skp2 and p27Kip1 in the FEA group were significantly different from both the DCIS and UDH groups (all P<0.05).p27Kip1 was negatively correlated with Skp2 in both the UDH group (r=-0.629,P=0.026) and DCIS group (r=-0.893,P=0.000).Conclusion Overexpression of Skp2 might be the mechanism underlying p27Kip1 over degradation.

  9. Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Tercia Rodrigues [Universidade do Estado do Rio de Janeiro (UERJ), Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biologia Celular, Laboratorio de Biologia da Celula Endotelial e da Angiogenese (LabAngio), Rio de Janeiro (Brazil); Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Carvalho da Fonseca, Anna Carolina [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Nunes, Sara Santana; Oliveira da Silva, Aline [Universidade do Estado do Rio de Janeiro (UERJ), Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biologia Celular, Laboratorio de Biologia da Celula Endotelial e da Angiogenese (LabAngio), Rio de Janeiro (Brazil); Dubois, Luiz Gustavo Feijo; Faria, Jane; Kahn, Suzana Assad [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Viana, Nathan Bessa [Universidade Federal do Rio de Janeiro, Laboratorio de Pincas Oticas, Coordenacao de Programas de Estudos Avancados, Instituto de Ciencias Biomedicas, Rio de Janeiro (Brazil); Universidade Federal do Rio de Janeiro, Instituto de Fisica, Rio de Janeiro (Brazil); Marcondes, Jorge [Universidade Federal do Rio de Janeiro, Hospital Universitario Clementino Fraga Filho, Servico de Neurocirurgia, Rio de Janeiro (Brazil); Legrand, Chantal [Institut Universitaire d' Hematologie, Universite Paris-Diderot, Paris 7, INSERM U553, Paris (France); Moura-Neto, Vivaldo [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); and others

    2011-09-10

    The extracellular matrix (ECM) contains important cues for tissue homeostasis and morphogenesis. The matricellular protein tenascin-C (TN-C) is overexpressed in remodeling tissues and cancer. In the present work, we studied the effect of different ECM-which exhibited a significant diversity in their TN-C content-in endothelial survival, proliferation and tubulogenic differentiation: autologous (endothelial) ECM devoid of TN-C, but bearing large amounts of FN; fibroblast ECM, bearing both high TN-C and FN contents; and finally, glioma-derived matrices, usually poor in FN, but very rich in TN-C. HUVECs initially adhered to the immobilized matrix produced by U373 MG glioma cells, but significantly detached and died by anoikis (50 to 80%) after 24 h, as compared with cells incubated with endothelial and fibroblast matrices. Surviving endothelial cells (20 to 50%) became up to 6-fold more proliferative and formed 74-97% less tube-like structures in vitro than cells grown on non-tumoral matrices. An antibody against the EGF-like repeats of tenascin-C (TN-C) partially rescued cells from the tubulogenic defect, indicating that this molecule is responsible for the selection of highly proliferative and tubulogenic defective endothelial cells. Interestingly, by using defined substrata, in conditions that mimic glioma and normal cell ECM composition, we observed that fibronectin (FN) modulates the TN-C-induced selection of endothelial cells. Our data show that TN-C is able to modulate endothelial branching morphogenesis in vitro and, since it is prevalent in matrices of injured and tumor tissues, also suggest a role for this protein in vascular morphogenesis, in these physiological contexts.

  10. Faster recovery after 25-gauge microincision vitrectomy surgery than after 20-gauge vitrectomy in patients with proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Ikeda T

    2012-11-01

    Full Text Available Tatsuhiko Sato, Kazuyuki Emi, Hajime Bando, Toshihide IkedaOsaka Rosai Hospital Clinical Research Center for Occupational Sensory Organ Disability, Sakai, JapanBackground and methods: We compared surgical procedures and outcomes, including duration of recovery period, in eyes with proliferative diabetic retinopathy that underwent 25-gauge microincision vitrectomy surgery with those that underwent 20-gauge vitrectomy. Seventy-two eyes from 53 patients that underwent 20-gauge vitrectomy in 2006 and 87 eyes from 55 patients that underwent 25-gauge vitrectomy in 2010 were studied. The surgical procedures, ie, number of vitreous procedures, operating time, and ratio of type of intraocular tamponade were compared between the two groups. In addition, the outcomes, ie, postoperative complications, anatomical success, postoperative best-corrected visual acuity (BCVA, and duration of hospitalization as an indicator of the postoperative recovery period were also compared.Results: There were no significant differences in surgical procedures or ratio of cases with postoperative complications between cases with 20-gauge and 25-gauge vitrectomy. The final anatomical success rate was 100% in the two groups. BCVA at 6 months after the final vitrectomy was significantly better than the preoperative BCVA for both types of vitrectomy (P < 0.05, and was not significantly different between the two groups. The average duration of hospitalization was 19.5 days after 20-gauge vitrectomy, which was significantly longer than the 11.0 days after 25-gauge vitrectomy (P < 0.001.Conclusion: These results indicate that the anatomical and functional improvements after 25-gauge microincision vitrectomy surgery are not significantly different from those after 20-gauge vitrectomy in eyes with proliferative diabetic retinopathy. However, the significantly shorter recovery period after 25-gauge microincision vitrectomy surgery suggests that it is less traumatic than 20-gauge

  11. Probing the GnRH receptor agonist binding site identifies methylated triptorelin as a new anti-proliferative agent

    Directory of Open Access Journals (Sweden)

    Robert P Millar

    2012-06-01

    Full Text Available D-amino acid substitutions at Glycine postion-6 in GnRH-I decapeptide can possess super-agonist activity and enhanced in vivo pharmacokinetics. Agonists elicit growth-inhibition in tumorigenic cells expressing the GnRH receptor above threshold levels. However, new agonists with modified properties are required to improve the anti-proliferative range. Effects of residue substitutions and methylations on tumourigenic HEK293[SCL60] and WPE-1-NB26-3 prostate cells expressing the rat GnRH receptor were compared. Peptides were ranked according to receptor binding affinity, induction of inositol phosphate production and cell growth-inhibition. Analogues possessing D-Trp6 (including Triptorelin, D-Leu6 (including Leuprolide, D-Ala6, D-Lys6, or D-Arg6 exhibited agonist and anti-proliferative activity. Residues His5 or His5,Trp7,Tyr8, corresponding to residues found in GnRH-II , were tolerated, with retention of sub-nanomolar/low nanomolar binding affinities and EC50s for receptor activation and IC50s for cell growth-inhibition. His5D-Arg6-GnRH-I exhibited reduced binding affinity and potency, effective in the mid-nanomolar range. However, all GnRH-II-like analogues were less potent than Triptorelin. By comparison, three methylated-Trp6 Triptorelin variants showed differential binding, receptor activation and anti-proliferation potency. Significantly, 5-Methyl-DL-Trp6-Triptorelin was equipotent to triptorelin. Subsequent studies should determine whether pharmacologically enhanced derivatives of Triptorelin can be developed by further alkylations, without substitutions or cleavable cytotoxic adducts, to improve the extent of growth-inhibition of tumour cells expressing the GnRH receptor.

  12. Autocrine/paracrine proliferative effect of ovarian GH and IGF-I in chicken granulosa cell cultures.

    Science.gov (United States)

    Ahumada-Solórzano, S Marisela; Martínez-Moreno, Carlos G; Carranza, Martha; Ávila-Mendoza, José; Luna-Acosta, José Luis; Harvey, Steve; Luna, Maricela; Arámburo, Carlos

    2016-08-01

    It is known that growth hormone (GH) and its receptor (GHR) are expressed in granulosa cells (GC) and thecal cells during the follicular development in the hen ovary, which suggests GH is involved in autocrine/paracrine actions in the female reproductive system. In this work, we show that the knockdown of local ovarian GH with a specific cGH siRNA in GC cultures significantly decreased both cGH mRNA expression and GH secretion to the media, and also reduced their proliferative rate. Thus, we analyzed the effect of ovarian GH and recombinant chicken GH (rcGH) on the proliferation of pre-hierarchical GCs in primary cultures. Incubation of GCs with either rcGH or conditioned media, containing predominantly a 15-kDa GH isoform, showed that both significantly increased proliferation as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, proliferating cell nuclear antigen (PCNA) quantification and ((3)H)-thymidine incorporation ((3)H-T) assays in a dose response fashion. Both, locally produced GH and rcGH also induced the phosphorylation of Erk1/2 in GC cultures. Furthermore, GH increased IGF-I synthesis and its release into the GC culture incubation media. These results suggest that GH may act through local IGF-I to induce GC proliferation, since IGF-I immunoneutralization completely abolished the GH-induced proliferative effect. These data suggest that GH and IGF-I may play a role as autocrine/paracrine regulators during the follicular development in the hen ovary at the pre-hierarchical stage.

  13. Relationship between proliferative activity of cancer cells and clinicopathological factors in patients with esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun-Xing Huang; Wei Yan; Zheng-Xiang Song; Rong-Yu Qian; Ping Chen; Eeva Salminen; Jorma Toppari

    2005-01-01

    AIM: To assess whether the molecular markers of malignant tumors could improve the understanding of tumor characteristics, and to observe the characteristics of expression of cell cycle markers Ki-67 and cydin A in esophageal carcinoma and to analyze the relationship between proliferative activity of cancer cells and clinicopathological factors.METHODS: Seventy of surgically resected esophageal squamous cell carcinoma (SCC) were examined by immunohistochemistry utilizing commercially available antibodies. Nuclear staining was regarded as a positive result. At least 50 fields in each tumor and non-tumor section were evaluated at a medium power (x200) to determine the proportion of tumor cells and the staining intensity of nuclei in the entire sections.RESULTS: Ki-67 and cyclin A were only expressed in base cells of normal esophageal mucosa. The positive immunostaining of nuclei of SCC was significantly higher than that in normal esophageal mucosa (t= 13.32 and t= 7.52,respectively, P<0.01). The distribution of positively stained was more diffuse and stronger in poorly differentiated SCC. Both Ki-67 and cyclin A expressions were related to histological grades of tumors (t = 3.5675 and t = 3.916; t= 2.13, respectively, P<0.05) but not to the sex and age of the patients, tumor size, lymphatic invasion, location, or stage grouping.CONCLUSION: The proliferative activity of cancer cells may be understood by immunohistochemistry of Ki-67 and cyclin A in Chinese patients with esophageal SCC. These cell cycle markers may serve as an indicator of cancer cell proliferation rate. The overexpression of cell cycle markers Ki-67 and cyclin A suggests the poor SCC differentiation in patients with esophageal carcinoma.

  14. Transfection of oral squamous cell carcinoma with human papillomavirus-16 induces proliferative and morphological changes in vitro

    Directory of Open Access Journals (Sweden)

    O'Malley Susan

    2006-05-01

    Full Text Available Abstract Background Human papillomavirus has been implicated in virtually all cervical cancers and is believed to be the primary etiological factor that transforms cervical epithelia. The presence of HPV in oral cancers suggests that HPV may play a similar role in transforming the oral epithelia. The prevalence of HPV in oral cancers is highly variable, however, presenting problematic issues regarding the etiology of oral cancers, which must be investigated more thoroughly. Past analyses of HPV in cancers of the oral cavity have largely been confined to retrospective studies of cancer patients. The purpose of this study was to examine the potential for HPV16 infection to alter the proliferative phenotype of oral squamous cell carcinoma in vitro. Results This study found that the oral squamous cell carcinoma cell line, CAL27, transfected with HPV16, exhibited significantly increased proliferation, compared with non-transfected CAL27. The increased proliferation was observed under low density conditions, even in the absence of serum. Moreover, these effects were specific to proliferation, adhesion, and morphology, while cell viability was not affected. Conclusion This study represents one of the first investigations of the effects of HPV16 infection on the proliferation, adhesion, and morphology of an oral squamous cell carcinoma cell line in vitro. The finding that HPV16 has the ability to measurably alter adhesion and proliferative potential is significant, indicating that HPV may have multiple influences on precancerous and cancerous lesions and should be explored as a risk factor and mediator of cancer phenotypes. These measurements and observations will be of benefit to researchers interested in elucidating the mechanisms of oral cancer transformation and the factors governing carcinogenesis and progression.

  15. TrkB Receptor Signalling: Implications in Neurodegenerative, Psychiatric and Proliferative Disorders

    Directory of Open Access Journals (Sweden)

    Stuart L. Graham

    2013-05-01

    Full Text Available The Trk family of receptors play a wide variety of roles in physiological and disease processes in both neuronal and non-neuronal tissues. Amongst these the TrkB receptor in particular has attracted major attention due to its critical role in signalling for brain derived neurotrophic factor (BDNF, neurotrophin-3 (NT3 and neurotrophin-4 (NT4. TrkB signalling is indispensable for the survival, development and synaptic plasticity of several subtypes of neurons in the nervous system. Substantial evidence has emerged over the last decade about the involvement of aberrant TrkB signalling and its compromise in various neuropsychiatric and degenerative conditions. Unusual changes in TrkB signalling pathway have also been observed and implicated in a range of cancers. Variations in TrkB pathway have been observed in obesity and hyperphagia related disorders as well. Both BDNF and TrkB have been shown to play critical roles in the survival of retinal ganglion cells in the retina. The ability to specifically modulate TrkB signalling can be critical in various pathological scenarios associated with this pathway. In this review, we discuss the mechanisms underlying TrkB signalling, disease implications and explore plausible ameliorative or preventive approaches.

  16. Infectious prions accumulate to high levels in non proliferative C2C12 myotubes.

    Directory of Open Access Journals (Sweden)

    Allen Herbst

    Full Text Available Prion diseases are driven by the strain-specific, template-dependent transconformation of the normal cellular prion protein (PrP(C into a disease specific isoform PrP(Sc. Cell culture models of prion infection generally use replicating cells resulting in lower levels of prion accumulation compared to animals. Using non-replicating cells allows the accumulation of higher levels of PrP(Sc and, thus, greater amounts of infectivity. Here, we infect non-proliferating muscle fiber myotube cultures prepared from differentiated myoblasts. We demonstrate that prion-infected myotubes generate substantial amounts of PrP(Sc and that the level of infectivity produced in these post-mitotic cells, 10(5.5 L.D.50/mg of total protein, approaches that observed in vivo. Exposure of the myotubes to different mouse-adapted agents demonstrates strain-specific replication of infectious agents. Mouse-derived myotubes could not be infected with hamster prions suggesting that the species barrier effect is intact. We suggest that non-proliferating myotubes will be a valuable model system for generating infectious prions and for screening compounds for anti-prion activity.

  17. Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis

    NARCIS (Netherlands)

    Arends, Suzanne; Grootscholten, Cecile; Derksen, Ronald H. W. M.; Berger, Stefan P.; de Sevaux, Ruud G. L.; Voskuyl, Alexandre E.; Bijl, Marc; Berden, Jo H. M.

    2012-01-01

    Objectives The objectives of this study are to analyse the long-term follow-up of a randomised controlled trial of induction treatment with azathioprine/methylprednisolone (AZA/MP) versus high-dose intravenous cyclophosphamide (ivCY) in patients with proliferative lupus nephritis (LN) and to evaluat

  18. Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis.

    NARCIS (Netherlands)

    Arends, S.; Grootscholten, C.; Derksen, R.H.W.M.; Berger, S.P.; Sevaux, R.G.L. de; Voskuyl, A.E.; Bijl, M. van der; Berden, J.H.M.

    2012-01-01

    OBJECTIVES: The objectives of this study are to analyse the long-term follow-up of a randomised controlled trial of induction treatment with azathioprine/methylprednisolone (AZA/MP) versus high-dose intravenous cyclophosphamide (ivCY) in patients with proliferative lupus nephritis (LN) and to evalua

  19. A genetic case-control study confirms the implication of SMAD7 and TNF locus in the development of proliferative vitreoretinopathy

    NARCIS (Netherlands)

    J. Rojas (Jimena); I. Fernández (Itziar); J.C. Pastor (Jose Carlos); R.E. MacLaren (Robert ); Y. Ramkissoon (Yashin); S. Harsum (Steven); D. Charteris (David); J.C. van Meurs (Jan); S. Amarakoon (Sankha); J.M. Ruiz-Moreno (Jose María); A. Rocha-Sousa (Amandio); M.-J. Brion (Maria); A. Carracedo (Angel)

    2013-01-01

    textabstractPurpose. Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (RD) surgery and although the risk for developing this complication is associated with some clinical characteristics, the correlation is far from absolute, raising the possibility of

  20. Chemical composition, and anti-proliferative and anti-inflammatory effects of the leaf and wholeplant samples of diploid and tetraploid gynostemma pentaphyllum

    Science.gov (United States)

    Leaf and whole-plant samples of the diploid and tetraploid Gynostemma pentaphyllum (GP)were investigated and compared for their chemical compositions, and their potential anti-proliferative and anti-inflammatory effects. The highest levels of total flavonoids and phenolics were observed in the diplo...

  1. The proliferative potential of the pilocytic astrocytoma : The relation between MIB-1 labeling and clinical and neuro-radiological follow-up

    NARCIS (Netherlands)

    Dirven, CMF; Koudstaal, J; Mooij, JJA; Molenaar, WM

    1998-01-01

    The proliferative potential of 39 pilocytic and 5 low grade astrocytomas was studied in relation to the Ki-67 activity as measured by the MIB-1 Labelings Index. The results were correlated to the biological behaviour of the tumor as measured by clinical and neuro-radiological (CT- or MRI-scans) foll

  2. 3'-Deoxy-3'-18F-Fluorothymidine PET-Derived Proliferative Volume Predicts Overall Survival in High-Grade Glioma Patients

    NARCIS (Netherlands)

    Idema, A.J.S.; Hoffmann, A.L.; Boogaarts, H.D.; Troost, E.G.C.; Wesseling, P.; Heerschap, A.; Graaf, W.T. van der; Grotenhuis, J.A.; Oyen, W.J.G.

    2012-01-01

    3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a radiopharmaceutical depicting tumor cell proliferation with PET. In malignancies of the lung, breast, head and neck, digestive tract, brain, and other organs, quantitative assessment of (18)F-FLT targeting has been shown to correlate with the prolif

  3. Making Women the Subjects of the Abortion Debate: A Class Exercise that Moves beyond "Pro-Choice" and "Pro-Life"

    Science.gov (United States)

    Crawley, Sara L.; Willman, Rebecca K.; Clark, Leisa; Walsh, Clare

    2009-01-01

    In this article, the authors describe a classroom exercise designed to put women (and children and men) back at the center of the abortion debate, avoiding the standard rhetoric and engaging reflection on how everyone might find common political goals among the so-called pro-life and pro-choice sides. The exercise the authors offer in this article…

  4. Cellular senescence in aging and age-related disease: from mechanisms to therapy

    NARCIS (Netherlands)

    Childs, B.G.; Durik, M.; Baker, D.J.; Deursen, J.M.A. van

    2015-01-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senesc

  5. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease

    NARCIS (Netherlands)

    Jiang, Hong; Schiffer, Eric; Song, Zhangfa; Wang, Jianwei; Zürbig, Petra; Thedieck, Kathrin; Moes, Suzette; Bantel, Heike; Saal, Nadja; Jantos, Justyna; Brecht, Meiken; Jenö, Paul; Hall, Michael N; Hager, Klaus; Manns, Michael P; Hecker, Hartmut; Ganser, Arnold; Döhner, Konstanze; Bartke, Andrzej; Meissner, Christoph; Mischak, Harald; Ju, Zhenyu; Rudolph, K Lenhard

    2008-01-01

    Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase

  6. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008016 Clinicopathological study of two subtypes of diffuse proliferative lupus nephritis. ZHENG Zhaohui(郑朝晖),et al. Dept Nephrol, 1st Affili Hosp, Zhengzhou Univ , Zhengzhou 450052. Chin J Nephrol 2007;23(11):696-699. Objective To investigate the clinicopathological characteristics and outcome of two subtypes of class Ⅳ lupus nephritis (LN).

  7. Glomerular disease

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009222 Clinical significance and histological origin of glomerular epithelial proliferative lesion in patients with focal segmental glomerulosclerosis.SHI Sufang(师素芳),et al.Div Nephrol,Dep Med,Instit Nephrol,1st Hosp,Peking Univ,Beijing 100034.Chin J Naphrol,2009;25(3):181-186.

  8. Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential

    Directory of Open Access Journals (Sweden)

    Brinton Roberta

    2008-12-01

    Full Text Available Abstract Background Factors that regulate intracellular calcium concentration are known to play a critical role in brain function and neural development, including neural plasticity and neurogenesis. We previously demonstrated that the neurosteroid allopregnanolone (APα; 5α-pregnan-3α-ol-20-one promotes neural progenitor proliferation in vitro in cultures of rodent hippocampal and human cortical neural progenitors, and in vivo in triple transgenic Alzheimer's disease mice dentate gyrus. We also found that APα-induced proliferation of neural progenitors is abolished by a calcium channel blocker, nifedipine, indicating a calcium dependent mechanism for the proliferation. Methods In the present study, we investigated the effect of APα on the regulation of intracellular calcium concentration in E18 rat hippocampal neurons using ratiometric Fura2-AM imaging. Results Results indicate that APα rapidly increased intracellular calcium concentration in a dose-dependent and developmentally regulated manner, with an EC50 of 110 ± 15 nM and a maximal response occurring at three days in vitro. The stereoisomers 3β-hydroxy-5α-hydroxy-pregnan-20-one, and 3β-hydroxy-5β-hydroxy-pregnan-20-one, as well as progesterone, were without significant effect. APα-induced intracellular calcium concentration increase was not observed in calcium depleted medium and was blocked in the presence of the broad spectrum calcium channel blocker La3+, or the L-type calcium channel blocker nifedipine. Furthermore, the GABAA receptor blockers bicuculline and picrotoxin abolished APα-induced intracellular calcium concentration rise. Conclusion Collectively, these data indicate that APα promotes a rapid, dose-dependent, stereo-specific, and developmentally regulated increase of intracellular calcium concentration in rat embryonic hippocampal neurons via a mechanism that requires both the GABAA receptor and L-type calcium channel. These data suggest that AP

  9. E series prostaglandins alter the proliferative, apoptotic and migratory properties of T98G human glioma cells in vitro

    Directory of Open Access Journals (Sweden)

    Gomes Renata N

    2012-12-01

    Full Text Available Abstract Background In many types of cancer, prostaglandin E2 (PGE2 is associated with tumour related processes including proliferation, migration, angiogenesis and apoptosis. However in gliomas the role of this prostanoid is poorly understood. Here, we report on the proliferative, migratory, and apoptotic effects of PGE1, PGE2 and Ibuprofen (IBP observed in the T98G human glioma cell line in vitro. Methods T98G human glioma cells were treated with IBP, PGE1 or PGE2 at varying concentrations for 24–72 hours. Cell proliferation, mitotic index and apoptotic index were determined for each treatment. Caspase-9 and caspase-3 activity was measured using fluorescent probes in live cells (FITC-LEHD-FMK and FITC-DEVD-FMK respectively. The migratory capacity of the cells was quantified using a scratch migration assay and a transwell migration assay. Results A significant decrease was seen in cell number (54% in the presence of 50 μM IBP. Mitotic index and bromodeoxyuridine (BrdU incorporation were also decreased 57% and 65%, respectively, by IBP. The apoptotic index was increased (167% and the in situ activity of caspase-9 and caspase-3 was evident in IBP treated cells. The inhibition of COX activity by IBP also caused a significant inhibition of cell migration in the monolayer scratch assay (74% and the transwell migration assay (36%. In contrast, the presence of exogenous PGE1 or PGE2 caused significant increases in cell number (37% PGE1 and 45% PGE2. When mitotic index was measured no change was found for either PG treatment. However, the BrdU incorporation rate was significantly increased by PGE1 (62% and to a greater extent by PGE2 (100%. The apoptotic index was unchanged by exogenous PGs. The addition of exogenous PGs caused an increase in cell migration in the monolayer scratch assay (43% PGE1 and 44% PGE2 and the transwell migration assay (28% PGE1 and 68% PGE2. Conclusions The present study demonstrated that treatments which alter PGE1 and PGE

  10. The proliferative potential of human cardiac stem cells was unaffected after a long-term cryopreservation of tissue blocks

    Science.gov (United States)

    Iguchi, Nobuo; Cho, Yasunori; Inoue, Masaki; Murakami, Tsutomu; Tabata, Minoru; Takanashi, Shuichiro; Tomoike, Hitonobu

    2017-01-01

    Background Human c-kit-positive cardiac stem cells (CSCs) have been used to treat patients suffering from ischemic cardiomyopathy. This study aimed to investigate whether a long-term storage of cardiac tissues would influence the growth potential of the subsequently isolated CSCs. Methods A total of 34 fresh samples were obtained from various cardiac regions [right atrium (RA), left atrium (LA), and/or left ventricle (LV)] of 21 patients. From 12 of these patients, 18 samples kept frozen for ~2 years were employed to prepare and characterize the CSCs. After confirming the specificity of the cell sorting by c-kit immunolabeling, the growth rate (number of doublings per day), BrdU positivity, and colony forming unit (CFU) were measured in each CSC population; the values were compared among distinct cardiac regions as well as between fresh and frozen tissues from which CSCs were derived. Results Among independent measurements indicating growth potential, the growth rate and BrdU positivity remarkably correlated in freshly prepared CSCs. The cells obtained from every examined region displayed a high proliferative capacity with the growth rate of 0.48±0.19 and the BrdU positivity of 15.0%±7.6%. The right atrial CSCs tended to show a greater growth than those in the other two areas. Similarly, the CSCs were isolated from tissue blocks, cryopreserved for ~2 years, and compared with CSCs derived from the fresh specimens of the same patients. Importantly, we were able to obtain and culture CSCs from every frozen material, and their proliferative potential, represented by the growth rate of 0.47±0.22 and the BrdU positivity of 13.7%±7.9%, was not inferior to that of the freshly prepared cells. Conclusions The long-term cryopreservation of cardiac tissues did not affect the growth potential of the derivative CSCs. Our findings should expand the therapeutic applications of these cells over a longer time span. PMID:28251120

  11. Prolonged effect of fluid flow stress on the proliferative activity of mesothelial cells after abrupt discontinuation of fluid streaming

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, Shigehisa, E-mail: aokis@cc.saga-u.ac.jp [Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga (Japan); Ikeda, Satoshi [Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga (Japan); Takezawa, Toshiaki [Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Ibaraki (Japan); Kishi, Tomoya [Department of Internal Medicine, Saga University, Saga (Japan); Makino, Junichi [Makino Clinic, Saga (Japan); Uchihashi, Kazuyoshi; Matsunobu, Aki [Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga (Japan); Noguchi, Mitsuru [Department of Urology, Faculty of Medicine, Saga University, Saga (Japan); Sugihara, Hajime [Department of Physical Therapy, International University of Health and Welfare, Fukuoka (Japan); Toda, Shuji [Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga (Japan)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Late-onset peritoneal fibrosis leading to EPS remains to be elucidated. Black-Right-Pointing-Pointer Fluid streaming is a potent factor for peritoneal fibrosis in PD. Black-Right-Pointing-Pointer We focused on the prolonged effect of fluid streaming on mesothelial cell kinetics. Black-Right-Pointing-Pointer A history of fluid streaming exposure promoted mesothelial proliferative activity. Black-Right-Pointing-Pointer We have thus identified a potent new factor for late-onset peritoneal fibrosis. -- Abstract: Encapsulating peritoneal sclerosis (EPS) often develops after transfer to hemodialysis and transplantation. Both termination of peritoneal dialysis (PD) and transplantation-related factors are risks implicated in post-PD development of EPS, but the precise mechanism of this late-onset peritoneal fibrosis remains to be elucidated. We previously demonstrated that fluid flow stress induced mesothelial proliferation and epithelial-mesenchymal transition via mitogen-activated protein kinase (MAPK) signaling. Therefore, we speculated that the prolonged bioactive effect of fluid flow stress may affect mesothelial cell kinetics after cessation of fluid streaming. To investigate how long mesothelial cells stay under the bioactive effect brought on by fluid flow stress after removal of the stress, we initially cultured mesothelial cells under fluid flow stress and then cultured the cells under static conditions. Mesothelial cells exposed to fluid flow stress for a certain time showed significantly high proliferative activity compared with static conditions after stoppage of fluid streaming. The expression levels of protein phosphatase 2A, which dephosphorylates MAPK, in mesothelial cells changed with time and showed a biphasic pattern that was dependent on the duration of exposure to fluid flow stress. There were no differences in the fluid flow stress-related bioactive effects on mesothelial cells once a certain time had passed

  12. Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.

    Directory of Open Access Journals (Sweden)

    Charles C Peyton

    Full Text Available Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU. Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP, muscularis propria (MP and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA, to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh, Gli-1 and bone morphogenic factor-4 (BMP-4 were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends

  13. Aged B lymphocytes retain their ability to express surface markers but are dysfunctional in their proliferative capability during early activation events

    Directory of Open Access Journals (Sweden)

    McGlauchlen Kiley

    2008-11-01

    Full Text Available Abstract Background Ageing is associated with dysfunction in the humoral response leading to decreased protection against infectious diseases. Defects in T cell function due to age have been well characterized but it is unclear if dysfunctions in antibody responses are due to deficiencies in a helper environment or intrinsic B cell defects. Previous studies from our laboratory have shown that aged B lymphocytes are able to differentiate into high affinity antibody-secreting cells at a frequency similar to their young counterparts. However, expansion of B cells in vivo was reduced in aged animals when compared to young. Methods To further investigate the cause of this reduced expansion, we have now examined early activation events of aged B cells in response to anti-CD40 monoclonal antibody (mAb and lipopolysaccharide (LPS stimulation in vitro. To do this spleen cells were harvested from young, middle-aged and aged quasi-monoclonal (QM mice and cultured in complete RPMI for 24 and 48 hours. Cultures contained either LPS or anti-CD40 mAb and murine IL-4. Cells were collected and analyzed using flow cytometry. To examine the proliferative capacity of aged B cells spleen cells were collected as before and cultured in 96 well microtiter plates with either LPS or anti-CD40 mAb and murine IL-4 for 24 hours. Tritiated thymidine ([3H]-Tdr was added to each well and incubated for another 24 hours after which cells were collected and analyzed using a scintillation counter. Results Resting aged B cells exhibited similar levels of CD40 expression when compared to young cells and efficiently up-regulated CD86 and CD69 and also down-regulated CD38 upon stimulation. However, aged B cells proliferated less than young B cells and showed a consistent, but not statistically significant, reduction in their ability to form blast cells. Conclusion Aged B cells exhibited a reduced response in some early activation events but produced at least a partial response in all

  14. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Barbara Iovine

    Full Text Available In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively. Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia

  15. Semiautomatic methods for segmentation of the proliferative tumour volume on sequential FLT PET/CT images in head and neck carcinomas and their relation to clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Arens, Anne I.J.; Grootjans, Willem; Oyen, Wim J.G.; Visser, Eric P. [Radboud University Medical Center, Department of Nuclear Medicine, P.O. Box 9101, Nijmegen (Netherlands); Troost, Esther G.C. [Radboud University Medical Center, Department of Radiation Oncology, Nijmegen (Netherlands); Maastricht University Medical Centre, MAASTRO clinic, GROW School for Oncology and Developmental Biology, Maastricht (Netherlands); Hoeben, Bianca A.W.; Bussink, Johan; Kaanders, Johannes H.A.M. [Radboud University Medical Center, Department of Radiation Oncology, Nijmegen (Netherlands); Lee, John A.; Gregoire, Vincent [St-Luc University Hospital, Department of Radiation Oncology, Universite Catholique de Louvain, Brussels (Belgium); Hatt, Mathieu; Visvikis, Dimitris [Laboratoire de Traitement de l' Information Medicale (LaTIM), INSERM UMR1101, Brest (France)

    2014-05-15

    Radiotherapy of head and neck cancer induces changes in tumour cell proliferation during treatment, which can be depicted by the PET tracer {sup 18}F-fluorothymidine (FLT). In this study, three advanced semiautomatic PET segmentation methods for delineation of the proliferative tumour volume (PV) before and during (chemo)radiotherapy were compared and related to clinical outcome. The study group comprised 46 patients with 48 squamous cell carcinomas of the head and neck, treated with accelerated (chemo)radiotherapy, who underwent FLT PET/CT prior to treatment and in the 2nd and 4th week of therapy. Primary gross tumour volumes were visually delineated on CT images (GTV{sub CT}). PVs were visually determined on all PET scans (PV{sub VIS}). The following semiautomatic segmentation methods were applied to sequential PET scans: background-subtracted relative-threshold level (PV{sub RTL}), a gradient-based method using the watershed transform algorithm and hierarchical clustering analysis (PV{sub W} and {sub C}), and a fuzzy locally adaptive Bayesian algorithm (PV{sub FLAB}). Pretreatment PV{sub VIS} correlated best with PV{sub FLAB} and GTV{sub CT}. Correlations with PV{sub RTL} and PV{sub W} and {sub C} were weaker although statistically significant. During treatment, the PV{sub VIS}, PV{sub W} and {sub C} and PV{sub FLAB} significant decreased over time with the steepest decline over time for PV{sub FLAB}. Among these advanced segmentation methods, PV{sub FLAB} was the most robust in segmenting volumes in the third scan (67 % of tumours as compared to 40 % for PV{sub W} and {sub C} and 27 % for PV{sub RTL}). A decrease in PV{sub FLAB} above the median between the pretreatment scan and the scan obtained in the 4th week was associated with better disease-free survival (4 years 90 % versus 53 %). In patients with head and neck cancer, FLAB proved to be the best performing method for segmentation of the PV on repeat FLT PET/CT scans during (chemo)radiotherapy. This may

  16. A comparative immunohistochemical study of aplastic thymuses for lymphocytic, epithelial, proliferative and apoptotic indices

    Directory of Open Access Journals (Sweden)

    Mahjoub F.

    2008-03-01

    Full Text Available Background: Immune deficiency is one of the major causes of morbidity and mortality in the modern world. Primary immunodeficiency comprises a wide range of disorders that mainly manifest in early childhood as devastating infections with opportunistic organisms. Thymic aplasia is found on autopsy of some patients afflicted with immune deficiency disorders, such as DiGeorge syndrome and severe combined immunodeficiency (SCID. After a thorough search of the literature, we found little information on the cellular characteristics of these thymuses. Our study aims to elucidate role of apoptosis in the pathogenesis of thymic aplasia and compare various lymphocytic and epithelial markers in normal and aplastic thymuses. Methods: We selected 12 subjects who died of severe infections with aplastic thymus found on autopsy, and 11 control subjects who died of unrelated causes, such as congenital heart disease. The presence of several markers, including Bcl2, P53, lymphocytic markers, and CD68, was examined using immunohistochemical methods on paraffin-embedded thymus sections. Positively-stained cells were counted per 1000 cells and the results stated as percentage of positive cells.                        Results: The mean age of the control group was between 7 days to 18 months (mean: 4.5 months. Parental consanguinity was present in 45.5% and 9.1% of the control and case groups, respectively; however, this was not statistically significant. We found significantly lower expression of Bcl2 in the case group (p value: 0.038. Furthermore, expression of CD68 was significantly higher in the case group. Epithelial markers were significantly higher in case subjects, although CD8 expression was higher in the control group. The presence of other markers was not significantly different between the two groups.Conclusions: Increase in apoptosis has a role in aplastic thymuses and prevention of apoptosis may halt this process. Also high CD68

  17. Neuropeptide Y (NPY) as a therapeutic target for neurodegenerative diseases.

    Science.gov (United States)

    Duarte-Neves, Joana; Pereira de Almeida, Luís; Cavadas, Cláudia

    2016-11-01

    Neuropeptide Y (NPY) and NPY receptors are widely expressed in the mammalian central nervous system. Studies in both humans and rodent models revealed that brain NPY levels are altered in some neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Machado-Joseph disease. In this review, we will focus on the roles of NPY in the pathological mechanisms of these disorders, highlighting NPY as a neuroprotective agent, as a neural stem cell proliferative agent, as an agent that increases trophic support, as a stimulator of autophagy and as an inhibitor of excitotoxicity and neuroinflammation. Moreover, the effect of NPY in some clinical manifestations commonly observed in Alzheimer's disease, Parkinson's disease, Huntington's disease and Machado-Joseph disease, such as depressive symptoms and body weight loss, are also discussed. In conclusion, this review highlights NPY system as a potential therapeutic target in neurodegenerative diseases.

  18. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection

    Directory of Open Access Journals (Sweden)

    Ewa Kwiatkowska

    2012-01-01

    Full Text Available Lyme borreliosis is a chronic illness caused by tick-transmitted spirochete Borrelia burgdorferi. Borreliosis can be extremely threatening if it is not diagnosed and treated in early stages. Kidneys are not typically involved in the disease. However, in infected dogs, Lyme nephritis is present in 5–10% of cases. It is associated with rapidly progressing renal failure. Histopathological examination shows mesangial proliferative glomerulonephritis with diffuse tubular necrosis, (Dambach et al. (1997. In available literature, there were reports of human's glomerulonephritis associated with Borrelia burgdorferi infection. These cases refer to membranous and mesangial proliferative glomerulonephritis (Kirmizis and Chatzidimitriou (2010, Zachäus (2008, and Kirmizis et al. (2004. In this paper, we present the case of minimal-change disease (MCD as a result of Borrelia burgdorferi infection.

  19. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection.

    Science.gov (United States)

    Kwiatkowska, Ewa; Gołembiewska, Edyta; Ciechanowski, Kazimierz; Kędzierska, Karolina

    2012-01-01

    Lyme borreliosis is a chronic illness caused by tick-transmitted spirochete Borrelia burgdorferi. Borreliosis can be extremely threatening if it is not diagnosed and treated in early stages. Kidneys are not typically involved in the disease. However, in infected dogs, Lyme nephritis is present in 5-10% of cases. It is associated with rapidly progressing renal failure. Histopathological examination shows mesangial proliferative glomerulonephritis with diffuse tubular necrosis, (Dambach et al. (1997)). In available literature, there were reports of human's glomerulonephritis associated with Borrelia burgdorferi infection. These cases refer to membranous and mesangial proliferative glomerulonephritis (Kirmizis and Chatzidimitriou (2010), Zachäus (2008), and Kirmizis et al. (2004)). In this paper, we present the case of minimal-change disease (MCD) as a result of Borrelia burgdorferi infection.

  20. Gene therapy in ocular diseases

    Directory of Open Access Journals (Sweden)

    Singh Vijay

    2002-01-01

    Full Text Available Gene therapy is a novel form of drug delivery that enlists the synthetic machinery of the patient′s cells to produce a therapeutic agent. Genes may be delivered into cells in vitro or in vivo utilising viral or non-viral vectors. Recent technical advances have led to the demonstration of the molecular basis of various ocular diseases. Ocular disorders with the greatest potential for benefit of gene therapy include hereditary diseases such as retinitis pigmentosa, tumours such as retinoblastoma or melanoma, and acquired proliferative and neovascular retinal disorders. Gene transfer into ocular tissues has been demonstrated with growing functional success and may develop into a new therapeutic tool for clinical ophthalmology in future.

  1. Anti-proliferative and apoptotic effects of S1, a tetrandrine derivative, in human gastric cancer BGC-823 cells.

    Science.gov (United States)

    Lei, Rong-Rong; Hu, Hai-Feng; Bai, Fan; Liu, Ying; Wu, Chun-Zhen; Huang, Xiao-Xing; Xie, Li-Ping; Hu, You-Jia

    2016-07-01

    The aim of the study was to investigate the anti-proliferation and apoptosis-inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer BGC-823 cells and explore the possible mechanism of action. The anti-proliferative activity was determined by MTT assay; the induction of cell cycle arrest and apoptosis were detected by flow cytometry. Quantitative real time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels in mitochondrial pathway. S1 significantly reduced cell viability and induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner. Further studies showed that S1 increased mRNA and protein expression of Bax and the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase-9 and procaspase-3, suggesting that the induction of apoptosis may be related to the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These findings suggested that S1 merits further investigation as a novel therapeutic agent for the treatment of human gastric cancer.

  2. Subfoveal Choroidal Thickness after Panretinal Photocoagulation with Red and Green Laser in Bilateral Proliferative Diabetic Retinopathy Patients: Short Term Results

    Science.gov (United States)

    Roohipoor, Ramak; Dantism, Sina; Karkhaneh, Reza; Zarei, Mohammad; Ghasemi, Fariba

    2016-01-01

    Purpose. To compare subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness after panretinal photocoagulation (PRP) with red and green laser in diabetic patients. Study Design. Randomized clinical trial. Methods. A total of 50 patients with bilateral proliferative diabetic retinopathy and no diabetic macular edema underwent PRP. One eye was randomly assigned to red or green laser. Subfoveal choroidal, central retinal, and RNFL thicknesses were evaluated at baseline and 6 weeks after treatment. Results. The mean subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness increased significantly in each eye 6 weeks after PRP (P values in red laser group: <0.01, 0.03, and <0.01, resp., and in green laser group <0.01, <0.01, and <0.01). There was no difference between red and green laser considering subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness increase after PRP (P values: 0.184, 0.404, and 0.726, resp.). Conclusion. Both red and green lasers increased mean subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness significantly 6 weeks after PRP, but there is no difference between these two modalities in this regard. PMID:27595017

  3. Biosynthesis of Anti-Proliferative Gold Nanoparticles Using Endophytic Fusarium oxysporum Strain Isolated from Neem (A. indica) Leaves.

    Science.gov (United States)

    Siddiqui, Ejaz Ahmad; Ahmad, Absar; Julius, Anju; Syed, Asad; Khan, Shadab; Kharat, Mahesh; Pai, Kalpana; Kadoo, Narendra; Gupta, Vidya

    2016-01-01

    Here we report a simple, rapid, environment friendly approach for the synthesis of gold nanoparticles using neem (Azadirachta indica A. Juss.) fungal endophyte, which based upon morphological and cultural characteristics was eventually identified as Fusarium oxysporum. The aqueous precursor (HAuCl4) solution when reacted with endophytic fungus resulted in the biosynthesis of abundant amounts of well dispersed gold nanoparticles of 10-40 nm with an average size of 22nm. These biosynthesized gold nanoparticles were then characterized by standard analytical techniques such as UV-Visible spectroscopy, X-ray diffraction, Transmission Electron Microscopy and Fourier Transform Infrared Spectroscopy. Cytotoxic activity of these nanoparticles was checked against three different cell types including breast cancer (ZR-75-1), Daudi (Human Burkitt's lymphoma cancer) and normal human peripheral blood mononuclear cells (PBMC), where it was found that our gold nanoparticles are anti-proliferative against cancer cells but completely safe toward normal cells. In addition to this, assessment of toxicity toward human RBC revealed less than 0.1 % hemolysis as compared to Triton X-100 suggesting safe nature of our biosynthesized gold nanoparticles on human cells. Also, our nanoparticles exhibited no anti-fungal (against Aspergillus niger) or anti-bacterial [against Gram positive (Bacillus subtilis & Staphylococcus aureus) and Gram negative (Escherichia coli & Pseudomonas aeruginosa) bacteria] activity thus suggesting their non-toxic, biocompatible nature. The present investigation opens up avenues for ecofriendly, biocompatible nanomaterials to be used in a wide variety of application such as drug delivery, therapeutics, theranostics and so on.

  4. Biological Characterization of Cynara cardunculus L. Methanolic Extracts: Antioxidant, Anti-proliferative, Anti-migratory and Anti-angiogenic Activities

    Directory of Open Access Journals (Sweden)

    Maria Duarte

    2012-12-01

    Full Text Available Cynara cardunculus (Cc is a multipurpose species; beyond its use in southwestern European cuisine, it is also used for the production of solid biofuel, seed oil, biodiesel, paper pulp and cheese, as well as animal feed. In addition, Cc has a long tradition of use in folk medicine as a diuretic and liver protector. The value of this species as a source of bioactive compounds is known; however, pharmacological use would further increase its cultivation. The main goal of the current work was to evaluate the potential of Cc as source of anti-carcinogenic phytochemicals. Different methanolic extracts obtained from wild and cultivated plants were tested for antioxidant activity and effect on breast tumor cell viability. The most effective extract, both as antioxidant and inhibition of tumor cell viability, was tested for effects on angiogenesis and tumor cell migration capacity. All the extracts tested had high antioxidant activity; however, only green leaves and dry head extracts exhibit anti-proliferative activity. Green cultivated leaves (GCL were the most effective extract both as antioxidant and inhibiting the proliferation of tumor cells; it is equally active inhibiting tumor cell migration and in vivo angiogenesis. GCL extract is an effective inhibitor of several key points in tumor development and thus a promising source of anti-carcinogenic phytochemicals.

  5. A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells.

    Directory of Open Access Journals (Sweden)

    Elena Bausch

    Full Text Available Microtubule inhibitors are invaluable tools in cancer chemotherapy: taxanes and vinca alkaloids have been successfully used in the clinic over the past thirty years against a broad range of tumors. However, two factors have limited the effectiveness of microtubule inhibitors: toxicity and resistance. In particular, the latter is highly unpredictable, variable from patient to patient and is believed to be the cause of treatment failure in most cases of metastatic cancers. For these reasons, there is an increasing demand for new microtubule inhibitors that can overcome resistance mechanisms and that, at the same time, have reduced side effects. Here we present a novel microtubule inhibitor, 4SC-207, which shows strong anti-proliferative activity in a large panel of tumor cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in vitro and in vivo and promotes, in a dose dependent manner, a mitotic delay/arrest, followed by apoptosis or aberrant divisions due to chromosome alignment defects and formation of multi-polar spindles. Furthermore, preliminary data from preclinical studies suggest low propensity towards bone marrow toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant xenograft models. In summary, our results suggest that 4SC-207 may be a potential anti-cancer agent.

  6. Influence of Melatonin on the Proliferative and Apoptotic Responses of the Prostate under Normal and Hyperglycemic Conditions

    Directory of Open Access Journals (Sweden)

    Marina G. Gobbo

    2015-01-01

    Full Text Available The antitumor properties of melatonin (MLT are known for prostate cancer cells. This study investigated whether MLT affects prostate maturation and interferes with tissue injuries induced by diabetes. MLT was administered to Wistar rats from 5 weeks of age in the drinking water (10 μg/kg b.w., and diabetes was induced at the 13th week by streptozotocin (4.5 mg/100g b.w., i.p.. The animals were euthanized in the 14th and 21st weeks. MLT reduced the immunostained cells for androgen receptor (AR by 10% in younger rats. Diabetes decreased cell proliferation and increased apoptosis. MLT treatment impeded apoptosis p=0.02 and augmented proliferation p=0.0008 and PCNA content in prostate following long-term diabetes due to restoration of testosterone levels and expression of melatonin receptor type 1B. The effect of MLT (500 µM, 5 mM, and 10 mM on androgen-dependent (22Rv1 and androgen-independent (PC3 cancer cells and human prostate epithelial cells (PNTA1 under normal and hyperglycemic conditions (HG, 450 mg/dL was analyzed. Contrary to PNTA1 and 22Rv1 cells, MLT improved the proliferation of PC3 cells in hyperglycemic medium. The combined data indicated that MLT had proliferative and antiapoptotic effects in prostate cells subjected to HG levels and it seems to involve specific MLT pathways rather than AR.

  7. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity.

    Science.gov (United States)

    Kontogianni, Vassiliki G; Tomic, Goran; Nikolic, Ivana; Nerantzaki, Alexandra A; Sayyad, Nisar; Stosic-Grujicic, Stanislava; Stojanovic, Ivana; Gerothanassis, Ioannis P; Tzakos, Andreas G

    2013-01-01

    The goal of this study was to monitor the anti-proliferative activity of Rosmarinus officinalis and Salvia officinalis extracts against cancer cells and to correlate this activity with their phytochemical profiles using liquid chromatography/diode array detection/electrospray ion trap tandem mass spectrometry (LC/DAD/ESI-MS(n)). For the quantitative estimation of triterpenic acids in the crude extracts an NMR based methodology was used and compared with the HPLC measurements, both applied for the first time, for the case of betulinic acid. Both extracts exerted cytotoxic activity through dose-dependent impairment of viability and mitochondrial activity of rat insulinoma m5F (RINm5F) cells. Decrease of RINm5F viability was mediated by nitric oxide (NO)-induced apoptosis. Importantly, these extracts potentiated NO and TNF-α release from macrophages therefore enhancing their cytocidal action. The rosemary extract developed more pronounced antioxidant, cytotoxic and immunomodifying activities, probably due to the presence of betulinic acid and a higher concentration of carnosic acid in its phytochemical profile.

  8. Number and proliferative capacity of osteogenic stem cells are maintained during aging and in patients with osteoporosis

    DEFF Research Database (Denmark)

    Dokkedahl, Karin Stenderup; Justesen, J; Eriksen, E F

    2001-01-01

    Decreased bone formation is an important pathophysiological mechanism responsible for bone loss associated with aging and osteoporosis. Osteoblasts (OBs), originate from mesenchymal stem cells (MSCs) that are present in the bone marrow and form colonies (termed colony-forming units-fibroblastic [......Decreased bone formation is an important pathophysiological mechanism responsible for bone loss associated with aging and osteoporosis. Osteoblasts (OBs), originate from mesenchymal stem cells (MSCs) that are present in the bone marrow and form colonies (termed colony-forming units......-fibroblastic [CFU-Fs]) when cultured in vitro. To examine the effect of aging and osteoporosis on the MSC population, we quantified the number of MSCs and their proliferative capacity in vitro. Fifty-one individuals were studied: 38 normal volunteers (23 young individuals [age, 22-44 years] and 15 old individuals...... [age, 66-74 years]) and 13 patients with osteoporosis (age, 58-83 years). Bone marrow was aspirated from iliac crest; mononuclear cells were enriched in MSCs by magnetic activated cell sorting (MACS) using STRO-1 antibody. Total CFU-F number, size distribution, cell density per CFU-F, number...

  9. Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

    Directory of Open Access Journals (Sweden)

    Maher Kurdi

    2014-01-01

    Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

  10. The prognostic influence of the proliferative discordance in metastatic pancreatic neuroendocrine carcinoma revealed by peptide receptor radionuclide therapy

    Science.gov (United States)

    Montanier, Nathanaëlle; Joubert-Zakeyh, Juliette; Pétorin, Caroline; Montoriol, Pierre François; Maqdasy, Salwan; Kelly, Antony

    2017-01-01

    Abstract Rationale: Pancreatic neuroendocrine tumors (pNET) are rare slowly growing tumors with a high metastatic potential. Peptide receptor radionuclide therapy (PRRT) with radiolabeled analogues has been developed as a new tool for the management of metastatic well-differentiated (grade 1 and 2) neuroendocrine tumors expressing somatostatin receptor (SSTR2). Chemotherapy is the mainstay in the management of grade 3 (G3) unresectable pancreatic neuroendocrine carcinoma (pNEC). To date, no study has evaluated the efficacy of PRRT in such tumors. Diagnoses and interventions: We describe a case of a progressive G3 pNEC with huge liver metastases successfully treated with PRRT (177Lu DOTATATE). Outcomes: Complete remission was obtained for 3 years. Indeed, the mitotic index was low (as G2 tumors) but with a very high Ki-67 index (45%–70%). Such discordance between the proliferative markers should consider the use of PRRT before chemotherapy in unresectable metastatic G3 tumors expressing SSTR2. Lessons: This case supports the hypotheses highlighting the heterogeneity of G3 pNEC. The latter should be subdivided into 2 distinct categories: proliferation-discordant (well differentiated) and concordant (poorly differentiated) NEC. PRRT could be suggested for the former group before the conventional chemotherapy. PMID:28178157

  11. Facile modification of gelatin-based microcarriers with multiporous surface and proliferative growth factors delivery to enhance cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Huang Sha [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Wang Yijuan [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Deng, Tianzheng [Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Jin Fang [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an, 710032 (China); Liu Shouxin [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Zhang Yongjie [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Feng Feng [Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Jin Yan [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China)], E-mail: yanjin@fmmu.edu.cn

    2008-07-28

    The design of microcarriers plays an important role in the success of cell expansion. The present article provides a facile approach to modify the gelatin-based particles and investigates the feasibility of their acting as microcarriers for cell attachment and growth. Gelatin particles (150-320 {mu}m) were modified by cryogenic treatment and lyophilization to develop the surface with the features of multiporous morphology and were incorporated with proliferative growth factors (bFGF) by adsorption during the post-preparation, which enables them to serve as microcarriers for cells amplification, together with the advantages of larger cell-surface contact area and capability of promoting cell propagation. The microstructure and release assay of the modified microcarriers demonstrated that the pores on surface were uniform and bFGF was released in a controlled manner. Through in vitro fibroblast culture, these features resulted in a prominent increase in the cell attachment rate and cell growth rate relative to the conditions without modification. Although the scanning electron microscopy and optical microscopy analysis results indicated that cells attached, spread, and proliferated on all the microcarriers, cell growth clearly showed a significant correlation with the multiporous structure of microcarriers, in particular on bFGF combined ones. These results validate our previous assumption that the facile modification could improve cell growth on the gelatin-based microcarriers obviously and the novel microcarriers may be a promising candidate in tissue engineering.

  12. Unsupervised lineage-based characterization of primate precursors reveals high proliferative and morphological diversity in the OSVZ.

    Science.gov (United States)

    Pfeiffer, Michael; Betizeau, Marion; Waltispurger, Julie; Pfister, Sabina Sara; Douglas, Rodney J; Kennedy, Henry; Dehay, Colette

    2016-02-15

    Generation of the primate cortex is characterized by the diversity of cortical precursors and the complexity of their lineage relationships. Recent studies have reported miscellaneous precursor types based on observer classification of cell biology features including morphology, stemness, and proliferative behavior. Here we use an unsupervised machine learning method for Hidden Markov Trees (HMTs), which can be applied to large datasets to classify precursors on the basis of morphology, cell-cycle length, and behavior during mitosis. The unbiased lineage analysis automatically identifies cell types by applying a lineage-based clustering and model-learning algorithm to a macaque corticogenesis dataset. The algorithmic results validate previously reported observer classification of precursor types and show numerous advantages: It predicts a higher diversity of progenitors and numerous potential transitions between precursor types. The HMT model can be initialized to learn a user-defined number of distinct classes of precursors. This makes it possible to 1) reveal as yet undetected precursor types in view of exploring the significant features of precursors with respect to specific cellular processes; and 2) explore specific lineage features. For example, most precursors in the experimental dataset exhibit bidirectional transitions. Constraining the directionality in the HMT model leads to a reduction in precursor diversity following multiple divisions, thereby suggesting that one impact of bidirectionality in corticogenesis is to maintain precursor diversity. In this way we show that unsupervised lineage analysis provides a valuable methodology for investigating fundamental features of corticogenesis.

  13. Plasma Plasminogen Activator Inhibitor-1 Is Associated with End-Stage Proliferative Diabetic Retinopathy in the Northern Chinese Han Population

    Directory of Open Access Journals (Sweden)

    Ze-Long Zhong

    2012-01-01

    Full Text Available Objective. To identify predictors of end-stage proliferative diabetic retinopathy (PDR in a cohort of individuals with type 2 diabetes mellitus (T2DM from the Northern Chinese Han population. Methods. We investigated characteristics of 153 consecutive diabetic patients with end-stage PDR (62 males, 91 females, 123 consecutive PDR patients without end-stage PDR (48 males, 75 females, and 151 normal subjects (63 males, 88 females. Only one eye of each patient or healthy subject was included in this study. Univariate logistic regression models and multivariate logistic regression models were constructed to evaluate the predictors of end-stage PDR. Results. In univariate analysis, systolic blood pressure, diastolic blood pressure, duration of diabetes, family history of T2DM, and plasminogen activator inhibitor-1 (PAI-1 were significently associated with end-stage PDR. After multivariate analysis, family history of T2DM, plasma PAI-1 levels, smoking, and duration of diabetes were four positive predictors associated with end-stage PDR. Conclusions. Higher plasma levels of PAI-1 were associated with end-stage PDR in the Northern Chinese Han population with T2DM.

  14. Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines.

    Science.gov (United States)

    Takeshima, Mikako; Ono, Misaki; Higuchi, Takako; Chen, Chen; Hara, Takayuki; Nakano, Shuji

    2014-03-01

    Although lycopene, a major carotenoid component of tomatoes, has been suggested to attenuate the risk of breast cancer, the underlying preventive mechanism remains to be determined. Moreover, it is not known whether there are any differences in lycopene activity among different subtypes of human breast cancer cells. Using ER/PR positive MCF-7, HER2-positive SK-BR-3 and triple-negative MDA-MB-468 cell lines, we investigated the cellular and molecular mechanism of the anticancer activity of lycopene. Lycopene treatment for 168 consecutive hours exhibited a time-dependent and dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0 /G1 phase at physiologically achievable concentrations found in human plasma. The greatest growth inhibition was observed in MDA-MB-468 where the sub-G0 /G1 apoptotic population was significantly increased, with demonstrable cleavage of PARP. Lycopene induced strong and sustained activation of the ERK1/2, with concomitant cyclin D1 suppression and p21 upregulation in these three cell lines. In triple negative cells, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax without affecting anti-apoptotic Bcl-xL. Taken together, these data indicate that the predominant anticancer activity of lycopene in MDA-MB-468 cells suggests a potential role of lycopene for the prevention of triple negative breast cancer.

  15. Vitamin D inhibits CEACAM1 to promote insulin/IGF-I receptor signaling without compromising anti-proliferative action.

    Science.gov (United States)

    Liu, Wei; Guo, Miao; Ezzat, Shereen; Asa, Sylvia L

    2011-01-01

    Population studies suggest putative links between vitamin D (VD)-deficiency and risk of cancer and diabetes. The insulin/IGF-I receptor represents a signaling target of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) that is implicated in both diabetes and cancer, therefore we hypothesized that VD actions may be mediated through this adhesion molecule. In this study, we show that 1,25 vitamin D3 and its analogues EB1089 and KH1060 potently inhibit CEACAM1 expression in cancer cells. This effect was associated with significant reductions in mRNA and protein levels, resulting from transcriptional and posttranslational actions respectively. Insulin/IGF-I-mediated IRS-1 and Akt activation were enhanced by VD treatment. Similarly, CEACAM1 downregulation significantly upregulated the insulin and IGF-I receptors and mimicked the effect of VD-mediated enhanced insulin/IGF-I receptor signaling. Despite improved insulin/IGF-I signaling, the anti-proliferative actions of VD were preserved in the absence or presence of forced CEACAM1 expression. Forced CEACAM1, however, abrogated the anti-invasive actions of VD. Our findings highlight CEACAM1 as a target of VD action. The resulting inhibition of CEACAM1 has potentially beneficial effects on metabolic disorders without necessarily compromising the anticancer properties of this vitamin.

  16. An interspecies conserved motif of the mouse immune system-released activating agent (ISRAA) induces proliferative effects on human cells.

    Science.gov (United States)

    Taha, Safa; Fathallah, Mohamed Dahmani; Bakhiet, Moiz

    2014-07-01

    We have recently described an immune system-released activating agent (ISRAA) as a nervous system-induced factor that stimulates immune responses in the mouse spleen. However, the human ISRAA has not yet been identified. In this study, we examined the effects of the mouse ISRAA protein on human peripheral blood mononuclear cells (PBMCs), to observe if the biological activity of this molecule is consistent between the two different species. Mouse ISRAA demonstrated dose-dependent dualistic effects on human cells, as 5 µg exhibited positive apoptosis and 50 pg exhibited significant proliferation (P<0.05). Furthermore, immunosuppressed cells from patients undergoing immunosuppressive therapy demonstrated significant proliferation to 50 pg ISRAA (P<0.05). Studies to compare sequences in different species revealed a preserved motif, exhibiting 72% similarity with the interspecies conserved signal peptide motif of tumor necrosis factor receptor 1 (TNFR1). A mutant ISRAA lacking this motif was produced and tested for its biological effects. The mutant ISRAA demonstrated neither apoptotic nor proliferative effects compared with wild type. Therefore, an interspecies conserved domain of ISRAA constitutes the active site of the molecule, and its effects on immunocompromised cells should be investigated for future therapies in the treatment of immunosuppressive disorders.

  17. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection

    OpenAIRE

    Ewa Kwiatkowska; Edyta Gołembiewska; Kazimierz Ciechanowski; Karolina Kędzierska

    2012-01-01

    Lyme borreliosis is a chronic illness caused by tick-transmitted spirochete Borrelia burgdorferi. Borreliosis can be extremely threatening if it is not diagnosed and treated in early stages. Kidneys are not typically involved in the disease. However, in infected dogs, Lyme nephritis is present in 5–10% of cases. It is associated with rapidly progressing renal failure. Histopathological examination shows mesangial proliferative glomerulonephritis with diffuse tubular necrosis, (Dambach et al. ...

  18. Changes in the proliferative activity of hippocampal neural stem cells from manganismus mice

    Institute of Scientific and Technical Information of China (English)

    Guohe Tan; Boning Yang; Guofu Tan; Bo Liang; Jiangu Gong; Xiaodong Ge; Songchao Guo

    2007-01-01

    BACKGROUND: Manganese neurotoxicity presents in the form of not only extracorticospinal tract injury of central nervous system (CNS), but also learning and memory ability damage. So, the mechanism of manganese neurotoxicity will be further studied from the angle ofhippocampus.OBJECTIVE: To observe the effects of manganism on learning and memory ability and the proliferation of neural stem cells (NSCs) in hippocampus of mouse brains, and analyze whether this effect has dose-dependence.DESIGN: Randomized controlled experiment.SETTING: Department of Human Anatomy, and Department of Industrial Hygiene and Occupational Diseases, Guangxi Medical University.MATERIALS: Twenty-eight male Kunming mice, aged 2 weeks, were involved in this experiment. The involved mice were randomized into 4 groups, with 7 in each: control group, low-dose manganism group,middle-dose manganism group and high-dose manganism group. Manganese chloride was purchased from Shantou Chemicals Factory.METHODS: This experiment was carried out in the Experimental Center for Preclinical Medicine, Guangxi Medical University from November 2005 to August 2006. Mice in the low-, middle- and high-dose manganism groups were intraperitoneally injected with 5, 20 and 50 mg/kg per day manganese chloride, once a day, for 2 weeks successively. Mice in the control group were injected with the same amount of stroke-physiological saline solution. Neurobehavioral detection of all the animals was performed in Morris water maze constantly from the 7th day after the first injection of manganese chloride solution. Learning ability was detected in the place navigation test. Mice were trained for 5 consecutive days with four trials per day. The time to find the platform was latency. Memory ability was detected in spatial probe test. Platform was withdrawn on the following day of place navigation. The mice were placed in the water from a random start in the edge of the pool. The number of times they traversed the plateform

  19. Giant Congenital Melanocytic Naevus with Proliferative Nodules Mimicking Congenital Malignant Melanoma: A Case Report and Review of the Literature of Congenital Melanoma

    Directory of Open Access Journals (Sweden)

    Massimiliano Scalvenzi

    2013-01-01

    Full Text Available Congenital malignant melanoma (CMM is a rare condition that is defined as malignant melanoma recognized at birth. CMM may develop in utero in one of three ways: (1 transmission by metastasis through the placenta from a mother with melanoma; (2 primary melanoma arising within a giant congenital melanocytic naevus (GCMN; (3 primary de novo cutaneous CMM arising in utero. CMM can be confused clinically and histologically with benign proliferative melanocytic lesions such as giant congenital nevi. We describe the case of a patient presenting a GCMN with proliferative nodules, clinically and dermoscopically resembling a CMM, demonstrating the importance of caution in making a diagnosis of MM and highlighting the possibility that benign lesions as GCMN can mimic a malignant melanoma in this age group.

  20. Influence of dietary supplementation with flaxseed and lactobacilli on the mucosal morphology and proliferative cell rate in the jejunal mucosa of piglets after weaning.

    Science.gov (United States)

    Jonecova, Zuzana; Toth, Stefan; Ciccocioppo, Rachele; Rodrigo, Luis; Kruzliak, Peter; Nemcova, Radomira

    2015-06-01

    The aim of the study was to investigate the influence of flaxseed and lactobacilli supplementation to the diet of piglets during the time period between 10 days before and 21 days after weaning. The morphometry of the jejunal mucosa and proliferative ratio of both epithelial and lamina propria cells were compared with those found in a group of piglets fed with the usual diet added with sunflower oil during the same time period. The addition of flaxseed oil to the diet significantly increased the crypt depth in comparison with both groups supplemented with sunflower (P lactobacilli showed significantly lower proliferative activity in the connective tissue cells from weaning up to 7 days after weaning (P < 0.05 all) in comparison with the flaxseed group.

  1. Korean Ginseng Berry Fermented by Mycotoxin Non-producing Aspergillus niger and Aspergillus oryzae: Ginsenoside Analyses and Anti-proliferative Activities.

    Science.gov (United States)

    Li, Zhipeng; Ahn, Hyung Jin; Kim, Nam Yeon; Lee, Yu Na; Ji, Geun Eog

    2016-01-01

    To transform ginsenosides, Korean ginseng berry (KGB) was fermented by mycotoxin non-producing Aspergillus niger and Aspergillus oryzae. Changes of ginsenoside profile and anti-proliferative activities were observed. Results showed that A. niger tended to efficiently transform protopanaxadiol (PPD) type ginsenosides such as Rb1, Rb2, Rd to compound K while A. oryzae tended to efficiently transform protopanaxatriol (PPT) type ginsenoside Re to Rh1 via Rg1. Butanol extracts of fermented KGB showed high cytotoxicity on human adenocarcinoma HT-29 cell line and hepatocellular carcinoma HepG2 cell line while that of unfermented KGB showed little. The minimum effective concentration of niger-fermented KGB was less than 2.5 µg/mL while that of oryzae-fermented KGB was about 5 µg/mL. As A. niger is more inclined to transform PPD type ginsenosides, niger-fermented KGB showed stronger anti-proliferative activity than oryzae-fermented KGB.

  2. [Hypocomplementary membrano-proliferative glomerulonephritis in a Malagasy patient with schistosomiasis mansoni (detection of bilharzial antigen on glomerular basement membrane using monoclonal antibodies)].

    Science.gov (United States)

    Rajaonarivelo, P; Rajaona, H R; Alix, J L; Couderc, P; Daveau, C; Santoro, F; Nogueira-Quetroz, J A; Lovens, M; Capron, A; Cordonnier, D

    1986-01-01

    Schistosomiasis due to Schistosoma mansoni affects more than 40 millions people all over the world. Renal involvement is observed mainly in endemic areas. We report a case of hypocomplementemic membrano-proliferative glomerulonephritis in a malagasy man who suffered also from hepatosplenic bilharziosis. The relation between Schistosoma mansoni and the nephropathy was proved by indirect immunofluorescence test using a monoclonal antibody directed against the caecum of adult Schistosoma mansoni.

  3. Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line.

    Directory of Open Access Journals (Sweden)

    Justyna Moskwa

    Full Text Available Honey has been used as food and a traditional medicament since ancient times. However, recently many scientists have been concentrating on the anti-oxidant, anti-proliferative, anti-inflammatory and other properties of honey. In this study, we investigated for the first time an anticancer effect of different honeys from Poland on tumor cell line - glioblastoma multiforme U87MG. Anti-proliferative activity of honeys and its interferences with temozolomide were determined by a cytotoxicity test and DNA binding by [H3]-thymidine incorporation. A gelatin zymography was used to conduct an evaluation of metalloproteinases (MMP-2 and MMP-9 expression in U87MG treatment with honey samples. The honeys were previously tested qualitatively (diastase activity, total phenolic content, lead and cadmium content. The data demonstrated that the examined honeys have a potent anti-proliferative effect on U87MG cell line in a time- and dose-dependent manner, being effective at concentrations as low as 0.5% (multifloral light honey - viability 53% after 72 h of incubation. We observed that after 48 h, combining honey with temozolomide showed a significantly higher inhibitory effect than the samples of honey alone. We observed a strong inhibition of MMP-2 and MMP-9 for the tested honeys (from 20 to 56% and from 5 to 58% compared to control, respectively. Our results suggest that Polish honeys have an anti-proliferative and anti-metastatic effect on U87MG cell line. Therefore, natural bee honey can be considered as a promising adjuvant treatment for brain tumors.

  4. Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G0/G1 arrest and apoptosis in Jurkat leukaemia cells.

    Science.gov (United States)

    Pereira, Andreia; Bester, Megan; Soundy, Puffy; Apostolides, Zeno

    2016-09-01

    Context Pelargonium sidoides DC (Geraniaceae) is an important medicinal plant indigenous to South Africa and Lesotho. Previous studies have shown that root extracts are rich in polyphenolic compounds with antibacterial, antiviral and immunomodulatory activities. Little is known regarding the anticancer properties of Pelargonium sidoides extracts. Objective This study evaluates the anti-proliferative effects of a Pelargonium sidoides radix mother tincture (PST). Materials and methods The PST was characterized by LC-MS/MS. Anti-proliferative activity was evaluated in the pre-screen panel of the National Cancer Institute (NCI-H460, MCF-7 and SF-268) and the Jurkat leukaemia cell line at concentrations of 0-150 μg/mL. The effect on cell growth was determined with sulphorhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after 72 h. The effect on cell cycle and apoptosis induction in Jurkat cells was determined by flow cytometry with propidium iodide and Annexin V: fluorescein isothiocyanate staining. Results Dihydroxycoumarin sulphates, gallic acid as well as gallocatechin dimers and trimers were characterized in PST by mass spectrometry. Moderate anti-proliferative effects with GI50 values between 40 and 80 μg/mL were observed in the NCI-pre-screen panel. Strong activity observed with Jurkat cells with a GI50 value of 6.2 μg/mL, significantly better than positive control 5-fluorouracil (GI50 value of 9.7 μg/mL). The PST arrested Jurkat cells at the G0/G1 phase of the cell cycle and increased the apoptotic cells from 9% to 21%, while the dead cells increased from 4% to 17%. Conclusion We present evidence that P. sidoides has cancer cell type-specific anti-proliferative effects and may be a source of novel anticancer molecules.

  5. Cytosol cathepsin-D content and proliferative activity of human breast cancer. The Comitato Italiano per il Controllo di Qualita del Laboratorio in Oncologia.

    Science.gov (United States)

    Paradiso, A; Mangia, A; Correale, M; Abbate, I; Ferri, G; Piffanelli, A; Catozzi, L; Amadori, D; Riccobon, A; De Lena, M

    1992-01-01

    Mitogenic properties have been demonstrated in vitro for the lysosomal acidic protease cathepsin-D (cath-D). We investigated possible relationships between cath-D cytosol cell content and tumor proliferative activity in a series of 129 operable breast cancer patients. For total cytosol cath-D evaluation, a solid phase two-site immunoradiometric assay was utilized on tumor cell cytosol obtained for hormone receptor assay (DCC method). The percentage of S-phase cells was analyzed by 3H-thymidine autoradiographic assay. Median 3H-thymidine Labeling Index (3H-Tdr-LI) of the series was 2.7%; median cath-D content resulted 57 pmol/mg of protein cytosol and was significantly higher in node-positive with respect to the node-negative subgroup (p < 0.03). When classified in low, intermediate or high tumor cath-D content and slow or fast proliferative activity (cut-off: median values of the series), no significant agreement was found between the two variables. Statistical analysis, however, showed that a significant inverse correlation existed in node positive tumors between cath-D and 3H-Tdr-LI values which was even more evident in N-positive high estrogen receptor-positive (ER+) cases (coefficient of correlation = 0.6828; p = 0.0001). Cytosol cath-D content cannot be generally proposed as a direct marker of proliferative activity for operable breast cancer.

  6. Anti-proliferative effects of raw and steamed extracts of Panax notoginseng and its ginsenoside constituents on human liver cancer cells

    Directory of Open Access Journals (Sweden)

    Neo Soek-Ying

    2011-01-01

    Full Text Available Abstract Background Panax notoginseng is a potential source of anticancer compounds. This study aims to investigate the effects of steaming on the chemical profile of P. notoginseng and the anti-proliferative effects of P. notoginseng on liver cancer cells. Methods Samples of powdered raw P. notoginseng roots were steamed for various durations. Extracts of the raw and steamed samples were subjected to ultra-high pressure liquid chromatography/mass spectrometry (UHPLC-MS analysis for chemical profiling. The anti-proliferative effects on three human liver cancer cells, namely SNU449, SNU182 and HepG2, were evaluated using colorimetric WST-1 assay. Results Steaming changed chromatographic and pharmacological profiles of P. notoginseng, causing differences in activities such as inhibition of cancer growth. Steamed P. notoginseng exhibited greater anti-proliferative effects against liver cancer cells (SNU449, SNU182 and HepG2 than its raw form; steaming up to 24 hours increased bioactivities. Steaming increased the concentrations of ginsenoside Rh2, Rk1, Rk3 and 20S-Rg3 and enhanced growth inhibition of liver cancer cells. Conclusion Steaming changes the chemical profile as well as anti-cancer biological activities of P. notoginseng. Steamed P. notoginseng contains potential compounds for the treatment of liver cancer.

  7. CXCR4 expression in feline mammary carcinoma cells: evidence of a proliferative role for the SDF-1/CXCR4 axis

    Directory of Open Access Journals (Sweden)

    Ferrari Angelo

    2012-03-01

    Full Text Available Abstract Background Mammary tumours frequently develop in female domestic cats being highly malignant in a large percentage of cases. Chemokines regulate many physiological and pathological processes including organogenesis, chemotaxis of inflammatory cells, as well as tumour progression and metastasization. In particular, the chemokine/receptor pair SDF-1/CXCR4 has been involved in the regulation of metastatic potential of neoplastic cells, including breast cancer. The aim of this study was the immunohistochemical defininition of the expression profile of CXCR4 in primary and metastatic feline mammary carcinomas and the evaluation of the role of SDF-1 in feline mammary tumour cell proliferation. Results A total of 45 mammary surgical samples, including 33 primary tumours (31 carcinomas and 2 adenomas, 6 metastases, and 4 normal mammary tissues were anlyzed. Tumor samples were collected from a total number of 26 animals, as in some cases concurrent occurrence of neoplasm in more than one mammary gland was observed. Tissues were processed for standard histological examination, and all lesions were classified according to the World Health Organization criteria. CXCR4 expression in neoplastic cells was evaluated by immunohistochemistry. The level of CXCR4 immunoreactivity was semi-quantitatively estimated as CXCR4 score evaluating both the number of positive cells and the intensity of staining. Six primary, fibroblast-free primary cultures were obtained from fresh feline mammary carcinomas and characterized by immunofluorescence for CXCR4 and malignant mammary cell marker expression. SDF-1-dependent in vitro proliferative effects were also assayed. CXCR4 expression was observed in 29 out of 31 malignant tissues with a higher CXCR4 score observed in 4 out of 6 metastatic lesions than in the respective primary tumours. In 2 benign lesions analyzed, only the single basaloid adenoma showed a mild positive immunostaining against CXCR4. Normal tissue did

  8. The calcium channel blocker amlodipine exerts its anti-proliferative action via p21(Waf1/Cip1) gene activation.

    Science.gov (United States)

    Ziesche, Rolf; Petkov, Ventzislav; Lambers, Christopher; Erne, Paul; Block, Lutz-Henning

    2004-10-01

    Proliferation of vascular smooth muscle cells (VSMC) contributes to the progression of atherosclerotic plaques. Calcium channel blockers have been shown to reduce VSMC proliferation, but the underlying molecular mechanism remains unclear. p21(Waf1/Cip1) is a potent inhibitor of cell cycle progression. Here, we demonstrate that amlodipine (10(-6) to 10(-8) M) activates de novo synthesis of p21(Waf1/Cip1) in vitro. We show that amlodipine-dependent activation of p21(Waf1/Cip1) involves the action of the glucocorticoid receptor (GR) and C/EBP-alpha. The underlying pathway apparently involves the action of mitogen-activated protein kinase or protein kinase C, but not of extracellular signal-related kinase or changes of intracellular calcium. Amlodipine-induced p21(Waf1/Cip1) promoter activity and expression were abrogated by C/EBP-alpha antisense oligonucleotide or by the GR antagonist RU486. Amlodipine-dependent inhibition of cell proliferation was partially reversed by RU486 at 10(-8) M (58%+/-29%), antisense oligonucleotides targeting C/EBP-alpha (91%+/-26%), or antisense mRNAs targeting p21(Waf1/Cip1) (96%+/-32%, n=6); scrambled antisense oligonucleotides or those directed against C/EBP-beta were ineffective. The data suggest that the anti-proliferative action of amlodipine is achieved by induction of the p21 (Waf1/Cip1) gene, which may explain beneficial covert effects of this widely used cardiovascular therapeutic drug beyond a more limited role as a vascular relaxant.

  9. Relationship of serum somatomedin-like activity and fibroblast proliferative activity with age and body weight gain in sheep.

    Science.gov (United States)

    Olsen, R F; Wangsness, P J; Patton, W H; Martin, R J

    1981-01-01

    The relationship between serum growth factors and body weight gain was examined in five Dorset lambs. The lambs were weighed and bled by jugular puncture at 2-week intervals between 2 and 18 weeks of age. Somatomedin-like activity (Sm) declined from initially high concentrations at 2 weeks to fairly constant concentrations between 6 and 18 weeks. Relative weight gain--i.e., gain expressed as a percentage of body weight--declined in a manner similar to that of Sm. Mean relative weight gain and mean Sm for the eight 2-week intervals were significantly related (r = .84). Absolute body weight gain--i.e., gain expressed in kilograms--remained fairly constant throughout the study and was not significantly correlated to Sm (r = .15). Serum fibroblast proliferative activity (FPA) was measured as a possible indicator of collective activities of serum growth factors. FPA initially followed a pattern similar to that of Sm, decreasing between 2 and 6 weeks and plateauing until 12 weeks. After 12 weeks, FPA increased to concentrations similar to those observed at 2 weeks. The increase in FPA after 12 weeks was apparently due to an increase in a non-Sm growth factor and had no obvious relationship to body weight changes. Results of the in vitro cell assay system might have been more meaningful if cell type(s) other than WI-38 fibroblasts (e.g., myogenic cells) had been used for estimating collective activities of serum mitogenic factors. The data suggest that serum Sm-like activity may be important in the regulation of growth in sheep.

  10. Elevated Levels of Cytokines Associated with Th2 and Th17 Cells in Vitreous Fluid of Proliferative Diabetic Retinopathy Patients.

    Directory of Open Access Journals (Sweden)

    Masaru Takeuchi

    Full Text Available Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM, 26 patients with idiopathic macular hole (MH, and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble sCD40L, and TNFα in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFα in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFα. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR.

  11. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Directory of Open Access Journals (Sweden)

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  12. MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

    Energy Technology Data Exchange (ETDEWEB)

    Balakrishnan, Anita, E-mail: anita.balakrishnan@doctors.org.uk [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); School of Clinical Sciences, Division of Gastroenterology, University of Liverpool, Liverpool L69 3GE (United Kingdom); Stearns, Adam T. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 2JD (United Kingdom); Park, Peter J. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Harvard Medical School, Center for Biomedical Informatics, Boston, MA 02115 (United States); Dreyfuss, Jonathan M. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Ashley, Stanley W. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Rhoads, David B. [Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Pediatric Endocrine Unit, MassGeneral Hospital for Children, Boston, MA 02114 (United States); Tavakkolizadeh, Ali, E-mail: atavakkoli@partners.org [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States)

    2010-12-10

    Background and aims: The intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation. Methods: Diurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting. Results: mir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16. Conclusions: This is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.

  13. Intracranial intermediate-grade meningeal melanocytoma with increased cellular proliferative index: an illustrative case associated with a nevus of Ota.

    Science.gov (United States)

    Navas, Marta; Pascual, José M; Fraga, Javier; Pedrosa, Manuel; Shakur, Sophia; Carrasco, Rodrigo; Martínez, Pedro; Manzanares, Rafael; de Sola, Rafael García

    2009-10-01

    Solitary primary melanocytic tumors of the central nervous system (CNS) represent a spectrum of lesions ranging from well-differentiated melanocytoma to melanoma. The association of a meningeal melanocytoma with an ipsilateral nevus of Ota is extremely rare, with only six cases reported in the literature to date. Only a minority of melanocytic tumors correspond to lesions of intermediate-grade malignancy, whose biological behavior and outcome remain undetermined. We report a new case of a 25-year-old man with a giant fronto-temporal intracranial meningeal melanocytoma associated with a congenital nevus of Ota, who suffered an acute neurological deterioration requiring an emergent surgical procedure. Despite total removal of the lesion, the patient did not recover from the operation due to a malignant infarct of the right hemisphere. The lesion showed no histological criteria of malignancy but did exhibit an elevated (8%) MIB-1/Ki-67 cell proliferative index, which suggested an intermediate-grade melanocytoma. In addition, its metabolic profile, determined by in vivo proton magnetic resonance spectroscopy (MRS), was similar to that observed in most high-grade gliomas. To our knowledge, this is the first case of a meningeal melanocytoma of intermediate grade associated with a nevus of Ota reported in the literature. Only two additional intermediate-grade melanocytomas showing an elevated MIB-1/Ki-67 labeling index have been previously reported. The MIB-1/Ki-67 labeling index may have potential prognostic value in helping the clinician to predict an aggressive clinical behavior and/or malignant progression for primary melanocytic neoplasms of the CNS.

  14. Comparison of Gene Expression Profile of Epiretinal Membranes Obtained from Eyes with Proliferative Vitreoretinopathy to That of Secondary Epiretinal Membranes

    Science.gov (United States)

    Asato, Ryo; Yoshida, Shigeo; Ogura, Atsushi; Nakama, Takahito; Ishikawa, Keijiro; Nakao, Shintaro; Sassa, Yukio; Enaida, Hiroshi; Oshima, Yuji; Ikeo, Kazuho; Gojobori, Takashi; Kono, Toshihiro; Ishibashi, Tatsuro

    2013-01-01

    Background Proliferative vitreoretinopathy (PVR) is a destructive complication of retinal detachment and vitreoretinal surgery which can lead to severe vision reduction by tractional retinal detachments. The purpose of this study was to determine the gene expression profile of epiretinal membranes (ERMs) associated with a PVR (PVR-ERM) and to compare it to the expression profile of less-aggressive secondary ERMs. Methodology/Principal Findings A PCR-amplified complementary DNA (cDNA) library was constructed using the RNAs isolated from ERMs obtained during vitrectomy. The sequence from the 5′ end was obtained for randomly selected clones and used to generate expressed sequence tags (ESTs). We obtained 1116 nonredundant clusters representing individual genes expressed in PVR-ERMs, and 799 clusters representing the genes expressed in secondary ERMs. The transcriptome of the PVR-ERMs was subdivided by functional subsets of genes related to metabolism, cell adhesion, cytoskeleton, signaling, and other functions, by FatiGo analysis. The genes highly expressed in PVR-ERMs were compared to those expressed in the secondary ERMs, and these were subdivided by cell adhesion, proliferation, and other functions. Querying 10 cell adhesion-related genes against the STRING database yielded 70 possible physical relationships to other genes/proteins, which included an additional 60 genes that were not detected in the PVR-ERM library. Of these, soluble CD44 and soluble vascular cellular adhesion molecule-1 were significantly increased in the vitreous of patients with PVR. Conclusions/Significance Our results support an earlier hypothesis that a PVR-ERM, even from genomic points of view, is an aberrant form of wound healing response. Genes preferentially expressed in PVR-ERMs may play an important role in the progression of PVR and could be served as therapeutic targets. PMID:23372684

  15. miR-203 inhibits melanoma invasive and proliferative abilities by targeting the polycomb group gene BMI1

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiao [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Sun, Yong [Department of Burn and Plastic Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an 223300 (China); Han, Siqi [Department of Medical Oncology, Jinling Hospital, Nanjing 210002 (China); Zhu, Wei [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhang, Haiping, E-mail: zhanghaiping_2000@163.com [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Lian, Shi, E-mail: lianshi_2020@163.com [Department of Dermatology and Venereal Disease, Capital Medical University, Beijing 100069 (China)

    2015-01-02

    Highlights: • First reported deregulation of miR-203 and up-regulation of BMI1 in metastatic melanoma. • miR-203 decreased BMI1 expression by directly binding to 3′UTR. • Further found miR-203 overexpression suppressed cell invasion and stemness. • Re-expression of BMI1 rescued miR-203-mediated suppression. • miR-203-BMI1 axis may be potential therapeutic targets of melanoma metastasis. - Abstract: Metastasis is the major problem in malignant melanoma, posing a therapeutic challenge to clinicians. The investigation of the underlying mechanism driving this progress remains a large unmet need. In this study, we revealed a miR-203-BMI1 axis that regulated melanoma metastasis. We found significantly deregulation of miR-203 and up-regulation of BMI1 in melanoma, particularly in metastatic melanoma. An inverse correlation between the levels of miR-203 and BMI1 was further observed in melanoma tissues and cell lines. We also identified BMI1 as a downstream target gene of miR-203, which bound to the 3′UTR of BMI1. Overexpression of miR-203 was associated with decreased BMI1 expression and impaired cell invasion and tumor sphere formation activities. Re-expression of BMI1 markedly rescued miR-203-mediated suppression of these events. Taken together, our results demonstrated that miR-203 regulated melanoma invasive and proliferative abilities in part by targeting BMI1, providing new insights into potential mechanisms of melanoma metastasis.

  16. Valved versus nonvalved cannula small-gauge pars plana vitrectomy for repair of retinal detachments with Grade C proliferative vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Oellers P

    2016-05-01

    Full Text Available Patrick Oellers, Sandra Stinnett, Paul Hahn Duke Eye Center, Duke University School of Medicine, Durham, NC, USA Purpose: Valved cannulas are a recent addition to small-gauge pars plana vitrectomy (PPV and provide stable intraocular fluidics. The goal of this study was to compare outcomes and postoperative complication rates of valved vs nonvalved cannula small-gauge PPV for repair of retinal detachments (RDs complicated by Grade C proliferative vitreoretinopathy (PVR.Methods: A retrospective chart review of 364 consecutive eyes with either valved or nonvalved cannula PPV for RD repair was performed. The primary outcomes were single surgery and final anatomic success and change in best-corrected visual acuity for repair of RDs complicated by Grade C PVR.Results: We identified 36 eyes in the valved group and 31 eyes in the nonvalved group with Grade C PVR RD. The single surgery success was 83% vs 77% (P=0.555 and the final anatomic success was 94% vs 87% (P=0.404 in the valved vs nonvalved eyes, respectively. The mean final visual acuity gain was −0.36 logarithm of the minimum angle of resolution (logMAR; approximate Early Treatment Diabetes Retinopathy Study [ETDRS] score =17 letters in valved eyes vs −0.33 logMAR (approximate ETDRS score =16 letters in nonvalved eyes (P=0.81. Postoperative complication rates including postoperative day 1 hypotony, hypertony, and anterior chamber fibrin formation; postoperative retention of intraocular or subretinal perfluorocarbon liquid; and subsequent epiretinal membrane peel were not statistically different between groups.Conclusion: Valved cannula PPV yields equivalent visual acuity and anatomic outcomes without increased postoperative complication rates compared to traditional nonvalved cannula PPV for Grade C PVR-associated RD repair. Keywords: 23 gauge, 25 gauge, PVR, RD, chronic, single surgery success, final anatomic success

  17. The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines.

    Science.gov (United States)

    Dicitore, Alessandra; Grassi, Elisa Stellaria; Caraglia, Michele; Borghi, Maria Orietta; Gaudenzi, Germano; Hofland, Leo J; Persani, Luca; Vitale, Giovanni

    2016-01-01

    The oncogenic activation of the rearranged during transfection (RET) proto-oncogene has a main role in the pathogenesis of medullary thyroid cancer (MTC). Several lines of evidence suggest that RET function could be influenced by cyclic AMP (cAMP)-dependent protein kinase A (PKA) activity. We evaluated the in vitro anti-tumor activity of 8-chloroadenosine-3',5'-cyclic monophosphate (8-Cl-cAMP) and PKA type I-selective cAMP analogs [equimolar combination of the 8-piperidinoadenosine-3',5'-cyclic monophosphate (8-PIP-cAMP) and 8-hexylaminoadenosine-3',5'-cyclic monophosphate (8-HA-cAMP) in MTC cell lines (TT and MZ-CRC-1)]. 8-Cl-cAMP and the PKA I-selective cAMP analogs showed a potent anti-proliferative effect in both cell lines. In detail, 8-Cl-cAMP blocked significantly the transition of TT cell population from G2/M to G0/G1 phase and from G0/G1 to S phase and of MZ-CRC-1 cells from G0/G1 to S phase. Moreover, 8-Cl-cAMP induced apoptosis in both cell lines, as demonstrated by FACS analysis for annexin V-FITC/propidium iodide, the activation of caspase-3 and PARP cleavage. On the other hand, the only effect induced by PKA I-selective cAMP analogs was a delay in G0/G1-S and S-G2/M progression in TT and MZ-CRC-1 cells, respectively. In conclusion, these data demonstrate that cAMP analogs, particularly 8-Cl-cAMP, significantly suppress in vitro MTC proliferation and provide rationale for a potential clinical use of cAMP analogs in the treatment of advanced MTC.

  18. Anti-proliferative and pro-apoptotic effects from sequenced combinations of andrographolide and cisplatin on ovarian cancer cell lines.

    Science.gov (United States)

    Yunos, Nurhanan M; Mutalip, Siti S M; Jauri, Muhammad H; Yu, Jun Q; Huq, Fazlul

    2013-10-01

    Andrographolide (Andro) is a diterpenoid that is isolated from Andrographis paniculata and reported to be active against several cancer cell lines. However, few in-depth studies have been carried out on its effects on ovarian cancer cell lines alone or in combination with cisplatin (Cis), which is commonly used to treat ovarian cancer. The aim of this study was to determine the anti-proliferative and apoptotic effects of Andro administered alone and in combination with Cis in the ovarian A2780 and A2780(cisR) cancer cell lines using five different sequences of administration (Cis/Andro h): 0/0h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The results were evaluated in terms of medium-effect dose (Dm) and combination indices (CI) using the CalcuSyn software. Unlike Cis, whose activity was lower in the resistant A2780(cisR) cell line than in the parent A2780 cell line, Andro was found to be three times more active in the A2780(cisR) cell line as compared to that in A2780 cell line. Synergism was observed when Cis and Andro were administered using the sequences 0/4 h and 4/0 h. The percentage of apoptotic cell death was found to be greater for the 0/4 h combination of Andro and Cis as compared to those values from single-drug treatments. The results may be clinically significant if confirmed in vivo.

  19. Elevated Levels of Cytokines Associated with Th2 and Th17 Cells in Vitreous Fluid of Proliferative Diabetic Retinopathy Patients.

    Science.gov (United States)

    Takeuchi, Masaru; Sato, Tomohito; Tanaka, Atsushi; Muraoka, Tadashi; Taguchi, Manzo; Sakurai, Yutaka; Karasawa, Yoko; Ito, Masataka

    2015-01-01

    Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR) by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th) cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes) with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM), 26 patients with idiopathic macular hole (MH), and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble sCD40L, and TNFα in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFα in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFα. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR.

  20. Influence of intravitreal avastin on the expression of cell factors in retinal proliferative membrane in proliferative diabetic retinopathy eye%Avastin玻璃体腔注射后糖尿病视网膜病变增生膜中细胞因子的变化

    Institute of Scientific and Technical Information of China (English)

    胡博杰; 曾勍; 刘新玲; 李筱荣; 宋文静

    2013-01-01

    Background A main cause of visual impairment in proliferative diabetic retinopathy (PDR) is vitreous hemorrhage and retinal detachment due to contraction of fibrovascular membrane.To explore the pathogenic mechanism of fibrovascular membrane is a new target for the prevention and management of PDR.Objective This study was to determine the change in expression of vascular endothelial growth factor (VEGF),connective tissue growth factor(CTGF) and pigment epithelium derived factor(PEDF) in the proliferative membranes of patients with PDR after intravitreal injection of avastin,an anti-VEGF agent.Methods This study was approved by the Medical Ethic Committee of Tianjin Medical College,and written informed consent was obtained from each patient before enrollment.A prospective randomized-controlled study was designed.Twenty-six eyes of 24 patients with PDR scheduled for surgery were enrolled from January to June,2008 in Tianjin Medical College Eye Hospital.The patients were randomized into the simple vitrectomy group and avastin injection combined with vitrectomy group,with matched gender,age and disease duration.1.25 mg (0.05 ml) of avastin was intravitreally injected prior to surgery,and vitrectomy was performed 10 days after injection in the avastin injection combined with vitrectomy group,and only vitrectomy was given in the simple vitrectomy group.Preretinal membrane was collected during the surgery.Expression of VEGF,CTGF and PEDF in the preretinal membranes was assayed by immunochemistry.Results VEGF,CTGF and PEDF were expressed in the cytoplasm.The rate of VEGF expression in the preretinal membranes was 30.77% in the avastin injection combined with vitrectomy group,showing a significant reduction in comparison with the simple vitrectomy group(100.00%)(U =4.000,P<0.01).The rate of expression CTGF was remarkable elevated in the avastin injection combined with vitrectomy group compared with the simple vitrectomy group (92.31% vs.62.54%)(U=7.500,P=0

  1. Fibrosarcoma versus fibromatoses and cellular nodular fasciitis. A comparative study of their proliferative activity using proliferating cell nuclear antigen, DNA flow cytometry, and p53.

    Science.gov (United States)

    Oshiro, Y; Fukuda, T; Tsuneyoshi, M

    1994-07-01

    We analyzed the proliferative activities, immunoreactivity of the p53 protein, and aneuploidy in patients with benign and malignant fibrous lesions, including 19 with nodular fasciitis (cellular type) (6-88 years old, mean 42.9), 11 with abdominal fibromatoses (22-74 years old, mean 37.9), 13 with extraabdominal fibromatoses (2-38 years old, mean 19.5), and 23 with fibrosarcomas (adult type: 16-71 years old, mean 47.3; infantile type: 3 months to 9 years, mean 2.9) using immunohistochemistry to determine proliferating cell nuclear antigen (PC10) and p53 protein (CM1) as well as performing DNA flow cytometry. The proliferating cell nuclear antigen (PCNA) score was measured as the ratio of PCNA-positive nuclear size/total nuclear size determined by an image analysis computer system. The distribution pattern of the PCNA-positive cells was uneven in each instance of nodular fasciitis, in contrast to the distribution in abdominal fibromatosis, extraabdominal fibromatosis, and fibrosarcoma. Both fibrosarcoma (28.4 +/- 20.0) and nodular fasciitis (33.6 +/- 20.9) exhibited a larger value and a greater variation in the PCNA score than did either abdominal (13.5 +/- 14.5) or extraabdominal fibromatosis (19.9 +/- 21.5). Abdominal fibromatosis exhibited a smaller value and less variation in the score. In short, the PCNA score did not correlate with the malignant potential. The proliferative index (S + G2 + M fraction) in fibrosarcoma was significantly higher than in either nodular fasciitis or abdominal fibromatosis. Aneuploidy was detected in five cases (26%) of fibrosarcoma, while six (26%) fibrosarcomas showed p53 positivity. Furthermore, p53-positive patients had a worse survival (0.01 < p < 0.05), and p53 positivity correlated with the proliferative index (p < 0.01). In conclusion, the PCNA score simply indicates the proliferative activity independent of malignant potential. On the other hand, p53 positivity, proliferative index, and aneuploidy are all indicators of

  2. GLD-4-mediated translational activation regulates the size of the proliferative germ cell pool in the adult C. elegans germ line.

    Science.gov (United States)

    Millonigg, Sophia; Minasaki, Ryuji; Nousch, Marco; Novak, Jakub; Eckmann, Christian R

    2014-09-01

    To avoid organ dysfunction as a consequence of tissue diminution or tumorous growth, a tight balance between cell proliferation and differentiation is maintained in metazoans. However, cell-intrinsic gene expression mechanisms controlling adult tissue homeostasis remain poorly understood. By focusing on the adult Caenorhabditis elegans reproductive tissue, we show that translational activation of mRNAs is a fundamental mechanism to maintain tissue homeostasis. Our genetic experiments identified the Trf4/5-type cytoplasmic poly(A) polymerase (cytoPAP) GLD-4 and its enzymatic activator GLS-1 to perform a dual role in regulating the size of the proliferative zone. Consistent with a ubiquitous expression of GLD-4 cytoPAP in proliferative germ cells, its genetic activity is required to maintain a robust proliferative adult germ cell pool, presumably by regulating many mRNA targets encoding proliferation-promoting factors. Based on translational reporters and endogenous protein expression analyses, we found that gld-4 activity promotes GLP-1/Notch receptor expression, an essential factor of continued germ cell proliferation. RNA-protein interaction assays documented also a physical association of the GLD-4/GLS-1 cytoPAP complex with glp-1 mRNA, and ribosomal fractionation studies established that GLD-4 cytoPAP activity facilitates translational efficiency of glp-1 mRNA. Moreover, we found that in proliferative cells the differentiation-promoting factor, GLD-2 cytoPAP, is translationally repressed by the stem cell factor and PUF-type RNA-binding protein, FBF. This suggests that cytoPAP-mediated translational activation of proliferation-promoting factors, paired with PUF-mediated translational repression of differentiation factors, forms a translational control circuit that expands the proliferative germ cell pool. Our additional genetic experiments uncovered that the GLD-4/GLS-1 cytoPAP complex promotes also differentiation, forming a redundant translational circuit with

  3. GLD-4-mediated translational activation regulates the size of the proliferative germ cell pool in the adult C. elegans germ line.

    Directory of Open Access Journals (Sweden)

    Sophia Millonigg

    2014-09-01

    Full Text Available To avoid organ dysfunction as a consequence of tissue diminution or tumorous growth, a tight balance between cell proliferation and differentiation is maintained in metazoans. However, cell-intrinsic gene expression mechanisms controlling adult tissue homeostasis remain poorly understood. By focusing on the adult Caenorhabditis elegans reproductive tissue, we show that translational activation of mRNAs is a fundamental mechanism to maintain tissue homeostasis. Our genetic experiments identified the Trf4/5-type cytoplasmic poly(A polymerase (cytoPAP GLD-4 and its enzymatic activator GLS-1 to perform a dual role in regulating the size of the proliferative zone. Consistent with a ubiquitous expression of GLD-4 cytoPAP in proliferative germ cells, its genetic activity is required to maintain a robust proliferative adult germ cell pool, presumably by regulating many mRNA targets encoding proliferation-promoting factors. Based on translational reporters and endogenous protein expression analyses, we found that gld-4 activity promotes GLP-1/Notch receptor expression, an essential factor of continued germ cell proliferation. RNA-protein interaction assays documented also a physical association of the GLD-4/GLS-1 cytoPAP complex with glp-1 mRNA, and ribosomal fractionation studies established that GLD-4 cytoPAP activity facilitates translational efficiency of glp-1 mRNA. Moreover, we found that in proliferative cells the differentiation-promoting factor, GLD-2 cytoPAP, is translationally repressed by the stem cell factor and PUF-type RNA-binding protein, FBF. This suggests that cytoPAP-mediated translational activation of proliferation-promoting factors, paired with PUF-mediated translational repression of differentiation factors, forms a translational control circuit that expands the proliferative germ cell pool. Our additional genetic experiments uncovered that the GLD-4/GLS-1 cytoPAP complex promotes also differentiation, forming a redundant

  4. Mycotic aneurysm and subarachnoid hemorrhage following tubercular meningitis in an infant with congenital tuberculosis and cytomegalovirus disease.

    Science.gov (United States)

    Gupta, Kirti; Radotra, Bishan Dass; Suri, Deepti; Sharma, Kusum; Saxena, Akshay Kumar; Singhi, Pratibha

    2012-10-01

    We describe autopsy findings in a 5-month-old infant with disseminated tuberculosis and congenital cytomegalovirus disease. The infant manifested with tubercular meningitis complicating as ruptured mycotic right middle cerebral artery aneurysm. Infiltrative, proliferative, and necrotizing vascular pathologies have been described; however, the occurrence of these is dependent on the duration of illness. The vessel pathology appears to be a payback of its immersion in the local inflammatory cell-rich exudates. Strokes early in the course of the disease are believed to be a consequence of vasospasm, and those occurring later during the disease course are due to proliferative intimal disease. Intracranial mycotic aneurysm following tubercular meningitis developing at such a young age has not been reported in the literature. The lung lesions in a congenitally transmitted tuberculosis and cytomegalovirus disease have also been elaborated.

  5. Trace Elements Iron, Copper and Zinc in Vitreous of Patients with Various Vitreoretinal Diseases

    Directory of Open Access Journals (Sweden)

    Sulochana Konerirajapuram

    2004-01-01

    Full Text Available Purpose: To measure the concentrations of iron, copper and zinc in human vitreous and to interpret their levels with various vitreoretinal diseases like proliferative diabetic retinopathy, retinal detachment, intraocular foreign body, Eales′ disease and macular hole. Methods: Undiluted vitreous fluid collected during pars plana vitrectomy was used to measure trace elements using an atomic absorption spectrophotometer. Results: The level of vitreous iron increased threefold in Eales′ disease (1.85 ± 0.36 pg/ml, 2.5-fold in proliferative diabetic retinopathy (1.534 ± 0.17 pg/ml and 2.3-fold in eyes with intraocular foreign body (1.341 ± 0.25 pg/ml when compared with macular hole (0.588 ± 0.16 pg/ml. This was statistically significant (P < 0.05. Zinc was found to be low in Eales′ disease (0.57 ± 0.22 pg/ml when compared with other groups, though the difference was not statistically significant. Conclusion: The increased level of iron with decreased zinc content in Eales′ disease confirms the earlier reported oxidative stress mechanism for the disease. In proliferative diabetic retinopathy and intraocular foreign body the level of iron increases. This is undesirable as iron can augment glycoxidation, which can lead to increased susceptibility to oxidative damage, in turn causing vitreous liquefaction, posterior vitreous detachment and ultimately retinal detachment and vision loss

  6. The Spectrum of Glomerular Diseases on Renal Biopsy: Data From A Single Tertiary Center In Oman

    Directory of Open Access Journals (Sweden)

    Dawood Al Riyami

    2013-05-01

    Full Text Available Objective: To study the pattern of glomerular disease (GD from the result of renal biopsies at our center.Methods: We conducted a retrospective review of 190 adult native renal biopsy reports from the pathology registry of renal biopsy performed at our hospital between 1992 and 2010.Results: Lupus nephritis was the most common pathology 48/133 (36.1% with a female preponderance. The most common primary glomerular disease was focal segmental glomerulosclerosis (FSGS 26/133(19.5%, followed by membranous glemerulopathy (MGN 13/133 (9.8%, and mesangial proliferative glomerulonephritis 6/133 (4.5%. IgA nephropathy and acute proliferative glomerulonephritis each accounted for 4/133 (3.0%. Membranoproliferative glomerulonephritis accounted for 3/133 (2.3%. Focal proliferative and cresentic glomerulonephritis each accounted for 2/133 (1.5%. Vasculitis was not common and there was no report of anti-GBM disease.Conclusion: Among the secondary glomerular diseases, lupus nephritis was the commonest condition with a female preponderance. Among the primary glomerular diseases, FSGS was the commonest. These results are consistent with global trend. IgA nephropathy is not common as the case in the Caucasian population. Vasculitis was not common and there was no report of anti-GBM disease.

  7. Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis.

    Directory of Open Access Journals (Sweden)

    Chaojun Qi

    Full Text Available Lupus nephritis (LN is among the most serious complications of systemic lupus erythematosus (SLE, which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN.For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry.Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages.Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an

  8. Hypoxia-Related Marker GLUT-1, CAIX, Proliferative Index and Microvessel Density in Canine Oral Malignant Neoplasia.

    Science.gov (United States)

    Meier, Valeria; Guscetti, Franco; Roos, Malgorzata; Ohlerth, Stefanie; Pruschy, Martin; Rohrer Bley, Carla

    2016-01-01

    67 score, or polarographic oxygen measurements. GLUT-1 continuous data and Ki-67 (pGLUT-1 (p = 0.043, rho = 0.408). GLUT-1, CAIX, proliferative index and MVD levels were established as microenvironmental descriptors with the purpose of creating a baseline in order to follow changes seen in the tumor microenvironment after hypofractionated radiation with high doses.

  9. Sildenafil potentiates the proliferative effect of porcine pulmonary artery smooth muscle cells induced by serotonin in vitro

    Institute of Scientific and Technical Information of China (English)

    LI Bing-bing; JIANG Zhen; SHENG Jian-yin; YAO Kang

    2011-01-01

    Background Sildenafil is one of the selective phosphodiesterase 5 inhibitors that has been proven by many investigators to suppress growth factor stimulated (e.g.platelet-derived growth factor (PDGF) or epidermal growth factor (EGF)) proliferation and hypertrophy of pulmonary artery smooth muscle cells (PASMCs) via cGMP/cGKIα pathway.Serotonin promotes cell cycle progression leading to cell mitogenesis and plays a key role in the pathogenesis of pulmonary artery hypertension.The role of sildenafil in proliferation of PASMCs induced by serotonin has not been investigated so far.In this study we explored the underlying mechanism of the effect of sildenafil on serotonin induced proliferation of porcine PASMCs.Methods PASMCs were cells from primary cultures by the explant method from the pulmonary artery of swine and cells at passage 3-5 were used in this study.MTT colorimetric assay and flow cytometry analysis were used to evaluate the cell proliferation and alterations in cell cycle progression respectively.Western blotting analysis was applied to determine the expression of phosphorylated extracellular signal-regulated kinase (ERK),proliferating cell nuclear antigen (PCNA)and mitogen activated protein kinase (MAPK) phosphatase-1 (MKP-1).Results Serotonin (10 μmol/L) induced the upregulation of phosphorylation of ERK1/ERK2 and PCNA,an increase in the percentage of cells in S phase and subsequent cell proliferation.Pretreatment with 1 μmol/L sildenafil potentiated the phosphorylation of ERK1/ERK2,an increase in the percentage of cells in S phase and cell proliferation,compared with serotonin stimulation alone (P <0.05).Furthermore,30-minute pretreatment with 10 μmol/L U0126,specific antagonist for ERK kinase (MEK) prevented the increase in phosphorylation of ERK1/ERK2 and abolished cell cycle progression and the proliferation of PASMCs induced by sildenafil.Conclusion This study shows that sildenafil potentiated the proliferative effect of serotonin on PASMCs

  10. Evaluation of chromosomal abnormalities by clg-FISH and association with proliferative and apoptotic indexes in multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Linardi, C.C.G.; Martinez, G.; Velloso, E.D.R.P.; Leal, A.M.; Kumeda, C.A.; Buccheri, V. [Disciplina de Hematologia e Hemoterapia, Departamento de Clínica Médica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Azevedo, R.S. [Departamento de Patologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Peliçario, L.M.; Dorlhiac-Llacer, P. [Disciplina de Hematologia e Hemoterapia, Departamento de Clínica Médica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-08-24

    Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.

  11. Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells

    Science.gov (United States)

    Wu, Feifei; Zhou, Li; Jin, Wangdong; Yang, Weiji; Wang, Ying; Yan, Bo; Du, Wenlin; Zhang, Qiang; Zhang, Lei; Guo, Yonghua; Zhang, Jin; Shan, Letian; Efferth, Thomas

    2016-01-01

    With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis) has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB) is one major kind of tea pigment responsible for the beneficial effects of tea liquor. However, its effect on NSCLC is unknown. The aim of the present study was to evaluate anti-proliferative and apoptosis-inducing effect of TB on NSCLC (A549) cells, using MTT assay, morphological observation (DAPI staining), in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and annexin-V/PI flow cytometry. Subsequently, the expression of several genes associated with cell proliferation and apoptosis were detected by real time PCR assay to explore its potential underlying mechanism. TB was revealed to inhibit cell proliferation of A549 cells in a concentration-dependent and time-dependent manner. Morphological observation, TUNEL assay and flow cytometric analysis evidenced an apoptosis-inducing effect of TB on A549 cells in a concentration-dependent manner. The real time PCR assay demonstrated that TB down-regulated the expression of TOPO I, TOPO II, and BCL-2, and up-regulated the expression of E2F1, P53, GADD45, BAX, BIM, and CASP 3,7,8,9, which suggests an activation of P53-mediated apoptotic (caspase-dependent) pathway in response to TB treatment. The western blot analysis showed a similar trend for the corresponding protein expression (P53, Bax, Bcl-2, caspase 3,9, and PARP) and further revealed DNA damage as a trigger of the apoptosis (phosphorylation of histone H2A.X). Accordingly, TB can be speculated as a DNA damage inducer and topoisomerase (Topo I and Topo II) inhibitor that can up-regulate P53 expression and subsequently modulate the expression of the downstream genes to induce cell proliferation inhibition and apoptosis of A549 cells

  12. Anti-proliferative and apoptosis-inducing effect of theabrownin against non-small cell lung adenocarcinoma A549 cells

    Directory of Open Access Journals (Sweden)

    Feifei Wu

    2016-12-01

    Full Text Available With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC, is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB is one major kind of tea pigment responsible for the beneficial effects of tea liquor. However, its effect on NSCLC is unknown. The aim of the present study was to evaluate anti-proliferative and apoptosis-inducing effect of TB on NSCLC (A549 cells, using MTT assay, morphological observation (DAPI staining, in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay, and annexin V/PI flow cytometry. Subsequently, the expression of several genes associated with cell proliferation and apoptosis were detected by real time PCR assay to explore its potential underlying mechanism. TB was revealed to inhibit cell proliferation of A549 cells in a concentration-dependent and time-dependent manner. Morphological observation, TUNEL assay and flow cytometric analysis evidenced an apoptosis-inducing effect of TB on A549 cells in a concentration-dependent manner. The real time PCR assay demonstrated that TB down-regulated the expression of TOPO I, TOPO II, and BCL-2, and up-regulated the expression of E2F1, P53, GADD45, BAX, BIM, and CASP 3,7,8,9, which suggests an activation of P53-mediated apoptotic (caspase-dependent pathway in response to TB treatment. The western blot analysis showed a similar trend for the corresponding protein expression (P53, Bax, Bcl-2, caspase 3,9, and PARP and further revealed DNA damage as a trigger of the apoptosis (phosphorylation of histone H2A.X. Accordingly, TB can be speculated as a DNA damage inducer and topoisomerase (Topo I and Topo II inhibitor that can up-regulate P53 expression and subsequently modulate the expression of the downstream genes to induce cell prolifera