Induction of reactive oxygen intermediates-dependent programmed cell death in human malignant ex vivo glioma cells and inhibition of the vascular endothelial growth factor production by taurolidine.

Science.gov (United States)

Rodak, Roksana; Kubota, Hisashi; Ishihara, Hideyuki; Eugster, Hans-Pietro; Könü, Dilek; Möhler, Hanns; Yonekawa, Yasuhiro; Frei, Karl

2005-06-01

Taurolidine, a derivative of the amino acid taurin, was recently found to display a potent antineoplastic effect both in vitro and in vivo. The authors therefore initiated studies to assess the potential antineoplastic activity of taurolidine in human glioma cell lines and in ex vivo malignant cell cultures. They also studied the mechanisms that induce cell death and the impact of taurolidine on tumor-derived vascular endothelial growth factor (VEGF) production. Cytotoxicity and clonogenic assays were performed using crystal violet staining. In the cytotoxicity assay 100% of glioma cell lines (eight of eight) and 74% of ex vivo glioma cultures (14 of 19) demonstrated sensitivity to taurolidine, with a mean median effective concentration (EC50) of 51 +/- 28 microg/ml and 56 +/- 23 microg/ml, respectively. Colony formation was inhibited by taurolidine, with a mean EC50 of 7 +/- 3 microg/ml for the cell lines and a mean EC50 of 3.5 +/- 1.7 microg/ml for the ex vivo glioma cultures. On observing this high activity of taurolidine in both assays, the authors decided to evaluate its cell death mechanisms. Fragmentation of DNA, externalization of phosphatidylserine, activation of poly(adenosine diphosphate-ribose) polymerase, loss of the mitochondrial membrane potential followed by a release of apoptosis-inducing factor, and typical apoptotic features were found after taurolidine treatment. Cell death was preceded by the generation of reactive O2 intermediates, which was abrogated by N-acetylcysteine but not by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Moreover, taurolidine also induced suppression of VEGF production on the protein and messenger RNA level, as shown by an enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction. Given all these findings, taurolidine may be a promising new agent in the treatment of malignant gliomas; it displays a combination of antineoplastic and antiangiogenic activities, inducing tumor cell

Chemical Constituents from Cimicifuga dahurica and Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells.

Science.gov (United States)

Huyen, Chu Thi Thanh; Luyen, Bui Thi Thuy; Khan, Ghulam Jilany; Oanh, Ha Van; Hung, Ta Manh; Li, Hui-Jun; Li, Ping

2018-05-04

This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz.) Maxim. (Ranunculaceae) was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3 , two new lignan glycosides 4 and 7 , one new 9,19-cycloartane triterpenoid glycoside 6 , and thirteen known constituents 1 , 2 , 5 , and 8 ⁻ 17 . The structures of 3 , 4 , 6 , and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects ( p ≤ 0.05), wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect ( p ≤ 0.05) which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica , including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.

Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line.

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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.

Anti-proliferative effect of Moringa oleifera Lam (Moringaceae) leaf ...

African Journals Online (AJOL)

Purpose: To investigate the in vitro anti-proliferative effect and mechanism of action of Moringa oleifera Lam. leaf extract on human colon carcinoma HCT116 cell line. Methods: M. oleifera leaves were extracted with methanol. It was fractionated by Sephadex LH-20 column chromatography. Several fractions were identified ...

Chemical Constituents from Cimicifuga dahurica and Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells

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Chu Thi Thanh Huyen

2018-05-01

Full Text Available This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz. Maxim. (Ranunculaceae was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3, two new lignan glycosides 4 and 7, one new 9,19-cycloartane triterpenoid glycoside 6, and thirteen known constituents 1, 2, 5, and 8–17. The structures of 3, 4, 6, and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects (p ≤ 0.05, wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect (p ≤ 0.05 which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica, including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.

Evaluation of the anti-proliferative and cytotoxic potentials of ...

African Journals Online (AJOL)

The partitioned aqueous and chloroform fractions obtained from the methanol extract of the leaf of Cnidoscolus aconitifolius were examined for anti-proliferative (1-30 mg/mL) and cytotoxic activities (20-400 μg/mL) using the seed radicle inhibition and tadpole mortality assays over a period of 24 and 96 h respectively.

Esculetin exerts anti-proliferative effects against non-small-cell lung carcinoma by suppressing specificity protein 1 in vitro.

Science.gov (United States)

Lee, Ra H; Jeon, Young-Joo; Cho, Jin H; Jang, Jeong-Yun; Kong, Il-Keun; Kim, Seok-Ho; Kim, MinSeok S; Chung, Hak-Jae; Oh, Keon B; Park, Seon-Min; Shin, Jae-Cheon; Seo, Jae-Min; Ko, Sungho; Shim, Jung-Hyun; Chae, Jung-Il

2017-01-01

Esculetin, a coumarin derivative, is a phenolic compound isolated from Artemisia capillaris, Citrus limonia, and Euphorbia lathyris. Although it has been reported to have anti-inflammatory, anti-oxidant, and anti-proliferative activities in several human cancers, its anti-proliferative activity against non-small-cell lung carcinoma (NSCLC) and the molecular mechanisms involved have not been adequately elucidated. In this study, we used two NSCLC cell lines (NCI-H358 and NCI-H1299) to investigate the anti-proliferative activity and apoptotic effect of esculetin. Our data showed that esculetin-treated cells exhibited reduced proliferation and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly suppressed by esculetin in a dose- and time-dependent manner. Furthermore, the levels of p27 and p21, two key regulators of the cell cycle, were up-regulated by the esculetin-mediated down-regulation of Sp1; the level of a third cell-cycle regulator, survivin, was decreased, resulting in caspase-dependent apoptosis. Therefore, we conclude that esculetin could be a potent anti-proliferative agent in patients with NSCLC.

In vitro anti-proliferative and anti-inflammatory activity of leaf and fruit extracts from Vaccinium bracteatum Thunb

Czech Academy of Sciences Publication Activity Database

Landa, Přemysl; Skálová, L.; Boušová, I.; Kutil, Zsófia; Langhansová, Lenka; Lou, J.D.; Vaněk, Tomáš

2014-01-01

Roč. 27, č. 1 (2014), s. 103-106 ISSN 1011-601X R&D Projects: GA MŠk ME08070 Institutional support: RVO:61389030 Keywords : anti-proliferative activity * anti-inflammatory activity * breast cancer Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.682, year: 2014 http://www.pjps.pk/wp-content/uploads/pdfs/27/1/Paper-15.pdf

The antiendotoxin agent taurolidine potentially reduces ischemia/reperfusion injury through its metabolite taurine.

LENUS (Irish Health Repository)

Doddakula, Kishore K

2010-09-01

Cardiopulmonary bypass results in ischemia\\/reperfusion (I\\/R)-induced endotoxemia. We conducted a prospective randomized trial to investigate the effect of taurolidine, an antiendotoxin agent with antioxidant and membrane-stabilizing properties, on patients undergoing coronary artery bypass grafting (CABG).

Evaluation of the anti-proliferative and cytostatic effect of Citrus sinensis (orange) fruit juice.

Science.gov (United States)

Chinedu, Enegide; Arome, David; Ameh, Solomon F; Ameh, Gift E

2014-09-01

This work has been designed to evaluate the anti-proliferative and cytostatic effects of Citrus sinensis (orange) fruit juice on rapidly proliferating cells. The study was carried out on the seeds of Sorghum bicolor for 72 h. The mean radicle length (mm) of the seeds was taken at 48 and 72 h. The result showed that when compared with the control, methotrexate, the standard drug showed a significant (P < 0.001) anti-proliferative effect throughout the experiment. The inhibition of the radicle growth was more after 72 h (87.42%). At a dose of 5% (v/v), the juice showed a slightly significant (P < 0.05) effect affect after 72 h; however, there was no significant effect at 48 h. The juice at doses of 10% and 20% (v/v) showed a highly significant (P < 0.001) anti-proliferative effect throughout the experiment; however, the percentage inhibitions were higher at 72 h. At 72 h, the percentage inhibition for juice at 10% (v/v) was 72.37% and at 20% (v/v) was 91.96%. The concentrations of 40% and 60% (v/v) showed cytostatic effects as no appreciable growth of the radicles of the seeds was observed throughout the experiment. The percentage inhibition for 40% (v/v) was 100% and 99.72% for 48 and 72 h, respectively, while that for the juice concentration of 60% (v/v) was 100% throughout the study. The experiment has shown that C. sinensis fruit juice has a potential for causing both anti-proliferative and cytostatic effects on fast proliferating cells and hence cancerous cells.

Daphne striata Tratt. and D. mezereum L.: a study of anti-proliferative activity towards human cancer cells and antioxidant properties.

Science.gov (United States)

Tundis, Rosa; Loizzo, Monica R; Bonesi, Marco; Peruzzi, Lorenzo; Efferth, Thomas

2018-02-12

In this study, we investigated for the first time the anti-proliferative and antioxidant properties of D. mezereum and D. striata. The aerial parts were extracted by maceration with n-hexane, dichloromethane, and methanol. MPLC, GC, and GC-MS were used for the phytochemical study. The anti-proliferative activity was tested against MCF-7, A549, LNCaP, ACHN, and C32 cancer human cells. The antioxidant activity was measured by employing β-carotene bleaching, ABTS, DPPH, and FRAP tests. The Relative Antioxidant Capacity Index (RACI) was applied from the perspective of statistics. D. mezereum dichloromethane extract showed a remarkable anti-proliferative with an IC 50 of 6.08 μg/mL against LNCaP cells. Experimental data indicate that Daphne species have interesting anti-proliferative and antioxidant properties that deserve more investigations to develop novel antineoplastic drugs.

Phytochemical properties and anti-proliferative activity of Olea europaea L. leaf extracts against pancreatic cancer cells.

Science.gov (United States)

Goldsmith, Chloe D; Vuong, Quan V; Sadeqzadeh, Elham; Stathopoulos, Costas E; Roach, Paul D; Scarlett, Christopher J

2015-07-17

Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 μg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 μg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits.

Heme oxygenase is not involved in the anti-proliferative effects of statins on pancreatic cancer cells

International Nuclear Information System (INIS)

Vanova, K.; Boukalova, S.; Gbelcova, H.; Muchova, L.; Neuzil, J.; Gurlich, R.; Ruml, T.; Vitek, L.

2016-01-01

Pancreatic cancer is recognized as one of the most fatal tumors due to its aggressiveness and resistance to therapy. Statins were previously shown to inhibit the proliferation of cancer cells via various signaling pathways. In healthy tissues, statins activate the heme oxygenase pathway, nevertheless the role of heme oxygenase in pancreatic cancer is still controversial. The aim of this study was to evaluate, whether anti-proliferative effects of statins in pancreatic cancer cells are mediated via the heme oxygenase pathway. In vitro effects of various statins and hemin, a heme oxygenase inducer, on cell proliferation were evaluated in PA-TU-8902, MiaPaCa-2 and BxPC-3 human pancreatic cancer cell lines. The effect of statins on heme oxygenase activity was assessed and heme oxygenase-silenced cells were used for pancreatic cancer cell proliferation studies. Cell death rate and reactive oxygen species production were measured in PA-TU-8902 cells, followed by evaluation of the effect of cerivastatin on GFP-K-Ras trafficking and expression of markers of invasiveness, osteopontin (SPP1) and SOX2. While simvastatin and cerivastatin displayed major anti-proliferative properties in all cell lines tested, pravastatin did not affect the cell growth at all. Strong anti-proliferative effect was observed also for hemin. Co-treatment of cerivastatin and hemin increased anti-proliferative potential of these agents, via increased production of reactive oxygen species and cell death compared to individual treatment. Heme oxygenase silencing did not prevent pancreatic cancer cells from the tumor-suppressive effect of cerivastatin or hemin. Cerivastatin, but not pravastatin, protected Ras protein from trafficking to the cell membrane and significantly reduced expressions of SPP1 (p < 0.05) and SOX2 (p < 0.01). Anti-proliferative effects of statins and hemin on human pancreatic cancer cell lines do not seem to be related to the heme oxygenase pathway. While hemin triggers reactive

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

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

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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.

Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis

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S. W. Olson

2017-01-01

Full Text Available Background. The subclinical pathophysiology of proliferative lupus nephritis (PLN has not been fully elucidated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA is associated with PLN, but prediagnostic levels have not been reported. Methods. We performed a retrospective case-control Department of Defense Serum Repository (DoDSR study comparing MPO-ANCA levels in longitudinal prediagnostic serum samples for 23 biopsy confirmed proliferative lupus nephritis (PLN patients to DoDSR identified age, sex, race, and age of serum matched healthy and SLE without LN disease controls. We also compared the temporal relationship of MPO-ANCA to anti-double stranded DNA antibodies (dsDNAab. Results. A greater proportion of PLN patients had prediagnostic MPO-ANCA levels above ≥3 U/mL and ≥6 U/mL compared to SLE without LN (91% versus 43%, p<0.001; 57% versus 5%, p<0.001, resp.. In subgroup analysis, the MPO-ANCA threshold of ≥3 U/mL was significant at <1 year (88% versus 39%, p=0.007 and 1–4 years (87% versus 38%, p=0.009 prior to diagnosis. Statistically significant subclinical MPO-ANCA levels (≥3 U/mL occurred prior to statistically significant dsDNAab ≥ 3 IU/ml (89% versus 11%, p=0.003. Conclusions. Subclinical MPO-ANCA levels could distinguish future PLN from SLE without LN. MPO-ANCA manifests prior to clinical disease and subclinical dsDNAab to suggest that it may contribute directly to PLN pathogenicity.

Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

Science.gov (United States)

Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

Triterpenoid Saponins from Anemone rivularis var. Flore-Minore and Their Anti-Proliferative Activity on HSC-T6 Cells.

Science.gov (United States)

Wang, Xiao-Yang; Gao, Hui; Xie, Xiao-Jie; Jurhiin, Jirimubatu; Zhang, Mu-Zi-He; Zhou, Yan-Ping; Liu, Rui; Ning, Meng; Han, Jin; Tang, Hai-Feng

2018-02-23

Five previously undescribed triterpenoid saponins ( 1 - 5 ), along with eight known ones ( 6 - 13 ), were isolated from the whole plants of Anemone rivularis var. flore-minore . Their structures were clarified by extensive spectroscopic data and chemical evidence. For the first time, the lupane-type saponins ( 3 and 12 ) were reported from the Anemone genus. The anti-proliferative activity of all isolated saponins was evaluated on hepatic stellate cells (HSC-T6). Saponins 12 and 13 , which possess more monosaccharides than the others, displayed potent anti-proliferative activity, with IC 50 values of 18.21 and 15.56 μM, respectively.

Taurolidine as an effective and biocompatible additive for plaque-removing techniques on implant surfaces.

Science.gov (United States)

John, Gordon; Schwarz, Frank; Becker, Jürgen

2015-06-01

The aim of the present study was the evaluation of the effectiveness and efficiency of two plaque-removing techniques, plastic curettes (PC) and glycine powder airflow (GLY) in combination with taurolidine (T), chlorhexidine (CHX), or pure water (PW) as additives and compared to groups without previous treatment (NT). Plaque was collected on titanium samples for 48 h in six subjects. Specimens were worn in a special splint in the upper jaw and randomly assigned to test and control groups. After biofilm removal procedures, clean implant surface (CIS) on the samples and treatment time were taken as parameters. Mean CIS was determined in the following descending order: T-GLY > CHX-GLY > NT-GLY > T-PC > PW-GLY > PW-PC > CHX-PC > NT-PC. Mean treatment time was determined in the following ascending order: T-GLY treatment times of the T groups were significantly lower than their corresponding PC or GLY groups. The results of the current study indicate that taurolidine seems to enhance effectiveness of plaque-removing procedures with plastic curettes and glycine powder airflow. Also, the efficiency of both treatment procedures seems to be increased.

Prevention of disease progression in a patient with a gastric cancer-re-recurrence. Outcome after intravenous treatment with the novel antineoplastic agent taurolidine. Report of a case

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Menenakos Charalambos

2006-06-01

Full Text Available Abstract Background Taurolidine (TRD is a novel agent with multimodal antineoplastic effects. We present the case of a tumor remission after intravenous administration of taurolidine in a patient with gastric cancer re-recurrence. Case presentation A 58 years old male patient suffering from a gastric adenocarcinoma was submitted to partial gastrectomy and partial liver resection (pT2, pN1, pM1L (liver segment 2, N0, V0. 24 months later a local recurrence was diagnosed and the patient was reoperated. Postoperatively the patient underwent a palliative chemotherapy with eloxatin, FU, and leucovorin. A subsequent CT-revealed a liver metastasis and a recurrence adjacent to the hepatic artery. After successful radiofrequency ablation of the liver metastasis the patient was intravenously treated with 2% taurolidine. The patient endured the therapy well and no toxicity was observed. CT-scans revealed a stable disease without a tumor progression or metastatic spread. After 39 cycles the patient was submitted to left nephrectomy due to primary urothelial carcinoma and died 2 days later due to myocardial infarction. Postmortem histology of the esophageal-jejunal anastomosis and liver revealed complete remission of the known metastasized gastric adenocarcinoma. Conclusion The intravenous treatment with 2% taurolidine led to a histological remission of the tumor growth without any toxicity for the patient.

In vitro anti-proliferative activity on colon cancer cell line (HT-29) of Thai medicinal plants selected from Thai/Lanna medicinal plant recipe database "MANOSROI III".

Science.gov (United States)

Manosroi, Aranya; Akazawa, Hiroyuki; Akihisa, Toshihiro; Jantrawut, Pensak; Kitdamrongtham, Worapong; Manosroi, Worapaka; Manosroi, Jiradej

2015-02-23

Thai/Lanna region has its own folklore wisdoms including the traditional medicinal plant recipes. Thai/Lanna medicinal plant recipe database "MANOSROI III" has been developed by Prof. Dr. Jiradej Manosroi. It consists of over 200,000 recipes for all diseases including cancer. To investigate the anti-proliferative and apoptotic activities on human colon cancer cell line (HT-29) as well as the cancer cell selectivity of the methanolic extracts (MEs) and fractions of the 23 selected plants from the "MANOSROI III" database. The 23 selected plants were extracted with methanol under reflux and evaluated for their anti-proliferative activity by sulforhodamine B assay. The 5 plants (Gloriosa superba, Caesalpinia sappan, Fibraurea tinctoria, Ventilago denticulata and Psophocarpus tetragonolobus) with potent anti-proliferative activity were fractionated by liquid-liquid partition to give 4 fractions including each hexane (HF), methanol-water (MF), n-butanol (BF) and water (WF) fractions. They were tested for anti-proliferative activity and cancer cell selectivity. The ME and fractions of G. superba which showed potent anti-proliferative activity were further examined for morphological changes and apoptotic activities by acridine orange (AO)/ethidium bromide (EB) staining. The ME of G. superba root showed active with the highest anti-proliferative activity at 9.17 and 1.58 folds of cisplatin and doxorubicin, respectively. After liquid-liquid partition, HF of V. denticulata, MFs of F. tinctoria, V. denticulata and BF of P. tetragonolobus showed higher anti-proliferative activities than their MEs. The MF of G. superba indicated the highest anti-proliferative activity at 7.73 and 1.34 folds of cisplatin and doxorubicin, respectively, but only 0.86 fold of its ME. The ME and HF, MF and BF of G. superba and MF of F. tinctoria demonstrated high cancer cell selectivity. At 50 µg/ml, ME, HF, MF and BF of G. superba demonstrated higher apoptotic activities than the two standard drugs

GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

International Nuclear Information System (INIS)

Lin, Tao; Meng, Lingjun; Tsai, Robert Y.L.

2011-01-01

Highlights: → Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. → Cell type-dependent synergy between MPA and anti-proliferative agents. → The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. → 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.

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

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Chun, Sung Kook [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Chung, Sooyoung [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Kim, Hee-Dae [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Lee, Ju Hyung [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Jang, Jaebong [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Kim, Jeongah; Kim, Doyeon [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Son, Gi Hoon [Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Oh, Young J. [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Suh, Young-Ger [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Lee, Cheol Soon [Gachon Clinical Trials Center, Gachon University, Incheon, 417-842 (Korea, Republic of); and others

2015-11-13

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

International Nuclear Information System (INIS)

Chun, Sung Kook; Chung, Sooyoung; Kim, Hee-Dae; Lee, Ju Hyung; Jang, Jaebong; Kim, Jeongah; Kim, Doyeon; Son, Gi Hoon; Oh, Young J.; Suh, Young-Ger; Lee, Cheol Soon

2015-01-01

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

Synthesis and Anti-Proliferative Effects of Mono- and Bis-Purinomimetics Targeting Kinases

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Andrea Bistrović

2017-11-01

Full Text Available A series of mono-pyrrolo[2,3-d]pyrimidines 4a–4k, unsymmetrical bis-purine isosteres 5a–5e and symmetrical bis-pyrrolo[2,3-d]pyrimidines 6a and 6b connected via di(1,2,3-triazolylphenyl linker were synthesized by click chemistry. Whereas mono- 4g and bis-pseudopurine 5e showed selective inhibitory activities on cervical carcinoma (HeLa cells, bis-pyrrolo[2,3-d]pyrimidine 6b exhibited potent and selective anti-proliferative effect in the nanomolar range on pancreatic carcinoma (CFPAC-1 cells. Among these, compound 6b induced a significant reduction in the expression level of CDK9 (cyclin-dependent kinase 9/cyclin T1 in CFPAC-1 cells concomitant with attenuation of proliferative signaling mediated by c-Raf (rapidly accelerated fibrosarcoma and p38 MAP (mitogen-activated protein kinases. Our findings encourage further development of novel structurally related analog of 6b to obtain more selective anticancer agent for treating pancreatic cancer.

Antimicrobial and Anti-Proliferative Effects of Skin Mucus Derived from Dasyatis pastinaca (Linnaeus, 1758

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Virginia Fuochi

2017-11-01

Full Text Available Resistance to chemotherapy occurs in various diseases (i.e., cancer and infection, and for this reason, both are very difficult to treat. Therefore, novel antimicrobial and chemotherapic drugs are needed for effective antibiotic therapy. The aim of the present study was to assess the antimicrobial and anti-proliferative effects of skin mucus derived from Dasyatis pastinaca (Linnaeus, 1758. Our results showed that skin mucus exhibited a significant and specific antibacterial activity against Gram-negative bacteria but not against Gram-positive bacteria. Furthermore, we also observed a significant antifungal activity against some strains of Candida spp. Concerning anti-proliferative activity, we showed that fish mucus was specifically toxic for acute leukemia cells (HL60 with an inhibition of proliferation in a dose dependent manner (about 52% at 1000 μg/mL of fish skin mucous, FSM. Moreover, we did not observe effects in healthy cells, in neuroblastoma cells (SH-SY5Y, and multiple myeloma cell lines (MM1, U266. Finally, it exhibited strong expression and activity of chitinase which may be responsible, at least in part, for the aforementioned results.

Potent anti-proliferative effects against oral and cervical cancers of Thai medicinal plants selected from the Thai/Lanna medicinal plant recipe database "MANOSROI III".

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Manosroi, Aranya; Akazawa, Hiroyuki; Pattamapun, Kassara; Kitdamrongtham, Worapong; Akihisa, Toshihiro; Manosroi, Worapaka; Manosroi, Jiradej

2015-07-01

Thai/Lanna medicinal plant recipes have been used for the treatment of several diseases including oral and cervical cancers. To investigate anti-proliferative activity on human cervical (HeLa) and oral (KB) cancer cell lines of medicinal plants selected from Thai/Lanna medicinal plant recipe database "MANOSROI III". Twenty-three methanolic plant crude extracts were tested for phytochemicals and anti-proliferative activity on HeLa and KB cell lines for 24 h by the sulforhodamine B (SRB) assay at the doses of 1 × 10(1)-1 × 10(-6 )mg/ml. The nine extracts with the concentrations giving 50% growth inhibition (GI50) lower than 100 µg/ml were further semi-purified by liquid/liquid partition in order to evaluate and enhance the anti-proliferative potency. All extracts contained steroids/triterpenoids, but not xanthones. The methanolic extracts of Gloriosa superba L. (Colchinaceae) root and Albizia chinensis (Osbeck) Merr. (Leguminosae-Mimosoideae) wood gave the highest anti-proliferative activity on HeLa and KB cell lines with the GI50 values of 0.91 (6.0- and 0.31-fold of cisplatin and doxorubicin) and 0.16 µg/ml (28.78- and 82.29-fold of cisplatin and doxorubicin), respectively. Hexane and methanol-water fractions of G. superba exhibited the highest anti-proliferative activity on HeLa and KB cell lines with the GI50 values of 0.15 (37- and 1.9-fold of cisplatin and doxorubicin) and 0.058 µg/ml (77.45- and 221.46-fold of cisplatin and doxorubicin), respectively. This study has demonstrated the potential of plants selected from MANOSROI III database especially G. superba and A. chinensis for further development as anti-oral and cervical cancer agents.

Anti-proliferative and mutagenic activities of aqueous and methanol extracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae).

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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.

Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

Science.gov (United States)

Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

2014-01-01

Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

Anti-Proliferative and Apoptotic Effects of Beta-Ionone in Human Leukemia Cell Line K562

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Zohreh Faezizadeh

2016-06-01

Full Text Available Background Beta-ionone is an aroma compound found in the Rosaceae family. Some evidence supported that beta-ionone has a great potential for cancer prevention. To date, the anti-proliferative and apoptotic effects of beta-ionone in human leukemia cell line K562 were not studied. Objectives Hence, we investigated whether beta-ionone could inhibit cell growth and induce apoptosis in the K562 cells. Materials and Methods In this experimental study, human leukemia cell line K562 was cultured and anti-proliferation effect of beta-ionone with different doses (25 - 400 µm at different times (24 - 96 hours on treated cells was evaluated by the MTT assay. To determine apoptosis rate, the Hoechst 33342 staining and flow cytometry was performed. Results The MTT assay showed that beta-ionone inhibited proliferation of K562 cells in a dose-dependent manner significantly (P = 0.0008. Moreover, the increased apoptotic rate was found after incubation of K562 cells with 200 µm beta-ionone. The Hoechst staining and flow cytometry analysis indicated that beta-ionone could increase apoptosis of K562 cells in a dose-dependent manner. Conclusions The results demonstrated that beta-ionone has anti-proliferative and apoptotic effects on K562 cells, and in the future may be used in the treatment of some leukemia sub-types.

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells

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Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E.; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S.; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

2016-01-01

Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 109 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 109 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

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Angeliki Tiptiri-Kourpeti

Full Text Available Probiotic microorganisms such as lactic acid bacteria (LAB exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof on murine (CT26 and human (HT29 colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells. In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

Science.gov (United States)

Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

2016-01-01

Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

GENE EXPRESSION CHANGES AND ANTI-PROLIFERATIVE EFFECT OF NONI (Morinda citrifolia FRUIT EXTRACT ANALYSED BY REAL TIME-PCR

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hermansyah hermansyah

2017-05-01

Full Text Available To elucidate the anti-proliferative effect of noni (Morinda citrifolia fruit extract for a Saccharomyces cerevisiae model organism, analysis of gene expression changes related to cell cycle associated with inhibition effect of noni fruit extract was carried out. Anti-proliferative of noni fruit extract was analyzed using gene expression changes of Saccharomyces cerevisiae (strains FY833 and BY4741.  Transcriptional analysis of genes that play a role in cell cycle was conducted by growing cells on YPDAde broth medium containing 1% (w/v noni fruit extract, and then subjected using quantitative real-time polymerase chain reaction (RT-PCR.  Transcriptional level of genes CDC6 (Cell Division Cycle-6, CDC20 (Cell Division Cycle-20, FAR1 (Factor ARrest-1, FUS3 (FUSsion-3, SIC1 (Substrate/Subunit Inhibitor of Cyclin-dependent protein kinase-1, WHI5 (WHIskey-5, YOX1 (Yeast homeobOX-1 and YHP1 (Yeast Homeo-Protein-1 increased, oppositely genes expression of DBF4 (DumbBell Forming, MCM1 (Mini Chromosome Maintenance-1 and TAH11 (Topo-A Hypersensitive-11 decreased, while the expression level of genes CDC7 (Cell Division Cycle-7, MBP1 (MIul-box Binding Protein-1 and SWI6 (SWItching deficient-6 relatively unchanged. These results indicated that gene expression changes might associate with anti-proliferative effect from noni fruit extract. These gene expressions changes lead to the growth inhibition of S.cerevisiae cell because of cell cycle defect.

Isoliquiritigenin exhibits anti-proliferative properties in the pituitary independent of estrogen receptor function

International Nuclear Information System (INIS)

Weis, Karen E.; Raetzman, Lori T.

2016-01-01

The plant flavonoid isoliquiritigenin (ISL) is a botanical estrogen widely taken as an herbal supplement to ease the symptoms of menopause. ISL has been also shown to have anti-tumor properties in a number of cancer cell backgrounds. However, the effects of ISL on normal cells are less well known and virtually unstudied in the context of the pituitary gland. We have established a pituitary explant culture model to screen chemical agents for gene expression changes within the pituitary gland during a period of active proliferation and differentiation. Using this whole-organ culture system we found ISL to be weakly estrogenic based on its ability to induce Cckar mRNA expression, an estrogen receptor (ER) mediated gene. Using a range of ISL from 200 nM to 200 μM, we discovered that ISL promoted cell proliferation at a low concentration, yet potently inhibited proliferation at the highest concentration. ICI 182,780 failed to antagonize ISL's repression of pituitary cell proliferation, indicating the effect is independent of ER signaling. Coincident with a decrease in proliferating cells, we observed down-regulation of transcript for cyclin D2 and E2 and a strong induction of mRNA and protein for the cyclin dependent kinase inhibitor Cdkn1a (p21). Importantly, high dose ISL did not alter the balance of progenitor vs. differentiated cell types within the pituitary explants and they seemed otherwise healthy; however, TUNEL staining revealed an increase in apoptotic cell death in ISL treated cultures. Our results merit further examination of ISL as an anti-tumor agent in the pituitary gland. - Highlights: • Isoliquiritigenin possesses weak estrogenic activity based on induction of Cckar. • ISL can be anti-proliferative in pituitary explants without altering cell lineages. • Anti-proliferative behavior of ISL is not estrogen receptor mediated. • ISL induces p21 expression leading to cell cycle arrest and apoptosis.

Isoliquiritigenin exhibits anti-proliferative properties in the pituitary independent of estrogen receptor function

Energy Technology Data Exchange (ETDEWEB)

Weis, Karen E.; Raetzman, Lori T., E-mail: raetzman@life.illinois.edu

2016-12-15

The plant flavonoid isoliquiritigenin (ISL) is a botanical estrogen widely taken as an herbal supplement to ease the symptoms of menopause. ISL has been also shown to have anti-tumor properties in a number of cancer cell backgrounds. However, the effects of ISL on normal cells are less well known and virtually unstudied in the context of the pituitary gland. We have established a pituitary explant culture model to screen chemical agents for gene expression changes within the pituitary gland during a period of active proliferation and differentiation. Using this whole-organ culture system we found ISL to be weakly estrogenic based on its ability to induce Cckar mRNA expression, an estrogen receptor (ER) mediated gene. Using a range of ISL from 200 nM to 200 μM, we discovered that ISL promoted cell proliferation at a low concentration, yet potently inhibited proliferation at the highest concentration. ICI 182,780 failed to antagonize ISL's repression of pituitary cell proliferation, indicating the effect is independent of ER signaling. Coincident with a decrease in proliferating cells, we observed down-regulation of transcript for cyclin D2 and E2 and a strong induction of mRNA and protein for the cyclin dependent kinase inhibitor Cdkn1a (p21). Importantly, high dose ISL did not alter the balance of progenitor vs. differentiated cell types within the pituitary explants and they seemed otherwise healthy; however, TUNEL staining revealed an increase in apoptotic cell death in ISL treated cultures. Our results merit further examination of ISL as an anti-tumor agent in the pituitary gland. - Highlights: • Isoliquiritigenin possesses weak estrogenic activity based on induction of Cckar. • ISL can be anti-proliferative in pituitary explants without altering cell lineages. • Anti-proliferative behavior of ISL is not estrogen receptor mediated. • ISL induces p21 expression leading to cell cycle arrest and apoptosis.

The Role of MKP-1 in the Anti-Proliferative Effects of Glucocorticoids in Primary Rat Pre-Osteoblasts.

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Micheline Sanderson

Full Text Available Glucocorticoid (GC-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK phosphatase-1 (MKP-1 in mediating the anti-proliferative effects of GCs in immortalized pre-osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs and ADSC-derived pre-osteoblasts (ADSC-OBs. ADSCs were isolated by means of collagenase digestion from adipose tissue biopsies harvested from adult male Wistar rats. ADSC-OBs were prepared by treating ADSCs with osteoblast differentiation media for 7 days. The effects of increasing concentrations of the GC dexamethasone on basal and mitogen-stimulated cell proliferation were quantified by tritiated thymidine incorporation. ERK1/2 activity was measured by Western blotting, while MKP-1 expression was quantified on both RNA and protein levels, using semi-quantitative real-time PCR and Western blotting, respectively. GCs were strongly anti-proliferative in both naïve ADSCs and ADSC-OBs, but had very little effect on mitogen-induced ERK1/2 activation and did not upregulate MKP-1 protein expression. These findings suggest that the anti-proliferative effects of GCs in primary ADSCs and ADSC-OBs in vitro do not require the inhibition of ERK1/2 activation by MKP-1, which is consistent with our in vivo findings in MKP-1 null mice.

Chromatographic analysis, anti-proliferative and radical scavenging activity of Pinus wallichina essential oil growing in high altitude areas of Kashmir, India.

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Yousuf Dar, Mohd; Shah, Wajaht A; Mubashir, Sofi; Rather, Manzoor A

2012-10-15

To evaluate the in vitro anti-proliferative and radical scavenging properties of the essential oil and its fractions and to determine the chemo-type of P. wallichiana essential oil. Pinus wallichiana oil was extracted by hydro-distillation and fractionated by silica gel column chromatography method. The oil and its fractions were analyzed by Gas chromatography, Gas chromatography-mass spectrometry and (13)C NMR. Different concentrations of oil 12.5, 25, 50 and 100μg/ml and single concentration 50μg/ml of its fractions B(1), B(2), A(2), G(2), Uk(13) and I(2) were evaluated for its anti-proliferative activity by in vitro {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} assay against human monocyte, lung carcinoma, liver adenocarcinoma, prostate and ovarian carcinoma, while as the radical scavenging activity was evaluated by different in vitro DPPH assays. The analyses indicated the presence of 17 constituents with β-pinene (46.8%) and α-pinene (25.2%) as major constituents. The oil and its fractions showed significant anti-proliferative activity. The radical scavenging activity also showed good results. The oil could be used as a drug to control the diseases like cancer, cirrhosis and arteriosclerosis, caused by reactive oxygen species. Copyright © 2012 Elsevier GmbH. All rights reserved.

In vitro anti-proliferative activity of clove extract on human gastric carcinoma

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A. Karimi

2017-10-01

Full Text Available Background and objectives: Cancer cell resistance to common chemotherapy agents is on rise. Plants are considered valuable sources of herbal drugs for cancer therapy. The present study was conducted to investigate the in vitro antioxidant, anti-proliferative, and apoptosis-inducing properties of clove (Syzygium aromaticum L. extract in human gastric carcinoma (AGS. Methods: Crude ethanol extract of S. aromaticum dried buds was prepared and  in vitro anti-proliferative effects of the extract on AGS and normal Human dermal fibroblasts (HDF cell lines were studied by MTT assay. To examine apoptosis induction, AGS cells were incubated with IC50 concentrations of the extract, stained with propidium iodide (PI and annexin V-fluorescein isothiocyanate (FITC, and analyzed by flow cytometry. Antioxidant activity and total phenolics and flavonoids contents were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method, respectively. Results: The IC50 of DPPH and total phenolics and flavonoids contents of the extract were 10.05±1.93 μg/mL, 225.6±40 mg GAE/g, and 29.30±2.35 mgRUT/g, respectively. The IC50 of the extract against HDFs was 649 µg/mL, higher than AGS cells, which was 118.7 g/mL at 48 h after treatment. Flow cytometric analysis showed that the extract induced cell apoptosis. Conclusions: Crude ethanol S. aromaticum extract had high total phenolics content, and suppressed the proliferation of human gastric cancer cells, likely due to apoptosis induction. Further studies should be conducted to determine the mechanisms of its anticancer effects.

Anti-proliferative action of vitamin D in MCF7 is still active after siRNA-VDR knock-down

NARCIS (Netherlands)

J.L. Costa (José); P.P. Eijk (Paul); M.A. van de Wiel (Mark); D. ten Berge (Derk); F. Schmitt (Fernando); C.J. Narvaez (Carmen); J. Welsh; B. Ylstra (Bauke)

2009-01-01

textabstractBackground: The active form of Vitamin D, 1,25-dihydroxyvitamin D3(1,25D), has strong anti-proliferative effects, yet the molecular mechanisms underneath this effect remain unclear. In contrast, the molecular mechanism of 1,25D for the regulation of calcium homeostasis has principally

Synthesis, characterization, in vitro anti-proliferative and hemolytic activity of hydroxyapatite

Science.gov (United States)

Palanivelu, R.; Ruban Kumar, A.

2014-06-01

Hydroxyapatite (Ca10(PO4)6(OH)2, HAP) nanoparticles are widely used in several biomedical applications due to its compositional similarities to bone mineral, excellent biocompatibility and bioactivity, osteoconductivity. In this present investigation, HAP nanoparticles synthesized by precipitation technique using calcium nitrate and di-ammonium phosphate. The crystalline nature and the functional group analysis are confirmed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Fourier transform Raman spectroscopy (FT-Raman) respectively. The morphological observations are ascertained from field emission electron scanning electron microscope (FE-SEM) and transmission electron microscope (TEM). In vitro anti-proliferative and hemolytic activities are carried out on the synthesized HAP samples and the studies reveals that HAP have mild activity against erythrocytes.

Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in type 1 diabetes.

Science.gov (United States)

Herold, Kevan C; Pescovitz, Mark D; McGee, Paula; Krause-Steinrauf, Heidi; Spain, Lisa M; Bourcier, Kasia; Asare, Adam; Liu, Zhugong; Lachin, John M; Dosch, H Michael

2011-08-15

Type 1 diabetes mellitus is believed to be due to the autoimmune destruction of β-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte Ab, can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease-associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease-associated target Ags, and C-peptide levels of participants who did (responders) or did not (nonresponders) show signs of β-cell preservation 1 y after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after four weekly doses of mAb. T cell proliferative responses to diabetes-associated Ags were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 mo (58%), the proliferative responses to diabetes-associated total (p = 0.032), islet-specific (p = 0.048), and neuronal autoantigens (p = 0.005) increased over the 12-mo observation period. This relationship was not seen in placebo-treated patients. We conclude that in patients with type 1 diabetes mellitus, anti-B cell mAb causes increased proliferative responses to diabetes Ags and attenuated β-cell loss. The way in which these responses affect the disease course remains unknown.

Anti-proliferative effect of 20-hydroxyecdysone in a lepidopteran cell line.

Science.gov (United States)

Auzoux-Bordenave, Stéphanie; Hatt, Philippe-Jacques; Porcheron, Patrick

2002-02-01

Ecdysteroids are steroid hormones involved in the epidermal growth of arthropods, controlling cell proliferation and further differentiation of target cells. The epidermal cell line IAL-PID2, established from imaginal discs of the Indian meal moth Plodia interpunctella kept its sensitivity to ecdysteroids in vitro, cells being able to respond to them by cytological and biochemical changes. When added to the culture medium, 20-hydroxyecdysone (20E) stopped cell proliferation and induced formation of epithelial-like aggregates. In order to better understand the cellular sequence of ecdysteroids signalling in epidermal cells we used the IAL-PID2 cell line for in vitro investigations of cytological events induced by the moulting hormone. After a 40 h serum deprivation, formazan assay (XTT) was routinely used to evaluate anti-proliferative effects of 20E during cell cycle. We established a more precise timing of the period of cell sensitivity to the hormone during the cell cycle, by the use of the mitotic index and the BrdU incorporation test. These in vitro assays were performed in parallel with the description of some hormone dependant cytological events, using immunofluorescent labelling with anti-beta tubulin/FITC antibodies and DNA staining.

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.

Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa

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Yue, Grace G. L.; Chan, Ben C. L.; Hon, Po-Ming; Lee, Mavis Y. H.; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara B. S.

2010-01-01

The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (3 curcuminoids and 2 turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0–41.8 μg/ml. Alpha-turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of ar-turmerone were shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent. PMID:20438793

Synthesis, characterization and anti-proliferative activity of heterocyclic hypervalent organoantimony compounds.

Science.gov (United States)

Chen, Yi; Yu, Kun; Tan, Nian-Yuan; Qiu, Ren-Hua; Liu, Wei; Luo, Ning-Lin; Tong, Le; Au, Chak-Tong; Luo, Zi-Qiang; Yin, Shuang-Feng

2014-05-22

Three heterocyclic hypervalent organoantimony chlorides RN(CH2C6H4)2SbCl (2a R = t-Bu, 2b R = Cy, 2c R = Ph) and their chalcogenide derivatives [RN(CH2C6H4)2Sb]2O (3a R = t-Bu, 3b R = Cy, 3c R = Ph) were synthesized and characterized by techniques such as (1)H NMR, (13)C NMR, X-ray diffraction, and elemental analysis. It is found that the anti-proliferative activity detected over these compounds can be attributed to the coordination bond between the antimony and nitrogen atoms of these compounds. Moreover, a preliminary study on mechanistic action suggests that the inhibition effect is ascribable to cell cycle arrest and cell apoptosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Eco-friendly synthesis, in vitro anti-proliferative evaluation, and 3D-QSAR analysis of a novel series of monocationic 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazole mesylates.

Science.gov (United States)

Racané, Livio; Ptiček, Lucija; Sedić, Mirela; Grbčić, Petra; Kraljević Pavelić, Sandra; Bertoša, Branimir; Sović, Irena; Karminski-Zamola, Grace

2018-04-17

Herein, we describe the synthesis of twenty-one novel water-soluble monocationic 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazole mesylates 3a-3u and present the results of their anti-proliferative assays. Efficient syntheses were achieved by three complementary simple two-step synthetic protocols based on the condensation reaction of aryl/heteroaryl carbaldehydes or carboxylic acid. We developed an eco-friendly synthetic protocol using glycerol as green solvent, particularly appropriate for the condensation of thermally and acid-sensitive heterocycles such as furan, benzofuran, pyrrole, and indole. Screening of anti-proliferative activity was performed on four human tumour cell lines in vitro including pancreatic cancer (CFPAC-1), metastatic colon cancer (SW620), hepatocellular carcinoma (HepG2), and cervical cancer (HeLa), as well as in normal human fibroblast cell lines. All tested compounds showed strong to moderate anti-proliferative activity on tested cell lines depending on the structure containing aryl/heteroaryl moiety coupled to 6-(2-imidazolinyl)benzothiazole moiety. The most potent cytostatic effects on all tested cell lines with [Formula: see text] values ranging from 0.1 to 3.70 [Formula: see text] were observed for benzothiazoles substituted with naphthalene-2-yl 3c, benzofuran-2-yl 3e, indole-3-yl 3j, indole-2-yl 3k, quinoline-2-yl 3s, and quinoline-3-yl 3t and derivatives substituted with phenyl 3a, naphthalene-1-yl 3b, benzothiazole-2-yl 3g, benzothiazole-6-yl 3h, N-methylindole-3-yl 3l, benzimidazole-2-yl 3n, benzimidazole-5(6)-yl 3o, and quinolone-4-yl 3u with [Formula: see text] values ranging from 1.1 to 29.1 [Formula: see text]. Based on obtained anti-proliferative activities, 3D-QSAR models for five cell lines were derived. Molecular volume, molecular surface, the sum of hydrophobic surface areas, molecular mass, and possibility of making dispersion forces were identified by QSAR analyses as molecular properties that are

DMPD: Endogenous anti-inflammatory substances, inter-alpha-inhibitor and bikunin. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17132099 Endogenous anti-inflammatory substances, inter-alpha-inhibitor and bikunin.... Kobayashi H. Biol Chem. 2006 Dec;387(12):1545-9. (.png) (.svg) (.html) (.csml) Show Endogenous anti-inflam...matory substances, inter-alpha-inhibitor and bikunin. PubmedID 17132099 Title Endogenous anti-inflammatory s

Anti-proliferative therapy for HIV cure: a compound interest approach.

Science.gov (United States)

Reeves, Daniel B; Duke, Elizabeth R; Hughes, Sean M; Prlic, Martin; Hladik, Florian; Schiffer, Joshua T

2017-06-21

In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4 + T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size. We frame this concept in terms of compounding interest: small changes in interest rate drastically improve returns over time. On ART, latent cell proliferation rates are orders of magnitude larger than activation and new infection rates. Contingent on subtypes of cells that may make up the reservoir and their respective proliferation rates, our model predicts that coupling clinically available, anti-proliferative therapies with ART could result in functional cure within 2-10 years rather than several decades on ART alone.

Gene expression analysis of cell death induction by Taurolidine in different malignant cell lines

International Nuclear Information System (INIS)

Chromik, Ansgar M; Weyhe, Dirk; Mittelkötter, Ulrich; Uhl, Waldemar; Hahn, Stephan A; Daigeler, Adrien; Flier, Annegret; Bulut, Daniel; May, Christina; Harati, Kamran; Roschinsky, Jan; Sülberg, Dominique

2010-01-01

The anti-infective agent Taurolidine (TRD) has been shown to have cell death inducing properties, but the mechanism of its action is largely unknown. The aim of this study was to identify potential common target genes modulated at the transcriptional level following TRD treatment in tumour cell lines originating from different cancer types. Five different malignant cell lines (HT29, Chang Liver, HT1080, AsPC-1 and BxPC-3) were incubated with TRD (100 μM, 250 μM and 1000 μM). Proliferation after 8 h and cell viability after 24 h were analyzed by BrdU assay and FACS analysis, respectively. Gene expression analyses were carried out using the Agilent -microarray platform to indentify genes which displayed conjoint regulation following the addition of TRD in all cell lines. Candidate genes were subjected to Ingenuity Pathways Analysis and selected genes were validated by qRT-PCR and Western Blot. TRD 250 μM caused a significant inhibition of proliferation as well as apoptotic cell death in all cell lines. Among cell death associated genes with the strongest regulation in gene expression, we identified pro-apoptotic transcription factors (EGR1, ATF3) as well as genes involved in the ER stress response (PPP1R15A), in ubiquitination (TRAF6) and mitochondrial apoptotic pathways (PMAIP1). This is the first conjoint analysis of potential target genes of TRD which was performed simultaneously in different malignant cell lines. The results indicate that TRD might be involved in different signal transduction pathways leading to apoptosis

A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

Energy Technology Data Exchange (ETDEWEB)

Min, Kyung-Won [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Zhang, Xiaobo [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi, 712100 (China); Imchen, Temjenmongla [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Baek, Seung Joon, E-mail: sbaek2@utk.edu [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States)

2012-09-01

MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

International Nuclear Information System (INIS)

Min, Kyung-Won; Zhang, Xiaobo; Imchen, Temjenmongla; Baek, Seung Joon

2012-01-01

MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

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

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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.

Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells

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Andrea del Pilar Sánchez-Camargo

2016-12-01

Full Text Available In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116. The processes, carried out under optimal conditions, were: (1 pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent at lab-scale; (2 Single-step supercritical fluid extraction (SFE at pilot scale; (3 Intensified two-step sequential SFE at pilot scale; (4 Integrated PLE plus supercritical antisolvent fractionation (SAF at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight, this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA and carnosol (CS at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide, suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

International Nuclear Information System (INIS)

Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming; Wang, Yujiong

2012-01-01

In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC 50 ) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC 50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs

Avicenna's Canon of Medicine: a review of analgesics and anti-inflammatory substances

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Shahla Mahdizadeh

2015-04-01

Full Text Available Naturally occurring substances mentioned in medieval medical literatures currently have, and will continue to have, a crucial place in drug discovery. Avicenna was a Persian physician who is known as the most influential medical writers in the Middle ages. Avicenna`s Canon of Medicine, the most famous books in the history of medicine, presents a clear and organized summary of all the medical knowledge of the time, including a long list of drugs. Several hundred substances and receipts from different sources are mentioned for treatment of different illnesses in this book. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs presented in this comprehensive encyclopedia of medicine. Data for this review were provided by searches of different sections of this book. Long lists of anti-inflammatory and analgesic substances used in the treatment of various diseases are provided. The efficacy of some of these drugs, such as opium, willow oil, curcuma, and garlic, was investigated by modern medicine; pointed to their potent anti-inflammatory and analgesic properties. This review will help further research into the clinical benefits of new drugs for treatment of inflammatory diseases and pain.

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

International Nuclear Information System (INIS)

Jeng, Yow-Jiun; Watson, Cheryl S

2009-01-01

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, GH 3 /B 6 /F 10 , originally subcloned from GH 3 cells based on its ability to express high levels of the membrane estrogen receptor-α. 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. Four phytoestrogens (coumestrol, daidzein, genistein, and trans-resveratrol) were studied over wide concentration ranges. Except trans-resveratrol, all phytoestrogens increased GH 3 /B 6 /F 10 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. 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 growth, such as in the pituitary

Plant derived substances with anti-cancer activity: from folklore to practice

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Marcelo eFridlender

2015-10-01

Full Text Available Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70-95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early 19th century. This trend led to the discovery of different active compounds that are derived from plants. In the last decades, more and more new materials derived from plants have been authorized and subscribed as medicines, including those with anti-cancer activity. Cancer is among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next 2 decades. Thus, there is a real need for new efficient anti-cancer drugs with reduced side effects, and plants are a promising source for such entities. Here we focus on some plant-derived substances exhibiting anti-cancer and chemoprevention activity, their mode of action and bioavailability. These include paclitaxel, curcumin and cannabinoids. In addition, development and use of their synthetic analogs, and those of strigolactones, are discussed. Also discussed are commercial considerations and future prospects for development of plant derived substances with anti-cancer activity.

Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines

International Nuclear Information System (INIS)

Lee, Do Kyung; Jang, Seok; Kim, Mi Jin; Kim, Jung Hyun; Chung, Myung Jun; Kim, Kyung Jae; Ha, Nam Joo

2008-01-01

Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of Bifidobacterium adolescentis isolated from healthy young Koreans. The anti-proliferative activity of B. adolescentis isolates was assessed by XTT assays on three human colon cancer cell lines (Caco-2, HT-29, and SW480). The effects of B. adolescentis SPM0212 butanol extract on tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production were tested using the murine macrophage RAW 264.7 cell line. The butanol extract of B. adolescentis SPM0212 dose-dependently inhibited the growth of Caco-2, HT-29, and SW480 cells by 70%, 30%, and 40%, respectively, at 200 μg/mL. Additionally, the butanol extract of B. adolescentis SPM0212 induced macrophage activation and significantly increased the production of TNF-α and NO, which regulate immune modulation and are cytotoxic to tumor cells. The butanol extract of B. adolescentis SPM0212 increased activity of the host immune system and may improve human health by helping to prevent colon cancer as a biological response modifier

Proliferative glomerulonephritis and primary antiphospholipid syndrome

International Nuclear Information System (INIS)

Abdalla, H. Abdalla; Kfoury, Hala K.; Al-Khader, Abdulla A.; Al-Suleiman, M.

2006-01-01

Little is known regarding the association of primary antiphospholipid syndrome (APLS) and proliferative glomerulonephiritis (GN). We describe a biopsy-documented case with primary APLS and proliferative (GN) with no evidence of thrombotic microangiopathy (TMA), and in the absence of other manifestations of systematic lupus erythematosus (SLE). She presented initially with left popliteal deep venous thrombosis and nephrotic syndrome. Her first pregnancy at the age of 26 years resulted in the intra-uterine fetal death at term. Two subsequent pregnancies ended up with miscarriages at 3 and 4 months of gestation. Urinalysis revealed glomerular red blood cells of 1.0000.000/ml and granular cast; proteinuria of 13.4grams/24 hours, which was non-selective; hemoglobin 12 gm/dl, normal white blood cell and platelets; serum albumin 2.6gm/dl; anti-nuclear antibody (ANA) and anti DNA were negative and complement levels normal. Lupus anticoagulant was positive leading to a diagnosis of primary APLS. The biopsy findings were consistent with membranoproliferative GN. She continued to have steroid-resistant proteinuria, but stable renal function after a 12-year follow up period. She had 2 pregnancies during this period and was delivered at term using caesarian section. She received heparin during the pregnancies. Later she developed hypertension easily controlled by atenolol. This case provides evidence that primary APLS can be associated with proliferative GN due to immune deposits and not only TMA as previously reported, and in the complete absence of SLE. Performing more renal biopsies in this group of patients may disclose a greater prevalence of proleferative GN and may help in devising a rationale for treatment. (author)

Two novel prenylated kaempferol derivatives from fresh bud's fur of Platanus acerifolia and their anti-proliferative activities.

Science.gov (United States)

Zuo, Bo; Liao, Zhi-Xin; Xu, Chen; Liu, Chao

2016-01-06

Two novel prenylated kaempferol derivatives (1, 2), together with seven known metabolites were isolated from ethanol extract of fresh Platanus acerifolia bud's fur by multistep chromatographic processing. Structure of compounds 1 and 2 was confirmed by 1D, 2D NMR spectra and HR-ESI-MS. In addition, compound 1 was further analysed by X-ray crystallography. Anti-proliferative activities in vitro against human breast carcinoma (MCF-7) and human hepatocellular carcinoma (Hep-G2) cell lines for compound 1, 2 and 8 were evaluated. Compound 1 exhibited cytotoxic activity towards MCF-7 and Hep-G2 cell lines with the IC 50 values 38.2 and 39.5 μM, respectively. Moreover, compound 2 showed weak cytotoxic activities against the two cell lines.

Pharmacokinetic aspects of the anti-epileptic drug substance vigabatrin

DEFF Research Database (Denmark)

Nøhr, Martha Kampp; Frølund, Sidsel; Holm, René

2014-01-01

are discussed in detail. Special focus is on the contribution of the proton-coupled amino acid transporter 1 (PAT1) for intestinal vigabatrin absorption. Furthermore, the review gives an overview of the pharmacokinetic parameters of vigabatrin across different species and drug-food and drug-drug interactions......Drug transporters in various tissues, such as intestine, kidney, liver and brain, are recognized as important mediators of absorption, distribution, metabolism and excretion of drug substances. This review gives a current status on the transporter(s) mediating the absorption, distribution......, metabolism and excretion properties of the anti-epileptic drug substance vigabatrin. For orally administered drugs, like vigabatrin, the absorption from the intestine is a prerequisite for the bioavailability. Therefore, transporter(s) involved in the intestinal absorption of vigabatrin in vitro and in vivo...

Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia.

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Bouhenna, Mustapha M; Orlikova, Barbora; Talhi, Oualid; Schram, Ben; Pinto, Diana C G A; Taibi, Nadia; Bachari, Khaldoun; Diederich, Marc; Silva, Artur M S; Mameri, Nabil

2017-09-01

NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Extraction, purification and anti-proliferative activities of polysaccharides from Lentinus edodes.

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Zhao, Yong-Ming; Wang, Jin; Wu, Zhi-Gang; Yang, Jian-Ming; Li, Wei; Shen, Li-Xia

2016-12-01

In this study, the enzyme-assisted extraction of polysaccharides from Lentinus edodes (LEPs) was optimized by response surface methodology, and a preliminary characterization of the extracted LEPs and their anti-proliferative activities were investigated. An orthogonal assay was constructed to determine the optimal amounts of cellulase, papain and pectinase, which were 15, 20 and 15g/kg, respectively. Then effects of extraction conditions were evaluated and optimized using a Box-Behnken design. The results showed that the highest polysaccharides yield of 15.65% was achieved with an extraction temperature of 54°C, pH 5.0, enzymatic treatment time of 93min and a liquid/material ratio of 29:1mL/g, which correlated well with the predicted yield of 15.58%. Subsequently, the crude LEPs were further purified by DEAE-cellulose and Sephadex-100 chromatography to obtain two fractions, which were designated as LEP-1 and LEP-2 and their monosaccharide compositions were characterized by GC. Fourier-transform infrared spectra demonstrated that LEP-1 and LEP-2 were distinct from each other regarding their chemical structures. In addition, the LEPs exhibited inhibition of cell proliferation on HCT-116 and HeLa cells in vitro. In summary, this study provides an efficient enzyme-assisted extraction for LEPs, which can be used as natural antitumor agents in the pharmaceutical and functional food industries. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-proliferative activity of 2,6-dichloro-9- or 7-(ethoxycarbonylmethyl)-9H- or 7H-purines against several human solid tumour cell lines.

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Morales, Fátima; Ramírez, Alberto; Conejo-García, Ana; Morata, Cynthia; Marchal, Juan A; Campos, Joaquín M

2014-04-09

As leads we took several benzo-fused seven- and six-membered scaffolds linked to the pyrimidine or purine moieties with notable anti-proliferative activity against human breast, colon and melanoma cancerous cell lines. We then decided to maintain the double-ringed nitrogenous bases and change the other components to the ethyl acetate moiety. This way six purine and two 5-fluorouracil derivatives were obtained and evaluated against the MCF-7, HCT-116, A-375 and G-361 cancer cell lines. Two QSARs are obtained between the anti-proliferative IC₅₀ values for compounds 26-33 and the clog P against the melanoma cell lines A-375 and G-361. Our results show that two of the analogues [ethyl 2-(2,6-dichloro-9H- or 7H-purine-9- or 7-yl)acetates (30 and 33, respectively)] are potent cytotoxic agents against all the tumour cell lines assayed, showing single-digit micromolar IC₅₀ values. This exemplifies the potential of our previously reported purine compounds to qualify as lead structures for medicinal chemistry campaigns, affording simplified analogues easy to synthesize and with a noteworthy bioactivity. The selective activity of 30 and 33 against the melanoma cell line A-375, via apoptosis, supposes a great advantage for a future therapeutic use. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Enhanced anti-proliferative efficacy of epothilone B loaded with Escherichia coli Nissle 1917 bacterial ghosts on the HeLa cells by mitochondrial pathway of apoptosis.

Science.gov (United States)

Zhu, Wenxing; Hao, Lujiang; Liu, Xinli; Orlando, Borrás-Hidalgo; Zhang, Yuyu

2018-03-20

Epothilones constitute a new class of microtubule-stabilizing anti-cancer agents with promising preclinical and clinical activity. However, its systemic application still causes some toxic side effects. To reduce these undesired effects, advanced drug delivery systems based on cell targeting carriers are needed currently. In this study, the high quality bacterial ghosts of the probiotic Escherichia coli Nissle 1917 (EcN) were prepared in a large scale and retained fully intact surface structures for specific attachment to mammalian cells. The EcN ghosts could be efficiently loaded with the low hydrophilic drug Epothilone B (Epo B) and the maximal load efficiency was approximately 2.5% (w/w). Cytotoxicity assays revealed that Epo B-ghosts exhibited enhanced anti-proliferative properties on the HeLa cells. The Epo B associated with EcN ghosts was more cytotoxic at least 10 times than the free Epo B at the same concentrations. Apoptosis assays showed that both Epo B-ghosts and free Epo B induced time course-dependent apoptosis and necrosis in HeLa cells, respectively. While the former induced more apoptosis and necrosis than the latter. Furthermore, the cytochrome C release and the activation of caspase-3 were more remarkable after treatment with the Epo B-ghosts compared to the free Epo B, which implied that Epo B-ghosts might more effectively induce the apoptosis mediated by mitochondrial pathway in HeLa cells. Therefore, the higher anti-proliferative effects of the Epo B-ghosts on the HeLa cells were mediated by mitochondrial pathway of apoptosis. The EcN ghosts may provide a useful drug delivery carrier for drug candidates in cancer therapy.

Differential expression of follistatin and FLRG in human breast proliferative disorders

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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

The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

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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

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

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Lee, Jessica J.; Prince, Lisa K.; Baker, Thomas P.; Papadopoulos, Patricia; Edison, Jess; Abbott, Kevin C.

2013-01-01

Summary Background and objectives Elevated anti–double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. Design, setting, participants, & measurements This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993–2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. Results More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Conclusions Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE. PMID:23833315

Cysteine-based 3-substituted 1,5-benzoxathiepin derivatives: Two new classes of anti-proliferative agents

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Nawal Mahfoudh

2018-03-01

Full Text Available Two distinct series of the 3-amino-1,5-benzoxathiepin scaffold, derived from L-cysteine, were synthesized and evaluated for their anti-proliferative activity in the breast cancer MDA-MB-231 and MCF-7 cells, and in the ovarian carcinoma SKOV-3 cell line. (3R-Amino-3,4-dihydro-2H-1,5-benzoxathiepin [(R-10] was diversified into two forms: (a by incorporating different amino acids at its position 3, through an amide bond; and (b by construction of the purine ring to give 6-chloro-9-[2-(3,4-dihydro-2H-1,5-benzoxathiepin-(3R-yl]-9H-purine [(R-28]. Nevertheless, when the introduction of iodine was tried at position 2 of the purine ring of (R-28, 2-{[2-(6-chloro-2-iodo-9H-purin-9-ylprop-2-en-1-yl]thio}phenol (34 was obtained. Compound 34 shows activity against cancer cells. Interestingly, 34 inhibits mammosphere formation at the micromolar range, demonstrating activity against cancer stem cells. Although further studies of its targets and mechanism of action are needed, these findings support the therapeutic potential of this compound in cancer.

Anti-vascular endothelial growth factor for prevention of postoperative vitreous cavity haemorrhage after vitrectomy for proliferative diabetic retinopathy.

Science.gov (United States)

Smith, Jonathan M; Steel, David H W

2015-08-07

Postoperative vitreous cavity haemorrhage (POVCH) is a significant complication following vitrectomy for proliferative diabetic retinopathy (PDR). It delays visual recovery and can make further treatment difficult if the view of the fundus is significantly obscured. A number of interventions to reduce the incidence of POVCH have been proposed, including the perioperative use of anti-vascular endothelial growth factor (anti-VEGF). Anti-VEGFs reduce vascular proliferation and the vascularity of neovascular tissue, which is often the source of bleeding following vitrectomy. This updated review aimed to summarise the effects of anti-VEGF use to reduce the occurrence of POVCH after vitrectomy surgery for PDR. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May 2015), PubMed (January 1966 to May 2015), EMBASE (January 1980 to May 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to May 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 26 May 2015. We included all randomised controlled trials (RCTs) and quasi-RCTs that looked at the use of anti-VEGFs and the incidence of POVCH in people undergoing vitrectomy for PDR. Both review authors independently assessed and extracted the data. We used standard methodological procedures expected by Cochrane.The primary outcomes of the review were the incidence of early and late POVCH following perioperative anti-VEGF administration. Secondary outcomes included best-corrected visual acuity at six months following

Social Activity, School-Related Activity, and Anti-Substance Use Media Messages on Adolescent Tobacco and Alcohol Use.

Science.gov (United States)

Moon, Sung Seek; Rao, Uma

2011-01-01

In this article, we present the effects of three hypothesized protective factors: social activities, school-related activities, and anti-substance use media messages on adolescent tobacco and alcohol use. Data were drawn from the "Monitoring the Future" (MTF) research project, which was conducted by the Institute for Social Research at the University of Michigan. The sample included 2,551 twelfth-grade students. The results of the structural equation model showed that exposure to media anti-drug messages had an indirect negative effect on tobacco and alcohol use through school-related activity and social activity. The results suggest that comprehensive ecological interventions encompassing media, family, and school can increase on the preventive effects of adolescent's substance use.

Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines

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Takeshima, Mikako; Ono, Misaki; Higuchi, Takako; Chen, Chen; Hara, Takayuki; Nakano, Shuji

2014-01-01

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. PMID:24397737

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.

Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma.

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Mauchle, Ulrike; Selvarajah, Gayathri T; Mol, Jan A; Kirpensteijn, Jolle; Verheije, Monique H

2015-08-01

Osteosarcoma is the most common primary bone tumour in dogs but various forms of therapy have not significantly improved clinical outcomes. As dysregulation of kinase activity is often present in tumours, kinases represent attractive molecular targets for cancer therapy. The purpose of this study was to identify novel compounds targeting kinases with the potential to induce cell death in a panel of canine osteosarcoma cell lines. The ability of 80 well-characterized kinase inhibitor compounds to inhibit the proliferation of four canine osteosarcoma cell lines was investigated in vitro. For those compounds with activity, the mechanism of action and capability to potentiate the activity of doxorubicin was further evaluated. The screening showed 22 different kinase inhibitors that induced significant anti-proliferative effects across the four canine osteosarcoma cell lines investigated. Four of these compounds (RO 31-8220, 5-iodotubercidin, BAY 11-7082 and an erbstatin analog) showed significant cell growth inhibitory effects across all cell lines in association with variable induction of apoptosis. RO 31-8220 and 5-iodotubercidin showed the highest ability to potentiate the effects of doxorubicin on cell viability. In conclusion, the present study identified several potent kinase inhibitors targeting the PKC, CK1, PKA, ErbB2, mTOR and NF-κB pathways, which may warrant further investigations for the treatment of osteosarcoma in dogs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Halofuginone has anti-proliferative effects in acute promyelocytic leukemia by modulating the transforming growth factor beta signaling pathway.

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Lorena L de Figueiredo-Pontes

Full Text Available Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα expression in acute promyelocytic leukemia (APL impairs transforming growth factor beta (TGFβ signaling, leading to cell growth advantage. Halofuginone (HF, a low-molecular-weight alkaloid that modulates TGFβ signaling, was used to treat APL cell lines and non-obese diabetic/severe combined immunodeficiency (NOD/SCID mice subjected to transplantation with leukemic cells from human chorionic gonadotrophin-PML-RARα transgenic mice (TG. Cell cycle analysis using incorporated bromodeoxyuridine and 7-amino-actinomycin D showed that, in NB4 and NB4-R2 APL cell lines, HF inhibited cellular proliferation (P<0.001 and induced apoptosis (P = 0.002 after a 24-hour incubation. Addition of TGFβ revealed that NB4 cells were resistant to its growth-suppressive effects and that HF induced these effects in the presence or absence of the cytokine. Cell growth inhibition was associated with up-regulation of TGFβ target genes involved in cell cycle regulation (TGFB, TGFBRI, SMAD3, p15, and p21 and down-regulation of MYC. Additionally, TGFβ protein levels were decreased in leukemic TG animals and HF in vivo could restore TGFβ values to normal. To test the in vivo anti-leukemic activity of HF, we transplanted NOD/SCID mice with TG leukemic cells and treated them with HF for 21 days. HF induced partial hematological remission in the peripheral blood, bone marrow, and spleen. Together, these results suggest that HF has anti-proliferative and anti-leukemic effects by reversing the TGFβ blockade in APL. Since loss of the TGFβ response in leukemic cells may be an important second oncogenic hit, modulation of TGFβ signaling may be of therapeutic interest.

Social Activity, School-Related Activity, and Anti-Substance Use Media Messages on Adolescent Tobacco and Alcohol Use

OpenAIRE

Moon, Sung Seek; Rao, Uma

2011-01-01

In this article, we present the effects of three hypothesized protective factors: social activities, school-related activities, and anti-substance use media messages on adolescent tobacco and alcohol use. Data were drawn from the “Monitoring the Future” (MTF) research project, which was conducted by the Institute for Social Research at the University of Michigan. The sample included 2,551 twelfth-grade students. The results of the structural equation model showed that exposure to media anti-d...

The Budding Yeast “Saccharomyces cerevisiae” as a Drug Discovery Tool to Identify Plant-Derived Natural Products with Anti-Proliferative Properties

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Bouchra Qaddouri

2011-01-01

Full Text Available The budding yeast Saccharomyces cerevisiae is a valuable system to study cell-cycle regulation, which is defective in cancer cells. Due to the highly conserved nature of the cell-cycle machinery between yeast and humans, yeast studies are directly relevant to anticancer-drug discovery. The budding yeast is also an excellent model system for identifying and studying antifungal compounds because of the functional conservation of fungal genes. Moreover, yeast studies have also contributed greatly to our understanding of the biological targets and modes of action of bioactive compounds. Understanding the mechanism of action of clinically relevant compounds is essential for the design of improved second-generation molecules. Here we describe our methodology for screening a library of plant-derived natural products in yeast in order to identify and characterize new compounds with anti-proliferative properties.

Cetuximab-Associated Crescentic Diffuse Proliferative Glomerulonephritis

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Sukesh Manthri

2017-01-01

Full Text Available Cetuximab-induced nephrotoxicity is very rare, occurring in less than 1% of colorectal cancer patients and not defined in other populations. We report a rare case of crescentic diffuse proliferative glomerulonephritis (GN that developed in close temporal association with cetuximab treatment. A 65-year-old female recently completed chemotherapy with cetuximab treatment for moderately differentiated oral squamous cell carcinoma. She was admitted with acute renal failure and nephrotic-range proteinuria. Laboratory data showed serum creatinine of 6.6 mg/dl and urinalysis showed proteinuria, moderate hemoglobinuria, hyaline casts (41/LPF, WBC (28/HPF, and RBC (81/HPF. Serologic studies were negative for ANA, anti-GBM, ANCA, hepatitis B, and hepatitis C. Serum C3 and C4 level were normal. Renal biopsy showed crescentic diffuse proliferative GN with focal features of thrombotic microangiopathy. Patient was started on cyclophosphamide and steroids. Her renal function did not improve on day 8 and she was started on hemodialysis. Previous reports suggest that EGFR-targeting medications can possibly trigger or exacerbate an IgA-mediated glomerular process leading to renal failure. This case suggests that cetuximab therapy may have triggered or exacerbated a severe glomerular injury with an unfavorable outcome. Treating physicians should maintain a high degree of caution and monitor renal function in patients on EGFR inhibitors.

Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects

International Nuclear Information System (INIS)

Corona, Giulia; Deiana, Monica; Incani, Alessandra; Vauzour, David; Assunta Dessi, M.; Spencer, Jeremy P.E.

2007-01-01

We investigated the anti-proliferative effects of an olive oil polyphenolic extract on human colon adenocarcinoma cells. Analysis indicated that the extract contained hydroxytyrosol, tyrosol and the various secoiridoid derivatives, including oleuropein. This extract exerted a strong inhibitory effect on cancer cell proliferation, which was linked to the induction of a G2/M phase cell cycle block. Following treatment with the extract (50 μg/ml) the number of cells in the G2/M phase increased to 51.82 ± 2.69% relative to control cells (15.1 ± 2.5%). This G2/M block was mediated by the ability of olive oil polyphenols (50 μg/ml) to exert rapid inhibition of p38 (38.7 ± 4.7%) and CREB (28.6 ± 5.5%) phosphorylation which led to a downstream reduction in COX-2 expression (56.9 ± 9.3%). Our data suggest that olive oil polyphenols may exert chemopreventative effects in the large intestine by interacting with signalling pathways responsible for colorectal cancer development

Lack of a differential radiation response for proliferative and non-proliferative rat thyroid cells (FRTL-5) in vitro

International Nuclear Information System (INIS)

Brosing, J.W.; Giese, W.L.; Mulcahy, R.T.

1989-01-01

FRTL-5 rat thyroid epithelial cells maintain normal thyroid function and morphology in vitro, exhibit an absolute requirement for thyroid stimulating hormone (TSH) for proliferation and display radiation dose response characteristics indistinguishable from those of rat thyroid epithelial cells in vivo. In TSH-free medium cells remain in a non-proliferative, yet viable, state for prolonged periods of time and respond to TSH re-stimulation by a return to exponential growth. Flow cytometric analysis using two-step acridine orange (AO) staining revealed an accumulation of cells in the G1 phase of the cell cycle accompanied by a pronounced reduction in red fluorescence (indicative of RNA content) in FRTL-5 cells cultured in the absence of TSH. The response of proliferative and non-proliferative FRTL-5 cells to single dose, split dose and fractionated radiation was compared to determine whether proliferative status was an important response determinant. The response of FRTL-5 cells was not influenced by proliferative status at the time of irradiation. Additionally, dose response was not altered by variable (12 hr-8 days) non-proliferative intervals before or after irradiation. As revealed by split dose experiments, the rate and extent of sublethal damage repair was likewise similar for proliferative and non-proliferative cells. Multifraction experiments employing three fractions separated by 6 hr intervals indicate that non-proliferative FRTL-5 cells completely repair sublethal damage between fractions. These results indicate that the radiation response of FRTL-5 cells is not influenced by the proliferative status of the cells prior to or post-irradiation

Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells

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Helson Lawrence

2007-01-01

Full Text Available Abstract Background With current treatment strategies, nearly half of all medulloblastoma (MB patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma – an embryonal tumor with biological similarities to MB – the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression. Methods To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected, D341 (c-MYC amplification and D425 (c-MYC amplification human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed. Results NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7 – 9.6 ng/ml and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary. Conclusion In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit

Antibacterial, antioxidant and anti-proliferative properties and zinc content of five south Portugal herbs.

Science.gov (United States)

Nunes, Ricardo; Pasko, Pawel; Tyszka-Czochara, Malgorzata; Szewczyk, Agnieszka; Szlosarczyk, Marek; Carvalho, Isabel S

2017-12-01

Crataegus monogyna L. (Rosaceae) (CM), Equisetum telmateia L. (Equisataceae) (ET), Geranium purpureum Vil. (Geraniaceae) (GP), Mentha suaveolens Ehrh. (Lamiaceae) (MS), and Lavandula stoechas L. spp. luisieri (Lamiaceae) (LS) are all medicinal. To evaluate the antioxidant, antiproliferative and antimicrobial activities of plant extracts and quantify individual phenolics and zinc. Aerial part extracts were prepared with water (W), ethanol (E) and an 80% mixture (80EW). Antioxidant activity was measured with TAA, FRAP and RP methods. Phenolics were quantified with a HPLC. Zinc was quantified using voltammetry. Antibacterial activity (after 48 h) was tested using Enterococcus faecalis, Bacillus cereus, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Listeria monocytogenes. Antiproliferative activity (after 24 h) was tested using HEP G2 cells and fibroblasts. Solvents influenced results; the best were E and 80EW. GP had the highest antioxidant activity (TAA and FRAP of 536.90 mg AAE/g dw and 783.48 mg TE/g dw, respectively). CM had the highest zinc concentration (37.21 mg/kg) and phenolic variety, with neochlorogenic acid as the most abundant (92.91 mg/100 g dw). LS was rich in rosmarinic acid (301.71 mg/100 g dw). GP and LS inhibited the most microorganisms: B. cereus, E. coli and S. aureus. GP also inhibited E. faecalis. CM had the lowest MIC: 5830 μg/mL. The antibacterial activity is explained by the phenolics present. LS and CM showed the most significant anti-proliferative activity, which is explained by their zinc content. The most promising plants for further studies are CM, LS and GP.

Cambogin exerts anti-proliferative and pro-apoptotic effects on breast adenocarcinoma through the induction of NADPH oxidase 1 and the alteration of mitochondrial morphology and dynamics.

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Shen, Kaikai; Lu, Fangfang; Xie, Jianling; Wu, Minfeng; Cai, Bo; Liu, Yurong; Zhang, Hong; Tan, Hongsheng; Pan, Yingyi; Xu, Hongxi

2016-08-02

Cambogin, a bioactive polycyclic polyprenylated acylphoroglucinol (PPAP) derived from the Garcinia genus, possesses proapoptotic effect in medulloblastoma and breast cancer cells. We have previously demonstrated that the proapoptotic effect of cambogin is driven by the production of reactive oxygen species (ROS). Here we have shown that the inhibitory effect of cambogin on cell proliferation is associated with the loss of mitochondrial transmembrane potential (ΔΨm) and mitochondrial fragmentation. Cambogin also promotes the mutual complex formation of the membrane-bound subunit p22phox of NADPH oxidase 1 (NOX1), as well as the phosphorylation of the cytosolic subunit p47phox, subsequently enhancing membrane-bound NOX1 activity, which leads to increases in intracellular and mitochondrial levels of O2.- and H2O2. Pharmacological inhibition of NOX1 using apocynin (pan-NOX inhibitor), ML171 (NOX1 inhibitor) or siRNA against NOX1 prevents the increases in O2.- and H2O2 levels and the anti-proliferative effect of cambogin. Antioxidants, including SOD (superoxide dismutase), CAT (catalase) and EUK-8, are also able to restore cell viability in the presence of cambogin. Besides, cambogin increases the dissociation of thioredoxin-1 (Trx1) from ASK1, switching the inactive form of ASK1 to the active kinase, subsequently leads to the phosphorylation of JNK/SAPK, which is abolished upon ML171 treatment. The proapoptotic effect of cambogin in breast cancer cells is also aggravated upon knocking down Trx1 in MCF-7 cells. Taken in conjunction, these data indicate that the anti-proliferative and pro-apoptotic effect of cambogin is mediated via inducing NOX1-dependent ROS production and the dissociation of ASK1 and Trx1.

Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34+ cells of juvenile myelomonocytic leukemia

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Yozo Nakazawa

2016-03-01

Full Text Available Abstract Background Juvenile myelomonocytic leukemia (JMML is a fatal, myelodysplastic/myeloproliferative neoplasm of early childhood. Patients with JMML have mutually exclusive genetic abnormalities in granulocyte-macrophage colony-stimulating factor (GM-CSF receptor (GMR, CD116 signaling pathway. Allogeneic hematopoietic stem cell transplantation is currently the only curative treatment option for JMML; however, disease recurrence is a major cause of treatment failure. We investigated adoptive immunotherapy using GMR-targeted chimeric antigen receptor (CAR for JMML. Methods We constructed a novel CAR capable of binding to GMR via its ligand, GM-CSF, and generated piggyBac transposon-based GMR CAR-modified T cells from three healthy donors and two patients with JMML. We further evaluated the anti-proliferative potential of GMR CAR T cells on leukemic CD34+ cells from six patients with JMML (two NRAS mutations, three PTPN11 mutations, and one monosomy 7, and normal CD34+ cells. Results GMR CAR T cells from healthy donors suppressed the cytokine-dependent growth of MO7e cells, but not the growth of K562 and Daudi cells. Co-culture of healthy GMR CAR T cells with CD34+ cells of five patients with JMML at effector to target ratios of 1:1 and 1:4 for 2 days significantly decreased total colony growth, regardless of genetic abnormality. Furthermore, GMR CAR T cells from a non-transplanted patient and a transplanted patient inhibited the proliferation of respective JMML CD34+ cells at onset to a degree comparable to healthy GMR CAR T cells. Seven-day co-culture of GMR CAR T cells resulted in a marked suppression of JMML CD34+ cell proliferation, particularly CD34+CD38− cell proliferation stimulated with stem cell factor and thrombopoietin on AGM-S3 cells. Meanwhile, GMR CAR T cells exerted no effects on normal CD34+ cell colony growth. Conclusions Ligand-based GMR CAR T cells may have anti-proliferative effects on stem and progenitor cells in JMML.

Efficacy and safety of adjuvant intravitreal injection of anti-vascular endothelial growth factors prior to vitrectomy in the treatment of proliferative diabetic retinopathy: A Meta-analysis

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Jun Li

2017-08-01

Full Text Available AIM: To investigate the effectiveness and safety of intravitreal injection of anti-vascular endothelial growth factors(VEGFdrugs to the patients with proliferative diabetic retinopathy before vitrectomy treatment.METHODS: A Meta-analysis. A comprehensive retrieval was conducted using the database including EMbase, the Cochrane Library, Pubmed, CBM, WanFang Database, CNKI and so on. The retrieval time was limited from the building time of database to Jan. 2017. The randomized controlled trial was adopted with no requirements on languages. The Jadad scale and Cochrance cooperation were used as the tool of the risk and bias evaluation to analyze the literature quality. Quality estimation of evidence-based medicine on the parameters of each evaluation index was made via GRADEpro Software. The publishing biases of enclosed documents were inspected with funnel plot. At last, the Meta analysis was conducted with Review Manager 5.3.RESULTS: Totally 16 literatures published from 2008-2016 were finally put into randomized controlled trial. A total of 923 cases were included, among which 493 cases were grouped as intravitreal injection of anti-VEGF before the combined operation of PPV group(the experimental group, and 430 cases were involved in simple PPV group(the control group. The results of Meta-analysis show:(1The probability of intraoperative bleeding was remarkably lower than the control group \\〖OR=0.06, 95%CI(0.02, 0.15, PWMD=-29.13, 95% CI(-36.95, -21.30, POR=0.34, 95%CI(0.20, 0.58, PWMD=-0.51(LogMAR, 95%CI(-1.10, 0.08, P=0.09\\〗 with no statistical significance.(5The occurrence of iatrogenic retinal rupture was lower than that of the control group\\〖OR=0.24, 95%CI(0.14, 0.40, PCONCLUSION: It is effective and safe for the patients with proliferative diabetic retinopathy to inject anti-VEGF drugs into vitreous cavity before vitrectomy. And it can reduce the occurrence of complications during and after surgery, improving the general treatment

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...... cohort. All type 1 diabetic patients from Fyn County, Denmark, were identified as of 1 July 1973. One hundred and eighty four patients were examined in 1981-1982 (baseline) and in 2007-2008 (follow-up). The level of retinopathy was graded by ophthalmoscopy at baseline and nine-field digital colour fundus...... and proliferative retinopathy, respectively. In conclusion, proliferative retinopathy is an independent marker of long-term nephropathy in type 1 diabetes. Upcoming studies should examine whether these microvascular complications are also causally linked in type 1 diabetes....

Non-Proliferative Diabetic Retinopathy Vision Simulator

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... Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis Focus On Pediatric Ophthalmology ... Retinopathy Diagnosis Diabetic Retinopathy Treatment Proliferative Diabetic Retinopathy Vision Simulator Non-Proliferative Diabetic ...

Synthesis and in vitro anti-proliferative effects of 3-(hetero)aryl substituted 3-[(prop-2-ynyloxy)(thiophen-2-yl)methyl]pyridine derivatives on various cancer cell lines.

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Reddy Chamakura, Upendar; Sailaja, E; Dulla, Balakrishna; Kalle, Arunasree M; Bhavani, S; Rambabu, D; Kapavarapu, Ravikumar; Rao, M V Basaveswara; Pal, Manojit

2014-03-01

A series of 3-(hetero)aryl substituted 3-[(prop-2-ynyloxy)(thiophen-2-yl)methyl]pyridine derivatives were designed as potential anticancer agents. These compounds were conveniently prepared by using Pd/C-Cu mediated Sonogashira type coupling as a key step. Many of these compounds were found to be promising when tested for their in vitro anti-proliferative properties against six cancer cell lines. All these compounds were found to be selective towards the growth inhibition of cancer cells with IC50 values in the range of 0.9-1.7 μM (against MDA-MB 231 and MCF7 cells), comparable to the known anticancer drug doxorubicin. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Partisan Trajectory of the American Pro-Life Movement: How a Liberal Catholic Campaign Became a Conservative Evangelical Cause

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Daniel K. Williams

2015-04-01

Full Text Available This article employs a historical analysis of the religious composition of the pro-life movement to explain why the partisan identity of the movement shifted from the left to the right between the late 1960s and the 1980s. Many of the Catholics who formed the first anti-abortion organizations in the late 1960s were liberal Democrats who viewed their campaign to save the unborn as a rights-based movement that was fully in keeping with the principles of New Deal and Great Society liberalism, but when evangelical Protestants joined the movement in the late 1970s, they reframed the pro-life cause as a politically conservative campaign linked not to the ideology of human rights but to the politics of moral order and “family values.” This article explains why the Catholic effort to build a pro-life coalition of liberal Democrats failed after Roe v. Wade, why evangelicals became interested in the antiabortion movement, and why the evangelicals succeeded in their effort to rebrand the pro-life campaign as a conservative cause.

Anti-proliferative effects of gold nanoparticles functionalized with Semaphorin 3F

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Tan, Gamze; Onur, Mehmet Ali

2017-08-01

The new vessel formations play a vital role in growth and spread of cancer. Current anti-angiogenic therapies, predominantly based on vascular endothelial growth factor (VEGF) inhibition, can inhibit vascular development; however, they are usually ineffective against the primary tumor occurrence. The aim of this study was to assess anti-angiogenic effects of gold nanoparticles (AuNPs) functionalized with Semaphorin (Sema) 3F protein. The polyethylene glycol (PEG)-coated AuNPs were covalently functionalized with Sema 3F and labeled with the TAMRA fluorescent dye. The effect of the NPs on human umbilical vein endothelial cells (HUVECs) is probed in the way of internalization and viability assays. AuNP-Sema 3F bioconjugates showed great endothelial cell uptake. AuNP-Sema 3F bioconjugates reduced VEGF165-induced endothelial cell proliferation more effectively than Sema 3F alone, suggesting that the therapeutic effects of Sema 3F can be improved by conjugation to AuNPs. Also, no significant toxicity effect was induced by bioconjugates. This is the first study that reports a covalent binding of full length Sema 3F to NPs. The exogenously administration of Sema 3F, which has both anti-angiogenic and anti-tumoral activity, to tumor vasculature via a carrying platform may not only lead to more effective anti-angiogenic treatment but also may make current approach more applicable in clinical use like drug delivery system. [Figure not available: see fulltext.

Australian athletes' knowledge of the WADA Prohibited Substances List and performance enhancing substances.

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Orr, Rhonda; Grassmayr, Matthew; Macniven, Rona; Grunseit, Anne; Halaki, Mark; Bauman, Adrian

2018-03-15

This study investigated athlete knowledge of the World Anti-doping Agency (WADA) Prohibited Substances List and the effects of four well-known performance enhancing substances (PES). A sample of 1925 elite and sub-elite athletes (mean age 20.6 years) completed a questionnaire about the banned status of 30 substances/methods and their knowledge of the effects of amphetamines, anabolic steroids, growth hormone and erythropoietin. Athletes showed limited understanding of the WADA Prohibited Substances List, scoring 32.2% correct, 36.3% incorrect, and 31.4% indicated they did not know the status of 30 substances. Responses of >50% correct were given for only eight substances/method: anabolic steroids, amphetamines, blood doping, erythropoietin, caffeine, vitamins/minerals, protein powders and iron. Athletes demonstrated moderate knowledge of the desired effects of the four PES (49% correct), but poor knowledge of their adverse effects (29% correct). Age, sex, ethnicity, professional/amateur status, and current competition level were significant predictors of the number of correct responses (r 2  = 0.16, p wide range of substances and PES. Better targeted drug education towards younger and non-professional athletes and evaluation of current anti-doping programs are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

Introducing the Table of the Elements of Anti-Substance, and the Theoretical Grounds to It

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Khazan A.

2009-04-01

Full Text Available Herein we study how the Hyperbolic Law acts in the Periodic Table of Elements, in each of the four quadrants of the plane “molecular mass X — contents of element Y ”. It is shown that the symmetry of the equation Y = K/X is permitted only in the 1st and 2nd quadrants. The negative numerical values on the X -axis, and also K < 0 , testify that the 2nd quadrant should contain the elements and compounds of anti-substances.

Anti-proliferative effect of olmesartan on Tenon's capsule fibroblasts

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Xuan Wang

2016-05-01

Full Text Available AIM: To evaluate the inhibitive effect of olmesartan to fibroblast proliferation and the anti-scarring effect in Tenon’s capsule, both in vitro and in vivo. METHODS: Human primary Tenon’s capsule fibroblasts were cultured in vitro, treated with up titrating concentrations of olmesartan. The rate of inhibition was tested with methyl thiazol tetrazolium (MTT method. Real-time PCR was performed to analyze changes in mRNA expressions of the fibrosis-related factors: matrix metalloproteinase-2 (MMP-2, tissue inhibitor of metalloproteinase (TIMP-1,2 and proliferating cell nuclear antigen (PCNA. Thirty rabbits were divided into 5 groups (3, 7, 14, 21, and 28d. A rabbit conjunctiva flap model was created in each eye. Olmesartan solution was injected subconjunctivally and then evaluated its anti-proliferation and anti-fibrosis effects through the histological morphology and immunohistochemistry of MMP-2 and PCNA in each group. Only the 7d group was treated with Masson’s trichrome to compare the neovascularization in the subconjunctiva area. RESULTS: In vitro, cultured Tenon's capsule human fibroblasts showed a dose dependent inhibition by olmesartan in MTT. Olmesartan reduced mRNA expressions of MMP-2 and PCNA but increased mRNA expressions of TIMP-1 and TIMP-2. In vivo, the rabbit eyes treated with olmesartan at 3rd, 7th, 14th and 21st days demonstrated a significant reduced expressions of MMP-2 and PCNA compared with control eye, no significant difference observed in 28th day group. The cellular proliferation and neovascularization was suppressed by olmesartan in Masson’s trichrome observation. CONCLUSION: By inhibiting fibroblasts in vitro and in vivo, olmesartan prevents the proliferation and activity of fibroblasts in scar tissue formation, which might benefit glaucoma filtering surgery.

Perceived Parental Legitimacy as a Moderator of Parent-Child Communication's Effects on Latina/o Adolescent Substance Use.

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Kam, Jennifer A; Pérez Torres, Debora

2018-06-01

Utilizing primary socialization theory (PST) and longitudinal survey data from 381 Latina/o sixth- through eighth-grade students, we hypothesized that four types of parent anti-substance use messages (i.e., parents' own past substance use, religious beliefs, respect for family, and peer resistance) would discourage Latina/o students' substance use, particularly when the students perceived their parents' anti-substance use messages were legitimate. The results supported moderation. For Latina/o students who thought that their parents' anti-substance use messages were legitimate, many of the anti-substance use messages were negatively related to substance use, but the associations were positive or nonsignificant for Latina/o students who thought that their parents' anti-substance use messages were not legitimate. The findings extend past work on PST and anti-substance use parent-child communication, highlighting the importance of perceived legitimacy and message content.

The list of prohibited substances and methods in sport: structure and review process by the world anti-doping agency.

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Mazzoni, Irene; Barroso, Osquel; Rabin, Olivier

2011-11-01

The List of Prohibited Substances and Methods (the List) is the International Standard that determines what is prohibited in sport in- and out-of-competition. The official text of the List is produced by the World Anti-Doping Agency (WADA), the international independent organization responsible for promoting, coordinating and monitoring the fight against doping in sport. The drafting of the annual List is a highly interactive and consultative process involving scientific and medical experts in anti-doping, sport federations and governments. In this article, the elements that compose the List as well as the process behind its annual revision and update are presented.

A possible anti-proliferative and anti-metastatic effect of irradiated riboflavin in solid tumours

NARCIS (Netherlands)

de Souza Queiroz, Karla Cristiana; Zambuzzi, Willian Fernando; de Souza, Ana Carolina Santos; da Silva, Rodrigo Augusto; Machado, Daisy; Justo, Giselle Zenker; Carvalho, Hernandes F.; Peppelenbosch, Maikel P.; Ferreira, Carmen Verissima

2007-01-01

Riboflavin is a potent photosensitizer as well as part of the vitamin B complex. Recently we demonstrated that the products generated by irradiation of riboflavin have potential as anti-leukaemic therapy. The possible action, however, of the riboflavin photoproducts in solid cancers has not been

Benign Proliferative Breast Lesions and Risk of Cancer

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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

Comorbidity of substance dependency in patients with cluster B personality disorders

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Faezeh Tatari

2016-01-01

Full Text Available Background: Personality disorders are considered as a risk factor for the development and intensification of substance dependency. This study was aimed to determine the comorbidity of substance dependency in patients with cluster B personality disorders. Method: This cross-sectional study was performed on 96 patients (71 males and 25 females referring to Farabi Hospital, Kermanshah, Iran .The data were gathered using a questionnaire. Data analysis was performed by SPSS software. Results: Data analysis revealed that borderline personality disorder with one year substance abuse, combination of histrionic, borderline, narcissistic and anti-social disorders with two years of substance abuse, borderline personality disorder or a combination of borderline, histrionic, narcissistic and anti-social disorders with three years of substance abuse and combination of narcissistic, borderline, histrionic and anti-social disorders in patients with more than three years of substance dependency had the highest prevalence. Narcissistic personality disorder in patients with no attempts to quit and combination of histrionic, borderline, narcissistic and anti-social disorders in patients with two or three attempts to quit had the highest prevalence. Conclusion: The results showed a relationship between substance dependency and cluster B personality disorders. Considering the prevalence of personality disorders among drug abusers, psychological and psychiatric interventions along with medication are necessary in substance abuse treatment centers.

Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models

NARCIS (Netherlands)

Kleemann, R.; Verschuren, L.; Morrison, M.; Zadelaar, A.S.M.; Erk, M.J. van; Wielinga, P.Y.; Kooistra, T.

2011-01-01

Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein

Proliferative lifespan is conserved after nuclear transfer.

Science.gov (United States)

Clark, A John; Ferrier, Patricia; Aslam, Samena; Burl, Sarah; Denning, Chris; Wylie, Diana; Ross, Arlene; de Sousa, Paul; Wilmut, Ian; Cui, Wei

2003-06-01

Cultured primary cells exhibit a finite proliferative lifespan, termed the Hayflick limit. Cloning by nuclear transfer can reverse this cellular ageing process and can be accomplished with cultured cells nearing senescence. Here we describe nuclear transfer experiments in which donor cell lines at different ages and with different proliferative capacities were used to clone foetuses and animals from which new primary cell lines were generated. The rederived lines had the same proliferative capacity and rate of telomere shortening as the donor cell lines, suggesting that these are innate, genetically determined, properties that are conserved by nuclear transfer.

T-dependence of human B lymphocyte proliferative response to mitogens.

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Brochier, J; Samarut, C; Gueho, J P; Revillard, J P

1976-01-01

Human peripheral blood and tonsil lymphocytes were fractionated on anti-Ig-coated Sephadex columns or by centrifugation after rosetting with native sheep erythrocytes. Both methods allowed the recovery of B and T-enriched populations the purity of which was checked by fluorescein-labelled anti-Ig serum, E and EAC rosette formation, and heterologous antisera specific for B or T lymphocytes. The proliferative response of T cells to PHA, Con A, PWM, and ALS was not found different from that of unfractionated cells, whereas no response of the B cells could be observed to these mitogens providing that no contaminating T cells were present. Addition of T lymphocytes to these unresponsive B cells allowed them to respond to phytomitogens, but not to ALS. X-irradiated T cells could, to some extent, replace the diving T lymphocytes; no T-replacing factor could be found in cell-free supernatants from T cells, whether or not they had been activated by mitrogens. This model of B-T cooperation appears useful for studying the differentiation and maturation of human B lymphocytes.

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.

MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

International Nuclear Information System (INIS)

Balakrishnan, Anita; Stearns, Adam T.; Park, Peter J.; Dreyfuss, Jonathan M.; Ashley, Stanley W.; Rhoads, David B.; Tavakkolizadeh, Ali

2010-01-01

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.

COMPARISONS BETWEEN THE NON-PROLIFERATIVE AND PROLIFERATIVE THERAPY IN FIBROCYSTIC MASTOSIS.

Science.gov (United States)

Carauleanu, A; Socolov, R; Rugina, V; Gabia, O; Carauleanu, Daniela Mihaela; Lupascu, Ivona Anghlcelache; Socolov, Demetra

2016-01-01

Fibrocystic mastosis (FCM) is the most frequent benign breast lesion. Most treatments for fibrocystic mastosis are: hormonl, with beneficial results and non-hormonal, with fluctuating results. A number of 210 cases were studied, which were divided into 7 groups. The study lasted for 9 months and it was carried out on the basis of a personal examination sheet. The following were monitored: age groups, mastodynia, reducing breast nodules, a significant reduction in the volume of the mastosic cysts, reducion of the fibrous tissue, medication tolerance. Mastodynia has declined by 90% in the cases treated with Tamoxifen and Danazol, by 70% in the case of Lynestrenol and Bromocriptine, by 50% in the 15 patients who were given Utrogestan. Knowing the advantages and disadvantages of drugs (contraindications, side effects), age category, breast pain reduction, antiproliferative activity, tolerability, relapse allow us to assess the benefit-risk. Even in those circumstances that remained incompletely clarified for objective reasons, related to the inaccurate/incorrect reporting by the patients, there is a significant difference (p < 0.05) between the frequency of relapses following the treatment with Tamoxifen and the other categories of drugs who were administered. Our study shows that in the groups that were administered Logest, Utrogestan and Bromocriptine, only antalgic effects were achieved (disappearance or only decrease of mastodynia) and no anti-proliferative effects were obtained. Basically, hormone treatment should be made based on a histopathological examination.

Potent anti-cervical cancer activity: synergistic effects of Thai medicinal plants in recipe N040 selected from the MANOSROI III database.

Science.gov (United States)

Kitdamrongtham, Worapong; Manosroi, Aranya; Akazawa, Hiroyuki; Gidado, Abubakar; Stienrut, Pramote; Manosroi, Worapaka; Lohcharoenkal, Warangkana; Akihisa, Toshihiro; Manosroi, Jiradej

2013-08-26

One of the prestigious Thai/Lanna folklore wisdoms is the medicinal plant recipes. Thai/Lanna medicinal plant recipe database MANOSROI III has been developed by Prof. Dr. Jiradej Manosroi. It consists of over 200,000 recipes covering all diseases including cancer. To investigate the in vitro and in vivo anti-cervical cancer activity and the active constituents of the Thai medicinal plant recipe N040 selected from the MANOSROI III database. The extracts of recipe N040 and single medicinal plants in the recipe were prepared by hot water and methanol extraction, respectively. The n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH) and water fractions of Caesalpinia sappan, the plant which showed the highest anti-proliferative activity were prepared by liquid-liquid partition extraction. The fraction which showed the highest anti-proliferative activity was further isolated for active constituents. Anti-proliferative activity of recipe N040, methanolic extracts, fractions of Caesalpinia sappan and brazilin, an active constituent on HeLa cell were investigated using sulforhodamine B (SRB) assay. Anti-oxidative activities including free radical scavenging and metal ion-chelating activities, as well as the phenolic and flavonoid contents of these fractions were also determined. The in vivo anti-cancer activity of recipe N040 on HeLa cell xenograft and the subchronic toxicity were performed in nude mice and rats, respectively. N040 showed the potent in vitro anti-proliferative activity on HeLa cell with the IC50 value of 0.11 µg/ml. Phytochemicals detected in the plants were steroids/triterpenoids, tannins, flavonoids, saponins and alkaloids. For the single plant, methanolic extract of Caesalpinia sappan gave the highest anti-proliferative activity with the IC50 of 33.46 µg/ml. EtOAc fraction of Caesalpinia sappan showed the highest anti-proliferative and free radical scavenging activities with the IC50 and SC50 of 17.81 and 21.95 µg/ml which were 1.88 and 0.83 folds of

The anti-proliferative effect of cation channel blockers in T lymphocytes depends on the strength of mitogenic stimulation.

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Petho, Zoltan; Balajthy, Andras; Bartok, Adam; Bene, Krisztian; Somodi, Sandor; Szilagyi, Orsolya; Rajnavolgyi, Eva; Panyi, Gyorgy; Varga, Zoltan

2016-03-01

Ion channels are crucially important for the activation and proliferation of T lymphocytes, and thus, for the function of the immune system. Previous studies on the effects of channel blockers on T cell proliferation reported variable effectiveness due to differing experimental systems. Therefore our aim was to investigate how the strength of the mitogenic stimulation influences the efficiency of cation channel blockers in inhibiting activation, cytokine secretion and proliferation of T cells under standardized conditions. Human peripheral blood lymphocytes were activated via monoclonal antibodies targeting the TCR-CD3 complex and the co-stimulator CD28. We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM-34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Five days after the stimulation ELISA and flow cytometric measurements were performed to determine IL-10 and IFN-γ secretion, cellular viability and proliferation. Our results showed that ion channel blockers and rapamycin inhibit IL-10 and IFN-γ secretion and cell division in a dose-dependent manner. Simultaneous application of the blockers for each channel along with rapamycin was the most effective, indicating synergy among the various activation pathways. Upon increasing the extent of mitogenic stimulation the anti-proliferative effect of the ion channel blockers diminished. This phenomenon may be important in understanding the fine-tuning of T cell activation. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Water-soluble derivatives of 25-OCH3-PPD and their anti-proliferative activities.

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Zhou, Wu-Xi; Sun, Yuan-Yuan; Yuan, Wei-Hui; Zhao, Yu-Qing

2017-05-01

(20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH 3 -PPD, AD-1) is a dammarane-type sapogenin showing anti-tumor potential. In the search for new anti-tumor agents with higher potency than our previously identified compound 25-OCH 3 -PPD, 11 novel sulfamic acid and diacid derivatives that could improve water solubility and contribute to good drug potency and pharmacokinetic profiles were designed and synthesized. Their in vitro anti-tumor activities in MCF-7, A-549, HCT-116, and BGC-823 cell lines and one normal cell line were tested by standard MTT assay. Results showed that compared with compound 25-OCH 3 -PPD, compounds 1, 4, and 5 exhibited higher cytotoxic activity on almost all cell lines, together with lower toxicity in the normal cell. In particular, compound 1 exhibited the best anti-tumor activity in the in vitro assays. The water solubility of 25-OCH 3 -PPD and its derivatives was tested and the results showed that the solubility of 25-OCH 3 -PPD sulfamic acid and diacid derivatives were better than that of 25-OCH 3 -PPD in water, which may provide valuable data for the research and development of new anti-tumor agents. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of performance- and image-enhancing substances among recreational athletes: a quantitative analysis of inquiries submitted to the Danish anti-doping authorities

DEFF Research Database (Denmark)

Bojsen-Møller, Jens; Christiansen, Ask Vest

2010-01-01

. The key findings were that the ADD information service is generally used by males in their mid-20s who exercise in gyms and are not engaged in competitive sports. Approximately 15% of the enquirers were users of anabolic androgenic steroids (AAS) or other substances banned within elite sports by the World...... Anti Doping Agency, and an additional 15% considered using such substances. The present results suggest that there is a pronounced interest in the use of AAS and other PIEDs among Danish gym members. http://www3.interscience.wiley.com/journal/122652704/abstract?CRETRY=1&SRETRY=0  ...

A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19ARF-p53 signaling

NARCIS (Netherlands)

Shvarts, A.; Brummelkamp, T.; Koh, E.; Daley, G.Q.; Bernards, R.A.

2002-01-01

Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass of this checkpoint. Using retroviral cDNA expression libraries, we identify BCL6 as a potent inhibitor of senescence. BCL6 is frequently activated in

A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling

NARCIS (Netherlands)

Shvarts, Avi; Brummelkamp, Thijn R.; Scheeren, Ferenc; Koh, Eugene; Daley, George Q.; Spits, Hergen; Bernards, René

2002-01-01

Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass of this checkpoint. Using retroviral cDNA expression libraries, we identify BCL6 as a potent inhibitor of senescence. BCL6 is frequently activated in

Polysaccharide peptide isolated from grass-cultured Ganoderma lucidum induces anti-proliferative and pro-apoptotic effects in the human U251 glioma cell line.

Science.gov (United States)

Wang, Chunhua; Lin, Dongmei; Chen, Quan; Lin, Shuqian; Shi, Songsheng; Chen, Chunmei

2018-04-01

The Ganoderma lucidum ( G. lucidum ) mushroom is one of the most extensively studied functional foods, known for its numerous health benefits, including the inhibition of tumor cell growth. The present study assessed the anti-proliferative and pro-apoptotic activity of a novel G. lucidum polysaccharide peptide (GL-PP) in human glioma U251 cells, which was purified from grass-cultured G. lucidum . GL-PP is a glycopeptide with an average molecular weight of 42,635 Da and a polysaccharide-to-peptide ratio of 88.70:11.30. The polysaccharides were composed of l-arabinose, d-mannose and d-glucose at a molar ratio of 1.329:0.372:2.953 and a total of 17 amino acids were detected. The results of the current study demonstrated that GL-PP significantly inhibited U251 cellular proliferation. The proportion of G 0 /G 1 phase cells and sub-G 1 phase cells significantly increased as the concentration of GL-PP increased, as did the activity of caspase-3. These results indicate that GL-PP directly inhibited human glioma U251 proliferation by inducing cell cycle arrest and promoting apoptosis.

Effect of new disinfectant substances on pseudomonas aeruginosa

International Nuclear Information System (INIS)

Majtan, V.

1998-01-01

The anti-bacterial effect of 13 new commercially manufactured disinfectant substances on P. aeruginosa strain was studied. The substances tested represent 9 quaternary ammonium salts QAT and 4 combined QAT with other ingredients. The antimicrobial efficacy was characterised by influencing the growth and reproduction of bacterial cells expressed either by MIC and ED 50 as well as and ED 50 , as well as by the inhibition of incorporation rate of incorporation rate of [ 14 C] adenine and [ 14 C] leucine. The method of inhibition of [ 14 C] precursors is suitable as one from possible evaluation criterion on anti-bacterial efficacy of synthetic disinfectant substances. (authors)

[Preclinical study of immunocorrection action of the sum of active substances of Coluria geoides (Pall.) Ledeb. (Rosaceae)].

Science.gov (United States)

Dutova, S V; Karpova, M R; Myadelets, M A; Myasnaya, N V; Sherstoboev, E Yu

2015-01-01

A preclinical study of the immunocorrection action of the sum of active substances isolated from ethereal-oil plants Coluria geoides (Pall.) Ledeb. (Rosaceae family) with respect to experimental immunodeficiency showed that preparations relieve symptoms of immunodeficiency caused by the administration of cyclophosphan: suppressed synthesis of anti-erythrocyte antibodies (agglutinine) and proliferative processes in the spleen. Under the influence of C. geoides preparations, the absolute numbers of cariocytes and antibody forming cells in spleen significantly increased (compared to the group of animals with experimental immunodeficiency) and in some cases reached the background level. The drugs studied produced a more pronounced stimulating effect on the synthesis of specific immunoglobulins and proliferation of antibody forming cells of spleen as compared to the effect of Echinacea tincture. Preparation C-2 (extract from underground organs and grass of C. geoides obtained by percolation method with 70% ethanol) is most promising for in-depth research and the development of new effective drugs with immunocorrecting properties.

Lifespan extension by preserving proliferative homeostasis in Drosophila.

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Benoît Biteau

2010-10-01

Full Text Available Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan.

Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

International Nuclear Information System (INIS)

Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long; Bao, Jin-ku

2011-01-01

Highlights: → ConA induces cancer cell death targeting apoptosis and autophagy. → ConA inhibits cancer cell angiogenesis. → ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca 2+ /Mn 2+ -dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-κB-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

Is there a danger for myopia in anti-doping education? Comparative analysis of substance use and misuse in Olympic racket sports calls for a broader approach.

Science.gov (United States)

Kondric, Miran; Sekulic, Damir; Petroczi, Andrea; Ostojic, Ljerka; Rodek, Jelena; Ostojic, Zdenko

2011-10-11

Racket sports are typically not associated with doping. Despite the common characteristics of being non-contact and mostly individual, racket sports differ in their physiological demands, which might be reflected in substance use and misuse (SUM). The aim of this study was to investigate SUM among Slovenian Olympic racket sport players in the context of educational, sociodemographic and sport-specific factors. Elite athletes (N=187; mean age=22±2.3; 64% male) representing one of the three racket sports, table tennis, badminton, and tennis, completed a paper-and-pencil questionnaire on substance use habits. Athletes in this sample had participated in at least one of the two most recent competitions at the highest national level and had no significant difference in competitive achievement or status within their sport. A significant proportion of athletes (46% for both sexes) reported using nutritional supplements. Between 10% and 24% of the studied males would use doping if the practice would help them achieve better results in competition and if it had no negative health consequences; a further 5% to 10% indicated potential doping behaviour regardless of potential health hazards. Females were generally less oriented toward SUM than their male counterparts with no significant differences between sports, except for badminton players. Substances that have no direct effect on sport performance (if timed carefully to avoid detrimental effects) are more commonly consumed (20% binge drink at least once a week and 18% report using opioids), whereas athletes avoid substances that can impair and threaten athletic achievement by decreasing physical capacities (e.g. cigarettes), violating anti-doping codes or potentially transgressing substance control laws (e.g. opiates and cannabinoids). Regarding doping issues, athletes' trust in their coaches and physicians is low. SUM in sports spreads beyond doping-prone sports and drugs that enhance athletic performance. Current anti

Is there a danger for myopia in anti-doping education? Comparative analysis of substance use and misuse in Olympic racket sports calls for a broader approach

Directory of Open Access Journals (Sweden)

Ostojic Ljerka

2011-10-01

Full Text Available Abstract Background Racket sports are typically not associated with doping. Despite the common characteristics of being non-contact and mostly individual, racket sports differ in their physiological demands, which might be reflected in substance use and misuse (SUM. The aim of this study was to investigate SUM among Slovenian Olympic racket sport players in the context of educational, sociodemographic and sport-specific factors. Methods Elite athletes (N = 187; mean age = 22 ± 2.3; 64% male representing one of the three racket sports, table tennis, badminton, and tennis, completed a paper-and-pencil questionnaire on substance use habits. Athletes in this sample had participated in at least one of the two most recent competitions at the highest national level and had no significant difference in competitive achievement or status within their sport. Results A significant proportion of athletes (46% for both sexes reported using nutritional supplements. Between 10% and 24% of the studied males would use doping if the practice would help them achieve better results in competition and if it had no negative health consequences; a further 5% to 10% indicated potential doping behaviour regardless of potential health hazards. Females were generally less oriented toward SUM than their male counterparts with no significant differences between sports, except for badminton players. Substances that have no direct effect on sport performance (if timed carefully to avoid detrimental effects are more commonly consumed (20% binge drink at least once a week and 18% report using opioids, whereas athletes avoid substances that can impair and threaten athletic achievement by decreasing physical capacities (e.g. cigarettes, violating anti-doping codes or potentially transgressing substance control laws (e.g. opiates and cannabinoids. Regarding doping issues, athletes' trust in their coaches and physicians is low. Conclusion SUM in sports spreads beyond doping

Iron(III-salophene: an organometallic compound with selective cytotoxic and anti-proliferative properties in platinum-resistant ovarian cancer cells.

Directory of Open Access Journals (Sweden)

Thilo S Lange

2008-05-01

Full Text Available In this pioneer study to the biological activity of organometallic compound Iron(III-salophene (Fe-SP the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovarian cancer cell lines were investigated.Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma cell lines at concentrations between 100 nM and 1 microM, while the viability of HeLa cells (epithelial cervix adenocarcinoma or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented nuclei, highly condensed chromatin and chromatin fragmentation. Fe-SP treatment led to the activation of markers of the extrinsic (Caspase-8 and intrinsic (Caspase-9 pathway of apoptosis as well as of executioner Caspase-3 while PARP-1 was deactivated. Fe-SP exerted effects as an anti-proliferative agent with an IC(50 value of 300 nM and caused delayed progression of cells through S-phase phase of the cell cycle resulting in a complete S-phase arrest. When intra-peritoneally applied to rats Fe-SP did not show any systemic toxicity at concentrations that in preliminary trials were determined to be chemotherapeutic relevant doses in a rat ovarian cancer cell model.The present report suggests that Fe-SP is a potent growth-suppressing agent in vitro for cell lines derived from ovarian cancer and a potential therapeutic drug to treat such tumors in vivo.

Anti-proliferative effect of the essential oil of Cymbopogon citratus (DC) Stapf (lemongrass) on intracellular amastigotes, bloodstream trypomastigotes and culture epimastigotes of Trypanosoma cruzi (Protozoa: Kinetoplastida).

Science.gov (United States)

Santoro, G F; Cardoso, M G; Guimarães, L G L; Freire, J M; Soares, M J

2007-10-01

This study analyses the anti-proliferative effect of lemongrass essential oil and its main constituent (citral) on all 3 evolutive forms of Trypanosoma cruzi. Steam distillation was used to obtain lemongrass essential oil, with chemical composition determined by gas chromatography (GC) and GC coupled to mass spectrometry (GC-MS). The IC50/24 h (concentration that reduced the parasite population by 50%) of the oil and of citral upon T. cruzi was determined by cell counting in a Neubauer chamber, while morphological alterations were visualized by scanning and transmission electron microscopy. Treatment with the essential oil resulted in epimastigote growth inhibition with IC50=126.5 microg/ml, while the IC50 for trypomastigote lysis was 15.5 microg/ml. The IC50/48 h for the Association Index (% macrophage infection x number of amastigotes per cell) was 5.1 microg/ml, with a strong inhibition of intracellular amastigote proliferation. Ultrastructural analysis demonstrated cytoplasmic and nuclear extraction, while the plasma membrane remained morphologically preserved. Our data show that lemongrass essential oil is effective against T. cruzi trypomastigotes and amastigotes, and that its main component, citral, is responsible for the trypanocidal activity. These results indicate that essential oils can be promising anti-parasitic agents, opening perspectives to the discovery of more effective drugs of vegetal origin for treatment of parasitic diseases. However, additional cytotoxicity experiments on different cell lines and tests in a T. cruzi-mouse model are needed to support these data.

DIAGNOSTIC CRITERIA FOR PROLIFERATIVE THYROID LESIONS IN BONY FISHES

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Thyroid proliferative lesions are rather common in bony fishes but disagreement exists in the fish pathology community concerning diagnostic criteria for hyperplastic versus neoplastic lesions. To simplify the diagnosis of proliferative thyroid lesions and to reduce confusion reg...

Proliferative and non-proliferative lesions of the rat and mouse integument.

Science.gov (United States)

Mecklenburg, Lars; Kusewitt, Donna; Kolly, Carine; Treumann, Silke; Adams, E Terence; Diegel, Kelly; Yamate, Jyoji; Kaufmann, Wolfgang; Müller, Susanne; Danilenko, Dimitry; Bradley, Alys

2013-01-01

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) project is a joint initiative of the societies of toxicological pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP). Its aim is to develop an internationally-accepted nomenclature for proliferative and non-proliferative lesions in laboratory rodents. A widely accepted international harmonization of nomenclature in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and will provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. The purpose of this publication is to provide a standardized nomenclature for classifying microscopical lesions observed in the integument of laboratory rats and mice. Example colour images are provided for most lesions. The standardized nomenclature presented in this document and additional colour images are also available electronically at http://www.goreni.org. The nomenclature presented herein is based on histopathology databases from government, academia, and industrial laboratories throughout the world, and covers lesions that develop spontaneously as well as those induced by exposure to various test materials. (DOI: 10.1293/tox.26.27S; J Toxicol Pathol 2013; 26: 27S-57S).

Proliferative capacity of murine hematopoietic stem cells

International Nuclear Information System (INIS)

Hellman, S.; Botnick, L.E.; Hannon, E.C.; Vigneulle, R.M.

1978-01-01

The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible

Cranberry and Grape Seed Extracts Inhibit the Proliferative Phenotype of Oral Squamous Cell Carcinomas

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Kourt Chatelain

2011-01-01

Full Text Available Proanthocyanidins, compounds highly concentrated in dietary fruits, such as cranberries and grapes, demonstrate significant cancer prevention potential against many types of cancer. The objective of this study was to evaluate cranberry and grape seed extracts to quantitate and compare their anti-proliferative effects on the most common type of oral cancer, oral squamous cell carcinoma. Using two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, assays were performed to evaluate the effects of cranberry and grape seed extract on phenotypic behaviors of these oral cancers. The proliferation of both oral cancer cell lines was significantly inhibited by the administration of cranberry and grape seed extracts, in a dose-dependent manner. In addition, key regulators of apoptosis, caspase-2 and caspase-8, were concomitantly up-regulated by these treatments. However, cranberry and grape seed extracts elicited differential effects on cell adhesion, cell morphology, and cell cycle regulatory pathways. This study represents one of the first comparative investigations of cranberry and grape seed extracts and their anti-proliferative effects on oral cancers. Previous findings using purified proanthocyanidin from grape seed extract demonstrated more prominent growth inhibition, as well as apoptosis-inducing, properties on CAL27 cells. These observations provide evidence that cranberry and grape seed extracts not only inhibit oral cancer proliferation but also that the mechanism of this inhibition may function by triggering key apoptotic regulators in these cell lines. This information will be of benefit to researchers interested in elucidating which dietary components are central to mechanisms involved in the mediation of oral carcinogenesis and progression.

Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

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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

Ganoderma lucidum Polysaccharides as An Anti-cancer Agent.

Science.gov (United States)

Sohretoglu, Didem; Huang, Shile

2017-11-13

The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Endothelin-1 is associated with fibrosis in proliferative diabetic retinopathy membranes.

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Chang, William; Lajko, Michelle; Fawzi, Amani A

2018-01-01

To characterize the relationship between endothelin-1 and fibrosis in epiretinal membranes in proliferative diabetic retinopathy and explore the role of endothelial-mesenchymal transition in these membranes. Membranes were obtained from eyes undergoing pars plana vitrectomy for complicated proliferative diabetic retinopathy or idiopathic epiretinal membrane. Through standard immunohistochemical techniques, we labeled membranes to explore the distribution of endothelin-1 and endothelin receptor B, comparing proliferative diabetic retinopathy and idiopathic epiretinal membranes. In addition, membranes were also labeled with markers for fibroblasts, endothelial, and glial cells and studied with confocal laser scanning microscopy. The intensity of endothelin-1 labeling was quantified using standard image analysis software. Fourteen membranes were included in the analysis, nine from eyes with proliferative diabetic retinopathy and five idiopathic membranes. Flatmount diabetic membranes showed co-localization of endothelin-1 with S100A4 and CD31. Immunohistochemistry and quantitative analysis of cross-sectional membranes showed significantly higher endothelin-1 labeling in proliferative diabetic retinopathy membranes compared to idiopathic membranes (pmembranes showed more elements staining positive for S100A4 compared to idiopathic membranes. Epiretinal membrane formation in proliferative diabetic retinopathy involves higher tissue levels of endothelin-1 and fibroblastic activity. Furthermore, endothelin-1, endothelial and fibroblastic staining appear to be correlated, suggestive of endothelial-to-mesenchymal transition in proliferative diabetic retinopathy.

Biofilm formation in long-term central venous catheters in children with cancer

DEFF Research Database (Denmark)

Handrup, Mette Møller; Fuursted, Kurt; Funch, Peter

2012-01-01

Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters. Forty-eight children with cancer were randomized to catheter locking by heparin (n...... = 22) or taurolidine (n = 26), respectively. After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Biofilm was present if morphologically typical structures and bacterial cells were identified. Quantitative and semi...... in the intraluminal biofilm formation and the rate of bacterial colonization detected by scanning electron microscopy in the two groups....

Leptin: A proliferative factor for breast cancer?

International Nuclear Information System (INIS)

Caldefie-Chezet, F.; Damez, M.; Latour, M. de; Konska, G.; Mishellani, F.; Fusillier, C.; Guerry, M.; Penault-Llorca, F.; Guillot, J.; Vasson, M.-P.

2005-01-01

Mammary adipose tissue is an important source of paracrine mitogens and anti-mitogens, including insulin-like growth factor, transforming growth factors, and cytokines (especially, TNFα and IL-1β). Nevertheless, it is also an important source of the adipocytokine, leptin. Recently, leptin was reported to stimulate the proliferation of various cell types (pancreatic β cells, prostate, colorectal, lung, etc.) as a new growth factor. It was also shown to stimulate the proliferation of breast cancer cell lines. In this study, we conducted an immunohistochemical analysis of leptin expression in normal tissue and benign and malignant ductal breast cell, representing the different states of the invasion process. We determined for the first time that leptin is expressed both by ductal breast tumors and by benign lesions as atypical hyperplasia. This suggests that leptin may be taken up or synthesized by all modified ductal breast cells, and may prove a proliferative factor. Moreover, leptin is unexpressed by normal tissue in the healthy breast but is exhibited by the normal tissue in near vicinity of the malignant ductal breast lesions. We also postulated that leptin may be a prognostic or diagnostic factor for ductal breast cancer. These putative hypotheses require further study

An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances.

Science.gov (United States)

Zeinali, Majid; Rezaee, Seyed Abdolrahim; Hosseinzadeh, Hossein

2017-08-01

Inflammation and the pro-inflammatory cytokines are associated with numerous chronic diseases. Studies suggest that flavonoids, plant polyphenolic compound derivatives from natural origin, have a wide range of putative biological activities. Similar to other flavonoids, chrysin (CH) by its anti-oxidative and anti-inflammatory effects is a potential prophylactic agent in immunopathological and physicochemical injuries. This is an overview on putative immunomodulatory activities of flavonoids and beneficial health effects of these substances particularly, CH in the immune system. CH possesses potent immune-protective effects and suppresses inflammation in innate immune system which results to avoid damages induced by neutrophils and macrophages and suppresses immuno-inflammatory responses. Furthermore, beneficial effects of chrysin on inhibition of serum levels nuclear transcription factor κB (NF-κB) p65 unit, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-12, IL-17A, interferon gamma (IFN-γ) was reported. Moreover, CH has been known as the antagonist of NF-kB and the agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ) which in down regulation of the key pro-inflammatory enzymes such as myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phospholipase A2, and prostanoids. Therefore, CH can improve immune system and neurodegenerative diseases. In recent years, there has been an increasing interest in compound derivatives from natural origin. Taken together, evidences show that flavonoids may have health-promoting and disease-preventing dietary compounds with important benefits in modern life styles. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Downregulation of TXNIP leads to high proliferative activity and estrogen-dependent cell growth in breast cancer.

Science.gov (United States)

Park, Jun Won; Lee, Su Hyung; Woo, Gye-Hyung; Kwon, Hyo-Jung; Kim, Dae-Yong

2018-04-06

TXNIP is a potent tumor suppressor with reduced expression in various types of human cancer. The prognostic and predictive power of TXNIP has been recognized in human breast cancer. The aim of this study is to investigate the clinical relevance and functional roles of TXNIP downregulation in breast cancer. We examined TXNIP expression at the protein level in tissue microarray (TMA)-based human breast cancers and its correlation with clinical parameters and molecular markers on immunohistochemistry (IHC). Compared with normal tissues, TXNIP expression was significantly decreased in human breast cancer tissues and animal mammary tumors, along with tumor progression. TXNIP was restored immediately after histone deacetylase inhibitor treatment in breast cancer cells, implying transcriptional regulation of TXNIP by histone modification. Decreased TXNIP protein levels were more common in tumors showing high proliferative activity, such as high Ki-67 labeling indexes and low p27 expression. TXNIP knockdown led to increased in vitro and in vivo breast cancer cell growth accompanied by p27 reduction and GLUT1 induction. Interestingly, estrogen receptor (ER)-positive breast cancer samples showed higher TXNIP expression compared to ER-negative samples. TXNIP expression decreased when ER signaling was activated by estradiol, while its expression increased under ER blockage by anti-estrogen fulvestrant. In addition, TXNIP knockdown in breast cancer cells caused significant reduction in the cell-growth inhibitory effect of anti-estrogen fulvestrant. In conclusion, our data demonstrated that TXNIP functions to suppress high proliferative activity and estrogen-dependent cell growth in breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Anti-tumor and anti-angiogenic ergosterols from Ganoderma lucidum

Science.gov (United States)

Chen, Shaodan; Yong, Tianqiao; Zhang, Yifang; Su, Jiyan; Jiao, Chunwei; Xie, Yizhen

2017-10-01

This study was carried out to isolate chemical constituents from the lipid enriched fraction of Ganoderma lucidum extract and to evaluate their anti-proliferative effect on cancer cell lines and human umbilical vein endothelial cells. Ergosterol derivatives (1-14) were isolated from the lipid enriched fraction of G. lucidum. Their structures were established on the basis of spectroscopic analyses or by comparison of mass and NMR spectral data with those reported previously. Amongst, compound 1 was isolated and identified as a new compound. All the compounds were evaluated for their inhibitory effect on tumor cells and human umbilical vein endothelial cells in vitro. Compounds 9-13 displayed inhibitory activity against two tumor cell lines and human umbilical vein endothelial cells, which indicated that these four compounds had both anti-tumor and anti-angiogenesis activities. Compound 2 had significant selective inhibition against two tumor cell lines, while 3 exhibited selective inhibition against human umbilical vein endothelial cells. The structure–activity relationships for inhibiting human HepG2 cells were revealed by 3D-QASR. Ergosterol content in different parts of the raw material and products of G. lucidum was quantified. This study provides a basis for further development and utilization of ergosterol derivatives as natural nutraceuticals and functional food ingredients, or as source of new potential antitumor or anti-angiogenesis chemotherapy agent.

Atypical proliferative myositis: original MR description with pathologic correlation: Case report

Energy Technology Data Exchange (ETDEWEB)

Jarraya, Mohamed; Guermazi, Ali [Boston University School of Medicine, Department of Radiology, Musculoskeletal Section, Boston, MA (United States); Parva, Pedram [VA Boston Healthcare System, Boston, MA (United States); Stone, Michael [Stamford Hospital, Department of Surgery, Stamford, CT (United States); Klein, Michael J. [Hospital for Special Surgery, Department of Pathology and Laboratory Medicine, New York, NY (United States)

2014-08-15

Proliferative myositis (PM) along with proliferative fasciitis and nodular fasciitis are a group of pseudosarcomatous myofibroblastic proliferations. Although the histologic presentation of each is almost identical, the magnetic resonance imaging (MRI) appearance of proliferative myositis is closer to that of inflammatory myopathies. We report a case of PM in which the imaging and histologic features combine typical findings of PM with unusual imaging features, suggesting of reactive (or nodular) fasciitis. (orig.)

Atypical proliferative myositis: original MR description with pathologic correlation: Case report

International Nuclear Information System (INIS)

Jarraya, Mohamed; Guermazi, Ali; Parva, Pedram; Stone, Michael; Klein, Michael J.

2014-01-01

Proliferative myositis (PM) along with proliferative fasciitis and nodular fasciitis are a group of pseudosarcomatous myofibroblastic proliferations. Although the histologic presentation of each is almost identical, the magnetic resonance imaging (MRI) appearance of proliferative myositis is closer to that of inflammatory myopathies. We report a case of PM in which the imaging and histologic features combine typical findings of PM with unusual imaging features, suggesting of reactive (or nodular) fasciitis. (orig.)

Correlation between proliferative activity and cellular thickness of human mesenchymal stem cells

International Nuclear Information System (INIS)

Katsube, Yoshihiro; Hirose, Motohiro; Nakamura, Chikashi; Ohgushi, Hajime

2008-01-01

A cell's shape is known to be related to its proliferative activity. In particular, large and flat mammalian adult stem cells seem to show slow proliferation, however using quantitative analysis to prove the phenomenon is difficult. We measured the proliferation and cellular thickness of human mesenchymal stem cells (MSCs) by atomic force microscopy and found that MSCs with high proliferative activity were thick while those with low proliferative activity were thin, even though these MSCs were early passage cells. Further, low proliferative MSCs contained many senescence-associated β-galactosidase positive cells together with high senescence-associated gene expression. These findings suggest that the measurement of cellular thickness is useful for estimating the proliferative activity of human MSCs and is expected to be a practical tool for MSC applications in regenerative medicine

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

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...... 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....

Proliferative changes in nonpalpable breast lesions detected by mammography

International Nuclear Information System (INIS)

Vega, A.; Delgado, A.; Ortega, E.; Garijo, F.; Mosquera, J.; Sogo, C.; Alvarez, A.

2000-01-01

To analyze retrospectively the radiological findings in nonpalpable breast lesions detected by mammography that lead to the performance of surgical biopsy, resulting in a histological diagnosis of proliferative breast disease with and without atypia. From two Spanish hospitals, 421 women with 429 biopsies indicative of the presence of proliferative breast disease with and without atypia were selected out of a total of 1252 surgical biopsies in nonpalpable lesions that proved to be benign. Age, personal and familial history of breast cancer, reason for requesting the mammography and radiological findings that had indicated the need for surgical biopsy were recorded for each patient. The diagnosis was proliferative breast disease (epithelial hyperplasia) in 347 women with 354 biopsies and atypical hyperplasia in the remaining 74 women with 75 biopsies, representing 28% and 6%, respectively, of the 1252 biopsies of lesions found to be benign. In 221 of the 354 cases of epithelial hyperplasia (62%) and 45 of the 75 cases of atypical hyperplasia (60%), the presence of calcifications was the most common radiological findings leading to biopsy (p<0.05). Parenchymal distortion, with or without calcifications, was the second most common radiological sign. The histological study revealed a close relationship between these proliferative events and radial scars. Calcifications are the radiological finding that most frequently indicate the need for surgical biopsy in nonpalpable lesions that results in a diagnosis of proliferative breast disease with and without atypia. (Author) 12 refs

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.

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)

2013-01-01

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. PMID:23865616

Tropical fruit camu-camu (Myrciaria dubia) has anti-oxidative and anti-inflammatory properties.

Science.gov (United States)

Inoue, Teruo; Komoda, Hiroshi; Uchida, Toshihiko; Node, Koichi

2008-10-01

Oxidative stress as well as inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Although, various anti-oxidative dietary supplements have been evaluated for their ability to prevent atherosclerosis, no effective ones have been determined at present. "Camu-camu" (Myrciaria dubia) is an Amazonian fruit that offers high vitamin C content. However, its anti-oxidative property has not been evaluated in vivo in humans. To assess the anti-oxidative and anti-inflammatory properties of camu-camu in humans, 20 male smoking volunteers, considered to have an accelerated oxidative stress state, were recruited and randomly assigned to take daily 70 ml of 100% camu-camu juice, corresponding to 1050 mg of vitamin C (camu-camu group; n=10) or 1050 mg of vitamin C tablets (vitamin C group; n=10) for 7 days. After 7 days, oxidative stress markers such as the levels of urinary 8-hydroxy-deoxyguanosine (P<0.05) and total reactive oxygen species (P<0.01) and inflammatory markers such as serum levels of high sensitivity C reactive protein (P<0.05), interleukin (IL)-6 (P<0.05), and IL-8 (P<0.01) decreased significantly in the camu-camu group, while there was no change in the vitamin C group. Our results suggest that camu-camu juice may have powerful anti-oxidative and anti-inflammatory properties, compared to vitamin C tablets containing equivalent vitamin C content. These effects may be due to the existence of unknown anti-oxidant substances besides vitamin C or unknown substances modulating in vivo vitamin C kinetics in camu-camu.

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

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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.

Bilateral proliferative retinopathy in B-cell acute lymphoblastic leukemia

Directory of Open Access Journals (Sweden)

Devesh Kumawat

2018-01-01

Full Text Available A 4-year-old child with B-cell acute lymphoblastic leukemia presented with vitreous hemorrhage due to proliferative retinopathy in both eyes. Pars plana vitrectomy was performed in both eyes to clear nonresolving vitreous hemorrhage after systemic stabilization. Visual recovery was limited by the disc drag in the right eye and subfoveal exudation in the left eye. Etiopathogenesis and management of proliferative retinopathy in acute leukemias are discussed.

Thujone-Rich Fraction of Thuja occidentalis Demonstrates Major Anti-Cancer Potentials: Evidences from In Vitro Studies on A375 Cells

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Raktim Biswas

2011-01-01

Full Text Available Crude ethanolic extract of Thuja occidentalis (Fam: Cupressaceae is used as homeopathic mother tincture (TOΦ to treat various ailments, particularly moles and tumors, and also used in various other systems of traditional medicine. Anti-proliferative and apoptosis-inducing properties of TOΦ and the thujone-rich fraction (TRF separated from it have been evaluated for their possible anti-cancer potentials in the malignant melanoma cell line A375. On initial trial by S-diphenyltetrazolium bromide assay, both TOΦ and TRF showed maximum cytotoxic effect on A375 cell line while the other three principal fractions separated by chromatography had negligible or no such effect, because of which only TRF was further characterized and subjected to certain other assays for determining its precise anti-proliferative and apoptotic potentials. TRF was reported to have a molecular formula of C10H16O with a molecular weight of 152. Exposure of TRF of Thuja occidentalis to A375 cells in vitro showed more cytotoxic, anti-proliferative and apoptotic effects as compared with TOΦ, but had minimal growth inhibitory responses when exposed to normal cells (peripheral blood mononuclear cell. Furthermore, both TOΦ and TRF also caused a significant decrease in cell viability, induced inter-nucleosomal DNA fragmentation, mitochondrial transmembrane potential collapse, increase in ROS generation, and release of cytochrome c and caspase-3 activation, all of which are closely related to the induction of apoptosis in A375 cells. Thus, TRF showed and matched all the anti-cancer responses of TOΦ and could be the main bio-active fraction. The use of TOΦ in traditional medicines against tumors has, therefore, a scientific basis.

Standard effective doses for proliferative tumours

International Nuclear Information System (INIS)

Jones, L.C.; Hoban, P.

1999-01-01

This study was undertaken to investigate the treatment schedules used clinically for highly proliferative tumours, particularly with reference to the effects of fraction size, fraction number and treatment duration. The linear quadratic model (with time component) is used here to compare non-standard treatment regimens (e.g. accelerated and hyperfractionated schedules), currently the focus of randomized trials, with each other and some common 'standard regimens'. To ensure easy interpretation of results, two parameters known as proliferative standard effective dose one (PSED 1 ) and proliferative standard effective dose two (PSED 2 ) have been calculated for each regimen. Graphs of PSED 1 and PSED 2 versus potential doubling time (T p ) have been generated for a range of fractionation regimens which are currently under trial in various randomized studies. From these graphs it can be seen that the highly accelerated schedules (such as CHART) only show advantages for tumours with very short potential doubling times. Calculations for most of the schedules considered showed at least equivalent tumour control expected for the trial schedule compared with the control arm used and these values agree quite well with clinical results. These calculations are in good agreement with clinical results available at present. The greater the PSED 1 or PSED 2 for the schedule considered the greater the tumour control, which can be expected. However, as has been seen with clinical trials, this higher cell kill also results in higher acute effects which have proved too great for some accelerated schedules to continue. (author)

Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system.

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Mark A Little

Full Text Available Evidence is lacking for direct pathogenicity of human anti-proteinase-3 (PR3 antibodies in development of systemic vasculitis and granulomatosis with polyangiitis (GPA, Wegener's granulomatosis. Progress in study of these antibodies in rodents has been hampered by lack of PR3 expression on murine neutrophils, and by different Fc-receptor affinities for IgG across species. Therefore, we tested whether human anti-PR3 antibodies can induce acute vasculitis in mice with a human immune system. Chimeric mice were generated by injecting human haematopoietic stem cells into irradiated NOD-scid-IL2Rγ⁻/⁻ mice. Matched chimera mice were treated with human IgG from patients with: anti-PR3 positive renal and lung vasculitis; patients with non-vasculitic renal disease; or healthy controls. Six-days later, 39% of anti-PR3 treated mice had haematuria, compared with none of controls. There was punctate bleeding on the surface of lungs of anti-PR3 treated animals, with histological evidence of vasculitis and haemorrhage. Anti-PR3 treated mice had mild pauci-immune proliferative glomerulonephritis, with infiltration of human and mouse leukocytes. In 3 mice (17% more severe glomerular injury was present. There were no glomerular changes in controls. Human IgG from patients with anti-PR3 autoantibodies is therefore pathogenic. This model of anti-PR3 antibody-mediated vasculitis may be useful in dissecting mechanisms of microvascular injury.

Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system.

LENUS (Irish Health Repository)

Little, Mark A

2012-01-01

Evidence is lacking for direct pathogenicity of human anti-proteinase-3 (PR3) antibodies in development of systemic vasculitis and granulomatosis with polyangiitis (GPA, Wegener\\'s granulomatosis). Progress in study of these antibodies in rodents has been hampered by lack of PR3 expression on murine neutrophils, and by different Fc-receptor affinities for IgG across species. Therefore, we tested whether human anti-PR3 antibodies can induce acute vasculitis in mice with a human immune system. Chimeric mice were generated by injecting human haematopoietic stem cells into irradiated NOD-scid-IL2Rγ⁻\\/⁻ mice. Matched chimera mice were treated with human IgG from patients with: anti-PR3 positive renal and lung vasculitis; patients with non-vasculitic renal disease; or healthy controls. Six-days later, 39% of anti-PR3 treated mice had haematuria, compared with none of controls. There was punctate bleeding on the surface of lungs of anti-PR3 treated animals, with histological evidence of vasculitis and haemorrhage. Anti-PR3 treated mice had mild pauci-immune proliferative glomerulonephritis, with infiltration of human and mouse leukocytes. In 3 mice (17%) more severe glomerular injury was present. There were no glomerular changes in controls. Human IgG from patients with anti-PR3 autoantibodies is therefore pathogenic. This model of anti-PR3 antibody-mediated vasculitis may be useful in dissecting mechanisms of microvascular injury.

Explicating how parent-child communication increases Latino and European American early adolescents' intentions to intervene in a friend's substance Use.

Science.gov (United States)

Kam, Jennifer A; Yang, Sijia

2014-08-01

This study used primary socialization theory and a focus theory of normative conduct to examine whether anti-substance-use norms mediated targeted parent-child communication against substance (alcohol, cigarette, and marijuana) use's effects on Latino and European American early adolescents' intentions to intervene in a friend's substance use. Further, this study investigated whether familism interacted with targeted parent-child communication to predict anti-substance-use norms, and whether this mediated moderation model functioned differently for Latino and European American early adolescents. Self-reported longitudinal survey data were collected from 6th-8th grade students (N = 627), attending rural IL public schools. Multigroup mediated moderation analyses revealed that as Latino and European American early adolescents engaged in targeted mother-child communication against substance use, they were more likely to develop anti-substance-use parent injunctive norms, and in turn, more likely to report anti-substance-use personal norms. Thus, they were more likely to report that if their friend used substances, they would talk to their friend, seek help from others, and end the friendship. They were, however, less likely to ignore the friend's substance use. Familism was not a significant moderator, and the hypothesized effects did not differ for Latino and European American early adolescents. The results suggest that parents of Latino and European American adolescents may discourage substance use by engaging in targeted parent-child communication, which may indirectly benefit their children's friends, as well.

Hepatic progenitor cell resistance to TGF-β1's proliferative and apoptotic effects

International Nuclear Information System (INIS)

Clark, J. Brian; Rice, Lisa; Sadiq, Tim; Brittain, Evan; Song, Lujun; Wang Jian; Gerber, David A.

2005-01-01

The success of hepatocellular therapies using stem or progenitor cell populations is dependent upon multiple factors including the donor cell, microenvironment, and etiology of the liver injury. The following experiments investigated the impact of TGF-β1 on a previously described population of hepatic progenitor cells (HPC). The majority of the hepatic progenitor cells were resistant to endogenously produced TGF-β1's proapoptotic and anti-proliferative effects unlike more well-differentiated cellular populations (e.g., mature hepatocytes). Surprisingly, in vitro TGF-β1 supplementation significantly inhibited de novo hepatic progenitor cell colony formation possibly via an indirect mechanism(s). Therefore despite the HPC's direct resistance to supplemental TGF-β1, this cytokine's inhibitory effect on colony formation could have a potential negative impact on the use of these cells as a therapy for patients with liver disease

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.

Determination of Anti-nutrients and Toxic Substances of Selected ...

African Journals Online (AJOL)

USER

ABSTRACT: Determination of antinutrients and toxic substances in leafy vegetables is an imperative facet in nutritional studies as it establishes the baseline concentrations index for phytotoxins in the vegetables. Concentrations of cyanide, nitrate, soluble and total oxalates were quantitatively determined in the common ...

Smoking among Patients in Substance Use Disorders Treatment: Associations with Tobacco Advertising, Anti-tobacco Messages and Perceived Health Risk

Science.gov (United States)

Campbell, Barbara K.; Le, Thao; Andrews, K. Blakely; Pramod, Sowmya; Guydish, Joseph

2016-01-01

Background Although tobacco control efforts have contributed to an overall decline in smoking, individuals with substance use disorders (SUDs) continue to smoke at high rates and remain targets of advertising to vulnerable groups, including those with mental health disorders and SUDs. Objective We examined associations of tobacco advertising exposure and receptivity, anti-tobacco message awareness, and health-risk perception with smoking status and cigarettes-per-day (CPD) in a national sample of SUD treatment patients. Method Patients (N=1,113) in 24 programs chosen randomly, stratified by program type, from among publicly funded, adult treatment programs within the National Drug Abuse Treatment Clinical Trials Network completed surveys of smoking, advertising exposure and receptivity, anti-tobacco message awareness and perceived health risks. Results Current smokers (77.9% of the sample) smoked a daily median of 10 cigarettes (IQR= 13). Participants reporting daily advertising exposure were 1.41 times more likely to be smokers (p=0.019) than others. Those highly receptive to advertising were 2.34 times more likely to be smokers (padvertising was 11.1% (95% CI: 2.8%-20.0%) higher than for smokers with low/moderate advertising receptivity. Anti-tobacco message awareness was not associated with smoking status or CPD. Conclusion The high rate of smoking among SUD treatment patients is associated with daily exposure and high receptivity to tobacco advertisements, and lower perception of health-related, smoking risks. Tobacco control efforts should target this vulnerable population. PMID:27314450

Smoking among patients in substance use disorders treatment: associations with tobacco advertising, anti-tobacco messages, and perceived health risks.

Science.gov (United States)

Campbell, Barbara K; Le, Thao; Andrews, K Blakely; Pramod, Sowmya; Guydish, Joseph

2016-11-01

Although tobacco control efforts have contributed to an overall decline in smoking, individuals with substance use disorders (SUDs) continue to smoke at high rates and remain targets of advertising to vulnerable groups, including those with mental health disorders and SUDs. We examined associations of tobacco advertising exposure and receptivity, anti-tobacco message awareness, and health-risk perception with smoking status and cigarettes-per-day (CPD) in a national sample of SUD treatment patients. The patients (N = 1,113) in 24 programs chosen randomly, stratified by program type, from among publicly funded adult treatment programs within the National Drug Abuse Treatment Clinical Trials Network completed surveys of smoking, advertising exposure and receptivity, anti-tobacco message awareness, and perceived health risks. Current smokers (77.9% of the sample) smoked a daily median of 10 cigarettes (IQR = 13). The participants reporting daily advertising exposure were 1.41 times more likely to be smokers (p = 0.019) than others. Those highly receptive to advertising were 2.34 times more likely to be smokers (p advertising was 11.1% (95% CI: 2.8%-20.0%) higher than for smokers with low/moderate advertising receptivity. Anti-tobacco message awareness was not associated with smoking status or CPD. The high rate of smoking among SUD treatment patients is associated with daily exposure and high receptivity to tobacco advertisements and lower perception of health-related smoking risks. Tobacco control efforts should target this vulnerable population.

The Relationship between Proliferative Scars and Endothelial Function in Surgically Revascularized Patients

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Murat Ziyrek

2015-12-01

Full Text Available Background: Proliferative scars are benign fibrotic proliferations which demonstrate abnormal wound healing in response to skin injuries. As postulated in the “response to injury hypothesis”, atherosclerosis is also triggered by an endothelial injury. Keloid and atherosclerotic processes have many pathophysiological and cytological features in common. Aims: In this study, we investigated the relationship between proliferative scars and endothelial function in surgically revascularized patients. We aimed to test the hypothesis that atherosclerosis is a wound healing abnormality. Study Design: Cross-sectional study. Methods: Consecutive patients who were admitted to the cardiology outpatient clinic with a history of coronary artery bypass grafting operation were evaluated. Thirty-three patients with proliferative scars at the median sternotomy site formed the keloid group, and 36 age- and sex-matched patients with no proliferative scar at the median sternotomy site formed the control group. Endothelial function was evaluated by flow-mediated vasodilatation of the brachial artery via ultrasonograhic examination. Results: There is no signicant difference according to the demographic data, biochemical parameters, clinical parameters and number of grafts between keloid and control groups. Endothelial-dependent vasodilatory response was lower in the keloid group than the control group (9.30±3.5 and 18.68±8.2, respectively; p=0.001. Conclusion: This study showed that endothalial dysfunction, which is strongly correlated with atherosclerosis, was more prominent in patients with proliferative scars. As proliferative scars and atherosclerosis have many features in common, we might conclude that atherosclerosis is a wound healing abnormality.

School victimization and substance use among lesbian, gay, bisexual, and transgender adolescents.

Science.gov (United States)

Huebner, David M; Thoma, Brian C; Neilands, Torsten B

2015-07-01

Lesbian, gay, bisexual, and transgender (LGBT) adolescents are at increased risk for substance use, relative to their heterosexual counterparts. Although previous research has demonstrated that experiences of anti-LGBT harassment, discrimination, and victimization may explain some of this disparity, little is known about the mechanisms whereby such mistreatment leads to substance abuse. This study aimed to examine whether mechanisms suggested by the Social Development Model might explain the links between school-based victimization and substance use in this population. Five hundred and four ethnically diverse LGBT adolescents ages 14-19 reported their experiences with school victimization, substance abuse, school bonding, and deviant peer group affiliation. Anti-LGBT victimization in school was associated with substance abuse, and although causality cannot be established, structural equation modeling confirmed that the data are consistent with a theoretical model in which this association was mediated by increased affiliation with deviant peers. Preventive interventions for LGBT adolescents must not only attempt to make schools safer for these youth, but also help keep them engaged in healthy peer groups when they are confronted with mistreatment in school.

School Victimization and Substance Use among Lesbian, Gay, Bisexual, and Transgender Adolescents

Science.gov (United States)

Huebner, David M.; Thoma, Brian C.; Neilands, Torsten B.

2014-01-01

Lesbian, gay, bisexual, and transgender (LGBT) adolescents are at increased risk for substance use, relative to their heterosexual counterparts. Although previous research has demonstrated that experiences of anti-LGBT harassment, discrimination, and victimization may explain some of this disparity, little is known about the mechanisms whereby such mistreatment leads to substance abuse. This study aimed to examine whether mechanisms suggested by the Social Development Model might explain the links between school-based victimization and substance use in this population. Five hundred and four ethnically diverse LGBT adolescents ages 14–19 reported their experiences with school victimization, substance abuse, school bonding, and deviant peer group affiliation. Anti-LGBT victimization in school was associated with substance abuse, and although causality cannot be established, structural equation modeling confirmed that the data are consistent with a theoretical model in which this association was mediated by increased affiliation with deviant peers. Preventive interventions for LGBT adolescents must not only attempt to make schools safer for these youth, but also help keep them engaged in healthy peer groups when they are confronted with mistreatment in school. PMID:25529390

Expression of the angiogenic mediator, angiopoietin-like 4, in the eyes of patients with proliferative sickle retinopathy.

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Kathleen Jee

Full Text Available The recent success of therapies directly targeting the angiogenic mediator, vascular endothelial growth factor (VEGF, for the treatment of proliferative diabetic retinopathy has encouraged clinicians to extend the use of anti-VEGF therapies for the treatment of another ischemic retinal vascular disease, proliferative sickle cell retinopathy (PSR, the most common cause of irreversible blindness in patients with sickle cell disease. However, results from case reports evaluating anti-VEGF therapies for PSR have been mixed. This highlights the need to identify alternative therapeutic targets for the treatment of retinal neovascularization in sickle cell patients. In this regard, angiopoietin-like 4 (ANGPTL4 is a novel angiogenic factor regulated by the transcription factor, hypoxia-inducible factor 1, the master regulator of angiogenic mediators (including VEGF in ischemic retinal disease. In an effort to identify alternative targets for the treatment of sickle cell retinopathy, we have explored the expression of ANGPTL4 in the eyes of patients with PSR. To this end, we examined expression and localization of ANGPTL4 by immunohistochemistry in autopsy eyes from patients with known PSR (n = 5 patients. Complementary studies were performed using enzyme-linked immunosorbent assays in aqueous (n = 8; 7 patients, 2 samples from one eye of same patient and vitreous (n = 3 patients samples from a second group of patients with active PSR. We detected expression of ANGPTL4 in neovascular tissue and in the ischemic inner retina in PSR, but not control, eyes. We further observed elevated expression of ANGPTL4 in the aqueous and vitreous of PSR patients compared to controls. These results suggest that ANGPTL4 could contribute to the development of retinal neovascularization in sickle cell patients and could therefore be a therapeutic target for the treatment of PSR.

PROSPECTIVE STUDY OF HISTOLOGICAL PROLIFERATIVE CHANGES IN ADJACENT AREAS OF BREAST CANCER

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Rema Nair Sarkar

2016-11-01

Full Text Available BACKGROUND Breast cancer remains a global health problem with an increasing incidence. Proliferative breast diseases are recognised as one of the risk factors in the development of carcinoma. This study was undertaken to know the frequency of proliferative lesions and other lesions in association with breast carcinomas in mastectomy specimens. MATERIALS AND METHODS 100 cases of excised carcinoma breast sent to the Department of Pathology for a three-year period at tertiary care centre was thoroughly examined and changes adjacent to the tumour was recorded and tissue was subjected for histopathological examination and results tabulated. RESULTS Infiltrating duct cell carcinoma, Not Otherwise Specified (NOS type was present in 89% of cases. Among the associated lesions, nonproliferative lesions constituted 16%, proliferative breast disease without atypia 29%, proliferative breast disease with atypia 10% and others 45%. Fibrocystic disease constituted 14% of cases, epithelial hyperplasia 15%, sclerosing adenosis 12% and atypical ductal hyperplasia in 10% of cases. Other types of associated lesions were duct carcinoma in situ in 4 cases. CONCLUSION Proliferative lesions adjacent to carcinoma breast were seen in 39% of cases. Fibrocystic disease, epithelial hyperplasia, sclerosing adenosis and atypical ductal hyperplasia being the commonest lesions adjacent to carcinoma breast in the present study.

The use of analogy in pro-life argumentation

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Simona Mazilu

2012-11-01

Full Text Available The paper is concerned with how analogy is strategically used in pro-life argumentation on abortion. Pragma-dialectics (van Eemeren and Grootendorst 1992 offers a set of critical questions by means of which I will evaluate the use of the argumentation based on a relation of analogy in terms of dialectical soundness. Examining various pro-life texts, I have noticed that the analogies employed remain unexplained. Therefore, despite the apparent similarities between abortion and the German holocaust or slavery, for instance, there are essential differences which are not mentioned. I claim that these analogies mainly have a rhetorical function, to operate what has been called by Micheli (2007: 960 “a transfer of emotional consensus”.

Perinatal exposure to mixtures of anti-androgenic chemicals causes proliferative lesions in rat prostate

DEFF Research Database (Denmark)

Boberg, Julie; Johansson, Hanna Katarina Lilith; Hadrup, Niels

2015-01-01

BACKGROUND: Elevated levels of endogenous or exogenous estrogens during fetal life can induce permanent disturbances in prostate growth and predispose to precancerous lesions. Recent studies have indicated that also early anti-androgen exposure may affect prostate cancer risk. METHODS: We examine...

Treatment and prevention of porcine proliferative enteropathy with oral tiamulin.

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McOrist, S; Smith, S H; Shearn, M F; Carr, M M; Miller, D J

The effect of an oral treatment or prevention programme, incorporating the antibiotic tiamulin, on the development of proliferative enteropathy in experimentally challenged pigs was studied. Twenty weaner pigs were challenged orally with a virulent inoculum of Lawsonia intracellularis strain LR189/5/83, a British isolate of the causative agent of porcine proliferative enteropathy, and seven control pigs were dosed with a buffer solution. Seven of the 20 challenged pigs were left untreated; they gained less weight than the controls and three of them developed mild to moderate diarrhoea two weeks after the challenge. All seven developed lesions, six visible grossly, of proliferative enteropathy, and numerous intracellular L intracellularis were detected in sections of the intestines examined three weeks after the challenge. To test a 'prevention' dosing strategy for tiamulin, six of the challenged pigs were dosed orally with 50 ppm tiamulin, incorporated in a 2 per cent stabilised premix, given from two days before the challenge until they were euthanased. To test a 'treatment' strategy, the remaining group of seven challenged pigs were dosed orally with 150 ppm tiamulin given in the premix from seven days after challenge until they were euthanased. All the control pigs and the 13 pigs treated with tiamulin, either before or after challenge, remained clinically normal and had no specific lesions of proliferative enteropathy in sections of the intestines examined post mortem.

Estrogen signaling in the proliferative endometrium: implications in endometriosis

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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.

Anti-helminth compound niclosamide downregulates Wnt Signaling and elicits antitumor responses in tumors with activating APC mutations

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Osada, Takuya; Chen, Minyong; Yang, Xiao Yi; Spasojevic, Ivan; Vandeusen, Jeffrey B.; Hsu, David; Clary, Bryan M.; Clay, Timothy M.; Chen, Wei; Morse, Michael A.; Lyerly, H. Kim

2011-01-01

Wnt/β-catenin pathway activation caused by APC mutations occurs in approximately 80% of sporadic colorectal cancers. The anti-helminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevelled-2 (Dvl2) expression, resulting in diminished downstream β-catenin signaling. In this study, we determined if niclosamide could inhibit the Wnt/ β-catenin pathway in human colorectal cancers and whether its inhibition might elicit antitumor effects in the presence of APC mutations. We found that niclosamide inhibited Wnt/ β-catenin pathway activation, downregulated Dvl2, decreased downstream β-catenin signaling and exerted anti-proliferative effects in human colon cancer cell lines and colorectal cancer cells isolated by surgical resection of metastatic disease, regardless of mutations in APC. In contrast, inhibition of NF-κB or mTOR did not exert similar anti-proliferative effects in these colorectal cancer model systems. In mice implanted with human colorectal cancer xenografts, orally administered niclosamide was well tolerated, achieved plasma and tumor levels associated with biologic activity and led to tumor control. Our findings support clinical explorations to reposition niclosamide for treatment of colorectal cancer. PMID:21531761

Engineered Mesenchymal Stem Cells as an Anti-Cancer Trojan Horse

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Nowakowski, Adam; Drela, Katarzyna; Rozycka, Justyna; Janowski, Miroslaw

2016-01-01

Cell-based gene therapy holds a great promise for the treatment of human malignancy. Among different cells, mesenchymal stem cells (MSCs) are emerging as valuable anti-cancer agents that have the potential to be used to treat a number of different cancer types. They have inherent migratory properties, which allow them to serve as vehicles for delivering effective therapy to isolated tumors and metastases. MSCs have been engineered to express anti-proliferative, pro-apoptotic, and anti-angiogenic agents that specifically target different cancers. Another field of interest is to modify MSCs with the cytokines that activate pro-tumorigenic immunity or to use them as carriers for the traditional chemical compounds that possess the properties of anti-cancer drugs. Although there is still controversy about the exact function of MSCs in the tumor settings, the encouraging results from the preclinical studies of MSC-based gene therapy for a large number of tumors support the initiation of clinical trials. PMID:27460260

Proliferative myositis: a case report

International Nuclear Information System (INIS)

Kim, Young Sook; Jeon, Ho Jong

2002-01-01

We report a case of proliferative myositis arising in the pectoralis major muscle of a 59-year-old man who presented with palpable mass. The initial clinical impression was a malignant tumor. Ultrasonography revealed the lesion as a spindle-shaped hypoechoic mass, and MR imaging of the left pectoralis major muscle showed hypointensity at T1-weighted imaging, hyperintensity at T2-weighted imaging, and strong enhancement at contrast-enhanced T1-weighted imaging

Proliferative myositis: a case report

Energy Technology Data Exchange (ETDEWEB)

Kim, Young Sook; Jeon, Ho Jong [Chosun University College of Medicine, Gwangju (Korea, Republic of)

2002-09-01

We report a case of proliferative myositis arising in the pectoralis major muscle of a 59-year-old man who presented with palpable mass. The initial clinical impression was a malignant tumor. Ultrasonography revealed the lesion as a spindle-shaped hypoechoic mass, and MR imaging of the left pectoralis major muscle showed hypointensity at T1-weighted imaging, hyperintensity at T2-weighted imaging, and strong enhancement at contrast-enhanced T1-weighted imaging.

Cannabis in sport: anti-doping perspective.

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Huestis, Marilyn A; Mazzoni, Irene; Rabin, Olivier

2011-11-01

Since 2004, when the World Anti-Doping Agency assumed the responsibility for establishing and maintaining the list of prohibited substances and methods in sport (i.e. the Prohibited List), cannabinoids have been prohibited in all sports during competition. The basis for this prohibition can be found in the World Anti-Doping Code, which defines the three criteria used to consider banning a substance. In this context, we discuss the potential of cannabis to enhance sports performance, the risk it poses to the athlete's health and its violation of the spirit of sport. Although these compounds are prohibited in-competition only, we explain why the pharmacokinetics of their main psychoactive compound, Δ(9)-tetrahydrocannabinol, may complicate the results management of adverse analytical findings. Passive inhalation does not appear to be a plausible explanation for a positive test. Although the prohibition of cannabinoids in sports is one of the most controversial issues in anti-doping, in this review we stress the reasons behind this prohibition, with strong emphasis on the evolving knowledge of cannabinoid pharmacology.

Dysregulation of T lymphocyte proliferative responses in autoimmunity.

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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.

Hepatitis C antibody prevalence among Mexico City prisoners injecting legal and illegal substances.

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Silverman-Retana, Omar; Serván-Mori, Edson; McCoy, Sandra I; Larney, Sarah; Bautista-Arredondo, Sergio

2017-12-01

Hepatitis C virus (HCV) infection is highly prevalent among prisoners and this prevalence estimates reach 64% among prisoners who inject illicit drugs. Prisons are important sites for HCV transmission in the absence of access to sterile injecting equipment; hence, it can be transmitted between prisoners who share contaminated needles and syringes. We aimed to estimate the prevalence of risk factors for anti-HCV prevalence, with particular interest on injecting behavior, and to assess correlates of anti-HCV positivity among Mexico City prisoners. Cross-sectional study based on information -collected in three male and two female prisons in Mexico City during 2010-2011- about sexually transmitted infections, socio-demographics, criminal history, substance use, vitamin injection, tattooing, among others (n=3,910). Weighted multivariable adjusted logistic regression models were estimated to assess the overall and differential odds for anti-HCV due to injecting behavior. Overall prevalence of anti-HCV was 3.3%. This figure rose to 43.1% among prisoners with a history of illicit drug injection. Prisoners with history of vitamin injection showed a similar prevalence of anti-HCV (43.8%). After stratifying by substance injected, the adjusted odds ratio was 9.8 (95% CI: 4.0, 23.8) for illicit drug injection and 11.9 (95% CI: 5.8, 23.8) for illicit drug and vitamin injection. Based on data from the most populous prisons in Mexico City, this study showed that anti-HCV is highly prevalent among prisoners with history of injecting behavior. In this sense, injecting behavior per-se, independent of the substance used, is associated with increased odds of anti-HCV positivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Proliferative activity as a prognostic factor of a human tumor radiation reactions

International Nuclear Information System (INIS)

Karakulov, R.K.; Pelevina, I.I.

1986-01-01

The following questions are considered: 1) whether cell proliferation initial parameters can serve for predicting the tumor radial reaction; 2) whether proliferative activity change can be a criterion for estimating the treatment efficiency; 3) acquisition of data on biological peculiarities of different types of tumors. Connection between proliferative activity drop and clinical reaction under tumor radiotherapy is ascertained

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

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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

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). 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. 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, r 2 =0.1043, P ≤0.0001; rs3025021 vs rs2010963: D'=0.442, r 2 =0.0446, P =0.149; rs3025035 vs rs2010963: D'=0.505, r 2 =0.0214, P =0.142. 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 different populations

The Dublin Declaration on Maternal Health Care and Anti-Abortion Activism

Science.gov (United States)

2017-01-01

Abstract The Dublin Declaration on Maternal Healthcare—issued by self-declared pro-life activists in Ireland in 2012—states unequivocally that abortion is never medically necessary, even to save the life of a pregnant woman. This article examines the influence of the Dublin Declaration on abortion politics in Latin America, especially El Salvador and Chile, where it has recently been used in pro-life organizing to cast doubt on the notion that legalizing abortion will reduce maternal mortality. Its framers argue that legalizing abortion will not improve maternal mortality rates, but reproductive rights advocates respond that the Dublin Declaration is junk science designed to preserve the world’s most restrictive abortion laws. Analyzing the strategy and impact of the Dublin Declaration brings to light one of the tactics used in anti-abortion organizing. PMID:28630540

Vitreous vascular endothelial growth factor concentrations in proliferative diabetic retinopathy versus proliferative vitreoretinopathy.

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Citirik, Mehmet; Kabatas, Emrah Utku; Batman, Cosar; Akin, Kadir Okhan; Kabatas, Naciye

2012-01-01

To assess vitreous vascular endothelial growth factor (VEGF) concentrations in proliferative diabetic retinopathy (PDR) in comparison to proliferative vitreoretinopathy (PVR). Vitreous samples were collected from 69 eyes of 69 patients with traumatic lens dislocation (n = 10), grade B PVR with rhegmatogenous retinal detachment (n = 13), grade C PVR with rhegmatogenous retinal detachment (n = 14), PDR with vitreous hemorrhage (n = 18), and PDR with vitreous hemorrhage and tractional retinal detachment (n = 14). Vitreous fluid samples were obtained at vitrectomy, and the levels of VEGF were measured by enzyme-linked immunosorbent assay. The mean vitreous level of VEGF was 15.14 ± 5.22 pg/ml in eyes with grade B PVR, 99.15 ± 38.58 pg/ml in eyes with grade C PVR, 4,534.01 ± 1,193.28 pg/ml in eyes with vitreous hemorrhage secondary to PDR, 5,157.29 ± 969.44 pg/ml in eyes with vitreous hemorrhage and tractional retinal detachment secondary to PDR, and 16.19 ± 5.76 pg/ml in eyes of the control group with traumatic lens dislocation. Vitreous VEGF concentrations were significantly higher in the patients with grade C PVR, PDR with vitreous hemorrhage and PDR with vitreous hemorrhage and tractional retinal detachment in comparison to the control patients (p < 0.05). A significant alteration was not observed in patients with grade B PVR (p = 0.55). Vitreous VEGF concentrations are increased in PDR and grade C PVR. The high VEGF concentrations could suggest a possible effect of VEGF on advanced PVR. Copyright © 2011 S. Karger AG, Basel.

Proliferative diabetic retinopathy is associated with microalbuminuria in patients with type 2 diabetes

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M.C. Boelter

2006-08-01

Full Text Available Diabetic retinopathy is one of the leading causes of blindness in working-age individuals. Diabetic patients with proteinuria or those on dialysis usually present severe forms of diabetic retinopathy, but the association of diabetic retinopathy with early stages of diabetic nephropathy has not been entirely established. A cross-sectional study was conducted on 1214 type 2 diabetic patients to determine whether microalbuminuria is associated with proliferative diabetic retinopathy in these patients. Patients were evaluated by direct and indirect ophthalmoscopy and grouped according to the presence or absence of proliferative diabetic retinopathy. The agreement of diabetic retinopathy classification performed by ophthalmoscopy and by stereoscopic color fundus photographs was 95.1% (kappa = 0.735; P < 0.001. Demographic information, smoking history, anthropometric and blood pressure measurements, glycemic and lipid profile, and urinary albumin were evaluated. On multiple regression analysis, diabetic nephropathy (OR = 5.18, 95% CI = 2.91-9.22, P < 0.001, insulin use (OR = 2.52, 95% CI = 1.47-4.31, P = 0.001 and diabetes duration (OR = 1.04, 95% CI = 1.01-1.07, P = 0.011 were positively associated with proliferative diabetic retinopathy, and body mass index (OR = 0.90, 95% CI = 0.86-0.96, P < 0.001 was negatively associated with it. When patients with macroalbuminuria and on dialysis were excluded, microalbuminuria (OR = 3.3, 95% CI = 1.56-6.98, P = 0.002 remained associated with proliferative diabetic retinopathy. Therefore, type 2 diabetic patients with proliferative diabetic retinopathy more often presented renal involvement, including urinary albumin excretion within the microalbuminuria range. Therefore, all patients with proliferative diabetic retinopathy should undergo an evaluation of renal function including urinary albumin measurements.

Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers.

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Samantha J Westrop

Full Text Available HIV-1(+ individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+ T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+ individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+ patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.

Thujone-Rich Fraction of Thuja occidentalis Demonstrates Major Anti-Cancer Potentials: Evidences from In Vitro Studies on A375 Cells

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Biswas, Raktim; Mandal, Sushil Kumar; Dutta, Suman; Bhattacharyya, Soumya Sundar; Boujedaini, Naoual; Khuda-Bukhsh, Anisur Rahman

2011-01-01

Crude ethanolic extract of Thuja occidentalis (Fam: Cupressaceae) is used as homeopathic mother tincture (TOΦ) to treat various ailments, particularly moles and tumors, and also used in various other systems of traditional medicine. Anti-proliferative and apoptosis-inducing properties of TOΦ and the thujone-rich fraction (TRF) separated from it have been evaluated for their possible anti-cancer potentials in the malignant melanoma cell line A375. On initial trial by S-diphenyltetrazolium brom...

Proliferative response of the murine esophageal epithelium to radiation: Modification by food consumption patterns

International Nuclear Information System (INIS)

Burholt, D.R.

1985-01-01

The single layer of proliferative epithelial cells of the murine esophagus undergoes a sequence of damage and recovery following cytotoxic insult. The modification of both damage and proliferative recovery by the alteration of animal eating patterns was investigated following thoracic field irradiation through the determination of /sup 3/H-TdR incorporation into the esophagus along with selective counting of labeled nuclei and mitotic figures. Initial radiation-induced damage, as determined by /sup 3/H-TdR incorporation suppression and mitotic delay, is under normal conditions dependent on the time of day of treatment. This circadian sensitivity may be altered by changing the eating pattern of the animal. The proliferative recovery following single dose irradiation is also dependent on food consumption patterns: fasting immediately following treatment and then refeeding 2 days later results in a more rapid proliferative recovery than observed under control eating conditions, while reduced food consumption during the period of proliferative hyperplasia reduces the extent of recovery. During multifraction radiation schedules both the damage produced by a subsequent dose and recovery capacity are influenced by the food consumption pattern between fractions

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

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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.

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

Atypical hyperplasia, proliferative fibrocystic change, and exogenous hormone use.

Science.gov (United States)

Zera, R T; Danielson, D; Van Camp, J M; Schmidt-Steinbrunn, B; Hong, J; McCoy, M; Anderson, W R; Linzie, B M; Rodriguez, J L

2001-10-01

The association between breast cancer development and exogenous hormone use (EHU) is suggested by indirect clinical evidence. We undertook this study to better define the relationship that EHU has with proliferative fibrocystic change (PFC) and atypical hyperplasia (AH). Women diagnosed with AH without associated carcinoma from January 1990 to December 1999 were compared with control subjects who underwent breast biopsy procedures during the same interval and who were diagnosed with either a proliferative fibrocystic change (PFC) or a nonproliferative fibrocystic change (NPFC). EHU was defined as the use of estrogen or progesterone taken together or separately within 3 months of biopsy. EHU was significantly higher in patients with AH compared with women with NPFC (P =.01). This observation was also significant if all proliferative change (both AH and PFC) was compared with NPFC (P =.03); it was not significant when PFC alone was compared with NPFC. No significant difference in EHU was demonstrated between women with AH and those with PFC. There is strong association between AH and EHU. These results support the theory that a continuum exists between hyperplasia and carcinoma and that EHU may influence the transition from one to the other in an undefined subset of women. We encourage our patients with AH to discontinue EHU.

Different proliferative capacity of lung fibroblasts obtained from control subjects and patients with emphysema

NARCIS (Netherlands)

Noordhoek, JA; Postma, DS; Chong, LL; Vos, JTWM; Kauffman, HF; Timens, W; van Straaten, JFM

2003-01-01

To characterize the possible role of a dysregulated proliferative capacity of pulmonary fibroblasts in insufficient tissue repair in lungs from patients with pulmonary emphysema, the authors undertook in vitro proliferative studies with pulmonary fibroblasts obtained from lung tissue of patients

Anti-angiogenic activity of a new andrographolide derivative in zebrafish and HUVECs.

Science.gov (United States)

Li, Jingjing; Peng, Yuran; Li, Shang; Sun, Yicheng; Chan, Judy Yuet-Wa; Cui, Guozhen; Wang, Decai; Zhou, Guo-Chun; Lee, Simon Ming-Yuen

2016-10-15

Andrographolide is among the most promising anti-tumor and anti-angiogenic components in Andrographis paniculata but its poor bioavailability and limited efficacy pose difficulties for its therapeutic development. Therefore, improving its pharmaceutical features and potency, by modifying its chemical structure, is desirable. In the present study, a new andrographolide derivative (AGP-40) was synthesized and characterized for its anti-angiogenic properties. Human umbilical vein endothelial cells (HUVECs) and zebrafish models were used to identify the anti-angiogenic activity of AGP-40. AGP-40 significantly suppressed the formation of blood vessels in zebrafish and inhibited proliferation, migration and tube formation in vitro. The anti-angiogenic effects of AGP-40 are at least partially mediated via the PI3K/Akt and MEK/Erk(1/2) signaling pathways. Furthermore, AGP-40 exhibited stronger anti-proliferative effects than andrographolide against A549, HepG2, Hela cancer cell lines. This study is the first to demonstrate the promising anti-angiogenic activity of the new andrographolide derivative AGP-40. Our results indicate that AGP-40 could serve as a potential therapeutic agent for the treatment and prevention of diseases associated with excessive angiogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Repeated episodes of ozone inhalation attenuates airway injury/repair and release of substance P, but not adaptation.

Science.gov (United States)

Schelegle, Edward S; Walby, William F; Alfaro, Mario F; Wong, Viviana J; Putney, Lei; Stovall, Mary Y; Sterner-Kock, Anja; Hyde, Dallas M; Plopper, Charles G

2003-02-01

To determine the impact of repeated episodes of ozone exposure on physiologic adaptation, epithelial injury/repair, and tracheal substance P levels, adult rats were subjected to episodes of ozone (5 days, 1 ppm, 8 h/day) followed by 9 days of filtered air for four cycles. Rats were sampled on days 1 and 5 of each episode and 9 days after day 5 of episodes 1, 2, and 4. One hour before being euthanized each rat was injected with 5-bromo-2'-deoxyuridine to label proliferating cells. Each 5-day episode showed a characteristic pattern of rapid shallow breathing (days 1 and 2), epithelial injury, and interstitial and intraluminal inflammation. In contrast, the neutrophil component of inflammation, tracheal substance P release, and cell proliferation became attenuated with each consecutive episode of exposure. Concurrent with this cyclic and attenuated response there was progressive hypercellularity and hyperplasia in all airways studied and a progressive remodeling present in the terminal bronchioles. Our findings are consistent with the notion that the cumulative distal airway lesion is at least in part the result of a depressed cell proliferative response to injury in these airways. This depressed cell proliferative response may be in part the result of diminished neutrophil inflammation and/or release of mitogenic neuropeptides in response to ozone-induced injury.

Proliferative Activity and Neuroprotective Effect of Ligustrazene ...

African Journals Online (AJOL)

Proliferative Activity and Neuroprotective Effect of. Ligustrazene Derivative by Irritation of Vascular. Endothelial Growth Factor Expression in Middle Cerebral. Artery Occlusion Rats. Zhang Huazheng1, Wang Penglong2, Ren Liwei1, Wang Xiaobo2, Li Guoliang2,. Wang Mina1, Chu Fuhao2, Gong Yan2, Xu Bing2, Bi Siling1, ...

Negative attributions towards people with substance use disorders in South Africa: Variation across substances and by gender

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Sorsdahl Katherine

2012-08-01

Full Text Available Abstract Background Little research has examined attitudes towards people who use substances in low and middle income countries (LMIC. Therefore, the present study examined the attributions made by the general South African population about people who use substances and whether these attributions differ by the type of substance being used, the gender of the person using the substance, or the characteristics of the person making the attribution. Method A convenience sample of 868 members of the general public was obtained through street-intercept methods. One of 8 vignettes portraying alcohol, cannabis, methamphetamine or heroin, with either a male or female as the protagonist was presented to each respondent. Respondents’ attitudes towards the specific cases were investigated. Results Respondents held equally negative views of the presented substances, with the exception of the cannabis vignette which was considered significantly less “dangerous” than the alcohol vignette. Respondents were more likely to offer “help” to women who use alcohol, but more likely to suggest “coercion into treatment” for men. Individuals who scored higher on the ASSIST were more likely to hold negative attitudes towards substance users and black African respondents were more likely to offer help to individuals who use substances. Conclusion The stigma associated with substance use in South Africa is high and not necessarily dependent on the drug of choice. However, a range of factors, including gender of the substance user, and ethnicity of the rater, may impact on stigma. Interventions designed to strengthen mental health literacy and gender-focused anti-stigma campaigns may have the potential to increase treatment seeking behaviour.

[A correlation between diffusion kurtosis imaging and the proliferative activity of brain glioma].

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Tonoyan, A S; Pronin, I N; Pitshelauri, D I; Shishkina, L V; Fadeeva, L M; Pogosbekyan, E L; Zakharova, N E; Shults, E I; Khachanova, N V; Kornienko, V N; Potapov, A A

2015-01-01

The aim of the study was to assess the capabilities of diffusion kurtosis imaging (DKI) in diagnosis of the glioma proliferative activity and to evaluate a relationship between the glioma proliferative activity index and diffusion parameters of the contralateral normal appearing white matter (CNAWM). The study included 47 patients with newly diagnosed brain gliomas (23 low grade, 13 grade III, and 11 grade IV gliomas). We determined a relationship between absolute and normalized parameters of the diffusion tensor (mean (MD), axial (AD), and radial (RD) diffusivities; fractional (FA) and relative (RA) anisotropies) and diffusion kurtosis (mean (MK), axial (AK), and radial (RK) kurtosis; kurtosis anisotropy (KA)) and the proliferative activity index in the most malignant glioma parts (pAK, and RK) and anisotropy (KA, FA, RA) values increased, and diffusivity (MD, AD, RD) values decreased as the glioma proliferative activity index increased. A strong correlation between the proliferative activity index and absolute RK (r=0,71; p=0.000001) and normalized values of MK (r=0.8; p=0.000001), AK (r=0.71; p=0.000001), RK (r=0.81; p=0.000001), and RD (r=-0.71; p=0.000001) was found. A weak, but statistically significant correlation between the glioma proliferative activity index and diffusion values RK (r=-0.36; p=0.014), KA (r=-0.39; p=0.007), RD (r=0.35; p=0.017), FA (r=-0.42; p=0.003), and RA (r=-0.41; p=0.004) of CNAWM was found. DKI has good capabilities to detect immunohistochemical changes in gliomas. DKI demonstrated a high sensitivity in detection of microstructural changes in the contralateral normal appearing white matter in patients with brain gliomas.

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

AIMS/HYPOTHESIS: This study aimed to evaluate the prevalence of retinopathy in long-surviving type 1 diabetic patients. It also investigated the 25 year incidence of proliferative retinopathy and associated risk factors in a Danish population-based cohort. METHODS: A population-based cohort of 727...... type 1 diabetic patients from Fyn County, Denmark, was identified in 1973. In 1981-1982, baseline retinopathy was graded and other risk factors were assessed in 573 patients. Twenty-five years later, 308 patients were still alive. Of these, 201 (65.3%) were re-examined at follow-up in 2007......-2008. RESULTS: The median age and duration of diabetes at follow-up were 58.8 and 43 years, respectively. At follow-up, the prevalence of diabetic retinopathy was 97.0%. Non-proliferative retinopathy was found in 45.8%, and 51.2% had proliferative retinopathy. The 25 year incidence of proliferative retinopathy...

Future of anti-addiction vaccines.

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Kosten, Thomas R

2005-01-01

The medical rational for using anti-drug antibodies in the serum as a treatment is to reduce drug levels in the brain and to bind drug before it enters the brain. Drugs of abuse are small molecules that can readily cross the blood brain barrier, while antibodies are larger molecules that cannot get into the brain. Thus, any drug that is bound to antibody also cannot cross the blood brain barrier and cannot enter the brain. Active anti-drug vaccines stimulate the body to makes its own antibodies, but the small size of abused drugs prevents them from stimulating an immune response. Thus, individuals do not ordinarily produce antibodies to abused drugs, and vaccines to stimulate antibodies are made by chemically linking these abused drugs to toxins such as cholera toxin. Alternatively, passive immunotherapy uses monoclonal antibodies that are generated in a laboratory and then administered via intravenous injection. Antibodies can be used to treat drug overdose; to reduce drug use relapse; or to protect certain at risk populations who have not yet become drug dependent. The advantages of anti-addiction vaccines are that antibodies target the drug, not the drug's sites of action in the brain and antibody binding inactivates the drug. These vaccines can complement behavioral and other medical therapies with minimal side effects and are not addictive like some chemical agonists. Technology advances in manufacturing and delivery systems will improve future anti-addiction vaccines, but social acceptance of anti-addiction vaccines will depend on substance abuse program staff and the families of substance abusers, who have some values that oppose medical solutions to addictive diseases and view addictions as moral problems.

Comments on 'Standard effective doses for proliferative tumours'

International Nuclear Information System (INIS)

Dasu, Iuliana Livia; Dasu, Alexandru; Denekamp, Juliana; Fowler, Jack F.

2000-01-01

We should like to make some comments on the paper published by Jones et al (1999). The paper presents some interesting and useful contributions on the theoretical evaluation of different fractionated schedules used now. The use of the linear quadratic equation has been very useful in focusing attention on the differences in fractionation responses of fast and slow proliferating normal tissues and tumours. Unfortunately the BED 10 or BED 3 units for (α/β ratios of 10 Gy and 3 Gy respectively) do not directly relate to anything used in routine clinical practice. The purpose of the paper by Jones et al (1999) is to covert any new schedule into the equivalent total dose as if it was given in the same size fractions as are in common use in that department. They illustrate that, if proliferation is taken into account for the altered schedule, it can be compared in two ways with the standard conventional schedule: (a) the proliferative standard effective dose one (PSED 1 ) in which the proliferation correction is applied in the altered schedule, but not in the standard schedule; (b) the proliferative standard effective dose two (PSED 2 ) in which the proliferation correction is applied to both schedules using the same proliferation parameters. This is expected to provide a better evaluation of the response of a 'real' tumour (i.e. a tumour that also proliferates during the standard treatment). However, there seem to be two errors in the paper. First, the authors quoted a wrong equation for calculating the proliferative standard effective dose two (PSED 2 ) (equations (2) and (A6) in their paper). There are also some special cases with respect to the time available for proliferation and the duration of the treatment that have been neglected in their paper and which require further specification. Therefore, we should like to give the full mathematical derivation of the correct equations for calculating the proliferative standard effective doses. We would also like to make

Polysaccharides from Sargassum thunbergii: Monthly variations and anti-complement and anti-tumour activities.

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Jin, Weihua; Liu, Ge; Zhong, Weihong; Sun, Chaomin; Zhang, Quanbin

2017-12-01

Monthly variations of polysaccharides from Sargassum thunbergii and their anti-complement and anti-tumour activities were investigated. It was observed that an increase in fucose and total sugar contents occurred during the growth period (from early April to mid-June), accompanied by a decrease in molar ratios of other monosaccharides to fucose. The highest yields were obtained from early July to early September, which was in accordance with the significant increase in molar ratio of glucose to fucose and decrease in molar ratio of other monosaccharides to fucose. And the above results suggested that S. Thunbergii synthesized large amount of laminaran, the storage substance of brown algae, during the senescence period. However, sulfate contents were relatively stable in the life cycle of S. thunbergii. These results suggested that S. thunbergii synthesized complex sulfated heteropolysacchairdes during inactive period, while during other periods, it synthesized more sulfated galactofucan. All polysaccharides showed anti-complement activity, suggesting that the harvesting time did not influence the anti-complement activities. In the anti-tumour assay in vitro, the polysaccharides taken during the senescence period had much lower anti-tumour activity, suggesting that fucoidan, but not laminaran, determined the anti-tumour activities. Therefore, polysaccharides from S. thunbergii might have great potential in anti-complement and anti-tumour application. Copyright © 2017 Elsevier B.V. All rights reserved.

Proliferative activity in oral pyogenic granuloma: A comparative immunohistochemical study

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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.

Proliferation Index and Karyometric Features of Pancreatic Intraductal Proliferative Lesions

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Romana Tomaszewska

1999-01-01

Full Text Available The increasing frequency and poor prognosis in pancreatic cancer prompt us to search for morphological lesions being a substrate for its development. Studies of autopsy and surgically resected material as well as recent molecular studies have proved that one of the possible pathways of pancreatic neoplasia is the intraepithelial proliferation – dysplasia – cancer sequence. In the present paper we studied the proliferative activity (Ki‐67 index in pancreatic intraepithelial proliferative lesions and its correlation with geometric features of cell nuclei as signs of increasing dysplasia. The studies were carried out in a group of 35 patients operated on for pancreatic cancer, chronic pancreatitis and other conditions not associated with the pancreas. We used immunohistochemical methods and basic morphometric parameters. The results of our studies indicate that the cell proliferative activity depends both on the type of epithelial proliferation and underlying pancreatic disease. The values of Ki‐67 index are significantly different in low‐grade proliferation (flat and papillary hyperplasia and high‐grade proliferation (atypical papillary hyperplasia and carcinoma in situ. A set of karyometric features correlates with Ki‐67 index but there is no single feature which would have a diagnostic value.

Intended or Unintended Doping? A Review of the Presence of Doping Substances in Dietary Supplements Used in Sports.

Science.gov (United States)

Martínez-Sanz, José Miguel; Sospedra, Isabel; Ortiz, Christian Mañas; Baladía, Eduard; Gil-Izquierdo, Angel; Ortiz-Moncada, Rocio

2017-10-04

The use of dietary supplements is increasing among athletes, year after year. Related to the high rates of use, unintentional doping occurs. Unintentional doping refers to positive anti-doping tests due to the use of any supplement containing unlisted substances banned by anti-doping regulations and organizations, such as the World Anti-Doping Agency (WADA). The objective of this review is to summarize the presence of unlabeled doping substances in dietary supplements that are used in sports. A review of substances/metabolites/markers banned by WADA in ergonutritional supplements was completed using PubMed. The inclusion criteria were studies published up until September 2017, which analyzed the content of substances, metabolites and markers banned by WADA. 446 studies were identified, 23 of which fulfilled all the inclusion criteria. In most of the studies, the purpose was to identify doping substances in dietary supplements. Substances prohibited by WADA were found in most of the supplements analyzed in this review. Some of them were prohormones and/or stimulants. With rates of contamination between 12 and 58%, non-intentional doping is a point to take into account before establishing a supplementation program. Athletes and coaches must be aware of the problems related to the use of any contaminated supplement and should pay special attention before choosing a supplement, informing themselves fully and confirming the guarantees offered by the supplement.

Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

Science.gov (United States)

Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

2018-01-01

The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

KAUST Repository

Hasan, Mohammed Nihal

2018-02-09

Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

KAUST Repository

Hasan, Mohammed Nihal; Choudhry, Hani; Razvi, Syed Shoeb; Moselhy, Said Salama; Kumosani, Taha Abduallah; Zamzami, Mazin A.; Omran, Ziad; Halwani, Majed A.; Al-Babili, Salim; Abualnaja, Khalid Omer; Al-Malki, Abdulrahman Labeed; Alhosin, Mahmoud; Asami, Tadao

2018-01-01

Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells

International Nuclear Information System (INIS)

Sasaki, Kazuhito; Hiyoshi, Masaya; Kaneko, Manabu; Kitayama, Joji; Takahashi, Koki; Nagawa, Hirokazu; Tsuno, Nelson H; Sunami, Eiji; Tsurita, Giichiro; Kawai, Kazushige; Okaji, Yurai; Nishikawa, Takeshi; Shuno, Yasutaka; Hongo, Kumiko

2010-01-01

Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells. HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed. 5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21 Cip1 and p27 Kip1 and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU. Our

Automatic non-proliferative diabetic retinopathy screening system based on color fundus image.

Science.gov (United States)

Xiao, Zhitao; Zhang, Xinpeng; Geng, Lei; Zhang, Fang; Wu, Jun; Tong, Jun; Ogunbona, Philip O; Shan, Chunyan

2017-10-26

Non-proliferative diabetic retinopathy is the early stage of diabetic retinopathy. Automatic detection of non-proliferative diabetic retinopathy is significant for clinical diagnosis, early screening and course progression of patients. This paper introduces the design and implementation of an automatic system for screening non-proliferative diabetic retinopathy based on color fundus images. Firstly, the fundus structures, including blood vessels, optic disc and macula, are extracted and located, respectively. In particular, a new optic disc localization method using parabolic fitting is proposed based on the physiological structure characteristics of optic disc and blood vessels. Then, early lesions, such as microaneurysms, hemorrhages and hard exudates, are detected based on their respective characteristics. An equivalent optical model simulating human eyes is designed based on the anatomical structure of retina. Main structures and early lesions are reconstructed in the 3D space for better visualization. Finally, the severity of each image is evaluated based on the international criteria of diabetic retinopathy. The system has been tested on public databases and images from hospitals. Experimental results demonstrate that the proposed system achieves high accuracy for main structures and early lesions detection. The results of severity classification for non-proliferative diabetic retinopathy are also accurate and suitable. Our system can assist ophthalmologists for clinical diagnosis, automatic screening and course progression of patients.

Impaired Upregulation of the Costimulatory Molecules, CD27 and CD28, on CD4+ T Cells from HIV Patients Receiving ART Is Associated with Poor Proliferative Responses.

Science.gov (United States)

Tanaskovic, Sara; Price, Patricia; French, Martyn A; Fernandez, Sonia

2017-02-01

HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency often retain low CD4 + T cell counts despite virological control. We examined proliferative responses and upregulation of costimulatory molecules, following anti-CD3 stimulation, in HIV patients with persistent CD4 + T cell deficiency on ART. Aviremic HIV patients with nadir CD4 + T cell counts cells/μL and who had received ART for a median time of 7 (range 1-11) years were categorized into those achieving low (cells/μL; n = 13) or normal (>500 cells/μL; n = 20) CD4 + T cell counts. Ten healthy controls were also recruited. CD4 + T cell proliferation (Ki67) and upregulation of costimulatory molecules (CD27 and CD28) after anti-CD3 stimulation were assessed by flow cytometry. Results were related to proportions of CD4 + T cells expressing markers of T cell senescence (CD57), activation (HLA-DR), and apoptotic potential (Fas). Expression of CD27 and/or CD28 on uncultured CD4 + T cells was similar in patients with normal CD4 + T cell counts and healthy controls, but lower in patients with low CD4 + T cell counts. Proportions of CD4 + T cells expressing CD27 and/or CD28 correlated inversely with CD4 + T cell expression of CD57, HLA-DR, and Fas. After anti-CD3 stimulation, induction of CD27 hi CD28 hi expression was independent of CD4 + T cell counts, but lower in HIV patients than in healthy controls. Induction of CD27 hi CD28 hi expression correlated with induction of Ki67 expression in total, naïve, and CD31 + naïve CD4 + T cells from patients. In HIV patients responding to ART, impaired induction of CD27 and CD28 on CD4 + T cells after stimulation with anti-CD3 is associated with poor proliferative responses as well as greater CD4 + T cell activation and immunosenescence.

Analysis of in situ proliferative activity in oral gingival epithelium in patients with xerostomia.

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Celenligil-Nazliel, Haviye; Palali, Ali; Ayhan, Ayşe; Ruacan, Sevket

2003-02-01

Sjögren's syndrome is an autoimmune disease characterized by xerostomia and keratoconjunctivitis sicca. The relationship between xero-stomia and proliferative activity in human gingival epithelium is not known. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. The aims of this study were to evaluate PCNA expression in oral gingival epithelium of healthy and inflamed gingiva obtained from patients with Sjögren's syndrome, and to compare the results to age- and gender-matched subjects with normal salivary function. Eighteen Sjögren's syndrome patients and 28 controls (14 with chronic periodontitis and 14 with no clinical evidence of periodontal disease) were included in the study. Biopsies were obtained from both inflamed and healthy gingiva. The expression of PCNA was evaluated in formalin-fixed, paraffin-embedded gingival samples using an immunoperoxidase technique and PC10 monoclonal antibody to PCNA. PCNA expression was observed both in the basal and suprabasal layers, and was found to be more prominent in the suprabasal layers. Proliferative index (PI) in inflamed gingiva was significantly lower in the Sjögren's syndrome group. However, no significant difference was observed between the study and control groups with respect to PI in healthy gingiva. In both groups, PI was found to be increased due to inflammation. Our data indicate that proliferative activity is observed in the suprabasal layers and, less frequently, in the basal layer. Inflammation caused increased proliferative activity. However, this positive effect of inflammation on epithelial cell proliferation decreased significantly with a lack of saliva. Therefore, it appears that saliva-derived biological mediators may also contribute to increased proliferative activity observed during inflammation.

Anti-glomerular basement membrane glomerulonephritis in an HIV positive patient: case report

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Eduardo José Bellotto Monteiro

Full Text Available We report on a case of a patient with HIV infection, diagnosed 18 months prior to the development of an anti-glomerular basement membrane (anti-GBM rapidly progressive glomerulonephritis; this is probably the first report of such an association. A 30-year-old white man presented with elevation of serum creatinine (1.3 - 13.5 mg/dL within one month. At admission, the urinalysis showed proteinuria of 7.2 g/L and 8,000,000 erythrocytes/mL. Renal biopsy corresponded to a crescentic diffuse proliferative glomerulonephritis mediated by anti-GBM, and serum testing for anti-GBM antibodies was positive; antinuclear antibodies (ANA and anti-neutrophilic cytoplasmic antibodies (ANCA were also positive. The patient underwent hemodyalisis and was treated with plasmapheresis, cyclophosphamide and prednisone. The association described here is not casual, as crescentic glomerulonephritis is not common in HIV-positive patients, anti-GBM glomerulonephritis is rare and anti-GBM antibodies are frequently observed in HIV-positive subjects when compared to the overall population. Based on the current case and on the elevated frequency of the positivity for such antibodies in this group of patients, it is advisable to be aware of the eventual association between these two conditions and to promote an active search for anti-GBM antibodies and early diagnosis of eventual urinary abnormalities in HIV-positive subjects, considering the severity of anti-GBM glomerulonephritis.

A Predictive Model for Estimation Risk of Proliferative Lupus Nephritis

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Dong-Ni Chen

2018-01-01

Conclusion: This study developed and validated a model including demographic and clinical indices to evaluate the probability of presenting proliferative LN to guide therapeutic decisions and outcomes.

Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest

Science.gov (United States)

Tarade, Daniel; Ma, Dennis; Pignanelli, Christopher; Mansour, Fadi; Simard, Daniel; van den Berg, Sean; Gauld, James; McNulty, James; Pandey, Siyaram

2017-01-01

The cis-stilbene, combretastatin A4 (CA4), is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses. Our current study provides a more comprehensive evaluation regarding the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models. Computational analysis has revealed that cytotoxicity of CA4 and biphenyl analogues correlates with predicted tubulin affinity. Additional mechanistic evaluation of the biphenyl derivatives found that their anti-cancer activity is dependent on prolonged mitotic arrest, in a similar manner to CA4. Lastly, we have shown that cancer cells deficient in the extrinsic pathway of apoptosis experience delayed cell death following treatment with CA4 or analogues. Biphenyl derivatives of CA4 represent structurally simplified analogues of CA4, which retain a similar mechanism of action. The biphenyl analogues warrant in vivo examination to evaluate their potential as vascular damaging agents. PMID:28253265

Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest.

Directory of Open Access Journals (Sweden)

Daniel Tarade

Full Text Available The cis-stilbene, combretastatin A4 (CA4, is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses. Our current study provides a more comprehensive evaluation regarding the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models. Computational analysis has revealed that cytotoxicity of CA4 and biphenyl analogues correlates with predicted tubulin affinity. Additional mechanistic evaluation of the biphenyl derivatives found that their anti-cancer activity is dependent on prolonged mitotic arrest, in a similar manner to CA4. Lastly, we have shown that cancer cells deficient in the extrinsic pathway of apoptosis experience delayed cell death following treatment with CA4 or analogues. Biphenyl derivatives of CA4 represent structurally simplified analogues of CA4, which retain a similar mechanism of action. The biphenyl analogues warrant in vivo examination to evaluate their potential as vascular damaging agents.

The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production

International Nuclear Information System (INIS)

Xu, Weihong; Xu, Bin; Yao, Yiting; Yu, Xiaoling; Shen, Jie

2015-01-01

In the current study, we investigated the potential activity of AR-42, a novel histone deacetylase (HDAC) inhibitor, against colon cancer cells. Our in vitro results showed that AR-42 induced ceramide production, exerted potent anti-proliferative and pro-apoptotic activities in established (SW-620 and HCT-116 lines) and primary human colon cancer cells. Exogenously-added sphingosine 1-phosphate (S1P) suppressed AR-42-induced activity, yet a cell-permeable ceramide (C4) facilitated AR-42-induced cytotoxicity against colon cancer cells. In addition, AR-42-induced ceramide production and anti-colon cancer cell activity were inhibited by the ceramide synthase inhibitor fumonisin B1, but were exacerbated by PDMP, which is a ceramide glucosylation inhibitor. In vivo, oral administration of a single dose of AR-42 dramatically inhibited SW-620 xenograft growth in severe combined immunodeficient (SCID) mice, without inducing overt toxicities. Together, these results show that AR-42 dramatically inhibits colon cancer cell proliferation in vitro and in vivo, and ceramide production might be the key mechanism responsible for its actions. - Highlights: • AR-42 is anti-proliferative against primary/established colon cancer cells. • AR-42 induces significant apoptotic death in primary/established colon cancer cells. • Ceramide production mediates AR-42-induced cytotoxicity in colon cancer cells. • AR-42 oral administration potently inhibits SW-620 xenograft growth in SCID mice

The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production

Energy Technology Data Exchange (ETDEWEB)

Xu, Weihong; Xu, Bin; Yao, Yiting; Yu, Xiaoling [Department of Clinical Laboratory, Tongren Hospital, Shanghai (China); Shen, Jie, E-mail: tongrensj163@163.com [Department of Administrative, Tongren Hospital, No. 786 Yuyuan Road, Changning District, Shanghai (China)

2015-08-07

In the current study, we investigated the potential activity of AR-42, a novel histone deacetylase (HDAC) inhibitor, against colon cancer cells. Our in vitro results showed that AR-42 induced ceramide production, exerted potent anti-proliferative and pro-apoptotic activities in established (SW-620 and HCT-116 lines) and primary human colon cancer cells. Exogenously-added sphingosine 1-phosphate (S1P) suppressed AR-42-induced activity, yet a cell-permeable ceramide (C4) facilitated AR-42-induced cytotoxicity against colon cancer cells. In addition, AR-42-induced ceramide production and anti-colon cancer cell activity were inhibited by the ceramide synthase inhibitor fumonisin B1, but were exacerbated by PDMP, which is a ceramide glucosylation inhibitor. In vivo, oral administration of a single dose of AR-42 dramatically inhibited SW-620 xenograft growth in severe combined immunodeficient (SCID) mice, without inducing overt toxicities. Together, these results show that AR-42 dramatically inhibits colon cancer cell proliferation in vitro and in vivo, and ceramide production might be the key mechanism responsible for its actions. - Highlights: • AR-42 is anti-proliferative against primary/established colon cancer cells. • AR-42 induces significant apoptotic death in primary/established colon cancer cells. • Ceramide production mediates AR-42-induced cytotoxicity in colon cancer cells. • AR-42 oral administration potently inhibits SW-620 xenograft growth in SCID mice.

Intended or Unintended Doping? A Review of the Presence of Doping Substances in Dietary Supplements Used in Sports

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José Miguel Martínez-Sanz

2017-10-01

Full Text Available Introduction: The use of dietary supplements is increasing among athletes, year after year. Related to the high rates of use, unintentional doping occurs. Unintentional doping refers to positive anti-doping tests due to the use of any supplement containing unlisted substances banned by anti-doping regulations and organizations, such as the World Anti-Doping Agency (WADA. The objective of this review is to summarize the presence of unlabeled doping substances in dietary supplements that are used in sports. Methodology: A review of substances/metabolites/markers banned by WADA in ergonutritional supplements was completed using PubMed. The inclusion criteria were studies published up until September 2017, which analyzed the content of substances, metabolites and markers banned by WADA. Results: 446 studies were identified, 23 of which fulfilled all the inclusion criteria. In most of the studies, the purpose was to identify doping substances in dietary supplements. Discussion: Substances prohibited by WADA were found in most of the supplements analyzed in this review. Some of them were prohormones and/or stimulants. With rates of contamination between 12 and 58%, non-intentional doping is a point to take into account before establishing a supplementation program. Athletes and coaches must be aware of the problems related to the use of any contaminated supplement and should pay special attention before choosing a supplement, informing themselves fully and confirming the guarantees offered by the supplement.

Intended or Unintended Doping? A Review of the Presence of Doping Substances in Dietary Supplements Used in Sports

Science.gov (United States)

Mañas Ortiz, Christian; Ortiz-Moncada, Rocio

2017-01-01

Introduction: The use of dietary supplements is increasing among athletes, year after year. Related to the high rates of use, unintentional doping occurs. Unintentional doping refers to positive anti-doping tests due to the use of any supplement containing unlisted substances banned by anti-doping regulations and organizations, such as the World Anti-Doping Agency (WADA). The objective of this review is to summarize the presence of unlabeled doping substances in dietary supplements that are used in sports. Methodology: A review of substances/metabolites/markers banned by WADA in ergonutritional supplements was completed using PubMed. The inclusion criteria were studies published up until September 2017, which analyzed the content of substances, metabolites and markers banned by WADA. Results: 446 studies were identified, 23 of which fulfilled all the inclusion criteria. In most of the studies, the purpose was to identify doping substances in dietary supplements. Discussion: Substances prohibited by WADA were found in most of the supplements analyzed in this review. Some of them were prohormones and/or stimulants. With rates of contamination between 12 and 58%, non-intentional doping is a point to take into account before establishing a supplementation program. Athletes and coaches must be aware of the problems related to the use of any contaminated supplement and should pay special attention before choosing a supplement, informing themselves fully and confirming the guarantees offered by the supplement. PMID:28976928

Do Actions Speak Louder Than Words?: Adolescent Interpretations of Parental Substance Use.

Science.gov (United States)

Ebersole, Diana S; Miller-Day, Michelle; Raup-Krieger, Janice

2014-01-01

Parents are powerful socialization agents for children and as children reach adolescence parental role models, among other sources of influence, become particularly salient in adolescents' decision-making regarding initiation of substance use. Open parent-adolescent communication about substances is associated with less substance use by adolescents; however, it is unclear how youth interpret anti-drug use messages from their parents, especially if the parents engage in legal and/or illicit substance use themselves. Framed by social learning theory and social constructionism, this study analyzed in-depth interviews with 108 adolescents about personal experiences with substance use, family communication about substance use, and adolescent interpretations of parental use. Emergent themes in the data include : positive parental influence , parental contradictions , and negative outcomes of use . Prevalence of parental use-regardless of legality, rarity of explicit communication about parental use, and various interpretations of parental use are discussed.

On the Upper Limit (Heaviest Element in the Periodic Table of Elements, and the Periodic Table of Anti-Substance

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Khazan A.

2009-04-01

Full Text Available On the basis of the method involving equilateral hyperbolas developed by us with ref- erence to the Periodic Table, its Top Limit has been established. It is the last element with atomic mass 411.66 and serial number 155. The great value, according to our calculation, has adjacent hyperbolas whose center is the point (0; 1. With the method, it has been possible to find just one element in the Periodic Table — Rhodium, which does not demand additional calculations involving the definition of the valid axes. Cal- culations towards updating the charge of a nucleus and the quantity of neutrons in end N-Z part of the diagram by means of the serial number 155 are herein executed. The variant of the Periodic Table of Elements with the eighth period is recommended. On the basis of symmetry, with the application of the Hyperbolic Law in the Periodic Table of Elements, the existence of Anti-Substances is herein indirectly proved.

Personality traits among individuals who as adolescents consulted for a substance use problem

OpenAIRE

Hemphälä, Malin

2013-01-01

Background: Adolescent antis ocial behavior including substance misuse is associated with negative consequences both for the individual and the society, for example school drop - out, and high costs in the criminal justice and health systems. Further understanding of adolescent substanc e misuse is needed to inform treatment programs. The main aim of this thesis is to advance understanding of personality traits, and most particularly psychopathic traits, among ...

Early pubertal onset and its relationship with sexual risk taking, substance use and anti-social behaviour: a preliminary cross-sectional study

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Bellis Mark A

2009-12-01

Full Text Available Abstract Background In many countries age at pubertal onset has declined substantially. Relatively little attention has been paid to how this decline may affect adolescent behaviours such as substance use, violence and unprotected sex and consequently impact on public health. Methods In the UK, two opportunistic samples (aged 16-45 years, paper-based (n = 976 and online (n = 1117, examined factors associated with earlier pubertal onset and whether earlier age of onset predicted sexual risk-taking, substance use and anti-social behaviours during early adolescence. Results Overall, 45.6% of females reported menarche ≤ 12 years and 53.3% of males were categorised as having pubertal onset ≤ 11 years. For both sexes earlier pubertal onset was associated with poorer parental socio-economic status. Other pre-pubertal predictors of early onset were being overweight, more childhood illnesses (females and younger age at time of survey (males. For both sexes earlier puberty predicted having drunk alcohol, been drunk, smoked and used drugs Conclusion Results provide sufficient evidence for changes in age of pubertal onset to be further explored as a potential influence on trends in adolescent risk behaviours. Further insight into the relationship between early puberty and both obesity and socio-economic status may help inform early interventions to tackle the development of risk behaviours and health inequalities during early adolescence.

Proliferative, necrotizing and crescentic immune complex-mediated glomerulonephritis in a cat

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Carolyn Gross

2015-09-01

Full Text Available Case Summary A 5-year-old cat was examined for vomiting and anorexia of 2 days’ duration. Azotemia, hyperphosphatemia and hypoalbuminemia were the main biochemical findings. Serial analyses of the urine revealed isosthenuria, proteinuria and eventual glucosuria. Hyperechoic perirenal fat was detected surrounding the right kidney by ultrasonography. Histopathologic evaluation of ante-mortem ultrasound-guided needle biopsies of the right kidney was consistent with proliferative, necrotizing and crescentic glomerulonephritis with fibrin thrombi, proteinaceous and red blood cell casts, and moderate multifocal chronic-active interstitial nephritis. Owing to a lack of clinical improvement, the cat was eventually euthanized. Post-mortem renal biopsies were processed for light microscopy, transmission electron microscopy and immunofluorescence. This revealed severe focal proliferative and necrotizing glomerulonephritis with cellular crescent formation, podocyte injury and secondary segmental sclerosis. Ultrastructural analysis revealed scattered electron-dense deposits in the mesangium, and immunofluorescence demonstrated positive granular staining for λ light chains, consistent with immune complex-mediated glomerulonephritis. Severe diffuse acute tubular epithelial injury and numerous red blood cell casts were also seen. Relevance and novel information To our knowledge, this is the first report of naturally occurring proliferative, necrotizing and crescentic immune complex glomerulonephritis in a cat.

Anti-cancer potential of banana flower extract: An in vitro study

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Varalakshmi Kilingar Nadumane

2014-12-01

Full Text Available Banana (Musa paradisiaca flower is rich in phytochemicals (vitamins, flavonoids, proteins and has antioxidant properties. The anti-cancer activity of banana flower extract has been evaluated on the cervical cancer cell line HeLa. The antiproliferative effects were evaluated by MTT assay. The extract was further purified by TLC and characterized by LC-MS method. The ethanol extract had significant cytotoxicity to HeLa cells with an IC50 of 20 µg/mL. By thin layer chromatography we could isolate three fractions out of which fraction 2 had exhibited maximum anti-proliferative effects with an IC50 value of <10 µg/mL. By LC-MS analysis, bioactive fraction was found to have an m/z value of 224.2 indicating it as a novel one.

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...... into the central retinal artery and vein equivalent (CRAE and CRVE). The purpose of this study was to evaluate retinal calibers as biomarkers for disease activity 3 months after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PDR). Methods: Fifty one eyes from 40 newly...... with proliferative diabetic retinopathy....

Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

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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.

VISUAL OUTCOME FOLLOWING PANRETINAL PHOTOCOAGULATION IN PROLIFERATIVE DIABETIC RETINOPATHY

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Nellaye Mani Sindhu

2018-01-01

Full Text Available BACKGROUND Diabetes mellitus can be called as a noninfectious pandemic and the incidence of diabetic retinopathy is also uncontrollable. This vision-threatening complication can be treated by early diagnosis and effective treatment like panretinal photocoagulation. The aim of the study is to evaluate the effect of panretinal photocoagulation on visual acuity, colour vision, contrast sensitivity and severity of visual field changes. MATERIALS AND METHODS Prospective study of visual outcome following panretinal photocoagulation in patients with proliferative diabetic retinopathy conducted in Retina Clinic, RIO, Trivandrum, during the time period one year from April 2008. Inclusion Criteria- Eyes with proliferative diabetic retinopathy, visual acuity better than or equal to 6/60, a follow up of at least 6 months after panretinal photocoagulation. Exclusion Criteria- Eyes with cataractous changes in the lens, eyes, which would be undergoing or have undergone focal photocoagulation eyes, which undergone barrage or sectoral retinal photocoagulation, patients with colour blindness, eyes with vitreous haemorrhage and macular preretinal haemorrhage, glaucomatous patients with peripheral field loss. RESULTS The mean age of the patients was 52 years. Male patients (30 outnumbered the female patients (23. Mean duration of diabetes was 14.42 years. Though, there is a statistically significant reduction in visual acuity in the first followup, which was improved and stabilised by 6 months. There is a statistically significant reduction in the contrast sensitivity, which was stabilised after 3 months. Only, 9.5% patients had peripheral constrictions of visual field and no significant change in the colour vision. CONCLUSION We recommend panretinal photocoagulation for all patients with proliferative diabetic retinopathy.

Antioxidant, anti-inflammatory and antinociceptive activities of ...

African Journals Online (AJOL)

Background of study: Plants used for traditional medicine contain a wide range of substances which can be used to treat various infectious diseases. Aim: The study evaluated the in vitro antioxidant, antinociceptive, and anti-inflammatory activities of the methanolic extract of Justicia secunda Vahl leaf. Methods: The acute ...

Scoring radiologic characteristics to predict proliferative potential in meningiomas

International Nuclear Information System (INIS)

Hashiba, Tetsuo; Hashimoto, Naoya; Maruno, Motohiko; Izumoto, Shuichi; Suzuki, Tsuyoshi; Kagawa, Naoki; Yoshimine, Toshiki

2006-01-01

We investigated the feasibility of using radiologic characteristics to predict the proliferative potential in meningiomas. Our statistical analysis revealed that the presence of peritumoral edema, an ambiguous brain-tumor border, and irregular tumor shape were significantly correlated with a higher MIB-1 staining index (SI) value. We developed the following scoring system for specific features in each tumor: peritumoral edema (tumor with edema=1, tumor without edema=0); brain-tumor border (tumor with any ambiguous border=1, tumor circumscribed by a distinct rim=0); and tumor shape (tumor with irregular shape=1, tumor with smooth shape=0). Using Spearman's correlation coefficient analysis, we found a significant correlation (P<0.005) between total score calculated for each patient and SI value. Our findings suggest that the proliferative potential of meningiomas can be predicted using a less invasive preoperative examination focusing on the presence of peritumoral edema, ambiguous brain-tumor border, and irregular tumor shape. (author)

Adult attention-deficit/hyperactivity disorder and its association with substance use and substance use disorders in young men.

Science.gov (United States)

Estévez, N; Dey, M; Eich-Höchli, D; Foster, S; Gmel, G; Mohler-Kuo, M

2016-06-01

Functional and mental health impairments that adults with attention-deficit/hyperactivity disorder (ADHD) experience may be exacerbated by regular substance use and co-morbidity with substance use disorders (SUD). This may be especially true during young adulthood, which represents a critical stage of life associated with increased substance use and associated problems. However, previous studies investigating the association between ADHD and substance use and SUD have demonstrated inconsistent results, probably due to methodological limitations (e.g., small and non-representative samples). Thus, the relationship of ADHD with substance use and related disorders remains unclear. The aim of the present study was to examine the association between ADHD and both the use of licit and illicit substances and the presence of SUD in a large, representative sample of young men. The sample included 5677 Swiss men (mean age 20 ± 1.23 years) who participated in the Cohort Study on Substance Use Risk Factors (C-SURF). ADHD was assessed using the adult ADHD Self Report Screener (ASRS). The association between ADHD and substance use and SUD was assessed for alcohol, nicotine, cannabis and other illicit drugs, while controlling for socio-demographic variables and co-morbid psychiatric disorders (i.e., major depression (MD) and anti-social personality disorder (ASPD)). Men with ADHD were more likely to report having used nicotine, cannabis and other illicit drugs at some time in their life, but not alcohol. ADHD was positively associated with early initiation of alcohol, nicotine and cannabis use, the risky use of these substances, and the presence of alcohol use disorders, and nicotine and cannabis dependence. Additionally, our analyses revealed that these patterns are also highly associated with ASPD. After adjusting for this disorder, the association between ADHD and licit and illicit substance use and the presence of SUDs was reduced, but remained significant. Our findings

Interleukin-9 receptor α chain mRNA formation in CD8+ T cells producing anti-human immunodeficiency virus type 1 substance(s)

International Nuclear Information System (INIS)

Hossain, M.M.; Tsuchie, H.; Detorio, M.A.; Shirono, H.; Hara, C.; Nishimoto, A.; Saji, A.; Koga, J.; Takata, N.; Maniar, J.K.; Saple, D.G.; Taniguchi, K.; Kageyama, S.; Ichimura, H.; Kurimura, T.

1998-01-01

A search for gene(s) associated with anti-human immunodeficiency virus type 1 (HIV-l) activity of CD8 + T cells was attempted using molecular cloning and the relation between the anti-HIV activity of CD8 + T cells and the interleukin-9 receptor a chain (IL-9R-α) mRNA expression from the cDNA clones obtained was examined. The anti-HIV-l activity of CD8 + T cell culture supernatants was assessed by measuring the level of HIV-l replication in a CD4 + T cell line transfected with an infectious HIV-l DNA clone. IL-9R-a mRNA was assayed by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 5 cases showing high level of anti-HIV-l activity (more than 80% suppression of HIV-l replication), the mRNA was detected in 4 cases. Of 10 cases showing low level of anti-HIV-l activity (less than 80% suppression of HIV-l replication), the mRNA was detected in one case. Soluble recombinant human IL-9 receptor (rhIL-9sR) did not suppress HIV-l replication at a concentration of 1 μg/ml. These data suggest that the IL-9R-a mRNA formation in CD8 + T cells may correlate with and play some role in the anti-HIV-l activity of CD8+ T cells from HIV-l-infected individuals. Key words: CD8+ T cells; anti-HIV-l activity; cytokines; interleukin-9 receptor (authors)

Curcumin exhibits anti-tumor effect and attenuates cellular migration via Slit-2 mediated down-regulation of SDF-1 and CXCR4 in endometrial adenocarcinoma cells.

Science.gov (United States)

Sirohi, Vijay Kumar; Popli, Pooja; Sankhwar, Pushplata; Kaushal, Jyoti Bala; Gupta, Kanchan; Manohar, Murli; Dwivedi, Anila

2017-06-01

Although curcumin shows anti-proliferative and anti-inflammatory activities in various cancers, the effect of curcumin on cellular migration in endometrial adenocarcinoma cells remains to be understood. The current investigation was aimed to explore the anti-proliferative and anti-migratory effects of curcumin and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo experimental studies showed that curcumin inhibited the proliferation of endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells. Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed by scratch wound assay. In transwell migration studies, knock down of Slit-2 reversed the anti-migratory effect of curcumin in these cell lines. Curcumin significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and primary endometrial cancer cells while it down-regulated the expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the migration of endometrial cancer cells. In summary, we have demonstrated that curcumin has inhibitory effect on cellular migration via Slit-2 mediated down-regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These findings helped explore the role of Slit-2 in endometrial cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Body linear traits for identifying prolific goats

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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

Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines

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Zou Zhengyun

2012-04-01

Full Text Available Summary Background Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death. Methods MTT assay was used to determine IC50 values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. Results Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells. Conclusions Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.

Proliferative Retinopathy in Type 1 Diabetes Is Associated With Cerebral Microbleeds, Which Is Part of Generalized Microangiopathy

NARCIS (Netherlands)

Woerdeman, J.P.; van Duinkerken, E.; Wattjes, M.P.; Barkhof, F.; Snoek, F.J.; Moll, A.C.; Klein, M.; de Boer, M.P.; IJzerman, R.G.; Serne, E.H.; Diamant, M.

2014-01-01

OBJECTIVE: We investigated whether proliferative diabetic retinopathy in type 1 diabetic patients can be generalized to cerebral small vessel disease and whether it is associated with impaired peripheral microvascular function. RESEARCH DESIGN AND METHODS: Thirty-three patients with proliferative

Proliferative and morphologic changes in rat colon following bypass surgery.

Science.gov (United States)

Barkla, D H; Tutton, P J

1985-06-01

In this study the proliferative and morphologic changes that occur in the colon of normal and dimethylhydrazine-treated rats following surgical bypass of the middle third of the colon are reported. Proliferative changes were measured by estimating accumulated mitotic indexes following vinblastine treatment and morphologic changes were observed with the use of light microscopy and scanning electron microscopy. Data were collected on Days 0, 7, 14, 30, and 72 after surgery. The results show that surgical bypass produces contrasting effects in the segments proximal to and distal to the suture line. In the proximal segment there was morphologic evidence of hyperplasia, although proliferative activity was unchanged except for an increase at 7 days in normal rats. In the distal segment there was a long-lived increase in the mitotic index, although morphologic changes were not seen. The results for DMH-treated rats were similar to those in normal rats. Groups of isolated dysplastic epithelial cells were often seen in the submucosa adjacent to sutures up to 72 days after surgery. Increased lymphoid infiltration was seen in segments proximal to but not distal to the suture line. It is hypothesized that the different responses of the proximal and distal segments may be related to the different embryologic origins of those segments. It is also hypothesized that the seeding of the submucosa with epithelial cells during suturing may be a factor in tumor recurrence.

Bio-normalyzer[reg]: An anti-cancer drug for neuroblastoma?

International Nuclear Information System (INIS)

Gouget, B.; Sergeant, C.; Llabador, Y.; Simonoff, M.

2001-01-01

Iron is an essential micronutrient required for cell division and growth. Incorporation of iron into cells is achieved by endocytosis of transferrin. Then, iron may be stored in ferritin and hemosiderin. Increased intracellular iron concentrations may promote malignant cell growth. Patients with advanced-stage neuroblastoma (NB) show abnormally high levels of serum ferritin, very likely synthesized and secreted by the tumor in vivo and consistent with a frequent accumulation of iron in ferritin in NB tumor tissues. In a previous study, we showed that there is no iron accumulation in cultured neuroblasts, and intracellular iron concentrations proved to be especially low. Bio-Normalizer[reg] (BioN) is a nutritional supplement sold to be an anti-oxidant and metal-chelator. In the present study, we tested cell viability and measured iron concentrations in neuroblasts treated or not with BioN. We found that BioN, probably thanks to papain, presents an anti-proliferative effect on NB cultured cells. Besides, preliminary results tend to prove that this natural anti-oxidant and iron-chelator could present interesting effects on trace metal concentrations in neuroblasts. Such a compound may be useful in treatment of this pathology

The Development of the World Anti-Doping Code.

Science.gov (United States)

Young, Richard

2017-01-01

This chapter addresses both the development and substance of the World Anti-Doping Code, which came into effect in 2003, as well as the subsequent Code amendments, which came into effect in 2009 and 2015. Through an extensive process of stakeholder input and collaboration, the World Anti-Doping Code has transformed the hodgepodge of inconsistent and competing pre-2003 anti-doping rules into a harmonized and effective approach to anti-doping. The Code, as amended, is now widely recognized worldwide as the gold standard in anti-doping. The World Anti-Doping Code originally went into effect on January 1, 2004. The first amendments to the Code went into effect on January 1, 2009, and the second amendments on January 1, 2015. The Code and the related international standards are the product of a long and collaborative process designed to make the fight against doping more effective through the adoption and implementation of worldwide harmonized rules and best practices. © 2017 S. Karger AG, Basel.

Anti-mitotic activity towards sea urchin eggs of dichloromethane fraction obtained from Allamanda schottii Pohl (Apocynaceae

Directory of Open Access Journals (Sweden)

Louisa M. A. Sousa

Full Text Available Allamanda (Apocynaceae is a genus of climbing shrubs known for producing compounds with a range of biological activities. Previous works have shown the anti-proliferative effect of the ethanolic extract of Allamanda schottii on leukemic cells. The present work was conducted to evaluate the effects of dichloromethane fraction, obtained from Allamanda schottii, on sea urchin Echinometra lucunter eggs, as a multicellular model for evaluating anti-tumor activity. Our results show an inhibition of sea urchin development in a dose-dependent manner in the presence of dichloromethane fraction. The IC50 values for first and third cleavage and blastulae stage were 103.7 µg/mL, 33.1 µg/mL and 10.2 µg/mL, respectively. These results also demonstrate the cumulative effect of this fraction on sea urchin embryos. In the present work, the expressive anti-mitotic activity of dichloromethane fraction towards sea urchin eggs, a multicellular model, reinforces the anti-tumor potential of the Allamanda schotti.

Lenalidomide, an anti-tumor drug, regulates retinal endothelial cell function: Implication for treating ocular neovascular disorder

International Nuclear Information System (INIS)

Dong, Ling-Feng; Yao, Jin; Wang, Xiao-Qun; Shan, Kun; Yang, Hong; Yan, Biao; Jiang, Qin

2015-01-01

Ocular angiogenesis is an important pathologic character of several ocular diseases, such as retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration (AMD). Inhibition of ocular angiogenesis has great therapeutic value for treating these dieses. Here we show that lenalidomide, an anti-tumor drug, has great anti-angiogenic potential in ocular diseases. Lenalidomide inhibits retinal endothelial cell viability in normal and pathological condition, and inhibits VEGF-induced endothelial cell migration and tube formation in vitro. Moreover, lenalidomide inhibits ocular angiogenesis in vivo through the reduction of angiogenesis- and inflammation-related protein expression. Collectively, lenalidomide is a promising drug for treating ocular angiogenesis through its anti-proliferative and anti-inflammatory property. - Highlights: • Lenalidomide inhibits retinal endothelial cell viability in vitro. • Lenalidomide inhibits retinal endothelial cell migration and tube formation. • Lenalidomide inhibits pathological ocular angiogenesis in vivo. • Lenalidomide inhibits angiogenesis- and inflammation-related protein expression.

Lenalidomide, an anti-tumor drug, regulates retinal endothelial cell function: Implication for treating ocular neovascular disorder

Energy Technology Data Exchange (ETDEWEB)

Dong, Ling-Feng; Yao, Jin; Wang, Xiao-Qun; Shan, Kun; Yang, Hong [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical 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); Jiang, Qin, E-mail: jiangqin710@126.com [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China)

2015-10-02

Ocular angiogenesis is an important pathologic character of several ocular diseases, such as retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration (AMD). Inhibition of ocular angiogenesis has great therapeutic value for treating these dieses. Here we show that lenalidomide, an anti-tumor drug, has great anti-angiogenic potential in ocular diseases. Lenalidomide inhibits retinal endothelial cell viability in normal and pathological condition, and inhibits VEGF-induced endothelial cell migration and tube formation in vitro. Moreover, lenalidomide inhibits ocular angiogenesis in vivo through the reduction of angiogenesis- and inflammation-related protein expression. Collectively, lenalidomide is a promising drug for treating ocular angiogenesis through its anti-proliferative and anti-inflammatory property. - Highlights: • Lenalidomide inhibits retinal endothelial cell viability in vitro. • Lenalidomide inhibits retinal endothelial cell migration and tube formation. • Lenalidomide inhibits pathological ocular angiogenesis in vivo. • Lenalidomide inhibits angiogenesis- and inflammation-related protein expression.

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).

Too much of a good thing? An observational study of prolific authors.

Science.gov (United States)

Wager, Elizabeth; Singhvi, Sanjay; Kleinert, Sabine

2015-01-01

Introduction. Researchers' productivity is usually measured in terms of their publication output. A minimum number of publications is required for some medical qualifications and professional appointments. However, authoring an unfeasibly large number of publications might indicate disregard of authorship criteria or even fraud. We therefore examined publication patterns of highly prolific authors in 4 medical specialties. Methods. We analysed Medline publications from 2008-12 using bespoke software to disambiguate individual authors focusing on 4 discrete topics (to further reduce the risk of combining publications from authors with the same name and affiliation). This enabled us to assess the number and type of publications per author per year. Results. While 99% of authors were listed on fewer than 20 publications in the 5-year period, 24 authors in the chosen areas were listed on at least 25 publications in a single year (i.e., >1 publication per 10 working days). Types of publication by the prolific authors varied but included substantial numbers of original research papers (not simply editorials or letters). Conclusions. Institutions and funders should be alert to unfeasibly prolific authors when measuring and creating incentives for researcher productivity.

Too much of a good thing? An observational study of prolific authors

Directory of Open Access Journals (Sweden)

Elizabeth Wager

2015-08-01

Full Text Available Introduction. Researchers’ productivity is usually measured in terms of their publication output. A minimum number of publications is required for some medical qualifications and professional appointments. However, authoring an unfeasibly large number of publications might indicate disregard of authorship criteria or even fraud. We therefore examined publication patterns of highly prolific authors in 4 medical specialties.Methods. We analysed Medline publications from 2008–12 using bespoke software to disambiguate individual authors focusing on 4 discrete topics (to further reduce the risk of combining publications from authors with the same name and affiliation. This enabled us to assess the number and type of publications per author per year.Results. While 99% of authors were listed on fewer than 20 publications in the 5-year period, 24 authors in the chosen areas were listed on at least 25 publications in a single year (i.e., >1 publication per 10 working days. Types of publication by the prolific authors varied but included substantial numbers of original research papers (not simply editorials or letters.Conclusions. Institutions and funders should be alert to unfeasibly prolific authors when measuring and creating incentives for researcher productivity.

Prolific plant regeneration through organogenesis from scalps of ...

African Journals Online (AJOL)

Four types of potting media comprising of sand, peat, sand + top soil + goat dung (3:2:1 v/v) and top soil + sand (1:1 v/v) were evaluated during acclimatization of the plantlets. Prolific shoot regeneration from scalps was obtained on MS medium containing 2.5 mM BAP, at 9.61 and 40.6 shoots per explant after 4 and 8 weeks ...

Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

Science.gov (United States)

Orekhov, Alexander N

2013-01-01

The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

Effect of С(60 fullerene on metabolic and proliferative activity of PKE cell line

Directory of Open Access Journals (Sweden)

I. V. Belochkina

2014-04-01

Full Text Available The effect of С60 fullerene aqueous colloid solution (C60FAS on activity of redox and proliferative processes in PKE (transplantable cell line of pig kidney embryo cells has been studied. In particular, it was established that the presence of С60 fullerene (127 μМ in culturing medium of PKE cells during 48 h did not change their ability to reduce non-toxic АlamarBlue redox indicator and proliferative acti­vity.

Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins.

Science.gov (United States)

Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A

2014-09-01

Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

Proliferative myositis in a patient with AIDS

International Nuclear Information System (INIS)

Wlachovska, B.; Deux, J.F.; Marsault, C.; Le Breton, C.; Abraham, B.; Sibony, M.

2004-01-01

We report a case of proliferative myositis in the right biceps of a 56-year-old man with acquired immune deficiency syndrome (AIDS). Imaging methods included sonography, computed tomography and magnetic resonance imaging. The diagnosis was made by a core-cut biopsy and fine needle aspiration biopsy with immunohistochemical analysis. The lesion disappeared after 2 months without treatment. It is particularly important to determine whether intramuscular masses arising in patients with AIDS are due to an infectious or malignant process. (orig.)

Proliferative myositis in a patient with AIDS

Energy Technology Data Exchange (ETDEWEB)

Wlachovska, B.; Deux, J.F.; Marsault, C.; Le Breton, C. [Department of Radiology, Hopital Tenon, 4 rue de la Chine, 75020, Paris (France); Abraham, B. [Department of Tropical and Infectious Diseases, Hopital Tenon, Paris (France); Sibony, M. [Department of Anatomy, Hopital Tenon, Paris (France)

2004-04-01

We report a case of proliferative myositis in the right biceps of a 56-year-old man with acquired immune deficiency syndrome (AIDS). Imaging methods included sonography, computed tomography and magnetic resonance imaging. The diagnosis was made by a core-cut biopsy and fine needle aspiration biopsy with immunohistochemical analysis. The lesion disappeared after 2 months without treatment. It is particularly important to determine whether intramuscular masses arising in patients with AIDS are due to an infectious or malignant process. (orig.)

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.

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

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.

ONC201 demonstrates anti-tumor effects in both triple negative and non-triple negative breast cancers through TRAIL-dependent and TRAIL-independent mechanisms

Science.gov (United States)

Ralff, Marie D.; Kline, Christina L.B.; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T.; Prabhu, Varun V.; Oster, Wolfgang; El-Deiry, Wafik S.

2017-01-01

Breast cancer is a major cause of cancer-related death. TRAIL has been of interest as a cancer therapeutic, but only a subset of triple negative breast cancers (TNBC) is sensitive to TRAIL. The small molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here we show that ONC201 is efficacious against both TNBC and non-TNBC cells (n=13). A subset of TNBC and non-TNBC cells succumb to ONC201-induced cell death. In 2/8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2. The pro-apoptotic effect of ONC201 translates to in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested (6/8) ONC201 has an anti-proliferative effect but does not induce apoptosis. ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the G1 phase of the cell cycle. pRb expression is associated with sensitivity to the anti-proliferative effects of ONC201, and the compound synergizes with taxanes in less sensitive cells. All non-TNBC cells (n=5) are growth inhibited following ONC201 treatment, and unlike what has been observed with TRAIL, a subset (n=2) show PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL-independent. Our data demonstrate that ONC201 has potent anti-proliferative and pro-apoptotic effects in a broad range of breast cancer subtypes, through TRAIL-dependent and TRAIL-independent mechanisms. These findings develop a pre-clinical rationale for developing ONC201 as a single agent and/or in combination with approved therapies in breast cancer. PMID:28424227

[Betel - the fourth most popular substance in the world].

Science.gov (United States)

Zdrojewicz, Zygmunt; Kosowski, Wojciech; Królikowska, Natalia; Stebnicki, Marek; Stebnicki, Michał R

2015-09-01

Betel is a kind of substance for chewing, that is made from piper betle, areca nuts and other, additional constituents. It is the fourth most popular psychoactive substance in the world, right after caffeine, nicotine and alcohol. It is particularly famous in Asia. Betel chewing induces euphoria and it is addictive. Similarly like in other substances such as nicotine or alcohol, betel also has detrimental effects. It causes e.g. oral cancer and cancer of the oesophagus, it contributes to the development of metabolic syndrome, liver cirrhosis and chronic kidney disease. There are also positive effects of chewing betel, because is has antioxidant, anti-inflammatory, antyparasitic and antiseptic properties. The aim of this paper was to expand knowledge about betel and its both: positive and negative influence on human health. In this article original and review papers associated with the topic were used. © 2015 MEDPRESS.

Global occurrence of anti-infectives in contaminated surface waters: Impact of income inequality between countries.

Science.gov (United States)

Segura, Pedro A; Takada, Hideshige; Correa, José A; El Saadi, Karim; Koike, Tatsuya; Onwona-Agyeman, Siaw; Ofosu-Anim, John; Sabi, Edward Benjamin; Wasonga, Oliver V; Mghalu, Joseph M; dos Santos Junior, Antonio Manuel; Newman, Brent; Weerts, Steven; Yargeau, Viviane

2015-07-01

The presence anti-infectives in environmental waters is of interest because of their potential role in the dissemination of anti-infective resistance in bacteria and other harmful effects on non-target species such as algae and shellfish. Since no information on global trends regarding the contamination caused by these bioactive substances is yet available, we decided to investigate the impact of income inequality between countries on the occurrence of anti-infectives in surface waters. In order to perform such study, we gathered concentration values reported in the peer-reviewed literature between 1998 and 2014 and built a database. To fill the gap of knowledge on occurrence of anti-infectives in African countries, we also collected 61 surface water samples from Ghana, Kenya, Mozambique and South Africa, and measured concentrations of 19 anti-infectives. A mixed one-way analysis of covariance (ANCOVA) model, followed by Turkey-Kramer post hoc tests was used to identify potential differences in anti-infective occurrence between countries grouped by income level (high, upper-middle and lower-middle and low income) according to the classification by the World Bank. Comparison of occurrence of anti-infectives according to income level revealed that concentrations of these substances in contaminated surface waters were significantly higher in low and lower-middle income countries (p=0.0001) but not in upper-middle income countries (p=0.0515) compared to high-income countries. We explained these results as the consequence of the absence of or limited sewage treatment performed in lower income countries. Furthermore, comparison of concentrations of low cost anti-infectives (sulfonamides and trimethoprim) and the more expensive macrolides between income groups suggest that the cost of these substances may have an impact on their environmental occurrence in lower income countries. Since wastewaters are the most important source of contamination of anti-infectives and other

Antibacterial, antioxidant and cell proliferative properties of Coccinia grandis fruits

Directory of Open Access Journals (Sweden)

Prashant Sakharkar

2017-06-01

Full Text Available Objective: Little knowledge is available on the antimicrobial and antioxidant properties of Coccina grandis fruits and no study has reported on its cell proliferative property. The aim of this study was to examine the antimicrobial, antioxidant and cell proliferative property of fruits of C. grandis. Material and Methods: Fruits of C. grandis were extracted using water; ethanol and acetone by cold and hot Soxhlet extraction. The antibacterial activities of the extracts were tested against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa using the modified Kirby-Bauer diffusion method and compared against erythromycin. The antioxidant property was determined using Cayman's antioxidant assay; whereas cell proliferation/cytotoxic properties were evaluated using the Cell Titer 96 Aqueous One Solution Cell MTS assay with MDA-MB 321 breast cancer cells. Data were analyzed for correlation and differences using unpaired student's t-test and one-way ANOVA. A p value of Results: Both cold and hot ethanol and acetone extracts of C. grandis fruits showed some degree of bacterial growth inhibition. Acetone extracts exhibited higher antibacterial activity. Both ethanol extracts showed antioxidant property when compared with standard Trolox. In contrary to cytotoxicity, all four extracts showed cell proliferation compared to controls at different concentrations. However, acetone extracts exhibited greater cell proliferation compared to ethanol extracts and cold extracts performed better than the hot extracts. Conclusion: C. grandis fruits exhibited some degree of antimicrobial, antioxidant and cell proliferative properties. Further investigation is warranted to isolate, confirm and characterize phytochemicals that are responsible for the medicinal properties observed.

Proliferative and nonproliferative breast disease in atomic-bomb survivors

International Nuclear Information System (INIS)

Tokunaga, Masayoshi; Land, C.E.; Aoki, Yoichiro; Yamamoto, Tsutomu; Asano, Masahide; Sato, Eiichi; Tokuoka, Shoji; Sakamoto, Goi; Page, D.L.

1993-10-01

The risk of female breast cancer in association with radiation exposure is well established, on the basis of follow-up studies of the atomic-bomb survivors and other exposed populations. This association is especially strong for women exposed before age 20 yr and appears to be much weaker among women exposed after age 40 yr. In this study, breast-tissue autopsy samples from high-dose and low-dose individuals in the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative or proliferative breast lesions are associated with radiation exposure. The results suggest that proliferative disease in general and atypical hyperplasia in particular are associated with radiation exposure and that the risk is strongest for subjects who were ages 40-49 yr at the time of the bombings. It is hypothesized that this finding may be related to the age dependence of radiation-induced breast cancer, in the sense that potential cancers reflecting early-stage changes induced at these ages by radiation exposure may receive too little hormonal promotion to progress to frank cancers. (author)

Education in Anti-Doping: The Art of Self-Imposed Constraints.

Science.gov (United States)

Loland, Sigmund

2017-01-01

The pillars of anti-doping are detection, deterrence, and prevention. Detection takes the form of testing for banned substances. Deterrence builds on testing and gathering evidence. Athletes who test positive are exposed to penalties. The main tool of prevention is education. Education takes many forms and can be implemented in many ways. This chapter addresses the nature and challenges of current anti-doping education. Firstly, general goals of education and their connection to sport are discussed. Secondly, three normative interpretations of sport are presented, and their implications for anti-doping education are examined. Instrumentalist interpretations and interpretations with emphasis on performance and enhancement challenge the anti-doping campaign. A human excellence interpretation is advocated in which anti-doping is considered a consistent and integral part of sport. Thirdly, future challenges for anti-doping education are reflected upon. © 2017 S. Karger AG, Basel.

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

Diagnostic value of ductogalactography and cytology in the proliferative changes of the mammary ducts

International Nuclear Information System (INIS)

Sessa, M.; Cerroni, L.; Bertolotti, A.

1991-01-01

Three hundred and thiyrty-six patients with nipple discharge and neither physical signs at breast examination nor pathological findings at mammography, were observed from 1984 to 1988 and studied by means of ductogalactography and cytology of discharge. Of this group, 76 patients (22%) underwent surgery and histology. In 65/76 cases proliferative pathologic conditions were demonstrated: 51 single/ multiple papillomas and 14 carcinomas. Ductogalactography suggested proliferative pathologic conditions in 59 cases and cytology of discharge showed blood in 44 patients, papillary clusters in 23, and atypical cells in 15 (both as single occurrences and in association). In cancer patients discharge appeared to be mostly spontaneous, monoductal and blood-stained. In papillomas, induced discharge was almost as frequent as spontaneous discharge, and milky discharge was also present. Ductogalactography confirmed its value in the diagnosis of proliferative pathologic conditions of the mammary ducts, being especially useful to detect carcinomas without palpable tumors. Cytology of discharge had poorer diagnostic significance

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.

Use of Nicotiana tabacum L extract for anti-Aedes Aegypti mosquito paint

Science.gov (United States)

Sandralintang, Trisiana Chrysanthi; Fauzantoro, Ahmad; Hermansyah, Heri; Jufri, Mahdi; Gozan, Misri

2018-02-01

This study intended to formulate mosquito repellent paints based tobacco leaf extracts-free pyrethroid substance which is safe for users. The active substance which was added to the paint as a mosquito repellent was an extract of tobacco leaves. The result of Anti-mosquito paint formulation produced was according to the Indonesia National Standard (SNI). The results of anti-Aedes Aegypti mosquito paint effectiveness test showed that 5% concentration of tobacco extract could kill half of the mosquito population (LC50) for 2 hours, the concentration of tobacco extract between 3-5% killed half the mosquito population (LC50) during 4 hours, while 1-3% and 0-1% concentration of tobacco extract killed half the mosquito population (LC50) for 6 and 24 hours, respectively.

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells

OpenAIRE

Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E.; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S.; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

2016-01-01

Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Admi...

Probabilistic cumulative risk assessment of anti-androgenic pesticides in food.

NARCIS (Netherlands)

Müller, A.K.; Bosgra, S.; Boon, P.E.; van der Voet, H.; Nielsen, E.; Ladefoged, O.

2009-01-01

In this paper, we present a cumulative risk assessment of three anti-androgenic pesticides (vinclozolin, procymidone and prochloraz) using the relative potency factor (RPF) approach and an integrated probabilistic risk assessment (IPRA) model. RPFs for each substance were estimated for three

Probabilistic cumulative risk assessment of anti-androgenic pesticides in food

NARCIS (Netherlands)

Muller, A.K.; Bosgra, S.; Boon, P.E.; Voet, van der H.; Nielsen, E.; Ladefoged, O.

2009-01-01

In this paper, we present a cumulative risk assessment of three anti-androgenic pesticides (vinclozolin, procymidone and prochloraz) using the relative potency factor (RPF) approach and an integrated probabilistic risk assessment (IPRA) model. RPFs for each substance were estimated for three

Dietary phenolics as anti-mutagens and inhibitors of tobacco-related DNA adduction in the urothelium of smokers.

Science.gov (United States)

Malaveille, C; Hautefeuille, A; Pignatelli, B; Talaska, G; Vineis, P; Bartsch, H

1996-10-01

Human urine is known to contain substances that strongly inhibit bacterial mutagenicity of aromatic and heterocyclic amines in vitro. The biological relevance of these anti-mutagens was examined by comparing levels of tobacco-related DNA adducts in exfoliated urothelial cells from smokers with the anti-mutagenic activity in corresponding 24-h urine samples. An inverse relationship was found between the inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-mutagenicity by urine extracts in vitro and two DNA adduct measurements: the level of the putatively identified N-(deoxyguanosine-8-yl)-4-aminobiphenyl adduct and the total level of all tobacco-smoke-related carcinogen adducts including those probably derived from PhIP. Urinary anti-mutagenicity in vitro appears thus to be a good indicator of the anti-genotoxicity exerted by substances excreted in urine, that protect the bladder mucosal cells (and possibly other cells) against DNA damage. These substances appear to be dietary phenolics and/or their metabolites because (i) the anti-mutagenic activity of urine extracts (n = 18) was linearly related to their content in phenolics; (ii) the concentration ranges of these substances in urine extracts were similar to those of various plant phenols (quercetin, isorhamnetin and naringenin) for which an inhibitory effect on the liver S9-mediated mutagenicity of PhIP was obtained; (iii) treatment of urines with beta-glucuronidase and arylsulfatase enhanced both anti-mutagenicity and the levels of phenolics in urinary extracts; (iv) urinary extracts inhibited noncompetitively the liver S9-mediated mutagenicity of PhIP as did quercetin, used as a model phenolics. Several structural features of the flavonoids were identified as necessary for the inhibition of PhIP and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxiline mutagenicity. Fractionation by reverse-phase HPLC and subsequent analysis of two urinary extracts, showed the presence of several anti

Anti-inflammatory and analgesic effects of coral reef associated ...

African Journals Online (AJOL)

Chellaram

2012-10-04

Oct 4, 2012 ... pharmacologists in 1989 and the potential of the oceans became clear with many unique bioactive substances .... their general behavior. Anti-inflammatory potential of the 100% acetone ... covery from the world's oceans has been accelerated by the chemical uniqueness of marine organisms and by the.

Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74

Science.gov (United States)

Djudjaj, Sonja; Lue, Hongqi; Rong, Song; Papasotiriou, Marios; Klinkhammer, Barbara M.; Zok, Stephanie; Klaener, Ole; Braun, Gerald S.; Lindenmeyer, Maja T.; Cohen, Clemens D.; Bucala, Richard; Tittel, Andre P.; Kurts, Christian; Moeller, Marcus J.; Floege, Juergen; Ostendorf, Tammo

2016-01-01

Pathologic proliferation of mesangial and parietal epithelial cells (PECs) is a hallmark of various glomerulonephritides. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that mediates inflammation by engagement of a receptor complex involving the components CD74, CD44, CXCR2, and CXCR4. The proliferative effects of MIF may involve CD74 together with the coreceptor and PEC activation marker CD44. Herein, we analyzed the effects of local glomerular MIF/CD74/CD44 signaling in proliferative glomerulonephritides. MIF, CD74, and CD44 were upregulated in the glomeruli of patients and mice with proliferative glomerulonephritides. During disease, CD74 and CD44 were expressed de novo in PECs and colocalized in both PECs and mesangial cells. Stress stimuli induced MIF secretion from glomerular cells in vitro and in vivo, in particular from podocytes, and MIF stimulation induced proliferation of PECs and mesangial cells via CD74. In murine crescentic GN, Mif-deficient mice were almost completely protected from glomerular injury, the development of cellular crescents, and the activation and proliferation of PECs and mesangial cells, whereas wild-type mice were not. Bone marrow reconstitution studies showed that deficiency of both nonmyeloid and bone marrow–derived Mif reduced glomerular cell proliferation and injury. In contrast to wild-type mice, Cd74-deficient mice also were protected from glomerular injury and ensuing activation and proliferation of PECs and mesangial cells. Our data suggest a novel molecular mechanism and glomerular cell crosstalk by which local upregulation of MIF and its receptor complex CD74/CD44 mediate glomerular injury and pathologic proliferation in GN. PMID:26453615

Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

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Danielle Ingrid Bezerra de Vasconcelos

2011-01-01

Full Text Available Ouabain, an inhibitor of the Na+/K+-ATPase pump, was identified as an endogenous substance of human plasma. Ouabain has been studied for its ability to interfere with various regulatory mechanisms. Despite the studies portraying the ability of ouabain to modulate the immune response, little is known about the effect of this substance on the inflammatory process. The aim of this work was to study the effects triggered by ouabain on inflammation and nociceptive models. Ouabain produced a reduction in the mouse paw edema induced by carrageenan, compound 48/80 and zymosan. This anti-inflammatory potential might be related to the inhibition of prostaglandin E2, bradykinin, and mast-cell degranulation but not to histamine. Ouabain also modulated the inflammation induced by concanavalin A by inhibiting cell migration. Besides that, ouabain presented antinociceptive activity. Taken these data together, this work demonstrated, for the first time, that ouabain presented in vivo analgesic and anti-inflammatory effects.

Study on proliferative responses to host Ia antigens in allogeneic bone marrow chimera in mice: sequential analysis of the reactivity and characterization of the cells involved in the responses

International Nuclear Information System (INIS)

Iwabuchi, K.; Ogasawara, K.; Ogasawara, M.; Yasumizu, R.; Noguchi, M.; Geng, L.; Fujita, M.; Good, R.A.; Onoe, K.

1987-01-01

Irradiation bone marrow chimeras were established by reconstitution of lethally irradiated AKR mice with C57BL/10 marrow cells to permit serial analysis of the developing reactivities of lymphocytes from such chimeras, [B10----AKR], against donor, host, or third party antigens. We found that substantial proliferative responses to Ia antigens of the recipient strain and also to third party antigens were generated by the thymocytes obtained from the irradiation chimeras at an early stage after bone marrow reconstitution. The majority of the responding thymocytes had surfaces lacking demonstrable peanut agglutinin receptors and were donor type Thy-1+, Ly-2-, and L3T4+ in both anti-recipient and anti-third party MLR. In anti-host responses, however, Ly-2+ thymocytes seemed to be at least partially involved. This capacity of thymus cells to mount a response to antigens of the recipient strain declined shortly thereafter, whereas the capacity to mount MLR against third party antigens persisted. The spleen cells of [B10----AKR] chimeras at the same time developed a more durable capability to exhibit anti-host reactivities and a permanent capability of reacting to third party allo-antigens. The stimulator antigens were Ia molecules on the stimulator cells in both anti-recipient and anti-third party MLR. The responding splenocytes were of donor origin and most of them had Thy-1+, Ly-1+2-, and L3T4+ phenotype

Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression

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Hanamura Ichiro

2006-10-01

the RB1 protein, it is not yet clear how other MM cell lines and tumors have become insensitive to the anti-proliferative effects of increased p18 expression.

Detection of endocrine active substances in the aquatic environment in southern Taiwan using bioassays and LC-MS/MS.

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Chen, Kuang-Yu; Chou, Pei-Hsin

2016-06-01

Endocrine active substances, including naturally occurring hormones and various synthetic chemicals have received much concern owing to their endocrine disrupting potencies. It is essential to monitor their environmental occurrence since these compounds may pose potential threats to biota and human health. In this study, yeast-based reporter assays were carried out to investigate the presence of (anti-)androgenic, (anti-)estrogenic, and (anti-)thyroid compounds in the aquatic environment in southern Taiwan. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was also used to measure the environmental concentrations of selected endocrine active substances for assessing potential ecological risks and characterizing contributions to the endocrine disrupting activities. Bioassay results showed that anti-androgenic (ND-7489 μg L(-1) flutamide equivalent), estrogenic (ND-347 ng L(-1) 17β-estradiol equivalent), and anti-thyroid activities were detected in the dissolved and particulate phases of river water samples, while anti-estrogenic activities (ND-10 μg L(-1) 4-hydroxytamoxifen equivalent) were less often found. LC-MS/MS analysis revealed that anti-androgenic and estrogenic contaminants, such as bisphenol A, triclosan, and estrone were frequently detected in Taiwanese rivers. In addition, their risk quotient values were often higher than 1, suggesting that they may pose an ecological risk to the aquatic biota. Further identification of unknown anti-androgenic and estrogenic contaminants in Taiwanese rivers may be necessary to protect Taiwan's aquatic environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Proliferative thyroid lesions in three diplodactylid geckos: Nephrurus amyae, Nephrurus levis, and Oedura marmorata.

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Hadfield, Catherine A; Clayton, Leigh A; Clancy, Meredith M; Beck, Sarah E; Mangus, Lisa M; Montali, Richard J

2012-03-01

Over a 5-mo period, three diplodactylid geckos housed at the National Aquarium were diagnosed with proliferative thyroid lesions: a rough knob-tail gecko (Nephrurus amyae), a smooth knob-tail gecko (Nephrurus levis), and a marbled velvet gecko (Oedura marmorata). Clinical signs included an intraoral mass or ventral throat swelling (or both), oral bleeding, and weight loss. Both of the knob-tail geckos died. The histologic diagnosis for the rough knob-tail gecko was thyroid carcinoma with metastases to the liver and lungs, and thyroid carcinoma with no metastases was reported in the smooth knob-tail gecko. A thyroidectomy was performed on the marbled velvet gecko with a histologic diagnosis of adenomatous hyperplasia. Postoperative weight loss and bradycardia resolved following oral supplementation with levothyroxine. The animal is in normal health 10 mo post-surgery. Five other diplodactylid geckos in the collection remain unaffected, giving a 38% prevalence of proliferative thyroid lesions (3/8). The etiology remains undetermined. This is the first report of a cluster of proliferative thyroid lesions in geckos.

The World Anti-Doping Code in sport: Update for 2015.

Science.gov (United States)

Hughes, David

2015-10-01

Some athletes cheat by using drugs or medical methods such as transfusion to enhance their performance. However, this may put their health at risk. The World Anti-Doping Agency prohibits certain methods and drugs that may enhance performance, harm the athlete or violate the spirit of sport. Some may be banned only during competitions, but others are banned at all times. Prohibited substances include over-the-counter and prescription medicines. It is therefore important for athletes and health professionals to check what is permitted. There are many resources available through organisations such as the Australian Sports Anti-Doping Authority and the World Anti-Doping Agency.

Annual banned-substance review: analytical approaches in human sports drug testing.

Science.gov (United States)

Thevis, Mario; Kuuranne, Tiia; Walpurgis, Katja; Geyer, Hans; Schänzer, Wilhelm

2016-01-01

The aim of improving anti-doping efforts is predicated on several different pillars, including, amongst others, optimized analytical methods. These commonly result from exploiting most recent developments in analytical instrumentation as well as research data on elite athletes' physiology in general, and pharmacology, metabolism, elimination, and downstream effects of prohibited substances and methods of doping, in particular. The need for frequent and adequate adaptations of sports drug testing procedures has been incessant, largely due to the uninterrupted emergence of new chemical entities but also due to the apparent use of established or even obsolete drugs for reasons other than therapeutic means, such as assumed beneficial effects on endurance, strength, and regeneration capacities. Continuing the series of annual banned-substance reviews, literature concerning human sports drug testing published between October 2014 and September 2015 is summarized and reviewed in reference to the content of the 2015 Prohibited List as issued by the World Anti-Doping Agency (WADA), with particular emphasis on analytical approaches and their contribution to enhanced doping controls. Copyright © 2016 John Wiley & Sons, Ltd.

Protein metabolism of prolific ewes during late gestation and early lactation

NARCIS (Netherlands)

Sebek, L.B.J.

2001-01-01

Subject headings: protein / metabolism / ewes

Introduction of prolific crossbred ewes and a new protein evaluation system for ruminants, the DVE/OEB system, necessitate a reconsideration of ewe feeding strategies. The objective of this thesis is to investigate the amount

Neoplastic and proliferative disorders of the perinephric space

International Nuclear Information System (INIS)

Heller, M.T.; Haarer, K.A.; Thomas, E.; Thaete, F.L.

2012-01-01

The perinephric space is a well-marginated central compartment of the retroperitoneum, located between the anterior and posterior pararenal spaces. Various neoplastic and proliferative disorders can affect the perinephric space, and there is a wide array of imaging findings. Although many perinephric lesions may extend directly from the kidney and adrenal gland, other lesions occur in the perinephric space due to haematogenous spread, as part of a systemic disease, or by extension from an adjacent retroperitoneal compartment. Imaging plays a pivotal role in the diagnosis of perinephric diseases, as many of the disease processes affecting this space will not result in clinical signs or symptoms until the disease is at an advanced stage. Despite the often shared non-specific clinical and imaging findings among these disease processes, application of a categorical differential diagnosis based on the imaging characteristics will serve to narrow the differential diagnosis and direct further evaluation and treatment. In this article, the lesions have been categorized as soft-tissue rind [nephroblastomatosis, fibrosis, Erdheim–Chester disease (ECD), extramedullary haematopoiesis, lymphoma, infiltrating metastases], focal solid lesions (extension of renal or adrenal malignancies, melanoma metastases, treated lymphoma), fat-containing lesions (angiomyolipoma, liposarcoma, myelolipoma), and cystic lesions (lymphangiomas, abscesses). The aim of this article is to demonstrate and describe the key imaging features of several neoplastic and proliferative disorders that affect the perinephric space.

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

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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.

Synthesis and Biological Evaluation of Novel Furozan-Based Nitric Oxide-Releasing Derivatives of Oridonin as Potential Anti-Tumor Agents

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Hao Cai

2012-06-01

Full Text Available To search for novel nitric oxide (NO releasing anti-tumor agents, a series of novel furoxan/oridonin hybrids were designed and synthesized. Firstly, the nitrate/nitrite levels in the cell lysates were tested by a Griess assay and the results showed that these furoxan-based NO-releasing derivatives could produce high levels of NO in vitro. Then the anti-proliferative activity of these hybrids against four human cancer cell lines was also determined, among which, 9h exhibited the most potential anti-tumor activity with IC₅₀ values of 1.82 µM against K562, 1.81 µM against MGC-803 and 0.86 µM against Bel-7402, respectively. Preliminary structure-activity relationship was concluded based on the experimental data obtained. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents.

Synergy among rat T cells in the proliferative response to alloantigen

International Nuclear Information System (INIS)

Wright, P.W.; Loop, S.M.; Bernstein, I.D.

1979-01-01

A synergistic interaction in the proliferative response to alloantigen is described for mixtures of rat thymus and lymph node cells. The optimal conditions for synergy are quantitatively defined. Regression analysis of the slope of the dose-response curve has been utilized to estimate the degree of interaction in thymus--lymph node cell mixtures. The slope of the response of cell mixtures was noted to be significantly greater than the slope for the response of lympth node cells alone. Irradiation was shown to have a differential effect on the response of thymus and lymph node cells in mixtures. Irradiated thymus cells retained the capacity for synergy in mixtures, whereas irradiated lymph node cells did not. Additional studies have demonstrated that both de novo protein synthesis and specific antigen recognition by both responding cell populations in mixtures was required for maximal synergy. These studies demonstrate that synergy cannot be explained as an artifact of altered cell density in vitro. They establish that thymus cells and lymph node cells represent distinct subsets which manifest qualitatively different functions in the proliferative response to alloantigen. Thymus cells can respond directly to alloantigen by proliferation but also have the capacity to amplify the proliferative response of lymph node cells, a capacity which is resistant to X irradiation but requires recognition of alloantigen and de novo protein synthesis. Lymph node cells may similarly respond by proliferation to alloantigen but lack the amplifier activity of thymus cells. Synergy for rat lymphoidcells, like mouse lymphoid cells, has been shown to involve an interaction of thymus-derived lymphocytes

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

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Michael Poulsen

2011-02-01

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.

Proliferative and Anti-Inflammatory Effects of Resveratrol and Silymarin on Human Gingival Fibroblasts: A View to the Future

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Minoo Shahidi

2017-10-01

Full Text Available Objectives: It has been demonstrated that polyphenol components such as silymarin and resveratrol have anti-inflammatory properties. Periodontitis is a chronic inflammatory disease that leads to the breakdown of dental supporting tissues and tooth loss. The purpose of this study was to investigate the anti-inflammatory effects of silymarin and resveratrol on lipopolysaccharide (LPS-induced inflammatory response in human gingival fibroblasts (HGFs.Materials and Methods: HGFs were treated with different concentrations of silymarin and/or resveratrol (25, 50, 100 and 200μg/ml. The effects of silymarin and resveratrol on cell viability and proliferation were assessed by MTT assay and cell cycle analysis, respectively. Also, HGFs were treated with silymarin and/or resveratrol and were stimulated with LPS. The levels of Interleukin-6 (IL-6 and IL-8 were assessed by enzyme-linked immunosorbent assay (ELISA.  Results: After treatment with silymarin, the viability of fibroblasts significantly increased, whereas treatment with resveratrol did not have any significant effect on cell viability. However, the combination of these flavonoids (50µg/ml silymarin and 100µg/ml resveratrol significantly increased the viability of fibroblasts. Resveratrol significantly inhibited LPS-induced IL-6 and IL-8 secretion by HGFs, but silymarin did not show such a significant effect.   Conclusions: The findings of the present study demonstrated the anti-inflammatory effects of resveratrol and its combination with silymarin. Therefore, the combination of silymarin and resveratrol may be useful as a therapeutic agent for treatment of periodontal diseases.

Changes in the Proliferative Program Limit Astrocyte Homeostasis in the Aged Post-Traumatic Murine Cerebral Cortex.

Science.gov (United States)

Heimann, Gábor; Canhos, Luisa L; Frik, Jesica; Jäger, Gabriele; Lepko, Tjasa; Ninkovic, Jovica; Götz, Magdalena; Sirko, Swetlana

2017-08-01

Aging leads to adverse outcomes after traumatic brain injury. The mechanisms underlying these defects, however, are not yet clear. In this study, we found that astrocytes in the aged post-traumatic cerebral cortex develop a significantly reduced proliferative response, resulting in reduced astrocyte numbers in the penumbra. Moreover, experiments of reactive astrocytes in vitro reveal that their diminished proliferation is due to an age-related switch in the division mode with reduced cell-cycle re-entry rather than changes in cell-cycle length. Notably, reactive astrocytes in vivo and in vitro become refractory to stimuli increasing their proliferation during aging, such as Sonic hedgehog signaling. These data demonstrate for the first time that age-dependent, most likely intrinsic changes in the proliferative program of reactive astrocytes result in their severely hampered proliferative response to traumatic injury thereby affecting astrocyte homeostasis. © The Author 2017. Published by Oxford University Press.

Vitamin E as an Antioxidant in Female Reproductive Health

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Siti Syairah Mohd Mutalip

2018-01-01

Full Text Available Vitamin E was first discovered in 1922 as a substance necessary for reproduction. Following this discovery, vitamin E was extensively studied, and it has become widely known as a powerful lipid-soluble antioxidant. There has been increasing interest in the role of vitamin E as an antioxidant, as it has been discovered to lower body cholesterol levels and act as an anticancer agent. Numerous studies have reported that vitamin E exhibits anti-proliferative, anti-survival, pro-apoptotic, and anti-angiogenic effects in cancer, as well as anti-inflammatory activities. There are various reports on the benefits of vitamin E on health in general. However, despite it being initially discovered as a vitamin necessary for reproduction, to date, studies relating to its effects in this area are lacking. Hence, this paper was written with the intention of providing a review of the known roles of vitamin E as an antioxidant in female reproductive health.

Challenges in Modern Anti-Doping Analytical Science.

Science.gov (United States)

Ayotte, Christiane; Miller, John; Thevis, Mario

2017-01-01

The challenges facing modern anti-doping analytical science are increasingly complex given the expansion of target drug substances, as the pharmaceutical industry introduces more novel therapeutic compounds and the internet offers designer drugs to improve performance. The technical challenges are manifold, including, for example, the need for advanced instrumentation for greater speed of analyses and increased sensitivity, specific techniques capable of distinguishing between endogenous and exogenous metabolites, or biological assays for the detection of peptide hormones or their markers, all of which require an important investment from the laboratories and recruitment of highly specialized scientific personnel. The consequences of introducing sophisticated and complex analytical procedures may result in the future in a change in the strategy applied by the Word Anti-Doping Agency in relation to the introduction and performance of new techniques by the network of accredited anti-doping laboratories. © 2017 S. Karger AG, Basel.

Protein oxidation and degradation during proliferative senescence of human MRC-5 fibroblasts.

Science.gov (United States)

Sitte, N; Merker, K; von Zglinicki, T; Grune, T

2000-03-01

One of the highlights of age-related changes of cellular metabolism is the accumulation of oxidized proteins. The aging process on a cellular level can be treated either as the ongoing proliferation until a certain number of cell divisions is reached (the Hayflick limit) or as the aging of nondividing cells, that is, the age-related changes in cells without proliferation. The present investigation was undertaken to reveal the changes in protein turnover, proteasome activity, and protein oxidation status during proliferative senescence. We were able to demonstrate that the activity of the cytosolic proteasomal system declines dramatically during the proliferative senescence of human MRC-5 fibroblasts. Regardless of the loss in activity, it could be demonstrated that there are no changes in the transcription and translation of proteasomal subunits. This decline in proteasome activity was accompanied by an increased concentration of oxidized proteins. Cells at higher proliferation stages were no longer able to respond with increased degradation of endogenous [(35)S]-Met-radiolabeled proteins after hydrogen peroxide- or quinone-induced oxidative stress. It could be demonstrated that oxidized proteins in senescent human MRC-5 fibroblasts are not as quickly removed as they are in young cells. Therefore, our study demonstrates that the accumulation of oxidized proteins and decline in protein turnover and activity of the proteasomal system are not only a process of postmitotic aging but also occur during proliferative senescence and result in an increased half-life of oxidized proteins.

Anti-inflammatory actions of acupuncture

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Freek J. Zijlstra

2003-01-01

Full Text Available Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of β-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-α and interleukin-10 are discussed.

Study protocol: a randomized controlled trial of a computer-based depression and substance abuse intervention for people attending residential substance abuse treatment

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Kelly Peter J

2012-02-01

Full Text Available Abstract Background A large proportion of people attending residential alcohol and other substance abuse treatment have a co-occurring mental illness. Empirical evidence suggests that it is important to treat both the substance abuse problem and co-occurring mental illness concurrently and in an integrated fashion. However, the majority of residential alcohol and other substance abuse services do not address mental illness in a systematic way. It is likely that computer delivered interventions could improve the ability of substance abuse services to address co-occurring mental illness. This protocol describes a study in which we will assess the effectiveness of adding a computer delivered depression and substance abuse intervention for people who are attending residential alcohol and other substance abuse treatment. Methods/Design Participants will be recruited from residential rehabilitation programs operated by the Australian Salvation Army. All participants who satisfy the diagnostic criteria for an alcohol or other substance dependence disorder will be asked to participate in the study. After completion of a baseline assessment, participants will be randomly assigned to either a computer delivered substance abuse and depression intervention (treatment condition or to a computer-delivered typing tutorial (active control condition. All participants will continue to complete The Salvation Army residential program, a predominantly 12-step based treatment facility. Randomisation will be stratified by gender (Male, Female, length of time the participant has been in the program at the commencement of the study (4 weeks or less, 4 weeks or more, and use of anti-depressant medication (currently prescribed medication, not prescribed medication. Participants in both conditions will complete computer sessions twice per week, over a five-week period. Research staff blind to treatment allocation will complete the assessments at baseline, and then 3, 6, 9

Complementary stable carbon isotope ratio and amount of substance measurements in sports anti-doping.

Science.gov (United States)

Cawley, Adam T; George, Adrian V

2012-12-01

The detection of steroids originating from synthetic precursors against a background of their chemically identical natural analogues has proven to be a significant challenge for doping control laboratories accredited by the World Anti-Doping Agency (WADA). The complementary application of gas chromatography-mass spectrometry (GC-MS) and gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) has been demonstrated to provide specific detection of endogenous steroid misuse for improved anti-doping analysis. Markers of synthetically derived steroids are reviewed on the basis of abnormal urinary excretions and low (13)C content. A combinatorial approach is presented for the interpretation of GC-MS and GC-C-IRMS data in the anti-doping context. This methodology can allow all relevant information concerning an individual's metabolism to be assessed in order to make an informed decision with respect to a doping violation. Copyright © 2012 John Wiley & Sons, Ltd.

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

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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.

Anti-nociceptive and anti-hyperprolactinemia activities of Fructus Viticis and its effective fractions and chemical constituents.

Science.gov (United States)

Hu, Y; Xin, H-L; Zhang, Q-Y; Zheng, H-C; Rahman, K; Qin, L-P

2007-10-01

Vitex rotundifolia L. is widely distributed along the sea coast of China. The aim of this study was to investigate the anti-nociceptive and anti-hyperprolactinemia activities of substances isolated from Fructus Viticis (the fruit of Vitex rotundifolia), which may be effective in the treatment of pre-menstrual symptoms, using acetic-acid-induced writhing and metoclopramide-dihydrochloride-induced hyperprolactinemia in mice. The fractions effective in terms of anti-nociceptive and anti-hyperprolactinemia activities were obtained from Fructus Viticis by elution through macro-porous resin, and polyamide and silica gel column chromatography. The standardization of the fractions obtained from the separation procedures was carried out by means of high-performance liquid chromatography (HPLC)-fingerprint. In this study, the flavone-enriched fraction (Fraction 6) showed a higher inhibitory rate than indomethacin (69.4% vs. 56.4%) at a dose of 50 mg/kg body wt., and significantly reduced the prolactin level as compared to HPRL-treated mice (8.2 ng/ml vs. 25.5 ng/ml). Furthermore, this fraction showed anti-nociceptive activity in a dose-dependent manner (10-50 mg/kg body wt., i.g.). On further purification with silica gel, Casticin was isolated from this fraction and it decreased abnormal serum levels of prolactin by approximately 50% (p screening methods, our results indicate that the presence of flavonoids such as Casticin in this plant may be responsible for the activity effects. Casticin has potent analgesic and anti-hyperprolactinaemia properties, is likely to be one of the active components of Fructus Viticis, and may have a role in treating PMS (premenstrual syndrom).

Substance Use and Mental Health Stigma in Veterans With Co-Occurring Disorders.

Science.gov (United States)

Harnish, Autumn; Corrigan, Patrick; Byrne, Thomas; Pinals, Debra A; Rodrigues, Stephanie; Smelson, David

2016-01-01

This pilot study examined whether substance use or mental illness was more stigmatizing among individuals with co-occurring mental health and substance abuse problems. This study included 48 individuals with co-occurring substance use and mental health problems enrolled in a Substance Abuse and Mental Health Services funded treatment program. Subjects received a baseline assessment that included addiction, mental health, and stigma measures. The sample consisted primarily of White males with an average age of 38 years. Substance abuse was found to be more stigmatizing than mental illness, F(1, 47) = 14.213, p stigma varied across four different levels of stigma (Aware, Agree, Apply, and Harm), F(2.099, 98.675) = 117.883, p stigma was also significant, F(2.41, 113.284) = 20.250, p stigma between types varied across levels of stigma. Post hoc tests found a significant difference between all levels of stigma except for the comparison between Apply and Harm. Reported stigma was significantly higher for substance abuse than mental illness at the Aware and Agree levels. In addition, pairwise comparisons found significant differences between all levels of stigma with the exception of the comparison between Apply and Harm, indicating a pattern whereby reported stigma generally decreased from the first level (Aware stage) to subsequent levels. These results have important implications for treatment, suggesting the need to incorporate anti-stigma interventions for individuals with co-occurring disorders with a greater focus on substance abuse.

Proliferative verrucous leukoplakia: an aggressive form of oral leukoplakia.

Science.gov (United States)

Shopper, Thomas P; Brannon, Robert B; Stalker, William H

2004-01-01

Proliferative verrucous leukoplakia (PVL) is an aggressive form of oral leukoplakia that is persistent, often multifocal, and refractory to treatment with a high risk of recurrence and malignant transformation. This article describes the clinical aspects and histologic features of a case that demonstrated the typical behavior pattern in a long-standing, persistent lesion of PVL of the mandibular gingiva and that ultimately developed into squamous cell carcinoma. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa.

Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells.

Science.gov (United States)

Gu, Mancang; Nishihara, Reiko; Chen, Yang; Li, Wanwan; Shi, Yan; Masugi, Yohei; Hamada, Tsuyoshi; Kosumi, Keisuke; Liu, Li; da Silva, Annacarolina; Nowak, Jonathan A; Twombly, Tyler; Du, Chunxia; Koh, Hideo; Li, Wenbin; Meyerhardt, Jeffrey A; Wolpin, Brian M; Giannakis, Marios; Aguirre, Andrew J; Bass, Adam J; Drew, David A; Chan, Andrew T; Fuchs, Charles S; Qian, Zhi Rong; Ogino, Shuji

2017-10-20

Evidence suggests that nonsteroidal anti-inflammatory drug aspirin (acetylsalicylic acid) may improve patient survival in PIK3CA -mutant colorectal carcinoma, but not in PIK3CA -wild-type carcinoma. However, whether aspirin directly influences the viability of PIK3CA -mutant colon cancer cells is poorly understood. We conducted in vitro experiments to test our hypothesis that the anti-proliferative activity of aspirin might be stronger for PIK3CA -mutant colon cancer cells than for PIK3CA -wild-type colon cancer cells. We measured the anti-proliferative effect of aspirin at physiologic concentrations in seven PIK3CA -mutant and six PIK3CA -wild-type human colon cancer cell lines. After exposure to aspirin, the apoptotic index and cell cycle phase of colon cancer cells were assessed. In addition, the effect of aspirin was examined in parental SW48 cells and SW48 cell clones with individual knock-in PIK3CA mutations of either c.3140A>G (p.H1047R) or c.1633G>A (p.E545K). Aspirin induced greater dose-dependent loss of cell viability in PIK3CA -mutant cells than in PIK3CA -wild-type cells after treatment for 48 and 72 hours. Aspirin treatment also led to higher proportions of apoptotic cells and G0/G1 phase arrest in PIK3CA -mutant cells than in PIK3CA -wild-type cells. Aspirin treatment of isogenic SW48 cells carrying a PIK3CA mutation, either c.3140A>G (p.H1047R) or c.1633G>A (p. E545K), resulted in a more significant loss of cell viability compared to wild-type controls. Our findings indicate that aspirin causes cell cycle arrest, induces apoptosis, and leads to loss of cell viability more profoundly in PIK3CA -mutated colon cancer cells than in PIK3CA -wild-type colon cancer cells. These findings support the use of aspirin to treat patients with PIK3CA -mutant colon cancer.

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.

Anatomical and functional outcomes of retinectomies in retinal detachments complicated by proliferative vitreoretinopathy

Directory of Open Access Journals (Sweden)

Mohammad Idrees Adhi

2017-10-01

Full Text Available Purpose: To study anatomical and functional outcomes of retinectomies in rhegmatogenous retinal detachments complicated by proliferative vitreoretinopathy. Methods: This is a retrospective interventional consecutive case series of eyes with rhegmatogenous retinal detachments complicated by advanced proliferative vitreoretinopathy and managed by relaxing retinectomy over a period of seventeen years. Three-port pars plana vitrectomy included core vitrectomy and removal of all epi-retinal membranes. On failure to flatten, retina was cut and excised. Basal vitrectomy and removal of anterior flap of retina then followed. Silicone oil was used as temponade in majority of cases. The dependent variables were anatomical and functional outcomes. The statistical analysis was performed on SPSS 21. Results: Series included 370 eyes of 337 patients. Mean follow up was 39 months. Scleral explant was used in 90(24.39% cases. Two hundred and nine (56.49% eyes were operated with trans conjunctival sutureless vitrectomy technique. Procedure was bilateral in 33 patients (09.79%. Retina attached in 311(84.05% eyes after initial surgery. Final re-attachment after one or more surgeries was achieved in 344(92.97% eyes. Two hundred and eleven (57.02% cases achieved visual acuity of 6/60 or better. Conclusion: Relaxing retinectomies have good and encouraging anatomical and functional outcomes. This surgery can be effectively carried out with trans conjunctival sutureless vitrectomy technique. Keywords: Retinotomy and retinectomy, Proliferative vitreoretinopathy, Trans conjunctival sutureless vitrectomy, Silicone oil

Challenges to promoting health for amateur athletes through anti-doping policy.

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Henning, April

2017-01-01

Anti-doping regulations are intended, at least in part, to promote the health of athletes. While most anti-doping efforts target elite and professional competitors, there have been recent moves by sport governing bodies to expand anti-doping testing to include amateur athletes. Drawing on previous critiques of anti-doping policies and illustrating cases, this article outlines five of the challenges to health promotion of applying the current detect and ban model to the amateur level of sport. I argue that the current approach is not effective and, in some ways, may undermine the goal of health promotion at the amateur level. In order to address these challenges, I propose alternative, health-centred strategies that focus on athlete empowerment and choice through critical awareness of a variety of substances, associated risks and rewards, and the role of expertise in decision-making.

History of Psychology Publish and Perish: Psychology's Most Prolific Authors Are Not Always the Ones We Remember.

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Green, Christopher D

2017-01-01

What is the relationship between being highly prolific in the realm of publication and being remembered as a great psychologist of the past? In this study, the PsycINFO database was used to identify the historical figures who wrote the most journal articles during the half-century from 1890 to 1939. Although a number of the 10 most prolific authors are widely remembered for their influence on the discipline today-E. L. Thorndike, Karl Pearson, E. B. Titchener, Henri Pi6ron-the majority are mostly forgotten. The data were also separated into the 5 distinct decades. Once again, a mixture of eminent and obscure individuals made appearances. Most striking, perhaps, was the great increase in articles published over the course of the half-century-approximately doubling each decade-and the enormous turnover in who was most prolific, decade over decade. In total, 100 distinct individuals appeared across just 5 lists of about 25 names each.

Cytological Study of Breast Carcinoma Before and After Oncotherapy with Special Reference to Morphometry and Proliferative Activity.

Science.gov (United States)

Koley, Sananda; Chakrabarti, Srabani; Pathak, Swapan; Manna, Asim Kumar; Basu, Siddhartha

2015-12-01

Our study was done to assess the cytological changes due to oncotherapy in breast carcinoma especially on morphometry and proliferative activity. Cytological aspirates were collected from a total of 32 cases of invasive ductal carcinoma both before and after oncotherapy. Morphometry was done on the stained cytological smears to assess the different morphological parameters of cell dimension by using the ocular morphometer and the software AutoCAD 2007. Staining was done with Ki-67 and proliferating cell nuclear antigen (PCNA) as proliferative markers. Different morphological parameters were compared before and after oncotherapy by unpaired Student's t test. Statistically significant differences were found in morphometric parameters, e.g., mean nuclear diameter, mean nuclear area, mean cell diameter, and mean cell area, and in the expression of proliferative markers (Ki-67 and PCNA). Statistical analysis was done by obtaining p values. There are statistically significant differences between morphological parameter of breast carcinoma cells before and after oncotherapy.

Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: Lessons from the human hair follicle matrix.

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Purba, Talveen S; Brunken, Lars; Peake, Michael; Shahmalak, Asim; Chaves, Asuncion; Poblet, Enrique; Ceballos, Laura; Gandarillas, Alberto; Paus, Ralf

2017-09-01

Human hair follicle (HF) growth and hair shaft formation require terminal differentiation-associated cell cycle arrest of highly proliferative matrix keratinocytes. However, the regulation of this complex event remains unknown. CIP/KIP family member proteins (p21 CIP1 , p27 KIP1 and p57 KIP2 ) regulate cell cycle progression/arrest, endoreplication, differentiation and apoptosis. Since they have not yet been adequately characterized in the human HF, we asked whether and where CIP/KIP proteins localise in the human hair matrix and pre-cortex in relation to cell cycle activity and HF-specific epithelial cell differentiation that is marked by keratin 85 (K85) protein expression. K85 expression coincided with loss or reduction in cell cycle activity markers, including in situ DNA synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1, affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of CIP/KIP proteins was found abundantly within the proliferative hair matrix, concomitant with a role in cell cycle checkpoint control. p21 CIP1 , p27 KIP1 and cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas p57 KIP2 protein decreased but became nuclear. These data imply a supportive role for CIP/KIP proteins in maintaining proliferative arrest, differentiation and anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft formation in anagen VI. Moreover, post-mitotic hair matrix regions contained cells with enlarged nuclei, and DNA in situ hybridisation showed cells that were >2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance cyclin E to control further rounds of DNA replication in a cell population that has a propensity to become tetraploid. These data shed new light on the in situ-biography of human hair matrix keratinocytes on their path of active cell cycling, arrest and terminal differentiation, and showcase the human HF as an excellent, clinically

Brief History of Anti-Doping.

Science.gov (United States)

Ljungqvist, Arne

2017-01-01

The fight against doping in sport as we know it today commenced by the creation of the International Olympic Committee (IOC) Medical Commission in 1961 following the death of a Danish cyclist during the Rome Olympic Games the year before. After a slow start, the fight got under way as from the early 1970s under the leadership of the IOC and of the International Association of Athletics Federations. Despite a lack of understanding and weak support even from the sports community, a series of measures were taken during the 1970s and 1980s which still form cornerstones of today's anti-doping strategy. In addition to information and education campaigns, the most important examples are the introduction of procedural rules for doping controls, the establishment and follow-up of a list of prohibited substances and methods, the accreditation of doping control laboratories, the introduction of in- and out-of-competition testing, rules for therapeutic use exemption, and the introduction of blood sampling. During the 1990s, the anti-doping fight gained increasing support both inside and outside the sport community. In order to harmonize the wide variety of rules that had developed both in sport organizations and at the domestic level and to promote anti-doping activities, the World Anti-Doping Agency (WADA) was jointly created by the Olympic movement and the public authorities in 1999. WADA is today carrying on the fight supported by the universally accepted WADA Code and an International Anti-Doping Convention under UNESCO. © 2017 S. Karger AG, Basel.

Ocular pulse amplitude after panretinal photocoagulation in normotensive eyes with proliferative diabetic retinopathy.

Science.gov (United States)

Bozic, Marija M; Karadzic, Jelena B; Kovacevic, Igor M; Marjanovic, Ivan S

2017-06-26

To assess the effect of panretinal laser photocoagulation on ocular pulse amplitude (OPA) in normotensive eyes with proliferative diabetic retinopathy. Prospectively, we performed unilateral argon laser panretinal photocoagulation (PRP) in 30 patients with diabetes mellitus type II and previously untreated bilateral proliferative diabetic retinopathy. Before and 7 and 30 days after the treatment, OPA was measured using dynamic contour tonometer. Compared with the untreated contralateral eyes, laser photocoagulation led to a reduction of OPA. Ocular pulse amplitude did not significantly differ in photocoagulated eyes 7 days after the treatment, but there was a significant difference in OPA 30 days after the treatment. The decrease in OPA values was 15% 7 days after PRP and 40% 30 days after PRP. Ocular pulse amplitude reduction after PRP indirectly informs us about choriocapillary closure, already reported in previous studies.

Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions

Science.gov (United States)

Sucker, Antje; Zhao, Fang; Pieper, Natalia; Heeke, Christina; Maltaner, Raffaela; Stadtler, Nadine; Real, Birgit; Bielefeld, Nicola; Howe, Sebastian; Weide, Benjamin; Gutzmer, Ralf; Utikal, Jochen; Loquai, Carmen; Gogas, Helen; Klein-Hitpass, Ludger; Zeschnigk, Michael; Westendorf, Astrid M.; Trilling, Mirko; Horn, Susanne; Schilling, Bastian; Schadendorf, Dirk; Griewank, Klaus G.; Paschen, Annette

2017-01-01

Melanoma treatment has been revolutionized by antibody-based immunotherapies. IFNγ secretion by CD8+ T cells is critical for therapy efficacy having anti-proliferative and pro-apoptotic effects on tumour cells. Our study demonstrates a genetic evolution of IFNγ resistance in different melanoma patient models. Chromosomal alterations and subsequent inactivating mutations in genes of the IFNγ signalling cascade, most often JAK1 or JAK2, protect melanoma cells from anti-tumour IFNγ activity. JAK1/2 mutants further evolve into T-cell-resistant HLA class I-negative lesions with genes involved in antigen presentation silenced and no longer inducible by IFNγ. Allelic JAK1/2 losses predisposing to IFNγ resistance development are frequent in melanoma. Subclones harbouring inactivating mutations emerge under various immunotherapies but are also detectable in pre-treatment biopsies. Our data demonstrate that JAK1/2 deficiency protects melanoma from anti-tumour IFNγ activity and results in T-cell-resistant HLA class I-negative lesions. Screening for mechanisms of IFNγ resistance should be considered in therapeutic decision-making. PMID:28561041

Detection of Lawsonia intracellularis in the tonsils of pigs with proliferative enteropathy

DEFF Research Database (Denmark)

Jensen, Tim Kåre; Møller, Kristian; Lindecrona, R. H.

2000-01-01

to necropsy but not in four pigs with moderate PE lesions. However, L. intracellularis was detected in the tonsils of 4/9 pigs with PE complicated with necroses and in 4/4 pigs with proliferative haemorrhagic enteropathy in which L. intracellularis antigen also was demonstrated in tonsillar macrophages...

Fiscal 2000 pioneering research report on the basic technology for novel DNA drug creation using anti-gene engineering; 2000 nendo anti gene kogaku ni yoru shinki DNA drug soshutsu kiban gijutsu chosa kenkyu hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

Research is conducted concerning the possibility of anti-gene engineering basic to the application of DNA (deoxyribonucleic acid) drugs capable of serving as functional DNAs to the control of the expression of industrially useful substance producing genes or of anomalous genes and concerning the possibility of novel industry creation on the strength of the said engineering. The specific research items are described below. Technical seeds are investigated relating to the tissue- and cell-specific drug delivery system for the expression of the molecular device function of the DNA drug. Concerning molecular target technologies such as the anti-sense method, possibilities are studied of utilizing the currently available technical seeds for the eventual creation of novel industries. Concerning novel designing methods utilizing genome information such as SNPs (single nucleotide polymorphisms), investigations are conducted to determine if they would help novel technology development and novel material development. The domestic state is surveyed in relation to DNA drugs, and possibilities are investigated of novel substance production and novel medicine creation with the aid of anti-gene engineering. (NEDO)

Anti-CD25 mAb administration prevents spontaneous liver transplant tolerance.

Science.gov (United States)

Li, W; Carper, K; Liang, Y; Zheng, X X; Kuhr, C S; Reyes, J D; Perkins, D L; Thomson, A W; Perkins, J D

2006-12-01

Liver allografts are accepted spontaneously in all mouse strain combinations without immunosuppressive therapy. The mechanisms underlying this phenomenon remain largely undefined. In this study, we examined the effect of CD4+ CD25+ T regulatory cells (Treg) on the induction of mouse liver transplant tolerance. Orthotopic liver transplantation was performed from B10 (H2b) to C3H (H2k) mice. Depleting rat anti-mouse CD25 mAb (PC61) was given to the donors or recipients (250 microg/d IP) pretransplant or to the recipients postoperatively. At day 5 posttransplantation, both effector T cells (mainly CD8) and CD4+ CD25+ Treg were increased in the liver allografts and host spleens compared to naïve mice. Anti-CD25 mAb administration, either pretransplantation or posttransplantation, reduced the ratio of CD4+ CD25+ Treg to the CD3 T cells of liver grafts and recipient spleens and induced liver allograft acute rejection compared to IgG treatment. Anti-CD25 mAb administration elevated anti-donor T-cell proliferative responses and CTL and NK activities of graft infiltrates and host splenocytes; reduced CTLA4, Foxp3, and IDO mRNA levels; increased IL-10 and IFN-gamma; and decreased IL-4 mRNA levels in the livers or host spleens. The number of apoptotic T cells was reduced significantly in the liver grafts and treated host spleens. Therefore, anti-CD25 mAb administration changed the balance of CD4+ CD25+ Treg to activated T cells of liver graft recipients, preventing liver transplant tolerance. This was associated with enhanced anti-donor immune reactivity, downregulated Treg gene expression, and reduced T cell apoptosis in the grafts and host spleens.

Effect of supplemented and topically applied antioxidant substances on human tissue.

Science.gov (United States)

Darvin, M; Zastrow, L; Sterry, W; Lademann, J

2006-01-01

Systemic and topical application of antioxidant substances for the medical treatment and prophylaxis of many diseases as well as additional protection of the skin against the destructive action of free radicals and other reactive species has become very popular during the past years. Stimulated by the positive results of a fruit and vegetable diet in supporting medical treatment and in cosmetics, artificial and extracted antioxidant substances have been broadly applied. Surprisingly, not only positive but also strong negative results have been obtained by different authors. According to study reports artificial and extracted antioxidant substances support different kinds of medical therapies, if they are applied in mixtures of different compounds at low concentration levels. In the case of the application of high concentration of some single compounds, side effects were often observed. Regarding skin treatment by systemically applied antioxidant substances for cosmetic purposes, positive cosmetic effects as well as no effects, but almost no side effects, apart from a number of allergic reactions, were reported. One reason for this seems to be the lower concentration of systemically applied antioxidant substances in comparison with a medical application. Topical application of antioxidant substances is closely related to cosmetic treatment for skin protection and anti-aging. Positive results were also obtained in this case. The present review is an attempt to classify and summarize the published literature concerning the efficiency of action of systemic and topical applications of antioxidant substances, such as carotenoids and vitamins, on human organism and especially on the skin. The available literature on this topic is very extensive and the results are often contradictory. Nevertheless, there are some clear tendencies concerning systemic and topical application of antioxidant substances in medicine and cosmetics, and we summarize them in the present paper.

[Influence of Aging on Severity and Anti-Inflammatory Treatment of Experimental Dry Eye Disease].

Science.gov (United States)

Steven, Philipp; Braun, Tobias; Krösser, Sonja; Gehlsen, Uta

2017-05-01

Purpose Aging is an important factor in dry-eye disease that has not been studied in the context of therapeutic measures. Aging-associated modifications of the ocular immune system implicate that anti-inflammatory therapies may act differently among younger individuals in terms of onset and effect of different substances. The goal of this study was to determine differences in clinical phenotype and topical anti-inflammatory therapy using a desiccating stress mouse model. Methods An experimental dry-eye disease (desiccating stress model) was induced in 12-week and 12-month-old female BALB/c mice. Topical therapy included 0.05% cyclosporine/F4H5 (Novaliq), F4H5, 0.05% cyclosporine (Restasis ® , Allergan) and dexamethasone (Monodex ® , Thea Pharma) for 3 consecutive weeks. A control group received no therapy whatsoever. Readout parameters included tear secretion, corneal fluorescein staining at 5 timepoints and histological analysis of goblet cell count at the end of the experiments. Results The older mice demonstrated a significantly stronger dry eye phenotype than the younger mice. Following therapy, the older mice responded to topical anti-inflammatory therapy significantly later than the younger individuals. Regarding the different substances used, cyclosporine/F4H5 showed a significantly faster decrease in corneal fluoresceine staining after only 1 week of therapy in comparison to all other groups. This substance was also superior regarding tear secretion and goblet cell count in age matched groups and in comparison to younger mice. Conclusions These experimental data support the implication that aging should be considered as an important factor in daily clinical practice. Furthermore, the differences found between substance classes, such as calcineurin antagonists and steroids, as well as different drug formulations, should be considered in future pre-clinical and clinical trials. Georg Thieme Verlag KG Stuttgart · New York.

T-cell proliferative responses following sepsis in neonatal rats.

Science.gov (United States)

Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

2003-01-01

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment

p53 is important for the anti-proliferative effect of ibuprofen in colon carcinoma cells

International Nuclear Information System (INIS)

Janssen, Astrid; Schiffmann, Susanne; Birod, Kerstin; Maier, Thorsten J.; Wobst, Ivonne; Geisslinger, Gerd; Groesch, Sabine

2008-01-01

S-ibuprofen which inhibits the cyclooxygenase-1/-2 and R-ibuprofen which shows no COX-inhibition at therapeutic concentrations have anti-carcinogenic effects in human colon cancer cells; however, the molecular mechanisms for these effects are still unknown. Using HCT-116 colon carcinoma cell lines, expressing either the wild-type form of p53 (HCT-116 p53 wt ) or being p(HCT-116 p53 -/- ), we demonstrated that both induction of a cell cycle block and apoptosis after S- and R-ibuprofen treatment is in part dependent on p53. Also in the in vivo nude mice model HCT-116 p53 -/- xenografts were less sensitive for S- and R-ibuprofen treatment than HCT-116 p53 wt cells. Furthermore, results indicate that induction of apoptosis in HCT-116 p53 wt cells after ibuprofen treatment is in part dependent on a signalling pathway including the neutrophin receptor p75 NTR , p53 and Bax

Anti-mitotic potential of 7-diethylamino-3(2′-benzoxazolyl)-coumarin in 5-fluorouracil-resistant human gastric cancer cell line SNU620/5-FU

International Nuclear Information System (INIS)

Kim, Nam Hyun; Kim, Su-Nam; Oh, Joa Sub; Lee, Seokjoon; Kim, Yong Kee

2012-01-01

Highlights: ► DBC exerts antiproliferative potential against 5FU-resistant human gastric cancer cells. ► This effect is mediated by destabilization of microtubules and subsequent mitotic arrest. ► DBC enhances apoptosis via caspase activation and downregulation of antiapoptotic genes. -- Abstract: In this study, we investigate an anti-mitotic potential of the novel synthetic coumarin-based compound, 7-diethylamino-3(2′-benzoxazolyl)-coumarin, in 5-fluorouracil-resistant human gastric cancer cell line SNU-620-5FU and its parental cell SNU-620. It exerts the anti-proliferative effects with similar potencies against both cancer cells, which is mediated by destabilization of microtubules and subsequent mitotic arrest. Furthermore, this compound enhances caspase-dependent apoptotic cell death via decreased expression of anti-apoptotic genes. Taken together, our data strongly support anti-mitotic potential of 7-diethylamino-3(2′-benzoxazolyl)-coumarin against drug-resistant cancer cells which will prompt us to further develop as a novel microtubule inhibitor for drug-resistant cancer chemotherapy.

HELICOBACTER PYLORI GROWTH INHIBITION BY SUBSTANCE PRODUCED PSEUDOMONAS BY AEROGINOSA: IN VTRO STUDY

Directory of Open Access Journals (Sweden)

A FAZELI

2003-03-01

Full Text Available Resistance of H.pylori against metronidazole is increasingly appeared in reports of investigators of gastric infections. So that, seeking to find more effective anti-helicobacter drugs is a necessity. In this study, inhibitory effect of the P. aeroginosa-produced substance on H. pylori growth was determined using two methods, Cross-streak and Well-diffusion Only two out of 37 P. aeroginosa isalates were able to inhibit H. pylori growth which one of them was chosen for further investigation. Its antibacterial activity was tested on 31 isolates of H. pylori consisting 27 metrondazole-sensitive and 4 metronidazole-resistant isolates. The inhibitory substance was enable to kill both metrondazole-sensitive and resistant isolates of H. pylori. The substance could also inhibit the of several other bacteria including E.coli, Salmonella sp., Klebsiella sp., S. aureus and a gram positive bacilli. While the inhibitory effect of the substance had no change at 40c for 30 days, its effect substantially reduced by treating at 600c for 15 minutes. Treatment of substance at 600c (30 min. 80?c and 100?c (15 & 30min, and freezing (-20?c and melting (37?c inactivated its inhibitory effect completely. Treatment with trips in also could inactivate it. Thus P. aeroginosa-produced substance, probably is a protein and may be classified in bacteriocin group.

Effectiveness of skill-based substance abuse intervention among male adolescents in an Islamic country: case of the Islamic Republic of Iran.

Science.gov (United States)

Allahverdipour, Hamid; Bazargan, Mohsen; Farhadinasab, Abdollah; Hidarnia, Alireza; Bashirian, Saeed

2009-01-01

The prevalence of substance abuse among adolescents from low- and middle-income countries is increasing drastically and requires immediate intervention. The objective of this longitudinal quasi-experimental panel study was to design and implement a skill-based intervention to prevent and reduce substance use among urban adolescents who attended 2 randomly selected high-schools in Tehran, Iran. One-year post intervention data show that substance abuse, knowledge, attitudes, peer resistance skills, level of self-control, self-efficacy, and perceived susceptibility among intervention group were significantly improved, whereas level of self control and attitudes against substance abuse among the control group deteriorated. To efficiently prevent substance abuse among youth primary preventive interventions should be implemented before onset of substance abuse to improve resistance skills and provide adolescents with information and skills needed to develop anti-drug norms.

[Prader-Willi syndrome case with proliferative diabetic retinopathy in both eyes treated by early vitrectomy under local anesthesia].

Science.gov (United States)

Hori, Hideyuki; Sato, Yukihiro; Nakashima, Motohiro; Nakajima, Motohiro

2012-02-01

Although patients with Prader-Willi syndrome have a high rate of diabetes, to date, there have been only 4 reported cases (6 eyes) undergoing vitrectomy for proliferative diabetic retinopathy. Herein, we report a case of Prader-Willi syndrome with proliferative diabetic retinopathy that was treated by early vitrectomy OU under local anesthesia. A 30-year-old man was diagnosed as having Prader-Willi syndrome at the age of 2 years and diabetes at age 17. He was referred to our hospital as diabetic retinopathy had been detected in his first ophthalmological examination at age 29. Visual acuity was 0.6 bilaterally. Proliferative retinopathy, with cataract and macular edema, was identified in both eyes. Panretinal photocoagulation was performed on both eyes. However, proliferative membranes developed bilaterally, and vitreous hemorrhage occurred OS. Visual acuity decreased to 0.3 OU. The patient was hospitalized at our internal medicine department for blood glucose control. Subsequently, with an anesthesiologist on standby, a hypnotic sedative was injected intramuscularly, achieving retro-bulbar anesthesia. Combined cataract and vitreous surgery was performed on the left eye. One week later, a similar operation was performed on the right eye. The patient was discharged four days later. In the two years since these operation, visual acuity has been maintained at 0.8 OU. Patients with Prader-Willi syndrome should be examined for early detection and treatment of diabetic retinopathy.

Chronic proliferative synovitis of the equine metacarpophalangeal joint

International Nuclear Information System (INIS)

Kannegieter, N.J.

1990-01-01

Chronic proliferative synovitis of 27 metacarpophalangeal joints in 16 horses is described. The diagnosis was based on a history of lameness and, or, poor performance, pain on flexion of the metacarpophalangeal joint, the response to intra-articular anaesthesia, and plain and contrast radiography. Radiographic findings included concavity of the distal dorsal metacarpus proximal to the sagittal ridge, and an increase in size of the synovial tissue adjacent to the proximal, dorsal attachment of the joint capsule. Mineralisation of the synovial tissue was present in some joints, and chip fractures from the dorsal aspect of the proximal phalanx were also occasionally seen. Treatment by arthroscopic resection of the tissue gave excellent results

Pharmacological features of osthole

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Agata Jarząb

2017-05-01

Full Text Available Coumarins are a group of naturally occurring compounds common in the plant world. These substances and their derivatives exhibit a broad range of biological activities.One of the naturally occurring coumarins is osthole, which can most frequently be found in plants of the Apiaceae family. Cnidium monnieri (L. Cusson ex Juss. Angelica pubescens Maxim. and Peucedanum ostruthium (L.. It has anti-proliferative, anti-inflammatory, anti-convulsant, and antiallergic properties; apart from that, inhibition of platelet aggregation has also been proved. The impact of osthole on bone metabolism has been demonstrated; also its hepatoprotective and neuroprotective properties have been confirmed. The inhibitory effect of this metokcompound on the development of neurodegenerative diseases has been proved in experimental models. Anticancer features of osthole have been also demonstrated both in vitro on different cell lines, and in vivo using animals xenografts. Osthole inhibited proliferation, motility and invasiveness of tumor cells, which may be associated with the induction of apoptosis and cell cycle slowdown. The exact molecular mechanism of osthole anti-cancer mode of action has not been fully elucidated. A synergistic effect of osthole with other anti-tumor substances has been also reported. Modification of its chemical structure led to the synthesis of many derivatives with significant anticancer effects.To sum up, osthole is an interesting therapeutic option, due to both its direct effect on tumor cells, as well as its neuroprotective or anti-inflammatory properties. Thus, there is a chance to use osthole or its synthetic derivatives in the treatment of cancer.

Aversion substance(s) of the rat coagulating glands

Science.gov (United States)

Gawienowski, Anthony M.; Berry, Iver J.; Kennelly, James J.

1982-01-01

The aversive substance(s) present in adult male urine were not found in castrate rat urine. Removal of the coagulating glands also resulted in a loss of the aversion compounds. The aversion substances were restored to the urine after androgen treatment of the castrate rats.

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China.

Science.gov (United States)

Shannon, Jackilen; King, Irena B; Lampe, Johanna W; Gao, Dao Li; Ray, Roberta M; Lin, Ming-Gang; Stalsberg, Helge; Thomas, David B

2009-01-01

Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes. The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1,030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons. Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.

The role of nutraceuticals in anti-aging medicine.

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Vranesić-Bender, Darija

2010-12-01

'Nutraceuticals' is a wide term including all kinds of food with health or medical effect. Regulations in the world on functional food and nutraceuticals are developed along with the development of new products. This nomenclature is not aligned across legal regulations in different countries. There are several theories trying to interpret the phenomenon of aging and the most interesting theory in terms of nutrition is free radical theory and the possible role of antioxidants in aging process. A large group of substances including vitamins, carotenoids, flavonoids and minerals have in vitro or in vivo clinically significant antioxidant characteristics. There is great interest in anti-aging substances derived from food, and the most popular ingredients are antioxidants, especially coenzyme Q10, phytoestrogens, probiotics and omega-3 fatty acids. These substances have beneficial effect on digestive and immune systems, and modulate inflammatory and degenerative processes in the body. The challenge in the future will be strategic combining of cosmeceuticals and nutraceuticals in order to intervene in biological aging processes and degenerative skin changes.

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

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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.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis.

Science.gov (United States)

Hammad, A; Yahia, S; Laimon, W; Hamed, S M; Shouma, A; Shalaby, N M; Abdel-Hady, D; Ghanem, R; El-Farahaty, R M; El-Bassiony, S R; Hammad, E M

2017-06-01

Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( Plupus erythematosus patients in comparison to controls ( P lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

Effect of intraperitoneal antimicrobials on the concentration of bacteria, endotoxin, and tumor necrosis factor in abdominal fluid and plasma in rats

NARCIS (Netherlands)

Rosman, C; Westerveld, GJ; vanOeveren, W; Kooi, K; Bleichrodt, RP

1996-01-01

The efficacy of intraperitoneal instillation of antimicrobial agents in eliminating the bacterial contaminant in patients with generalized peritonitis remains controversial. We determined the effect of intraperitoneal instillation of taurolidine or imipenem on mortality, and on the concentration of

Local treatment of generalised peritonitis in rats; Effects on bacteria, endotoxin and mortality

NARCIS (Netherlands)

Rosman, C; Westerveld, GJ; Kooi, K; Bleichrodt, RP

Objective. To assess the effect of debridement, intraoperative lavage with saline, and additional instillation of taurolidine or imipenem/cilastatin in rats with faecal peritonitis. Design: Laboratory study. Setting: University hospital, The Netherlands. Material: 60 male Wister rats. Interventions:

Histone deacetylase inhibitors: can we consider potent anti-neoplastic agents for the treatment of asthma?

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Royce, Simon G; Ververis, Katherine; Karagiannis, Tom C

2012-01-01

Histone deacetylase inhibitors have emerged as a new class of anti-cancer therapeutics due to their potent anti-proliferative and apoptotic effects in malignant cells. Accumulating evidence is indicating that histone deacetylase inhibitors may also have potential clinical utility in non-oncological applications, including asthma. However, the potential of histone deacetylase inhibitors in asthma remains controversial. For example, the mechanisms of action of the broad-spectrum histone deacetylase inhibitor, Trichostatin A, in animal models of allergic airways disease are conflicting. Further, there is evidence suggesting potential problems associated with histone deacetylase 2 inhibition and conventional glucocorticosteroid therapy. Similarly, disparate findings are emerging following modulation of the class III, sirtuin 1 enzyme. Indeed, it is becoming apparent that the mechanism of action may not be related to histone deacetylase inhibition activity per se. Further, there is only limited evidence that these compounds possess anti-inflammatory effects in models of asthma. In this review, we provide an overview of the biology of the metal-dependent and sirtuin deacetylases in the context of asthma. The controversies surrounding the potential use of histone deacetylase inhibitors in asthma are discussed and future directions involving the investigation of more specific analogues are explored.

Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review.

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Surh, Young-Joon

2002-08-01

A wide variety of phenolic substances derived from spice possess potent antimutagenic and anticarcinogenic activities. Examples are curcumin, a yellow colouring agent, contained in turmeric (Curcuma longa L., Zingiberaceae), [6]-gingerol, a pungent ingredient present in ginger (Zingiber officinale Roscoe, Zingiberaceae) and capsaicin, a principal pungent principle of hot chili pepper (Capsicum annuum L, Solanaceae). The chemopreventive effects exerted by these phytochemicals are often associated with their antioxidative and anti-inflammatory activities. Cyclo-oxygenase-2 (COX-2) has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. Recent studies have shown that COX-2 is regulated by the eukaryotic transcription factor NF-kappaB. This short review summarizes the molecular mechanisms underlying chemopreventive effects of the aforementioned spice ingredients in terms of their effects on intracellular signaling cascades, particularly those involving NF-kappaB and mitogen-activated protein kinases.

Definition of Substance and Non-substance Addiction.

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Zou, Zhiling; Wang, Huijun; d'Oleire Uquillas, Federico; Wang, Xiaomei; Ding, Jianrui; Chen, Hong

2017-01-01

Substance addiction (or drug addiction) is a neuropsychiatric disorder characterized by a recurring desire to continue taking the drug despite harmful consequences. Non-substance addiction (or behavioral addiction) covers pathological gambling, food addiction, internet addiction, and mobile phone addiction. Their definition is similar to drug addiction but they differ from each other in specific domains. This review aims to provide a brief overview of past and current definitions of substance and non-substance addiction, and also touches on the topic of diagnosing drug addiction and non-drug addiction, ultimately aiming to further the understanding of the key concepts needed for a foundation to study the biological and psychological underpinnings of addiction disorders.

PRGF exerts more potent proliferative and anti-inflammatory effects than autologous serum on a cell culture inflammatory model.

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Anitua, E; Muruzabal, F; de la Fuente, M; Riestra, A; Merayo-Lloves, J; Orive, G

2016-10-01

Ocular graft versus host disease (oGVHD) is part of a systemic inflammatory disease that usually affects ocular surface tissues manifesting as a dry eye syndrome. Current treatments provide unsatisfactory results. Blood-derived products, like plasma rich in growth factors (PRGF) emerge as a potential therapy for this disease. The purpose of this study was to evaluate the tissue regeneration and anti-inflammatory capability of PRGF, an autologous platelet enriched plasma eye-drop, compared to autologous serum (AS) obtained from oGVHD patients on ocular surface cells cultured in a pro-inflammatory environment. PRGF and AS were obtained from four GVHD patients. Cell proliferation and inflammation markers, intercellular adhesion molecule-1 (ICAM-1) and cyclooxygenase-2 (COX-2), were measured in corneal and conjunctival fibroblastic cells cultured under pro-inflammatory conditions and after treatment with PRGF or AS eye drops. Moreover, cell proliferation increased after treatment with PRGF and AS, though this enhancement in the case of keratocytes was significantly higher with PRGF. PRGF eye drops showed a significant reduction of both inflammatory markers with respect to the initial inflammatory situation and to the AS treatment. Our results concluded that PRGF exerts more potent regenerative and anti-inflammatory effects than autologous serum on ocular surface fibroblasts treated with pro-inflammatory IL-1β and TNFα. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oral proliferative verrucous leukoplakia: A case report with an update

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Rakhi Issrani

2013-01-01

Full Text Available White lesions both physiologic as well as pathologic are relatively frequent in the oral cavity, the most common pathology being oral leukoplakia (OL. There are many variants of OL, one of which is oral proliferative verrucous leukoplakia (OPVL. OPVL is a rare clinico-pathological entity, which is slow growing, long-term progressive lesion, but remains an enigmatic and difficult to define. The etiology of OPVL remains still unclear. Tobacco use does not seem to have a significant influence on the appearance of OPVL. These lesions may occur both in smokers and non-smokers. It is observed more frequently in women and elderly patients 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. Various published case series have presented OPVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa. This article describes the clinical aspects and histologic features of an OPVL case that demonstrated the typical behavior pattern in a long-standing, persistent lesion and discusses this relatively rare entity in light of current information.

New psychoactive substances of natural origin: A brief review

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Ling-Yi Feng

2017-07-01

Full Text Available Plant-based drugs of abuse are as old as recorded human history. Although traditional addictive substances, such as opium, cannabis and coca, have been controlled by the United Nations anti-drug conventions, many, if not most, natural plants with addictive or abuse liability remain elusive. Therefore, the United Nations Office on Drugs and Crime (UNODC has warned the emerging threat from new psychoactive substances (NPS, which are mostly derived or modified from the constituents of natural origin. For example, synthetic cannabinoids and synthetic cathinones are derived from the cannabis and khat plant, respectively. In this review, we briefly discussed the chemistry, pharmacology and toxicology of five common NPS of natural origin, i.e., khat, kratom, salvia, magic mushroom and mandrake. Through the review, we hope that professionals and general public alike can pay more attention to the potential problems caused by natural NPS, and suitable control measures will be taken.

Mass Spectrometry Imaging Can Distinguish on a Proteomic Level Between Proliferative Nodules Within a Benign Congenital Nevus and Malignant Melanoma.

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Lazova, Rossitza; Yang, Zhe; El Habr, Constantin; Lim, Young; Choate, Keith Adam; Seeley, Erin H; Caprioli, Richard M; Yangqun, Li

2017-09-01

Histopathological interpretation of proliferative nodules occurring in association with congenital melanocytic nevi can be very challenging due to their similarities with congenital malignant melanoma and malignant melanoma arising in association with congenital nevi. We hereby report a diagnostically challenging case of congenital melanocytic nevus with proliferative nodules and ulcerations, which was originally misdiagnosed as congenital malignant melanoma. Subsequent histopathological examination in consultation by one of the authors (R.L.) and mass spectrometry imaging analysis rendered a diagnosis of congenital melanocytic nevus with proliferative nodules. In this case, mass spectrometry imaging, a novel method capable of distinguishing benign from malignant melanocytic lesions on a proteomic level, was instrumental in making the diagnosis of a benign nevus. We emphasize the importance of this method as an ancillary tool in the diagnosis of difficult melanocytic lesions.

Ceramic core with polymer corona hybrid nanocarrier for the treatment of osteosarcoma with co-delivery of protein and anti-cancer drug

Science.gov (United States)

Ram Prasad, S.; Sampath Kumar, T. S.; Jayakrishnan, A.

2018-01-01

For the treatment of metastatic bone cancer, local delivery of therapeutic agents is preferred compared to systemic administration. Delivery of an anti-cancer drug and a protein that helps in bone regeneration simultaneously is a challenging approach. In this study, a nanoparticulate carrier which delivers a protein and an anti-cancer drug is reported. Bovine serum albumin (BSA) as a model protein was loaded into hydroxyapatite (HA) nanoparticles (NPs) and methotrexate (MTX) conjugated to poly(vinyl alcohol) was coated onto BSA-loaded HA NPs. Coating efficiency was in the range of 10-17 wt%. In vitro drug release showed that there was a steady increase in the release of both BSA and MTX with 76% of BSA and 88% of MTX being released in 13 days. Cytotoxicity studies of the NPs performed using human osteosarcoma (OMG-63) cell line showed the NPs were highly biocompatible and exhibited anti-proliferative activity in a concentration-dependent manner.

Proliferative changes in nonpalpable breast lesions detected by mammography; Alteraciones profiferativas de la mama en lesiones no palpables detectadas por mamografia

Energy Technology Data Exchange (ETDEWEB)

Vega, A.; Delgado, A.; Ortega, E.; Garijo, F. [Hospital Universitario Marques de Valdecilla. Santander (Spain); Mosquera, J.; Sogo, C.; Alvarez, A. [Complejo Hospitalario Juan Canalejo. La Coruna (Spain)

2000-07-01

To analyze retrospectively the radiological findings in nonpalpable breast lesions detected by mammography that lead to the performance of surgical biopsy, resulting in a histological diagnosis of proliferative breast disease with and without atypia. From two Spanish hospitals, 421 women with 429 biopsies indicative of the presence of proliferative breast disease with and without atypia were selected out of a total of 1252 surgical biopsies in nonpalpable lesions that proved to be benign. Age, personal and familial history of breast cancer, reason for requesting the mammography and radiological findings that had indicated the need for surgical biopsy were recorded for each patient. The diagnosis was proliferative breast disease (epithelial hyperplasia) in 347 women with 354 biopsies and atypical hyperplasia in the remaining 74 women with 75 biopsies, representing 28% and 6%, respectively, of the 1252 biopsies of lesions found to be benign. In 221 of the 354 cases of epithelial hyperplasia (62%) and 45 of the 75 cases of atypical hyperplasia (60%), the presence of calcifications was the most common radiological findings leading to biopsy (p<0.05). Parenchymal distortion, with or without calcifications, was the second most common radiological sign. The histological study revealed a close relationship between these proliferative events and radial scars. Calcifications are the radiological finding that most frequently indicate the need for surgical biopsy in nonpalpable lesions that results in a diagnosis of proliferative breast disease with and without atypia. (Author) 12 refs.

Innate immunity in the vagina (Part II): Anti-HIV activity and antiviral content of human vaginal secretions.

Science.gov (United States)

Patel, Mickey V; Ghosh, Mimi; Fahey, John V; Ochsenbauer, Christina; Rossoll, Richard M; Wira, Charles R

2014-07-01

Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions change across the menstrual cycle is unknown. Using a menstrual cup, vaginal secretions from pre-menopausal women were recovered at the proliferative (d6-8), mid-cycle (d13-15), and secretory (d21-23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. CCL20, RANTES, elafin, HBD2, SDF-1α, and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women and in consecutive cycles from the same woman. The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and interindividual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. © 2014 John Wiley & Sons Ltd.

Vitrectomy for proliferative diabetic retinopathy

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Chao Peng

2013-10-01

Full Text Available AIM:To observe the clinical effect of vitrectomy for proliferative diabetic retinopathy(PDR.METHODS: The clinical data of 55 cases(65 eyes, underwent vitrectomy, membrane peeling, endolaser photocoagulation and silicone oil or C3F8 injection, were retrospectively studied. During 6 months to 1 year follow-up period, visual acuity, intraocular pressure, retinal conditions and complications were observed.RESULTS: All 65 eyes received vitrectomy, of which silicone oil was tamponaded in 32 eyes, C3F8 was injected in 8 eyes, BBS was filled in 25 eyes. Visual improvement achieved in 42 eyes. Two eyes were manually vision, form count fingers to 0.05 in 18 eyes, >0.05-0.1 in 28 eyes, >0.1-0.3 in 12 eyes and >0.3 in 5 eyes. Retinal hole was occurred in 7 eyes, limitations fibrosis membrane remained in 8 eyes, retinal detachment appeared in 5 eyes, IOP increased in 18 eyes, vitreous hemorrhage relapsed in 12 eyes, 36 eyes received supplemental photocoagulation treatment 1-3 times after operation.CONCLUSION:Vitrectomy combined endophotocoagulation is an effective treatment for PDR. Silicone oil tamponade can limit the hemorrhage.

Substance Identification Information from EPA's Substance Registry

Data.gov (United States)

U.S. Environmental Protection Agency — The Substance Registry Services (SRS) is the authoritative resource for basic information about substances of interest to the U.S. EPA and its state and tribal...

Inhibin B and anti-Müllerian hormone/Müllerian-inhibiting substance may contribute to the male bias in autism.

Science.gov (United States)

Pankhurst, M W; McLennan, I S

2012-08-14

The autistic spectrum disorders have a significant male bias in incidence, which is unexplained. The Sertoli cells of the immature testes secrete supra-adult levels of Müllerian-inhibiting substance/anti-Müllerian hormone (AMH) and inhibin B (InhB), with both hormones being putative regulators of brain development. We report here, that 82 boys with an autism spectrum disorder have normal levels of InhB and AMH. However, the boys' level of InhB correlated with their autism diagnostic interview-revised (ADI-R) scores for the social interaction (R=0.29, P=0.009, N=82) and communication domains (R=0.29, P=0.022, N=63), and with the number of autistic traits the boys exhibited (R=0.34 and 0.27, respectively). The strengths of the abovementioned correlates were stronger in the boys with milder autism (R=0.42 and 0.50, respectively), with AMH exhibiting a significant negative correlation to the ADI-R score in these boys (R=-0.44 and R=-0.39, respectively). Neither hormone correlated to the incidence of stereotyped and repetitive behaviours. This suggests that the male bias in the autistic spectrum has multiple determinants, which modulate the effects of an otherwise non-dimorphic pathology. Furthermore, AMH and InhB have opposing effects on the SMAD1/5/8 pathway, and opposing correlates to autistic traits, implicating the SMAD pathways as a putative point of molecular convergence for the autistic spectrum.

Semi-synthetic preparation of the rare, cytotoxic, deep-sea sourced sponge metabolites discorhabdins P and U.

Science.gov (United States)

Grkovic, Tanja; Kaur, Balwinder; Webb, Victoria L; Copp, Brent R

2006-04-01

Semi-synthetic routes to the enzyme inhibitory and potently anti-proliferative marine natural products discorhabdins P and U were developed by one-step methylation reactions of discorhabdins C and B, respectively. Two novel semi-synthetic derivatives of discorhabdin U were also prepared, one of which (6) exhibited significant anti-proliferative activity.

Tiff over anti-tetanus vaccine now erupted into battle. International / Philippines.

Science.gov (United States)

1995-07-24

Anti-abortionists in the Philippines have generated widespread fears in the country that tetanus toxoid used in the anti-tetanus vaccine campaign contains trace amounts of human chorionic gonadotropin (HCG) to induce abortion. The World Health Organization (WHO) notes that this widespread, unfounded fear has already resulted in a 45% drop in tetanus toxoid coverage during national immunization days in 1995 compared to 1994. Since up to 5 million women were not immunized in 1995, 300-400 more babies will contract tetanus and die in the year to come. Pro-life Philippines is ostensibly the creator and supporter of these newly-generated fears about tetanus toxoid. The mass hysteria is, however, most likely part of a church-led campaign against the government's population policies and the popularity of former Health Secretary Juan Flavier. Millions of Filipino women have for years received anti-tetanus vaccines to prevent tetanus in both mothers and their newborn children. Tetanus remains a problem for newborns in the Philippines where local midwives often use unsanitary knives to sever the umbilical cord at birth. Since the immunization drive was stepped up in 1990, the number of babies affected by tetanus has fallen from more than 25 per day in the mid-1980s to four currently. The vaccine currently supplied by UNICEF has been used for more than 50 years in many countries and is one of the basics in immunization. The Department of Health notes no unusual increase in abortions since 1990, the year the anti-tetanus drive was accelerated. Prior to 1990, anti-tetanus vaccination had been going on in the Philippines since 1983. Even WHO assurances that tetanus toxoid contains no abortifacients have failed to allay public fear. It is unfortunate that the people and groups behind this misinformation campaign have done so much damage to a decidedly beneficial and needed health program.

Anti-fibrotic and anti-tumorigenic effects of rhein, a natural anthraquinone derivative, in mammalian stellate and carcinoma cells.

Science.gov (United States)

Tsang, Siu Wai; Bian, Zhao-Xiang

2015-03-01

Anthraquinone compounds have been recognized to possess antiinflammatory, anti-fibrotic and anti-tumour properties and thus applied in human and veterinary therapeutics as active substances of medicinal products. Amongst the anthraquinones isolated from Rheum palmatum, also known as da-huang, rhein was detected as one of the highest metabolite contents in the bloodstream of mammals. The biological activities of rhein therefore deserve detailed investigation. In this study, we aimed to delineate the mechanism of inhibitory actions of rhein on fibrotic and tumorigenic processes by means of various biochemical assays, such as immunofluorescent staining, real-time polymerase chain reaction (PCR) and western blotting analyses in rat pancreatic stellate cells (LTC-14), human pancreatic ductal adenocarcinoma cells (PANC-1) and human colon carcinoma cells (SW480 and SW620). Our results demonstrated that the application of rhein notably suppressed the mRNA and protein levels of various fibrotic and tumorigenic mediators including alpha-smooth muscle actin, type I collagen, fibronectin, N-cadherin and matrix metalloproteinases in the testing mammalian cells. The mechanism of the suppressive actions of rhein was associated with the modulation of the sonic hedgehog and serine-threonine kinase signalling pathways. In conclusion, we suggest that rhein may serve as a therapeutic or an adjuvant agent in anti-fibrotic and anti-tumorigenic approaches. Copyright © 2014 John Wiley & Sons, Ltd.

Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Devarbhavi, Harshad; Andrade, Raúl J

2014-05-01

Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Plant polyphenols and their anti-cariogenic properties: a review

OpenAIRE

Ferrazzano, G.F.; Amato, I.; Ingenito, A.; Zarrelli, A.; Pinto, G.; Pollio, A.

2011-01-01

Polyphenols constitute one of the most common groups of substances in plants. Polyphenolic compounds have been reported to have a wide range of biological activities, many of which are related to their conventional antioxidant action; however, increasing scientific knowledge has highlighted their potential activity in preventing oral disease, including the prevention of tooth decay. The aim of this review is to show the emerging findings on the anti-cariogenic properties of polyphenols, which...

Substance use - prescription drugs

Science.gov (United States)

Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

Immunity in the Vagina (Part II): Anti-HIV Activity and Antiviral Content of Human Vaginal Secretions

Science.gov (United States)

Patel, Mickey V.; Ghosh, Mimi; Fahey, John V.; Ochsenbauer, Christina; Rossoll, Richard M.; Wira, Charles R.

2015-01-01

Problem Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions changes across the menstrual cycle is unknown. Method of Study Using a menstrual cup, vaginal secretions from premenopausal women were recovered at the proliferative (d6–8), mid-cycle (d13–15) and secretory (d21–23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. Results CCL20, RANTES, elafin, HBD2, SDF-1α and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women, and in consecutive cycles from the same woman. Conclusion The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and inter-individual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. PMID:24806967

Study of specific pharmacological activity of standardized composition of bee product substances for treatment of urogenital system

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V. M. Koval

2017-10-01

Full Text Available Introduction. The work presents review of the data literature, which indicate the prospects of creation new highly efficient drugs for the treatment of chronic prostatitis and prostate gland adenoma based bioactive standardized substances of bee products, including powdered honey (PH, propolis phenolic hydrophobic drug (PPHD and bee pollen (BP. Materials and methods. Results of discussion of preclinical pharmacological studies of standardized substances of bee products composition – PH, PPHD and BP for the treatment of specified pathology is given in the experimental part. Results. It was found that the most pronounced anti-inflammatory effect on the level 40 % the mixture of APIs (PH, PPHD and BP detects at a dose of 100 mg/kg in relation to the reference drug – trianom capsules in doses of 100 and 130 mg/kg. Conclusions. Usage of bee products is grounded in creation of the new drug on their basis in the form of standardized substances of bee products composition –PH, PPHD and BP for chronic prostatitis and prostate gland adenoma. It was found that the most pronounced anti-inflammatory effect on 40 % the mixture of APIs (PH, PPHD and BP detects at a dose of 100 mg/kg. It was established that the composition of standard substances of bee products – PH, PPHD and BP at a dose of 100 mg/kg shows a more pronounced specific pharmacological effect in comparison to the reference product – trianom capsules at doses of 100 and 130 mg/kg, which positively affect the course of the pilot prostatitis in male rats caused by dichloroethyl.

Substance misuse and substance use disorders in sex offenders: a review

NARCIS (Netherlands)

Kraanen, F.L.; Emmelkamp, P.M.G.

2011-01-01

Substance abuse has often been associated with committing sex offenses. In this article, the following will be reviewed: 1) studies that assessed substance abuse in sex offenders; 2) differences in substance abuse among different types of sex offenders; 3) differences in substance abuse between sex

21 CFR 178.3130 - Antistatic and/or anti-fogging agents in food-packaging materials.

Science.gov (United States)

2010-04-01

...-packaging materials. 178.3130 Section 178.3130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF.../or anti-fogging agents in food-packaging materials. The substances listed in paragraph (b) of this section may be safely used as antistatic and/or antifogging agents in food-packaging materials, subject to...

Autoradiographic localization of substance P receptors using 125I substance P

International Nuclear Information System (INIS)

Shults, C.W.; Quirion, R.; Jensen, R.T.; Moody, T.W.; O'Donohue, T.L.; Chase, T.N.

1982-01-01

This paper describes a method for localization of substance P receptors in the rat central nervous system using 125 I labeled substance P in an autoradiographic procedure. Particularly high densities of substance P receptors were observed in the olfactory bulb, dentate gyrus, amygdala, superior colliculus, and locus coeruleus. Surprisingly low densities of substance P receptors were found in the substantia nigra pars reticulata, a region which contains high concentrations of substance P

Probabilistic cumulative risk assessment of anti-androgenic pesticides in food

DEFF Research Database (Denmark)

Müller, Anne Kirstine; Bosgra, Sieto; Boon, Polly E.

2009-01-01

In this paper, we present a cumulative risk assessment of three anti-androgenic pesticides (vinclozolin, procymidone and prochloraz) using the relative potency factor (RPF) approach and an integrated probabilistic risk assessment (IPRA) model. RPFs for each substance were estimated for three......) and the fraction of individuals with IMoEs vinclozolin, procymidone and prochloraz is not likely to be of concern for the reproductive development of their male foetuses. However...

Can We Better Integrate the Role of Anti-Doping in Sports and Society? A Psychological Approach to Contemporary Value-Based Prevention.

Science.gov (United States)

Petróczi, Andrea; Norman, Paul; Brueckner, Sebastian

2017-01-01

In sport, a wide array of substances with established or putative performance-enhancing properties is used. Most substances are fully acceptable, whilst a defined set, revised annually, is prohibited; thus, using any of these prohibited substances is declared as cheating. In the increasingly tolerant culture of pharmacological and technical human enhancements, the traditional normative approach to anti-doping, which involves telling athletes what they cannot do to improve their athletic ability and performance, diverges from the otherwise positive values attached to human improvement and enhancement in society. Today, doping is the epitome of conflicting normative expectations about the goal (performance enhancement) and the means by which the goal is achieved (use of drugs). Owing to this moral-functional duality, addressing motivations for doping avoidance at the community level is necessary, but not sufficient, for effective doping prevention. Relevant and meaningful anti-doping must also recognise and respect the values of those affected, and consolidate them with the values underpinning structural, community level anti-doping. Effective anti-doping efforts are pragmatic, positive, preventive, and proactive. They acknowledge the progressive nature of how a "performance mindset" forms in parallel with the career transition to elite level, encompasses all levels and abilities, and directly addresses the reasons behind doping use with tangible solutions. For genuine integration into sport and society, anti-doping should consistently engage athletes and other stakeholders in developing positive preventive strategies to ensure that anti-doping education not only focuses on the intrinsic values associated with the spirit of sport but also recognises the values attached to performance enhancement, addresses the pressures athletes are under, and meets their needs for practical solutions to avoid doping. Organisations involved in anti- doping should avoid the image of

In Silico Identification and In Vitro and In Vivo Validation of Anti-Psychotic Drug Fluspirilene as a Potential CDK2 Inhibitor and a Candidate Anti-Cancer Drug.

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Xi-Nan Shi

Full Text Available Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related deaths worldwide. Surgical resection and conventional chemotherapy and radiotherapy ultimately fail due to tumor recurrence and HCC's resistance. The development of novel therapies against HCC is thus urgently required. The cyclin-dependent kinase (CDK pathways are important and well-established targets for cancer treatment. In particular, CDK2 is a key factor regulating the cell cycle G1 to S transition and a hallmark for cancers. In this study, we utilized our free and open-source protein-ligand docking software, idock, prospectively to identify potential CDK2 inhibitors from 4,311 FDA-approved small molecule drugs using a repurposing strategy and an ensemble docking methodology. Sorted by average idock score, nine compounds were purchased and tested in vitro. Among them, the anti-psychotic drug fluspirilene exhibited the highest anti-proliferative effect in human hepatocellular carcinoma HepG2 and Huh7 cells. We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. We also examined the anti-cancer effect of fluspirilene in vivo in BALB/C nude mice subcutaneously xenografted with human hepatocellular carcinoma Huh7 cells. Our results showed that oral fluspirilene treatment significantly inhibited tumor growth. Fluspirilene (15 mg/kg exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil (10 mg/kg. Moreover, the cocktail treatment with fluspirilene and 5-fluorouracil exhibited the highest therapeutic effect. These results suggested for the first time that fluspirilene is a potential CDK2 inhibitor and a candidate anti-cancer drug for the treatment of human hepatocellular carcinoma. In view of the fact that fluspirilene has a long history

Substance misuse and substance use disorders in sex offenders: a review.

Science.gov (United States)

Kraanen, Fleur L; Emmelkamp, Paul M G

2011-04-01

Substance abuse has often been associated with committing sex offenses. In this article, the following will be reviewed: 1) studies that assessed substance abuse in sex offenders; 2) differences in substance abuse among different types of sex offenders; 3) differences in substance abuse between sex offenders and nonsexual offenders and substance abuse in the normal population; 4) sex offenders' intoxication at the time of the offense; and 5) differences in intoxication at the time of the offense among different types of sex offenders. Studies will be discussed according to the method they used to assess substance abuse, i.e., file research, screening instruments or semi-structured interviews. This review shows that about half of the sex offenders has a history of substance abuse, a quarter to half of the sex offenders has a history of alcohol misuse and that about one fifth to a quarter of the sex offenders has a history of drug misuse. Furthermore, about a quarter to half of the sex offenders appeared to be intoxicated at the time of the offense. The review results in recommendations for future research. Because of the high prevalence of substance abuse in sex offenders it is advisable to routinely screen for substance abuse and, if necessary, to treat substance abuse. Copyright © 2010 Elsevier Ltd. All rights reserved.

Survivin inhibits anti-growth effect of p53 activated by aurora B

International Nuclear Information System (INIS)

Jung, Ji-Eun; Kim, Tae-Kyung; Lee, Joong-Seob; Oh, Se-Yeong; Kwak, Sungwook; Jin, Xun; Sohn, Jin-Young; Song, Min-Keun; Sohn, Young-Woo; Lee, Soo-Yeon; Pian, Xumin; Lee, Jang-Bo; Chung, Yong Gu; Choi, Young Ki; You, Seungkwon; Kim, Hyunggee

2005-01-01

Genomic instability and apoptosis evasion are hallmarks of cancer, but the molecular mechanisms governing these processes remain elusive. Here, we found that survivin, a member of the apoptosis-inhibiting gene family, and aurora B kinase, a chromosomal passenger protein, were co-overexpressed in the various glioblastoma cell lines and tumors. Notably, exogenous introduction of the aurora B in human BJ cells was shown to decrease cell growth and increase the senescence-associated β-galactosidase activity by activation of p53 tumor suppressor. However, aurora B overexpression failed to inhibit cell proliferation in BJ and U87MG cells transduced with dominant-negative p53 as well as in p53 -/- mouse astrocytes. Aurora B was shown to increase centrosome amplification in the p53 -/- astrocytes. Survivin was shown to induce anchorage-independent growth and inhibit anti-proliferation and drug-sensitive apoptosis caused by aurora B. Overexpression of both survivin and aurora B further accelerated the proliferation of BJ cells. Taken together, the present study indicates that survivin should accelerate tumorigenesis by inhibiting the anti-proliferative effect of p53 tumor suppressor that is activated by aurora B in normal and glioblastoma cells containing intact p53

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China123

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Shannon, Jackilen; King, Irena B; Lampe, Johanna W; Gao, Dao Li; Ray, Roberta M; Lin, Ming-Gang; Stalsberg, Helge; Thomas, David B

2009-01-01

Background: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n–3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n–3 fatty acids with risk of benign fibrocystic breast changes. Objectives: The objectives of the study were to evaluate the role of n–3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. Design: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. Results: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. γ-Linolenic acid (18:3n–6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n–7 saturation index) was inversely associated with risk in all comparisons. Conclusion: Our results support a protective effects of n–3 fatty acid intake and the n–7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer. PMID:19056601

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

NARCIS (Netherlands)

Peters, FTM; Ganesh, S; Kuipers, EJ; De Jager-Krikken, A; Karrenbeld, A; Harms, Geert; Sluiter, WJ; Koudstaal, J; Klinkenberg-Knol, EC; Lamers, CBHW; Kleibeuker, JH

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

Current anti-doping policy: a critical appraisal.

Science.gov (United States)

Kayser, Bengt; Mauron, Alexandre; Miah, Andy

2007-03-29

Current anti-doping in competitive sports is advocated for reasons of fair-play and concern for the athlete's health. With the inception of the World Anti Doping Agency (WADA), anti-doping effort has been considerably intensified. Resources invested in anti-doping are rising steeply and increasingly involve public funding. Most of the effort concerns elite athletes with much less impact on amateur sports and the general public. We review this recent development of increasingly severe anti-doping control measures and find them based on questionable ethical grounds. The ethical foundation of the war on doping consists of largely unsubstantiated assumptions about fairness in sports and the concept of a "level playing field". Moreover, it relies on dubious claims about the protection of an athlete's health and the value of the essentialist view that sports achievements reflect natural capacities. In addition, costly antidoping efforts in elite competitive sports concern only a small fraction of the population. From a public health perspective this is problematic since the high prevalence of uncontrolled, medically unsupervised doping practiced in amateur sports and doping-like behaviour in the general population (substance use for performance enhancement outside sport) exposes greater numbers of people to potential harm. In addition, anti-doping has pushed doping and doping-like behaviour underground, thus fostering dangerous practices such as sharing needles for injection. Finally, we argue that the involvement of the medical profession in doping and anti-doping challenges the principles of non-maleficience and of privacy protection. As such, current anti-doping measures potentially introduce problems of greater impact than are solved, and place physicians working with athletes or in anti-doping settings in an ethically difficult position. In response, we argue on behalf of enhancement practices in sports within a framework of medical supervision. Current anti

Proliferative retinopathy and proteinuria predict mortality rate in type 1 diabetic patients from Fyn County, Denmark

DEFF Research Database (Denmark)

Grauslund, J; Green, A; Sjølie, A K

2008-01-01

AIMS/HYPOTHESIS: We evaluated the effect of diabetic retinopathy on 25 year survival rate among a population-based cohort of type 1 diabetic patients from Fyn County, Denmark. METHODS: In 1973 all diabetic patients from Fyn County, Denmark with onset before the age of 30 years as of 1 July 1973...... were identified (n=727). In 1981, only 627 patients were still alive and resident in Denmark. Of these, 573 (91%) participated in a clinical baseline examination, in which diabetic retinopathy was graded and other markers of diabetes measured. Mortality rate was examined in a 25 year follow....../INTERPRETATION: Proliferative retinopathy and proteinuria predict mortality rate in a population-based cohort of type 1 diabetic patients. In combination they act even more strongly. Non-proliferative diabetic retinopathy did not affect survival rate....

Targeted delivery of anti-tuberculosis drugs to macrophages: targeting mannose receptors

Science.gov (United States)

Filatova, L. Yu; Klyachko, N. L.; Kudryashova, E. V.

2018-04-01

The development of systems for targeted delivery of anti-tuberculosis drugs is a challenge of modern biotechnology. Currently, these drugs are encapsulated in a variety of carriers such as liposomes, polymers, emulsions and so on. Despite successful in vitro testing of these systems, virtually no success was achieved in vivo, because of low accessibility of the foci of infection located in alveolar macrophage cells. A promising strategy for increasing the efficiency of therapeutic action of anti-tuberculosis drugs is to encapsulate the agents into mannosylated carriers targeting the mannose receptors of alveolar macrophages. The review addresses the methods for modification of drug substance carriers, such as liposomes and biodegradable polymers, with mannose residues. The use of mannosylated carriers to deliver anti-tuberculosis agents increases the drug circulation time in the blood stream and increases the drug concentration in alveolar macrophage cells. The bibliography includes 113 references.

Correlation of proliferative and clonogenic tumor cells in multiple myeloma

International Nuclear Information System (INIS)

Karp, J.E.; Burke, P.J.; Saylor, P.L.; Humphrey, R.L.

1984-01-01

To expand on the findings from previous clinical trials that the growth of residual tumor is increased at a predictable time following initial drug administration, malignant plasma cells from bone marrows of patients with multiple myeloma (MM) were examined for changes in proliferation and clonogenicity induced in vivo by cyclophosphamide and in vitro by drug-induced humoral stimulatory activity. Peak plasma cell [ 3 H]thymidine labeling index (LI) occurred predictably following drug and paralleled changes in agar colony formation by marrow cells obtained during therapy. Colony-forming capacity of pretreatment MM marrow populations was enhanced when those cells were cultured with humoral stimulatory activity, similar to the increased colony formation detected in Day 9 postcyclophosphamide marrows at the time of peak plasma cell LI. To further define a relationship between proliferative plasma cells and colony-forming tumor cells, MM marrows were fractionated by sedimentation on an isokinetic gradient. Enrichment of a proliferative tumor cell cohort was achieved, evidenced by [ 3 H]thymidine LI. Colony-forming cells were also enriched by isokinetic gradient sedimentation, and agar colony formation by MM marrow cell fractions correlated with the kinetic characteristics of the isolated subpopulations. These studies of whole and fractionated human MM marrow cell populations suggest that the kinetically active cells which are induced to proliferate in vivo and in vitro are closely related to the clonogenic tumor cells which produce colonies in agar and which, like those cells measured by [ 3 H]thymidine LI, respond to growth stimulation by drug-induced humoral stimulatory activity

Easy labeling of proliferative phase and sporogonic phase of microsporidia Nosema bombycis in host cells.

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Jie Chen

Full Text Available Microsporidia are eukaryotic, unicellular parasites that have been studied for more than 150 years. These organisms are extraordinary in their ability to invade a wide range of hosts including vertebrates and invertebrates, such as human and commercially important animals. A lack of appropriate labeling methods has limited the research of the cell cycle and protein locations in intracellular stages. In this report, an easy fluorescent labeling method has been developed to mark the proliferative and sporogonic phases of microsporidia Nosema bombycis in host cells. Based on the presence of chitin, Calcofluor White M2R was used to label the sporogonic phase, while β-tubulin antibody coupled with fluorescence secondary antibody were used to label the proliferative phase by immunofluorescence. This method is simple, efficient and can be used on both infected cells and tissue slices, providing a great potential application in microsporidia research.

Anti-inflammatory and anti-allergic properties of the essential oil and active compounds from Cordia verbenacea.

Science.gov (United States)

Passos, Giselle F; Fernandes, Elizabeth S; da Cunha, Fernanda M; Ferreira, Juliano; Pianowski, Luiz F; Campos, Maria M; Calixto, João B

2007-03-21

The anti-inflammatory and anti-allergic effects of the essential oil of Cordia verbenacea (Boraginaceae) and some of its active compounds were evaluated. Systemic treatment with the essential oil of Cordia verbenacea (300-600mg/kg, p.o.) reduced carrageenan-induced rat paw oedema, myeloperoxidase activity and the mouse oedema elicited by carrageenan, bradykinin, substance P, histamine and platelet-activating factor. It also prevented carrageenan-evoked exudation and the neutrophil influx to the rat pleura and the neutrophil migration into carrageenan-stimulated mouse air pouches. Moreover, Cordia verbenacea oil inhibited the oedema caused by Apis mellifera venom or ovalbumin in sensitized rats and ovalbumin-evoked allergic pleurisy. The essential oil significantly decreased TNFalpha, without affecting IL-1beta production, in carrageenan-injected rat paws. Neither the PGE(2) formation after intrapleural injection of carrageenan nor the COX-1 or COX-2 activities in vitro were affected by the essential oil. Of high interest, the paw edema induced by carrageenan in mice was markedly inhibited by both sesquiterpenic compounds obtained from the essential oil: alpha-humulene and trans-caryophyllene (50mg/kg, p.o.). Collectively, the present results showed marked anti-inflammatory effects for the essential oil of Cordia verbenacea and some active compounds, probably by interfering with TNFalpha production. Cordia verbenacea essential oil or its constituents might represent new therapeutic options for the treatment of inflammatory diseases.

Cdc6 is a rate-limiting factor for proliferative capacity during HL60 cell differentiation

International Nuclear Information System (INIS)

Barkley, Laura R.; Hong, Hye Kyung; Kingsbury, Sarah R.; James, Michelle; Stoeber, Kai; Williams, Gareth H.

2007-01-01

The DNA replication (or origin) licensing pathway represents a critical step in cell proliferation control downstream of growth signalling pathways. Repression of origin licensing through down-regulation of the MCM licensing factors (Mcm2-7) is emerging as a ubiquitous route for lowering proliferative capacity as metazoan cells exit the cell division cycle into quiescent, terminally differentiated and senescent 'out-of-cycle' states. Using the HL60 monocyte/macrophage differentiation model system and a cell-free DNA replication assay, we have undertaken direct biochemical investigations of the coupling of origin licensing to the differentiation process. Our data show that down-regulation of the MCM loading factor Cdc6 acts as a molecular switch that triggers loss of proliferative capacity during early engagement of the somatic differentiation programme. Consequently, addition of recombinant Cdc6 protein to in vitro replication reactions restores DNA replication competence in nuclei prepared from differentiating cells. Differentiating HL60 cells over-expressing either wild-type Cdc6 or a CDK phosphorylation-resistant Cdc6 mutant protein (Cdc6A4) exhibit an extended period of cell proliferation compared to mock-infected cells. Notably, differentiating HL60 cells over-expressing the Cdc6A4 mutant fail to down-regulate Cdc6 protein levels, suggesting that CDK phosphorylation of Cdc6 is linked to its down-regulation during differentiation and the concomitant decrease in cell proliferation. In this experimental model, Cdc6 therefore plays a key role in the sequential molecular events leading to repression of origin licensing and loss of proliferative capacity during execution of the differentiation programme

Endothelial cell-based methods for the detection of cyanobacterial anti-inflammatory and wound-healing promoting metabolites.

Science.gov (United States)

Wiesner, Christoph; Kopecky, Jiri; Pflueger, Maren; Hundsberger, Harald; Entler, Barbara; Kleber, Christoph; Atzler, Josef; Hrouzek, Pavel; Stys, Dalibor; Lukesova, Alena; Schuett, Wolfgang; Lucas, Rudolf

2007-12-01

Acute lung injury is accompanied by an increased endothelial chemokine production and adhesion molecule expression, which may result in an extensive neutrophil infiltration. Moreover, a destruction of the alveolar epithelium and capillary endothelium may result in permeability edema. As such, the search for novel anti-inflammatory substances, able to downregulate these parameters as well as the tissue damage holds therapeutic promise. We therefore describe here the use of human endothelial cell-based in vitro assays for the detection of anti-inflammatory and wound-healing metabolites from cyanobacteria.

QSAR pre-screen of 70,983 substances for genotoxic carcinogenicity, mutagenicity and developmental toxicity in the EU FP7 project ChemScreen

DEFF Research Database (Denmark)

Wedebye, Eva Bay; Dybdahl, Marianne; Nikolov, Nikolai Georgiev

2014-01-01

be performed in REACH on known genotoxic carcinogens or germ cell mutagens with appropriate risk management measures implemented, a QSAR pre-screen for genotoxic carcinogenicity, germ cell mutagenicity and (limited) developmental toxicity was included in the project. Predictions for estrogenic and anti...... algorithms were applied to combine the predictions from the individual models to reach overall predictions for genotoxic carcinogenicity, germ cell mutagenicity and developmental toxicity. Furthermore, the full list of REACH pre-registered substances (143,835) was searched for substances containing certain...

Developmental control of transcriptional and proliferative potency during the evolutionary emergence of animals

Science.gov (United States)

Arenas-Mena, Cesar; Coffman, James A.

2016-01-01

Summary It is proposed that the evolution of complex animals required repressive genetic mechanisms for controlling the transcriptional and proliferative potency of cells. Unicellular organisms are transcriptionally potent, able to express their full genetic complement as the need arises through their life cycle, whereas differentiated cells of multicellular organisms can only express a fraction of their genomic potential. Likewise, whereas cell proliferation in unicellular organisms is primarily limited by nutrient availability, cell proliferation in multicellular organisms is developmentally regulated. Repressive genetic controls limiting the potency of cells at the end of ontogeny would have stabilized the gene expression states of differentiated cells and prevented disruptive proliferation, allowing the emergence of diverse cell types and functional shapes. We propose that distal cis-regulatory elements represent the primary innovations that set the stage for the evolution of developmental gene regulatory networks and the repressive control of key multipotency and cell-cycle control genes. The testable prediction of this model is that the genomes of extant animals, unlike those of our unicellular relatives, encode gene regulatory circuits dedicated to the developmental control of transcriptional and proliferative potency. PMID:26173445

Current Status of Doping in Japan Based on Japan Anti-Doping Disciplinary Panels of the Japan Anti-Doping Agency (JADA): A Suggestion on Anti-Doping Activities by Pharmacists in Japan.

Science.gov (United States)

Imanishi, Takashi; Kawabata, Takayoshi; Takayama, Akira

2017-01-01

In 2009, the Japan Anti-Doping Agency (JADA) established the "Sports Pharmacist Accreditation Program" to prevent doping in sports. Since then, anti-doping activities in Japan have been attracting attention. In this study, we investigated research about the current status of doping from 2007 to 2014 in Japan to make anti-doping activities more concrete, and we also discussed future anti-doping activities by pharmacists. In Japan, bodybuilding was the sporting event with the highest number and rate of doping from 2007 to 2014. Many of the positive doping cases were detected for class S1 (anabolic agents), S5 (diuretics and masking agents), and S6 (stimulants). Within class S1, supplements were the main cause of positive doping. Within class S5, medicines prescribed by medical doctors were the main cause of positive doping. Within class S6, non-prescription medicines (e.g., OTC) were the main cause of positive doping. When we looked at the global statistics on doping, many of the positive doping cases were detected for class S1. On comparing the Japanese statistics with the global statistics, the rate of positive doping caused by class S1 was significantly lower, but that caused by classes S5 and S6 was significantly higher in Japan than in the world. In conclusion, pharmacists in Japan should pay attention to class S1, S5, and S6 prohibited substances and to the sport events of bodybuilding. Based on this study, sports pharmacists as well as common pharmacists should suggest new anti-doping activities to prevent doping in the future.

National All Schedules Prescription Electronic Reporting Act (NASPER): balancing substance abuse and medical necessity.

Science.gov (United States)

Manchikanti, Laxmaiah; Brown, Keith R; Singh, Vijay

2002-07-01

The National All Schedules Prescription Electronic Reporting Act, or NASPER, is a bill proposed by the American Society of Interventional Pain Physicians to provide and improve patient access with quality care, and protect patients and physicians from deleterious effects of controlled substance misuse, abuse and trafficking. Controlled prescription drugs, including narcotic analgesics, anxiolytics, anti-depressants, stimulants, and sedative-hypnotics play a significant and legitimate role in interventional pain management practices in managing chronic pain and related disorders. Based on the 1997 household survey on drug abuse it is estimated that 76.9 million Americans had used an illicit drug at least once in their life. In 1997, 4.2 million people used analgesics, 2.1 million used tranquillizers, and an additional 2.3 million people used various other drugs, including sedatives, tranquillizers, etc. The non-medical use of prescription drugs exceeds that of all illicit substances except for marijuana and hashish. The report on epidemiology trends in drug abuse, based on community epidemiology work group analysis showed continued increase of abuse of prescription drugs in urban, suburban, and rural areas. The most commonly abused drugs include oxycodone, hydrocodone, hydromorphone, morphine, codeine, clonazepam, alprazolam, lorazepam, diazepam and carisoprodol. The diversion of prescription controlled substances to illicit channels is a public health and safety issue. This review describes the role of controlled substances in chronic pain management, prevalence and economic impact of controlled substance abuse, prescription accountability, effectiveness of prescription monitoring programs, and rationale for national controlled substance electronic reporting system.

Synthetic Receptors Induce Anti Angiogenic and Stress Signaling on Human First Trimester Cytotrophoblast Cells

Directory of Open Access Journals (Sweden)

Ahmed F. Pantho

2017-05-01

Full Text Available The cytotrophoblast (CTB cells of the human placenta have membrane receptors that bind certain cardiotonic steroids (CTS found in blood plasma. One of these, marinobufagenin, is a key factor in the etiology of preeclampsia. Herein, we used synthetic receptors (SR to study their effectiveness on the angiogenic profile of human first trimester CTB cells. The humanextravillous CTB cells (Sw.71 used in this study were derived from first trimester chorionic villus tissue. Culture media of CTB cells treated with ≥1 nM SR level revealed sFlt-1 (Soluble fms-like tyrosine kinase-1 was significantly increased while VEGF (vascular endothelial growth factor was significantly decreased in the culture media (* p < 0.05 for each The AT2 receptor (Angiotensin II receptor type 2 expression was significantly upregulated in ≥1 nM SR-treated CTB cells as compared to basal; however, the AT1 (Angiotensin II receptor, type 1 and VEGFR-1 (vascular endothelial growth factor receptor 1 receptor expression was significantly downregulated (* p < 0.05 for each. Our results show that the anti-proliferative and anti-angiogenic effects of SR on CTB cells are similar to the effects of CTS. The observed anti angiogenic activity of SR on CTB cells demonstrates that the functionalized-urea/thiourea molecules may be useful as potent inhibitors to prevent CTS-induced impairment of CTB cells.

Nanodiamonds as Carriers for Address Delivery of Biologically Active Substances

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Petunin AI

2010-01-01

Full Text Available Abstract Surface of detonation nanodiamonds was functionalized for the covalent attachment of immunoglobulin, and simultaneously bovine serum albumin and Rabbit Anti-Mouse Antibody. The nanodiamond-IgGI125 and RAM-nanodiamond-BSAI125 complexes are stable in blood serum and the immobilized proteins retain their biological activity. It was shown that the RAM-nanodiamond-BSAI125 complex is able to bind to the target antigen immobilized on the Sepharose 6B matrix through antibody–antigen interaction. The idea can be extended to use nanodiamonds as carriers for delivery of bioactive substances (i.e., drugs to various targets in vivo.

An overview of anti-diabetic plants used in Gabon: Pharmacology and toxicology.

Science.gov (United States)

Bading Taika, B; Bouckandou, M; Souza, A; Bourobou Bourobou, H P; MacKenzie, L S; Lione, L

2018-04-24

The management of diabetes mellitus management in African communities, especially in Gabon, is not well established as more than 60% of population rely on traditional treatments as primary healthcare. The aim of this review was to collect and present the scientific evidence for the use of medicinal plants that are in currect by Gabonese traditional healers to manage diabetes or hyperglycaemia based here on the pharmacological and toxicological profiles of plants with anti-diabetic activity. There are presented in order to promote their therapeutic value, ensure a safer use by population and provide some bases for further study on high potential plants reviewed. Ethnobotanical studies were sourced using databases such as Online Wiley library, Pubmed, Google Scholar, PROTA, books and unpublished data including Ph.D. and Master thesis, African and Asian journals. Keywords including 'Diabetes', 'Gabon', 'Toxicity', 'Constituents', 'hyperglycaemia' were used. A total of 69 plants currently used in Gabon with potential anti-diabetic activity have been identified in the literature, all of which have been used in in vivo or in vitro studies. Most of the plants have been studied in human or animal models for their ability to reduce blood glucose, stimulate insulin secretion or inhibit carbohydrates enzymes. Active substances have been identified in 12 out of 69 plants outlined in this review, these include Allium cepa and Tabernanthe iboga. Only eight plants have their active substances tested for anti-diabetic activity and are suitables for further investigation. Toxicological data is scarce and is dose-related to the functional parameters of major organs such as kidney and liver. An in-depth understanding on the pharmacology and toxicology of Gabonese anti-diabetic plants is lacking yet there is a great scope for new treatments. With further research, the use of Gabonese anti-diabetic plants is important to ensure the safety of the diabetic patients in Gabon. Copyright �

A method and apparatus for preparing the storage of noxious substances, in particular radioactive substances

International Nuclear Information System (INIS)

1974-01-01

The invention relates to the storage of radioactive substances. It deals with a method for storing a substance, in particular a noxious or radioactive substance, comprising trapping said substance in a solid substance by bombarding said solid substance with ions of the above substance, so that the latter reaches a certain concentration level in the solid substance. This is applicable to the storage of radioactive wastes [fr

Effect of postradiation bleeding on proliferative activity of cells in small intestine crypts of rats

Energy Technology Data Exchange (ETDEWEB)

Petrovic, N V [Institut za Nuklearne Nauke Boris Kidric, Vinca (Yugoslavia)

1975-12-01

The effect of postradiation bleeding on the dynamics of duodenal crypt's cell proliferation in rats was studied. The animals, females, three months old, weighing 170 or 180 g, were exposed to radiation of 800 R (115 R/min) and immediately after irradiation were bled by cardiac puncture to 50% of total blood volume. Proliferative activity of duodenal epithelium cells was monitored for a period of five days after irradiation. For control purposes normal, irradiated and only bled animals were used. The results demonstrated that although there are no significant differences in proliferative activity of duodenal epithelium cells in irradiated and bled animals and only irradiated animals, the postradiation reparative processes in irradiated and bled animals is considerably more stable. It is considered that bleeding itself by its hypoxic activity reduced the sensitivity of epithelium to the dose of radiation used. On the other hand, bleeding removed the damaging agents which appear after total body irradiation.

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

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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

[Effect of internal limiting membrane peeling on morpho-functional state of the retina in patients with proliferative diabetic retinopathy (preliminary report)].

Science.gov (United States)

Bikbov, M M; Fayzrakhmanov, R R; Kalanov, M R

2018-01-01

To compare morpho-functional parameters of retina during vitrectomy with and without internal limiting membrane (ILM) peeling in patients with proliferative diabetic retinopathy. The study included 55 patients (55 eyes) that had underwent vitreoretinal surgery in the setting of antivasoproliferative therapy for proliferative diabetic retinopathy. Patients of the 1 st group (n=27) underwent vitrectomy with silicone tamponade, 2 nd group (n=28) received similar treatment with the addition of ILM peeling. Three months after the treatment, all patients had silicone oil removed. Best Corrected Visual Acuity before treatment was 0.06±0.02 in both groups; after the treatment it improved to 0.1±0.05 (ppeeling during vitrectomy with following silicone oil tamponade eliminates the risk of ERM formation in patients with proliferative diabetic retinopathy in the follow-up period of up to 6-month and results in better morpho-functional parameters in comparison with patients who received similar treatment but without peeling.

The proliferative human monocyte subpopulation contains osteoclast precursors

Science.gov (United States)

Lari, Roya; Kitchener, Peter D; Hamilton, John A

2009-01-01

Introduction Immediate precursors of bone-resorbing osteoclasts are cells of the monocyte/macrophage lineage. Particularly during clinical conditions showing bone loss, it would appear that osteoclast precursors are mobilized from bone marrow into the circulation prior to entering tissues undergoing such loss. The observed heterogeneity of peripheral blood monocytes has led to the notion that different monocyte subpopulations may have special or restricted functions, including as osteoclast precursors. Methods Human peripheral blood monocytes were sorted based upon their degree of proliferation and cultured in macrophage colony-stimulating factor (M-CSF or CSF-1) and receptor activator of nuclear factor-kappa-B ligand (RANKL). Results The monocyte subpopulation that is capable of proliferation gave rise to significantly more multinucleated, bone-resorbing osteoclasts than the bulk of the monocytes. Conclusions Human peripheral blood osteoclast precursors reside in the proliferative monocyte subpopulation. PMID:19222861

APPROACHES TO THE CONSTRUCTION OF THE VITRECTOMY RISK MANAGEMENT SYSTEM IN PATIENTS WITH PROLIFERATIVE DIABETIC RETINOPATHY

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A. M. Ruban

2016-08-01

Full Text Available The article presents the some approaches to create a system support of making decision during vitrectomy in patients with diabetic proliferative retinopathy, promotes objective assessment of individual risk-management for patient and allows optimize ophthalmological care for them.

Questions of fairness and anti-doping in US cycling: The contrasting experiences of professionals and amateurs

Science.gov (United States)

Henning, April D.; Dimeo, Paul

2015-01-01

Abstract The focus of researchers, media and policy on doping in cycling is often limited to the professional level of the sport. However, anti-doping test results since 2001 demonstrate that banned substances are also used by US cyclists at lower levels of the sport, necessitating a broader view of the patterns and motivations of substance use within the sport. In this article, we describe and explain the doping culture that has emerged in domestic US cycling among amateur and semi-professionals. Through analysis of records from sports governing bodies and journalistic reports, we assess the range of violation types and discuss the detection and punishing of riders who were not proven to have intended to cheat but became “collateral damage” in the war on doping. We argue that the phenomenon of doping is more complex than what has been shown to occur in elite sport, as it includes a wider variety of behaviours, situations and motivations. We develop fresh insights by examining cases where doping has been accidental, intrinsically motivated, non-performance enhancing or the result of prescribed medical treatments banned by anti-doping authorities. Such trends call into question the fairness of anti-doping measures, and we discuss the possibility of developing localised solutions to testing and sanctioning amateur athletes. PMID:26692658

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...

The anti-inflammatory activity of dillapiole and some semisynthetic analogues.

Science.gov (United States)

Parise-Filho, Roberto; Pastrello, Michelli; Pereira Camerlingo, Carla Emygdio; Silva, Gisele Juni; Agostinho, Leonardo Aguiar; de Souza, Thaís; Motter Magri, Fátima Maria; Ribeiro, Roberto Rodrigues; Brandt, Carlos Alberto; Polli, Michelle Carneiro

2011-11-01

Piper aduncum L. (Piperaceae) produces an essential oil (dillapiole) with great exploitative potential and it has proven effects against traditional cultures of phytopathogens, such as fungi, bacteria and mollusks, as well as analgesic action with low levels of toxicity. This study investigated the in vivo anti-inflammatory activity of dillapiole. Furthermore, in order to elucidate its structure-anti-inflammatory activity relationship (SAR), semisynthetic analogues were proposed by using the molecular simplification strategy. Dillapiole and safrole were isolated and purified using column chromatography. The semisynthetic analogues were obtained by using simple organic reactions, such as catalytic reduction and isomerization. All the analogues were purified by column chromatography and characterized by (1)H and (13)C NMR. The anti-inflammatory activities of dillapiole and its analogues were studied in carrageenan-induced rat paw edema model. Dillapiole and di-hydrodillapiole significantly (p<0.05) inhibited rat paw edema. All the other substances tested, including safrole, were less powerful inhibitors with activities inferior to that of indomethacin. These findings showed that dillapiole and di-hydrodillapiole have moderate anti-phlogistic properties, indicating that they can be used as prototypes for newer anti-inflammatory compounds. Structure-activity relationship studies revealed that the benzodioxole ring is important for biological activity as well as the alkyl groups in the side chain and the methoxy groups in the aromatic ring.

Effect of BCAA intake during endurance exercises on fatigue substances, muscle damage substances, and energy metabolism substances.

Science.gov (United States)

Kim, Dong-Hee; Kim, Seok-Hwan; Jeong, Woo-Seok; Lee, Ha-Yan

2013-12-01

The increase rate of utilization of branched-chain amino acids (BCAA) by muscle is reduced to its plasma concentration during prolonged exercise leading to glycogen. BCAA supplementation would reduce the serum activities of intramuscular enzymes associated with muscle damage. To examine the effects of BCAA administration on fatigue substances (serotonin, ammonia and lactate), muscle damage substances (CK and LDH) and energy metabolism substances (FFA and glucose) after endurance exercise. Subjects (n = 26, college-aged males) were randomly divided into an experimental (n = 13, EXP) and a placebo (n = 13, CON) group. Subjects both EXP and CON performed a bout of cycle training (70% VO2max intensity) to exhaustion. Subject in the EXP were administrated BCAA (78ml/kg·w) prior to the bout of cycle exercise. Fatigue substances, muscle damage substances and energy metabolism substances were measured before ingesting BCAAs and placebos, 10 min before exercise, 30 min into exercise, immediately after exercise, and 30 min after exercise. Data were analyzed by two-way repeated measure ANCOVA, correlation and statistical significance was set at p BCAA decreased serum concentrations of the intramuscular enzymes as CK and LDH following exhaustive exercise. This observation suggests that BCAA supplementation may reduce the muscle damage associated with endurance exercise.

Characteristics of indomethacin-saccharin (IMC-SAC) co-crystals prepared by an anti-solvent crystallization process.

Science.gov (United States)

Chun, Nan-Hee; Wang, In-Chun; Lee, Min-Jeong; Jung, Yun-Taek; Lee, Sangkil; Kim, Woo-Sik; Choi, Guang J

2013-11-01

The creation of co-crystals of various insoluble drug substances has been extensively investigated as a promising approach to improve their pharmaceutical performance. In this study, co-crystal powders of indomethacin and saccharin (IMC-SAC) were prepared by an anti-solvent (water) addition and compared with co-crystals by evaporation method. No successful synthesis of a pharmaceutical co-crystal powder via an anti-solvent approach has been reported. Among solvents examined, methanol was practically the only one that resulted in the formation of highly pure IMC-SAC co-crystal powders by anti-solvent approach. The mechanism of a preferential formation of IMC-SAC co-crystal to IMC was explained with two aspects: phase solubility diagram and solution complexation concept. Accordingly, the anti-solvent approach can be considered as a competitive route for producing pharmaceutical co-crystal powders with acceptable properties. Copyright © 2013 Elsevier B.V. All rights reserved.

Analysis of the proliferative potential of odontogenic epithelial cells of pericoronal follicles.

Science.gov (United States)

Cimadon, Natalia; Lauxen, Isabel Silva; Carrard, Vinicius Coelho; Sant'Ana Filho, Manoel; Rados, Pantelis Varvaki; Oliveira, Márcia Gaiger

2014-11-01

To evaluate the proliferative potential and the cell proliferation rate of odontogenic epithelial cells. Forty-two cases of pericoronal follicles of impacted third molars were submitted to silver impregnation technique for quantification of argyrophilic nucleolar organizer regions (AgNOR) and immunohistochemical staining for EGFR and Ki-67. For AgNOR quantification, the mean number of active nucleolar organizer regions per nucleus (mAgNOR) and the percentage of cells with 1, 2, 3 and 4 or more AgNORs per nucleus (pAgNOR) were quantified. Ki-67 immunolabeling was quantified, whereas for EGFR, a descriptive analysis of staining patterns (membrane, cytoplasm or membrane + cytoplasm positivity) was performed. We evaluated the reduced epithelium of the enamel organ and/or islands of odontogenic epithelium present in the entire connective tissue. mAgNOR were 1.43 (1.0-2.42) and were significantly different among pericoronary follicles from upper and lower teeth (p = 0.041). Immunostaining of Ki-67 was negative in all cases. EGFR immunolabeling was found mainly in the cytoplasm and was more intense in islands and cords when compared to reduced epithelium of the enamel organ. Odontogenic epithelial cells of some pericoronal follicles have proliferative potential, suggesting their association with the development of odontogenic lesions. The authors suggest that nonerupted, especially of the lower teeth, should be monitored and if necessary removed.

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

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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

MANAJEMEN KURIKULUM DALAM PERSPEKTIF ANTI-RADIKALISME

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Kisbiyanto Kisbiyanto

2016-02-01

Full Text Available The curriculum management in the college of Islamic religious affairs (PTKIN has a strategic role in achieving the vision of the implementation of the higher education especially in Indonesia that has the majority muslim population. PTKIN is responsible in the development of religious harmony and transform the Islamic values that peace and anti-radicalism. The purpose of this research is: (1 designing the Islamic education policy in anti-radicalism perspective at STAIN Kudus; (2 the contents of the curriculum for Islamic education anti-radicalism perspective in STAIN Kudus. This research is used qualitative approach. The data collected by the documentation technique and the triangulation validity. Data analysis by interactive. The results of this research is: (1 Curriculum planning policy Islamic Education department STAIN Kudus is arrangement periodically start from the curriculum 1997, 2003, and 2008. The three periods of curriculum is re-arrange and evaluated by involve the lecturers and experts. This curriculum pattern is called curriculum corelated approach; it is classified from one family courses. This means that the curriculum 2008 is not the curriculum with subject pattern matte curriculum aproach, it emphasizes on courses in a separate settlements. The elective courses is clasified into five groups, namely personality development courses (MPK, scholarly and skills (MKK, courses work (MKB, behavior courses work (MPB, social life courses (MBB. (2 The Islamic education curriculum substance is spread in almost all courses and content on the tendency of the anti-radicalism curriculum and learning, it is a Islamic movements and discourse that give education and peacefull dakwah as a prior, tolerance, humanity, and respect differences as a mercy for the universe.

[Evaluation of anti-inflammatory activity of extracts from Siberian plants].

Science.gov (United States)

Nesterova, Iu V; Povet'eva, T N; Aksinenko, S G; Suslov, N I; Gaĭdamovich, N N; Nagorniak, Iu G; Popova, E V; Kravtsova, S S; Andreeva, T I

2009-01-01

Experimental investigations have shown that water-alcohol extracts from plants containing alkaloids (Aconitum baikalense, Aconitum septentrionale, Delphinium elatum L., Conium maculatum) and salicylic acid (Filipendula ulmaria, Salix viminalis, Fragaria vesca, Rubus idaeus) inhibited the development of main symptoms of inflammation, viz. exudation, pain, fever, to the same extent as non-steroidal anti-inflammatory agents. The substances studied in this work may be used to develop new efficient pharmacological preparations for the treatment of different inflammatory conditions associated with severe pain syndrome.

MO-AB-BRA-06: Dynamic FLT PET for Investigating Potential Synergistic Therapeutic Targets During Anti-Angiogenic Treatment

Energy Technology Data Exchange (ETDEWEB)

Scarpelli, M; Perlman, S; Liu, G [University of Wisconsin-Madison, Madison, WI (United States); Simoncic, U [Jozef Stefan Institute, Ljubljana (Slovenia); Jeraj, R [University of Wisconsin-Madison, Madison, WI (United States); Jozef Stefan Institute, Ljubljana (Slovenia)

2016-06-15

Purpose: Novel treatment strategies for metastatic cancer patients involve synergistically combining treatments with the hope of improving outcomes. This study investigated changes in tumor proliferative and vascular characteristics derived from dynamic [F-18]FLT PET during antiangiogenic treatment with the goal of identifying synergistic treatment opportunities. Methods: Patients with various solid cancers underwent continuous three-week cycles of anti-angiogenic treatment with intermittent dosing (two-weeks-on/one-week-off). Patients received up to six dynamic FLT PET/CT scans (days 0, 14, and 21 of cycle 1 (C1) and cycle 3 (C3)). Tumor proliferative (Kflt, net uptake rate) and vascular parameters (K1 blood-to-tissue transfer; Vb, vascular fraction) were calculated using a two-tissue compartment four-rate parameter kinetic model. Relative changes in these parameters, from day 0 to 14 (TxResp) and day 14 to 21 (offTxResp), were calculated. Significant differences were tested using Wilcoxon signed-rank test and significant correlations were tested using Spearman correlation. Results: Thirty patients were evaluable for C1 offTxResp with median values for Kflt, K1, and Vb of +30%, +35% and +30%, respectively. The fractions of patients with positive C1 offTxResp were: 21/30 for Ki, 24/30 for K1, 21/30 for Vb, and 12/30 had positive offTxResp for all three kinetic parameters. The offTxResp in C3 was not significantly different from C1 for any of the kinetic parameters. Significant correlations were found between TxResp and offTxResp in C1 for Kflt (ρ=-0.52, p=0.014), K1 (ρ=−0.61, p=0.003) and Vb (ρ=−0.80, p<0.001). Similar correlations were found for Kflt (ρ=-1, p=0.017) and K1 (ρ=−1, p=0.017) for the five patients evaluable in C3. Conclusion: Dynamic FLT PET showed evidence of distinct vascular and proliferative increases during off treatment weeks that could potentially be targeted with synergistic therapy. Early changes in kinetic parameters were

Post-proliferative immature radial glial cells female-specifically express aromatase in the medaka optic tectum.

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Akio Takeuchi

Full Text Available Aromatase, the key enzyme responsible for estrogen biosynthesis, is present in the brain of all vertebrates. Much evidence has accumulated that aromatase is highly and exclusively expressed in proliferating mature radial glial cells in the brain of teleost fish even in adulthood, unlike in other vertebrates. However, the physiological significance of this expression remains unknown. We recently found that aromatase is female-specifically expressed in the optic tectum of adult medaka fish. In the present study, we demonstrated that, contrary to the accepted view of the teleost brain, female-specific aromatase-expressing cells in the medaka optic tectum represent a transient subset of post-proliferative immature radial glial cells in the neural stem cell lineage. This finding led us to hypothesize that female-specific aromatase expression and consequent estrogen production causes some sex difference in the life cycle of tectal cells. As expected, the female tectum exhibited higher expression of genes indicative of cell proliferation and radial glial maturation and lower expression of an anti-apoptotic gene than did the male tectum, suggesting a female-biased acceleration of the cell life cycle. Complicating the interpretation of this result, however, is the additional observation that estrogen administration masculinized the expression of these genes in the optic tectum, while simultaneously stimulating aromatase expression. Taken together, these results provide evidence that a unique subpopulation of neural stem cells female-specifically express aromatase in the optic tectum and suggest that this aromatase expression and resultant estrogen synthesis have an impact on the life cycle of tectal cells, whether stimulatory or inhibitory.

Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate

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Kenichiro Ishii

2018-04-01

Full Text Available Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers.

PECULIARITIES OF PROLIFERATIVE ACTIVITY OF CERVICAL SQUAMOUS CANCER IN HIV INFECTION.

Science.gov (United States)

Lytvynenko, M; Shkolnikov, V; Bocharova, T; Sychova, L; Gargin, V

2017-09-01

Patients with human immunodeficiency virus (HIV) infection have a statistically significant increased risk of developing cervical cancer. The expression of the human Ki-67 protein is strictly associated with cell proliferation. The purpose of our work was detection of proliferative activity in cervical squamous cancer in women with HIV infection. We investigated 24 cases (12 patients with HIV and 12 patients without HIV infection) of cervical carcinoma, where biopsy had been performed before the treatment. According to histopathological diagnoses, well-differentiated, moderately and poorly differentiated squamous cell carcinoma (7, 13 and 4 cases respectively) was determined. Mean age of women in the group with HIV infection was 32.7 years, and 38.2 years in the group without HIV infection. Detection of protein Ki-67 expression was performed with nuclear staining in the intermediate and superficial cells. The results of this work show that proliferative activity of cervical squamous cancer in women with HIV infection is characterized by a higher level of Ki-67 with averaging level for all histological types of squamous cell carcinoma 62.5±5.6% that is one and half times higher than in group without HIV infection. Depending on a histological type, expression of Ki-67 has increased from 4.7±3.8% in well-differentiated squamous cell carcinoma up to 89.2±5.1% in poorly differentiated squamous cell carcinoma for group with HIV, and from 21.3±2.4% to 79.4±3.7 in group without HIV.

Sexual orientation, substance use behaviors and substance dependence in the United States

Science.gov (United States)

McCabe, Sean Esteban; Hughes, Tonda L.; Bostwick, Wendy B.; West, Brady T.; Boyd, Carol J.

2009-01-01

Aims To assess past-year prevalence rates of substance use behaviors and substance dependence across three major dimensions of sexual orientation (identity, attraction, and behavior) in a large national sample of adult women and men in the United States. Design Data were collected from structured diagnostic face-to-face interviews using the Alcohol Use Disorder and Associated Disabilities Interview Schedule DSM-IV Version (AUDADIS-IV). Setting Prevalence estimates were based on data collected from the 2004–2005 (Wave 2) National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Participants A large national sample of 34,653 adults aged 20 years and older: 52% female, 71% White, 12% Hispanic, 11% African American, 4% Asian, and 2% Native American or other racial/ethnic categories. Findings Approximately 2% of the sample self-identified as lesbian, gay or bisexual; 4% reported at least one lifetime same-sex sexual partner, and 6% reported same-sex sexual attraction. Although non-heterosexual orientation was generally associated with a higher risk of substance use and substance dependence, the majority of sexual minority respondents did not report substance use or meet criteria for DSM-IV substance dependence. There was considerable variation in substance use outcomes across sexual orientation dimensions; these variations were more pronounced among women than among men. Conclusions Results support previous research findings of heightened risk of substance use and substance dependence among some sexual minority groups and point to the need for research that examines reasons for such differences. Results also highlight important gender differences and question previous findings indicating uniformly higher risk for substance dependence among sexual minorities. Risks appear to vary based on gender and how sexual orientation is defined. Findings have implications for prevention and intervention efforts that more effectively target subgroups at greatest

Anti-Dengue Virus Constituents from Formosan Zoanthid Palythoa mutuki

Science.gov (United States)

Lee, Jin-Ching; Chang, Fang-Rong; Chen, Shu-Rong; Wu, Yu-Hsuan; Hu, Hao-Chun; Wu, Yang-Chang; Backlund, Anders; Cheng, Yuan-Bin

2016-01-01

A new marine ecdysteroid with an α-hydroxy group attaching at C-4 instead of attaching at C-2 and C-3, named palythone A (1), together with eight known compounds (2–9) were obtained from the ethanolic extract of the Formosan zoanthid Palythoa mutuki. The structures of those compounds were mainly determined by NMR spectroscopic data analyses. The absolute configuration of 1 was further confirmed by comparing experimental and calculated circular dichroism (CD) spectra. Anti-dengue virus 2 activity and cytotoxicity of five isolated compounds were evaluated using virus infectious system and [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assays, respectively. As a result, peridinin (9) exhibited strong antiviral activity (IC50 = 4.50 ± 0.46 μg/mL), which is better than that of the positive control, 2′CMC. It is the first carotene-like substance possessing anti-dengue virus activity. In addition, the structural diversity and bioactivity of the isolates were compared by using a ChemGPS–NP computational analysis. The ChemGPS–NP data suggested natural products with anti-dengue virus activity locate closely in the chemical space. PMID:27517937

Proliferative diabetic retinopathy after vitrectomy early factors affect IOP

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Shi-Bo Liu

2013-05-01

Full Text Available AIM:To explore possible causes of early postoperative elevated intraocular pressure caused by proliferative diabetic retinopathy(PDRvitrectomy. METHODS:Totally 72 cases(100 eyeswhich have performed vitrectomy for proliferative diabetic retinopathy were retrospectively analyzed to observe the incidence of postoperative ocular hypertension, and the relevant factors that caused postoperative high intraocular pressure were statistically analyzed. Early postoperative ocular hypertension diagnostic criteria: any time after 2 weeks of non-contact tonometer measured IOP> 25mmHg(1mmHg=0.133kPa. RESULTS:High intraocular pressure after vitrectomy occurred in 27 eyes(27%, the incidence of male and female were 27.27%, 26.79%, the difference was not statistically significant(P>0.05. Eyes filled with balanced liquid filling incidence rate of 30.95%, 6.25%, and the difference was statistically significant(P0.05. Incidences of intraoperative panretinal photocoagulation and additional retinal photocoagulation group were 41%, 20%, and the difference was statistically significant(P<0.05. Preoperative retinopathy of four, five, six groups of incidence were 9.52%, 23.81%, 40.56%, and the groups were statistically significant(P<0.05. Unconsolidated preoperative retinal detachment and retinal detachment incidence rate of 19%, 41%, and the difference was statistically significant(P<0.05. Surgery in the united lens resection with intraoperative unfederated lens the resection group's incidence rate of 34%, 15%, the difference was statistically significant(P<0.05. Logistic regression analysis showed that retinal detachment preoperative and intraoperative intraocular filling were independent risk factors that caused early postoperative ocular hypertension after vitrectomy. CONCLUSION:Post-operative ocular hypertension after PDR vitrectomy is related to preoperative retinal detachment, intraoperative lensectomy, intraoperative intraocular filling, and intraoperative

Metformin anti-tumor effect via disruption of the MID1 translational regulator complex and AR downregulation in prostate cancer cells

International Nuclear Information System (INIS)

Demir, Ummuhan; Koehler, Andrea; Schneider, Rainer; Schweiger, Susann; Klocker, Helmut

2014-01-01

Metformin is an approved drug prescribed for diabetes. Its role as an anti-cancer agent has drawn significant attention because of its minimal side effects and low cost. However, its mechanism of anti-tumour action has not yet been fully clarified. The effect on cell growth was assessed by cell counting. Western blot was used for analysis of protein levels, Boyden chamber assays for analyses of cell migration and co-immunoprecipitation (CoIP) followed by western blot, PCR or qPCR for analysis of protein-protein and protein-mRNA interactions. Metformin showed an anti-proliferative effect on a wide range of prostate cancer cells. It disrupted the AR translational MID1 regulator complex leading to release of the associated AR mRNA and subsequently to downregulation of AR protein in AR positive cell lines. Inhibition of AR positive and negative prostate cancer cells by metformin suggests involvement of additional targets. The inhibitory effect of metformin was mimicked by disruption of the MID1-α4/PP2A protein complex by siRNA knockdown of MID1 or α4 whereas AMPK activation was not required. Findings reported herein uncover a mechanism for the anti-tumor activity of metformin in prostate cancer, which is independent of its anti-diabetic effects. These data provide a rationale for the use of metformin in the treatment of hormone naïve and castration-resistant prostate cancer and suggest AR is an important indirect target of metformin

The potential of the essential fatty acid-deficient hairless rat as a psoriasis screening model for topical anti-proliferative drugs

DEFF Research Database (Denmark)

Jensen, Mette; Groth, L.; Holmer, G.

2002-01-01

were fed with a fat-free diet lacking linoleic acid. The EFAD condition was established within 8 weeks. In order to ensure that this condition had been established, several parameters were measured and observed, i.e. animal weight, water consumption, transepidermal water loss, clinical skin symptoms...... with calcipotriol. Dithranol and its coal tar-containing vehicle also showed a reductive effect on epidermal thickness. EFAD hairless rats possess various histological changes resembling psoriasis. These histological changes normalise during treatment with anti-psoriatic drugs as calcipotriol, dithranol and coal...

Sport, Society, and Anti-Doping Policy: An Ethical Overview.

Science.gov (United States)

Bloodworth, Andrew J; McNamee, Mike

2017-01-01

The purpose of this chapter is to provide an overview of the philosophical and ethical underpinnings of anti-doping policy. The nature of sport and its gratuitous logic is explored. The doping rules in sport, such as the Prohibited List, are ways of drawing a line to facilitate a certain sort of competition. Sports can be understood as a means of testing the natural physical abilities of the athlete, combined with the hard work they put into improving their performance. A test promoted by the anti-doping laws. Permitting certain forms of performance enhancement would threaten the special nature of such a test. Doping can be seen as a threat to the integrity of sport, not just because of the rule breaking doping currently entails. The chapter explores the ethical issues that arise with such forms of enhancement, such as fairness, harms to health, and indeed a refusal to accept human limitations. Finally, the criteria upon which a substance or method may be prohibited by the World Anti-Doping Agency (WADA) is addressed. The 3-part criteria, concerning (1) enhancement, (2) health, and (3) the spirit of sport are described, and literature that takes a critical line is addressed. Particular reference is made to the public health agenda explicit within anti-doping policy. © 2017 S. Karger AG, Basel.

2-methoxyestradiol-mediated anti-tumor effect increases osteoprotegerin expression in osteosarcoma cells.

Science.gov (United States)

Benedikt, Michaela B; Mahlum, Eric W; Shogren, Kristen L; Subramaniam, Malayannan; Spelsberg, Thomas C; Yaszemski, Michael J; Maran, Avudaiappan

2010-04-01

Osteosarcoma is a bone tumor that frequently develops during adolescence. 2-Methoxyestradiol (2-ME), a naturally occurring metabolite of 17beta-estradiol, induces cell cycle arrest and cell death in human osteosarcoma cells. To investigate whether the osteoprotegrin (OPG) protein plays a role in 2-ME actions, we studied the effect of 2-ME treatment on OPG gene expression in human osteosarcoma cells. 2-ME treatment induced OPG gene promoter activity and mRNA levels. Also, Western blot analysis showed that 2-ME treatment increased OPG protein levels in MG63, KHOS, 143B and LM7 osteosarcoma cells by 3-, 1.9-, 2.8-, and 2.5-fold, respectively, but did not affect OPG expression in normal bone cells. In addition, increases in OPG protein levels were observed in osteosarcoma cell culture media after 3 days of 2-ME treatment. The effect of 2-ME on osteosarcoma cells was ligand-specific as parent estrogen, 17beta-estradiol and a tumorigenic estrogen metabolite, 16alpha-hydroxyestradiol, which do not affect osteosarcoma cell cycle and cell death, had no effect on OPG protein expression. Furthermore, co-treating osteosarcoma cells with OPG protein did not further enhance 2-ME-mediated anti-tumor effects. OPG-released in 2-ME-treated cultures led to an increase in osteoblastic activity and a decrease in osteoclast number, respectively. These findings suggest that OPG is not directly involved in 2-ME-mediated anti-proliferative effects in osteosarcoma cells, but rather participates in anti-resorptive functions of 2-ME in bone tumor environment. Copyright 2010 Wiley-Liss, Inc.

A glycoprotein with anti-inflammatory properties secreted by an Aspergillus nidulans modified strain

Directory of Open Access Journals (Sweden)

J. C. F. Queiroz

2007-01-01

Full Text Available Total RNA from lipopolysaccharide (LPS-stimulated rat macrophages used to treat protoplasts from an Aspergillus nidulans strain originated the RT2 regenerated strain, whose culture supernatant showed anti-inflammatory activity in Wistar rats. The protein fraction presenting such anti-inflammatory activity was purified and biochemically identified. The screening of the fraction responsible for such anti-inflammatory property was performed by evaluating the inhibition of carrageenan-induced paw edema in male Swiss mice. Biochemical analyses of the anti-inflammatory protein used chromatography, carbohydrates quantification of the protein sample, amino acids content analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. Total sugar quantification revealed 32% glycosylation of the protein fraction. Amino acid analysis of such fraction showed a peculiar pattern presenting 29% valine. SDS-PAGE revealed that the protein sample is pure and its molecular weight is about 40kDa. Intravenous injection of the isolated substance into mice significantly inhibited carrageenan-induced paw edema. The isolated glycoprotein decreased carrageenan-induced paw edema in a prostaglandin-dependent phase, suggesting an inhibitory effect of the isolated glycoprotein on prostaglandin synthesis.

Medicinal plants and their isolated compounds showing anti-Trichomonas vaginalis- activity.

Science.gov (United States)

Mehriardestani, Mozhgan; Aliahmadi, Atousa; Toliat, Tayebeh; Rahimi, Roja

2017-04-01

Trichomonas vaginalis is a major of non-viral sexually-transmitted infection and an important cause of serious obstetrical and gynecological complications. Treatment options for trichomoniasis are limited to nitroimidazole compounds. The increasing resistance and allergic reactions to nitroimidazole and recurrent trichomoniasis make it essential to identify and develop new drugs against trichomoniasis. Medicinal plants are an important source for discovery of new medications. This review discusses the anti-trichomonas effects of medicinal plants and their chemical constituents to find better options against this pathogenic protozoon. Electronic databases were searched to collect all data from the year 2000 through September 2015 for in vitro, in vivo and clinical studies on the effect of medicinal plants on T. vaginalis. A total of 95 in vitro and clinical studies were identified. Only four human studies were found in this review. The Asteracea, Lamiaceae and Myrtaceae families contained the greatest number of plants with anti-trichomonas activity. Persea americana, Ocimum basilicum and Verbascum thapsus were the most efficacious against T. vaginalis. Plant metabolites containing alkaloids, isoflavonoid glucosides, essential oils, lipids, saponins and sesquiterpene lactones were found to possess anti-trichomonas properties. Assessing the structure-activity of highly-potent anti-trichomonas phytochemicals is suggested for finding natural, semisynthetic and synthetic anti-trichomonas compounds. Further clinical studies are necessary for confirmation of natural anti-trichomonas substances and completion of their safety profiles. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

THE BIOTIC FACTOR OF TREMATOD OPISTHORHIS FELINEUS INVASION INFLUENCE ON HOST IMMUNE STATUS AND SOMATIC CELLS PROLIFERATIVE ACTIVITY

Directory of Open Access Journals (Sweden)

A. G. Rybka

2016-01-01

Full Text Available The paper confirms long-time opisthorhis invasion role as a risk factor of host immune system reconstitution as well as an important factor in holangiocarcinomas development. It was shown that opisthorhosis invasion primal stage induce host immune system reconstitution. Host immune B-cells system is activated by metacercaria antigens, while the same antigens inhibits T-cells activity. Opisthorhis metabolites stimulate proliferative mithogen-induced T-cells acti vity. Chronic opisthorchis invasion leads to immune system disbalance. It means: decrease of specific and non-speci fic natural killers activity, number of high proliferative activity T-lymphocytes and the shift of regulatory T-cells subset to suppressors prevalence. At the same time specific as well as non-specific T-suppressors functional ability is very low. It was shown T-cells helper-amplifier activation. Despite of circulating B-cells decrease the antibody produced cells number is spleen increases significantly at the same time with circulating immune complexes accumulation. Even 3–6 month after dehelmintisation the immune system disbalance decreases but lefts. In addition, chronic opisthorhis invasion leads to the proliferative processes activation in ductal epithelium, liver, lymph nodes and in other organs which leads to cancer proliferation. According to the results obtained the opisthorhis infected patients needs to be immunocorrected before as well as after dehelmintisation for holangiocancerogenesis profylaxis.

Effect of exercise on the pulmonary system in proliferative phase of menstrual cycle in a group of perimenopausal women

Directory of Open Access Journals (Sweden)

Amrith Pakkala

2014-01-01

Full Text Available Background: Hormonal levels influence dynamic lung function parameters. Significant increase in both progesterone (37% and estradiol (13.5%; where as, no change in plasma follicle stimulating hormone (FSH and luteinizing hormone (LH was observed in exercising women in previous studies. Therefore, this study was intended to see the limitations of the pulmonary system in adaptability to exercise in proliferative phase of menstrual cycle in perimenopausal women. Material and Methods: The present study was conducted as a part of cardiopulmonary efficiency studies on two groups of nonathletes (n = 10 and athletes (n = 10 comparable in age and sex. Menstrual history was ascertained to confirm proliferative phase of menstrual cycle. Dynamic lung functions were measured in both groups before exercise and immediately after exercise. Results: It was observed that exercise per se does not cause a statistically significant change in dynamic lung function parameters maximum mid-expiratory flow (MMEF, peak expiratory flow rate (PEFR, and MEF 25-75% in either of the groups. Conclusion: This finding supports the hypothesis that the respiratory system is not normally the most limiting factor in the delivery of oxygen even under the predominant influence of estrogen in proliferative phase, which is further accentuated by exercise.

The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

International Nuclear Information System (INIS)

Wheldon, T.E.; Michalowski, A.S.

1982-01-01

The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as ''hierarchical'' (like haemopoietic tissues) or as ''flexible'' (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the ''flexible'' or ''F-type'' category display a variety of novel radiobiological properties, different from those of the more familiar ''hierarchical'' or ''H-type'' tissues. The ''F-type'' responses are strongly influenced by radiation-sterilised (''doomed'') cells, and is is suggested that the role of ''doomed'' cells has been undervalued relative to that of clonogenic survivors. Since ''F-type'' tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy. (author)

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.

Anti-proliferative activity of recombinant melittin expressed in ...

African Journals Online (AJOL)

kesiena

2012-02-09

Feb 9, 2012 ... 44 amino acid residues mediated by dipeptidylpeptidase. IV (Vlasak et al., 1983). It has been reported that the melittin exhibits antimicrobial activity and pro- ... Construction of recombinant expression vector. A pair of complementary oligonucleotides named Mel-1 (5′-GAT. CCG GAA TTG GAG CAG TTC ...

Antioxidant and Anti-proliferative Activities of Flavonoids from ...

African Journals Online (AJOL)

significant growth inhibitory effect on RKO cells with IC50 of 39.08 μmol/L and 17.68 μmol/L, respectively ..... YJ.. Essential oil from rhizomes of Ligusticum chuanxiong induces apoptosis in hypertrophic scar ... Liu H, Mou Y, Zhao J, Wang J, Zhou L, Wang M, Wang. D, Han J, Yu Z, Yang F. Flavonoids from Halostachys.

Decoding the anti-Trypanosoma cruzi action of HIV peptidase inhibitors using epimastigotes as a model.

Directory of Open Access Journals (Sweden)

Leandro S Sangenito

Full Text Available BACKGROUND: Aspartic peptidase inhibitors have shown antimicrobial action against distinct microorganisms. Due to an increase in the occurrence of Chagas' disease/AIDS co-infection, we decided to explore the effects of HIV aspartic peptidase inhibitors (HIV-PIs on Trypanosoma cruzi, the etiologic agent of Chagas' disease. METHODOLOGY AND PRINCIPAL FINDINGS: HIV-PIs presented an anti-proliferative action on epimastigotes of T. cruzi clone Dm28c, with IC50 values ranging from 0.6 to 14 µM. The most effective inhibitors, ritonavir, lopinavir and nelfinavir, also had an anti-proliferative effect against different phylogenetic T. cruzi strains. The HIV-PIs induced some morphological alterations in clone Dm28c epimastigotes, as reduced cell size and swollen of the cellular body. Transmission electron microscopy revealed that the flagellar membrane, mitochondrion and reservosomes are the main targets of HIV-PIs in T. cruzi epimastigotes. Curiously, an increase in the epimastigote-into-trypomastigote differentiation process of clone Dm28c was observed, with many of these parasites presenting morphological alterations including the detachment of flagellum from the cell body. The pre-treatment with the most effective HIV-PIs drastically reduced the interaction process between epimastigotes and the invertebrate vector Rhodnius prolixus. It was also noted that HIV-PIs induced an increase in the expression of gp63-like and calpain-related molecules, and decreased the cruzipain expression in epimastigotes as judged by flow cytometry and immunoblotting assays. The hydrolysis of a cathepsin D fluorogenic substrate was inhibited by all HIV-PIs in a dose-dependent manner, showing that the aspartic peptidase could be a possible target to these drugs. Additionally, we verified that ritonavir, lopinavir and nelfinavir reduced drastically the viability of clone Dm28c trypomastigotes, causing many morphological damages. CONCLUSIONS AND SIGNIFICANCE: The results

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.

Validating Female Psychopathy Subtypes: Differences in Personality, Antisocial and Violent Behavior, Substance Abuse, Trauma, and Mental Health

Science.gov (United States)

Hicks, Brian M.; Vaidyanathan, Uma; Patrick, Christopher J.

2010-01-01

Recent empirical investigations utilizing male prisoners have begun to validate clinical conceptualizations of primary and secondary psychopathy subtypes. We extended this literature by identifying similar psychopathic subtypes in female prisoners on the basis of personality structure using model-based cluster analysis. Secondary psychopaths (n = 39) were characterized by personality traits of negative emotionality and low behavioral constraint, an early onset of antisocial and criminal behavior, greater substance use and abuse, more violent behavior and institutional misconduct, and more mental health problems including symptoms of post-traumatic stress disorder and suicide attempts. Primary psychopaths (n = 31) exhibited few distinguishing personality features but were prolific criminals especially in regards to non-violent crime, and exhibited relatively few mental health problems despite substantial exposure to traumatic events. The results support alternative etiological pathways to antisocial and criminal behavior that are evident in personality structure as well as gender similarities and differences in the manifestation of psychopathic personalities. PMID:20582155

Pricing hazardous substance emissions

Energy Technology Data Exchange (ETDEWEB)

Staring, Knut; Vennemo, Haakon

1997-12-31

This report discusses pricing of emissions to air of several harmful substances. It combines ranking indices for environmentally harmful substances with economic valuation data to yield price estimates. The ranking methods are discussed and a relative index established. Given the relative ranking of the substances, they all become valued by assigning a value to one of them, the `anchor` substance, for which lead is selected. Valuations are provided for 19 hazardous substances that are often subject to environmental regulations. They include dioxins, TBT, etc. The study concludes with a discussion of other categories of substances as well as uncertainties and possible refinements. When the valuations are related to CO, NOx, SOx and PM 10, the index system undervalues these pollutants as compared to other studies. The scope is limited to the outdoor environment and does not include global warming and eutrophication. The indices are based on toxicity and so do not apply to CO{sub 2} or other substances that are biologically harmless. The index values are not necessarily valid for all countries and should be considered as preliminary. 18 refs., 6 tabs.

Pricing hazardous substance emissions

Energy Technology Data Exchange (ETDEWEB)

Staring, Knut; Vennemo, Haakon

1998-12-31

This report discusses pricing of emissions to air of several harmful substances. It combines ranking indices for environmentally harmful substances with economic valuation data to yield price estimates. The ranking methods are discussed and a relative index established. Given the relative ranking of the substances, they all become valued by assigning a value to one of them, the `anchor` substance, for which lead is selected. Valuations are provided for 19 hazardous substances that are often subject to environmental regulations. They include dioxins, TBT, etc. The study concludes with a discussion of other categories of substances as well as uncertainties and possible refinements. When the valuations are related to CO, NOx, SOx and PM 10, the index system undervalues these pollutants as compared to other studies. The scope is limited to the outdoor environment and does not include global warming and eutrophication. The indices are based on toxicity and so do not apply to CO{sub 2} or other substances that are biologically harmless. The index values are not necessarily valid for all countries and should be considered as preliminary. 18 refs., 6 tabs.

The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy

NARCIS (Netherlands)

S. Pastor-Idoate (Salvador); I. Rodriguez-Hernández (Irene); J. Rojas (Jimena); I. Fernandez (Itziar); M.T. García-Gutierrez (María Teresa); J.M. Ruiz-Moreno (Jose María); A. Rocha-Sousa (Amandio); Y. Ramkissoon (Yashin); S. Harsum (Steven); R.E. MacLaren (Robert ); D. Charteris (David); J.C. Vanmeurs (Jan C.); R. González-Sarmiento (Rogelio); J.C. Pastor (Jose Carlos)

2013-01-01

textabstractProliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism

Selection of organic process and source indicator substances for the anthropogenically influenced water cycle.

Science.gov (United States)

Jekel, Martin; Dott, Wolfgang; Bergmann, Axel; Dünnbier, Uwe; Gnirß, Regina; Haist-Gulde, Brigitte; Hamscher, Gerd; Letzel, Marion; Licha, Tobias; Lyko, Sven; Miehe, Ulf; Sacher, Frank; Scheurer, Marco; Schmidt, Carsten K; Reemtsma, Thorsten; Ruhl, Aki Sebastian

2015-04-01

An increasing number of organic micropollutants (OMP) is detected in anthropogenically influenced water cycles. Source control and effective natural and technical barriers are essential to maintain a high quality of drinking water resources under these circumstances. Based on the literature and our own research this study proposes a limited number of OMP that can serve as indicator substances for the major sources of OMP, such as wastewater treatment plants, agriculture and surface runoff. Furthermore functional indicators are proposed that allow assessment of the proper function of natural and technical barriers in the aquatic environment, namely conventional municipal wastewater treatment, advanced treatment (ozonation, activated carbon), bank filtration and soil aquifer treatment as well as self-purification in surface water. These indicator substances include the artificial sweetener acesulfame, the anti-inflammatory drug ibuprofen, the anticonvulsant carbamazepine, the corrosion inhibitor benzotriazole and the herbicide mecoprop among others. The chemical indicator substances are intended to support comparisons between watersheds and technical and natural processes independent of specific water cycles and to reduce efforts and costs of chemical analyses without losing essential information. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibitory effect of the Pseudobrickellia brasiliensis (Spreng R.M. King & H. Rob. aqueous extract on human lymphocyte proliferation and IFN-γ and TNF-α production in vitro

Directory of Open Access Journals (Sweden)

V.G. Almeida

Full Text Available Pseudobrickellia brasiliensis (Asteraceae is a plant commonly known as arnica-do-campo and belongs to the native flora of the Brazilian Cerrado. The alcoholic extract of the plant has been used as an anti-inflammatory agent in folk medicine, but the biological mechanism of action has not been elucidated. The present study evaluated the composition of P. brasiliensis aqueous extract and its effects on pro-inflammatory cytokine production and lymphocyte proliferation. The extracts were prepared by sequential maceration of P. brasiliensis leaves in ethanol, ethyl acetate, and water. Extract cytotoxicity was evaluated by trypan blue exclusion assay, and apoptosis and necrosis were measured by staining with annexin V-FITC and propidium iodide. The ethanolic (ETA and acetate (ACE extracts showed cytotoxic effects. The aqueous extract (AQU was not cytotoxic. Peripheral blood mononuclear cells stimulated with phorbol myristate acetate and ionomycin and treated with AQU (100 μg/mL showed reduced interferon (IFN-γ and tumor necrosis factor (TNF-α expression. AQU also inhibited lymphocyte proliferative response after nonspecific stimulation with phytohemagglutinin. The aqueous extract was analyzed by liquid chromatography coupled with photodiode array detection and mass spectrometry. Quinic acid and its derivatives 5-caffeoylquinic acid and 3,5-dicaffeoylquinic acid, as well as the flavonoids luteolin and luteolin dihexoside, were detected. All these compounds are known to exhibit anti-inflammatory activity. Taken together, these findings demonstrate that P. brasiliensis aqueous extract can inhibit the pro-inflammatory cytokine production and proliferative response of lymphocytes. These effects may be related to the presence of chemical substances with anti-inflammatory actions previously reported in scientific literature.

Inhibitory effect of the Pseudobrickellia brasiliensis (Spreng) R.M. King & H. Rob. aqueous extract on human lymphocyte proliferation and IFN-γ and TNF-α production in vitro.

Science.gov (United States)

Almeida, V G; Avelar-Freitas, B A; Santos, M G; Costa, L A; Silva, T J; Pereira, W F; Amorim, M L L; Grael, C F F; Gregório, L E; Rocha-Vieira, E; Brito-Melo, G E A

2017-07-10

Pseudobrickellia brasiliensis (Asteraceae) is a plant commonly known as arnica-do-campo and belongs to the native flora of the Brazilian Cerrado. The alcoholic extract of the plant has been used as an anti-inflammatory agent in folk medicine, but the biological mechanism of action has not been elucidated. The present study evaluated the composition of P. brasiliensis aqueous extract and its effects on pro-inflammatory cytokine production and lymphocyte proliferation. The extracts were prepared by sequential maceration of P. brasiliensis leaves in ethanol, ethyl acetate, and water. Extract cytotoxicity was evaluated by trypan blue exclusion assay, and apoptosis and necrosis were measured by staining with annexin V-FITC and propidium iodide. The ethanolic (ETA) and acetate (ACE) extracts showed cytotoxic effects. The aqueous extract (AQU) was not cytotoxic. Peripheral blood mononuclear cells stimulated with phorbol myristate acetate and ionomycin and treated with AQU (100 μg/mL) showed reduced interferon (IFN)-γ and tumor necrosis factor (TNF)-α expression. AQU also inhibited lymphocyte proliferative response after nonspecific stimulation with phytohemagglutinin. The aqueous extract was analyzed by liquid chromatography coupled with photodiode array detection and mass spectrometry. Quinic acid and its derivatives 5-caffeoylquinic acid and 3,5-dicaffeoylquinic acid, as well as the flavonoids luteolin and luteolin dihexoside, were detected. All these compounds are known to exhibit anti-inflammatory activity. Taken together, these findings demonstrate that P. brasiliensis aqueous extract can inhibit the pro-inflammatory cytokine production and proliferative response of lymphocytes. These effects may be related to the presence of chemical substances with anti-inflammatory actions previously reported in scientific literature.

Peer Substance Use and Homelessness Predicting Substance Abuse from Adolescence Through Early Adulthood

OpenAIRE

Tompsett, Carolyn J.; Domoff, Sarah E.; Toro, Paul A.

2013-01-01

Adolescents who experience homelessness are at higher risk for abusing substances, and for being exposed to substance-using peers. The current study used a longitudinal design to track substance abuse, affiliation with substance-using peers, and episodes of homelessness among a sample of 223 adolescents who were homeless at thebaseline data collection and 148 adolescents who were housed at baseline. Participants were interviewed at six waves over 6.5 years, covering an age rang...

Stochastic cellular automata model of neurosphere growth: Roles of proliferative potential, contact inhibition, cell death, and phagocytosis.

Science.gov (United States)

Sipahi, Rifat; Zupanc, Günther K H

2018-05-14

Neural stem and progenitor cells isolated from the central nervous system form, under specific culture conditions, clonal cell clusters known as neurospheres. The neurosphere assay has proven to be a powerful in vitro system to study the behavior of such cells and the development of their progeny. However, the theory of neurosphere growth has remained poorly understood. To overcome this limitation, we have, in the present paper, developed a cellular automata model, with which we examined the effects of proliferative potential, contact inhibition, cell death, and clearance of dead cells on growth rate, final size, and composition of neurospheres. Simulations based on this model indicated that the proliferative potential of the founder cell and its progenitors has a major influence on neurosphere size. On the other hand, contact inhibition of proliferation limits the final size, and reduces the growth rate, of neurospheres. The effect of this inhibition is particularly dramatic when a stem cell becomes encapsulated by differentiated or other non-proliferating cells, thereby suppressing any further mitotic division - despite the existing proliferative potential of the stem cell. Conversely, clearance of dead cells through phagocytosis is predicted to accelerate growth by reducing contact inhibition. A surprising prediction derived from our model is that cell death, while resulting in a decrease in growth rate and final size of neurospheres, increases the degree of differentiation of neurosphere cells. It is likely that the cellular automata model developed as part of the present investigation is applicable to the study of tissue growth in a wide range of systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Improved detection of endoparasite DNA in soil sample PCR by the use of anti-inhibitory substances.

Science.gov (United States)

Krämer, F; Vollrath, T; Schnieder, T; Epe, C

2002-09-26

Although there have been numerous microbial examinations of soil for the presence of human pathogenic developmental parasite stages of Ancylostoma caninum and Toxocara canis, molecular techniques (e.g. DNA extraction, purification and subsequent PCR) have scarcely been applied. Here, DNA preparations of soil samples artificially contaminated with genomic DNA or parasite eggs were examined by PCR. A. caninum and T. canis-specific primers based on the ITS-2 sequence were used for amplification. After the sheer DNA preparation a high content of PCR-interfering substances was still detectable. Subsequently, two different inhibitors of PCR-interfering agents (GeneReleaser, Bioventures Inc. and Maximator, Connex GmbH) were compared in PCR. Both substances increased PCR sensitivity greatly. However, comparison of the increase in sensitivity achieved with the two compounds demonstrated the superiority of Maximator, which enhanced sensitivity to the point of permitting positive detection of a single A. caninum egg and three T. canis eggs in a soil sample. This degree of sensitivity could not be achieved with GeneReleaser for either parasite Furthermore, Maximator not only increased sensitivity; it also cost less, required less time and had a lower risk of contamination. Future applications of molecular methods in epidemiological examinations of soil samples are discussed/elaborated.

Apoptotic Cell Death and the Proliferative Capacity of Human Breast Cancers

Directory of Open Access Journals (Sweden)

Gabriele A. Losa

1998-01-01

Full Text Available The proliferative capacity (%S‐phase fraction, DNA ploidy, apoptosis frequency (DNA fragmentation and steroid hormone receptor status (estrogen receptor, ER; progesterone receptor, PR of 110 samples of human breast tissues with ductal invasive carcinoma were measured using biochemical and cytofluorimetric procedures. The DNA fragmentation had a left‐skewed frequency distribution and an overall median value of 1.64%, whilst the median %S‐phase fraction was 8%. The median %DNA fragmentation and %S‐phase fraction were 1.96% and 16% in hyperdiploid tumours (n=29; DNA index >1.1 higher than in hypodiploid tumors (n=10; DNA index 0.96, 0.38% and 7.5%. DNA diploid tumours (n=71 had median %DNA fragmentation and %S‐phase values of 1.68% and 6%, consistently lower than the median values of DNA hyperdiploid tumours. The ER content of hypodiploid tumours was about one half (median: 5.9 fmol/mg the median values in hyperdiploid (10.6 fmol/mg and diploid tumours (14.6 fmol/mg. This may correlate with the lowest frequency of apoptosis in hypodiploid tumours, at least when measured by biochemical methods which only detect cells in the late phases of apoptosis. In contrast, the median PR was lowest in hyperdiploid tumours than in hypo and/or diploid tumours. The %S‐phase/%fragmented DNA ratio for the hypodiploid tumours was 19.7, significantly higher than the ratios for hyperdiploid (8.2 and diploid tumours (3.6. These findings indicated that there is an imbalance between proliferative capacity and cell death or growth arrest in human breast tumours. This imbalance may well be linked to a loss of steroid hormone control.

Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth

NARCIS (Netherlands)

Xue, Y.; Sonke, G.; Schoots, C.; Schalken, J.; Verhofstad, A.; de la Rosette, J.; Smedts, F.

2001-01-01

To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity. Consecutive

Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth.

NARCIS (Netherlands)

Xue, Y.; Sonke, G.S.; Schoots, C.; Schalken, J.A.; Verhofstad, A.A.J.; Rosette, J.J.M.H.C. de la; Smedts, F.

2001-01-01

BACKGROUND: To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity.

VISUALIZATION FROM INTRAOPERATIVE SWEPT-SOURCE MICROSCOPE-INTEGRATED OPTICAL COHERENCE TOMOGRAPHY IN VITRECTOMY FOR COMPLICATIONS OF PROLIFERATIVE DIABETIC RETINOPATHY.

Science.gov (United States)

Gabr, Hesham; Chen, Xi; Zevallos-Carrasco, Oscar M; Viehland, Christian; Dandrige, Alexandria; Sarin, Neeru; Mahmoud, Tamer H; Vajzovic, Lejla; Izatt, Joseph A; Toth, Cynthia A

2018-01-10

To evaluate the use of live volumetric (4D) intraoperative swept-source microscope-integrated optical coherence tomography in vitrectomy for proliferative diabetic retinopathy complications. In this prospective study, we analyzed a subgroup of patients with proliferative diabetic retinopathy complications who required vitrectomy and who were imaged by the research swept-source microscope-integrated optical coherence tomography system. In near real time, images were displayed in stereo heads-up display facilitating intraoperative surgeon feedback. Postoperative review included scoring image quality, identifying different diabetic retinopathy-associated pathologies and reviewing the intraoperatively documented surgeon feedback. Twenty eyes were included. Indications for vitrectomy were tractional retinal detachment (16 eyes), combined tractional-rhegmatogenous retinal detachment (2 eyes), and vitreous hemorrhage (2 eyes). Useful, good-quality 2D (B-scans) and 4D images were obtained in 16/20 eyes (80%). In these eyes, multiple diabetic retinopathy complications could be imaged. Swept-source microscope-integrated optical coherence tomography provided surgical guidance, e.g., in identifying dissection planes under fibrovascular membranes, and in determining residual membranes and traction that would benefit from additional peeling. In 4/20 eyes (20%), acceptable images were captured, but they were not useful due to high tractional retinal detachment elevation which was challenging for imaging. Swept-source microscope-integrated optical coherence tomography can provide important guidance during surgery for proliferative diabetic retinopathy complications through intraoperative identification of different complications and facilitation of intraoperative decision making.

Japan turns pro-life: recent change in reproductive health policy and challenges by new technologies

OpenAIRE

Okamoto, Etsuji

2014-01-01

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”.

Cytotoxic, Anti-Proliferative and Apoptosis Activity of l-Amino Acid Oxidase from Malaysian Cryptelytrops purpureomaculatus (CP-LAAO) Venom on Human Colon Cancer Cells.

Science.gov (United States)

Zainal Abidin, Syafiq Asnawi; Rajadurai, Pathmanathan; Hoque Chowdhury, Md Ezharul; Othman, Iekhsan; Naidu, Rakesh

2018-06-08

The aim of this study is to investigate the potential anti-cancer activity of l-amino acid oxidase (CP-LAAO) purified from the venom of Cryptelytrops purpureomaculatus on SW480 and SW620 human colon cancer cells. Mass spectrometry guided purification was able to identify and purify CP-LAAO. Amino acid variations identified from the partial protein sequence of CP-LAAO may suggest novel variants of these proteins. The activity of the purified CP-LAAO was confirmed with o-phenyldiamine (OPD)-based spectrophotometric assay. CP-LAAO demonstrated time- and dose-dependent cytotoxic activity and the EC 50 value was determined at 13 µg/mL for both SW480 and SW620 cells. Significant increase of caspase-3 activity, reduction of Bcl-2 levels, as well as morphological changes consistent with apoptosis were demonstrated by CP-LAAO. Overall, these data provide evidence on the potential anti-cancer activity of CP-LAAO from the venom of Malaysian C. purpureomaculatus for therapeutic intervention of human colon cancer.

Expression of p75NGFR, a Proliferative and Basal Cell Marker, in the Buccal Mucosa Epithelium during Re-epithelialization

International Nuclear Information System (INIS)

Ishii, Akihiro; Muramatsu, Takashi; Lee, Jong-Min; Higa, Kazunari; Shinozaki, Naoshi; Jung, Han-Sung; Shibahara, Takahiko

2014-01-01

We investigated the expression of p75 NGFR , a proliferative and basal cell marker, in the mouse buccal mucosa epithelium during wound healing in order to elucidate the role of epithelial stem cells. Epithelial defects were generated in the epithelium of the buccal mucosa of 6-week-old mice using CO 2 laser irradiation. BrdU was immediately administered to mice following laser irradiation. They were then sacrificed after 1, 3, 7, and 14 days. Paraffin sections were prepared and the irradiated areas were analyzed using immunohistochemistry with anti-p75 NGFR , BrdU, PCNA, and CK14 antibodies. During re-epithelialization, PCNA (–)/p75 NGFR (+) cells extended to the wound, which then closed, whereas PCNA (+)/p75 NGFR (+) cells were not observed at the edge of the wound. In addition, p75 NGFR (–)/CK14 (+), which reflected the presence of post-mitotic differentiating cells, was observed in the supra-basal layers of the extended epithelium. BrdU (+)/p75 NGFR (+), which reflected the presence of epithelial stem cells, was detected sparsely in buccal basal epithelial cells after healing, and disappeared after 7 days. These results suggest that p75 NGFR (+) keratinocytes are localized in the basal layer, which contains oral epithelial stem cells, and retain the ability to proliferate in order to regenerate the buccal mucosal epithelium

Anticardiolipin antibodies in proliferative diabetic retinopathy: An additional risk factor

International Nuclear Information System (INIS)

Shahin, Maha; ElDiasty, Amany M; Mabed, Mohamed

2009-01-01

To report the prevalence of anticardiolipin antibodies in patients with proliferative diabetic retinopathy (PDR) having high-risk criteria (HRC). Diabetic patients having PDR with HRC and diabetics free of retinopathy were compared for the presence of anticardiolipin antibodies. Among the 34 patients, 6 (17.7%) of diabetics having PDR with HRC were positive for anticardiolipin antibodies. There was no significant association of aCL antibodies with sex or type of diabetes. Using Pearson's correlation test, no significant associations of aCL antibodies with duration of diabetes or age of patients were found. All patients who were positive for anticardiolipin antibodies had PDR with HRC. The difference was statistically significant. Presence of anticardiolipin antibodies may represent an additional risk factor for PDR. (author)

Echography of the Cervix and Uterus during the Proliferative and Secretory Phases of the Menstrual Cycle in Bonnet Monkeys (Macaca radiata)

Science.gov (United States)

Chaudhari, Uddhav K; Metkari, Siddnath M; Manjaramkar, Dhyananjay D; Sachdeva, Geetanjali; Katkam, Rajendra; Bandivdekar, Atmaram H; Mahajan, Abhishek; Thakur, Meenakshi H; Kholkute, Sanjiv D

2014-01-01

We undertook the present study to investigate the echographic characteristics of the uterus and cervix of female bonnet monkeys (Macaca radiata) during the proliferative and secretory phases of the menstrual cycle. The cervix was tortuous in shape and measured 2.74 ± 0.30 cm (mean ± SD) in width by 3.10 ± 0.32 cm in length. The cervical lumen contained 2 or 3 colliculi, which projected from the cervical canal. The echogenicity of cervix varied during proliferative and secretory phases. The uterus was pyriform in shape (2.46 ± 0.28 cm × 1.45 ± 0.19 cm) and consisted of serosa, myometrium, and endometrium. The endometrium generated a triple-line pattern; the outer and central lines were hyperechogenic, whereas the inner line was hypoechogenic. The endometrium was significantly thicker during the secretory phase (0.69 ± 0.12 cm) than during the proliferative phase (0.43 ± 0.15 cm). Knowledge of the echogenic changes in the female reproductive organs of bonnet monkeys during a regular menstrual cycle may facilitate understanding of other physiologic and pathophysiologic changes. PMID:24411775

Modulation of the formation and release of bovine SRS-A in vitro by several anti-anaphylactic drugs.

Science.gov (United States)

Burka, J F; Eyre, P

1975-01-01

Slow-reacting substance of anaphylaxis (SRS-A) is released immunologically from bovine lung in vitro. Various drugs known to protect calves and other animals during anaphylaxis were tested to investigate their modulation of the formation and release of SRS-A. The anti-inflammatory drugs, meclofenamate and aspirin, potentiated SRS-A release. Chlorphenesin and diethylcarbamazine citrate at high concentrations both inhibited SRS-A release. Two new anti-anaphylactic drugs, PR-D-92-EA and M&B 22,948, were particularly effective in inhibiting SRS-A release at low concentrations. The possible modes of actions of these drugs are discussed.

Anti-virulence approaches and novel peptidomimetics for combating resistant and biofilm associated bacteria

DEFF Research Database (Denmark)

Liu, Yang

Anti-virulence approaches and novel peptidomimetics for combating resistant and biofilm associated bacteria The misuse and overuse of antibiotics has a broad impact on the environment. Antibiotic resistance has become a major threat for modern medical treatment of infectious diseases. There are m......Anti-virulence approaches and novel peptidomimetics for combating resistant and biofilm associated bacteria The misuse and overuse of antibiotics has a broad impact on the environment. Antibiotic resistance has become a major threat for modern medical treatment of infectious diseases...... consisting of microcolonies embedded in self-produced extracellular polymer substances (EPS). EPS can contribute to cell-cell adhesion and restrict antibiotic penetration. Biofilm cells show much greater resistance to stressful conditions than their free-living counterparts. Conventional treatment strategies...

The anti-oxidant effects of melatonin derivatives on human gingival fibroblasts.

Science.gov (United States)

Phiphatwatcharaded, Chawapon; Puthongking, Ploenthip; Chaiyarit, Ponlatham; Johns, Nutjaree Pratheepawanit; Sakolchai, Sumon; Mahakunakorn, Pramote

2017-07-01

Aim of this in vitro study was to evaluate the anti-oxidant activity of indole ring modified melatonin derivatives as compared with melatonin in primary human gingival fibroblast (HGF) cells. Anti-oxidant activity of melatonin (MLT), acetyl-melatonin (AMLT) and benzoyl-melatonin (BMLT) was evaluated by5 standard methods as follows: 2, 2-diphenyl-1-picrylhydrazyl (DPPH); ferric ion reducing antioxidant power (FRAP); superoxide anion scavenging; nitric oxide (NO) scavenging; and thiobarbituric acid reactive substances (TBARs).Evaluation of cellular antioxidant activity (CAA) and protectivity against H 2 O 2 induced cellular damage was performed via MTT assay in HGF cells. According to the standard anti-oxidant assays, the antioxidant power of AMLT and BMLT were slightly less than MLT in FRAP and superoxide scavenging assays. In the NO scavenging and TBARs assays, BMLT and AMLT were more potent than MLT, whereas DPPH assays demonstrated that MLT was more potent than others. BMLT and AMLT had more potent anti-oxidant and protective activities against H 2 O 2 in HGF cells as compared with MLT. MLT derivatives demonstrated different anti-oxidant activities as compared with MLT, depending upon assays. These findings imply that N-indole substitution of MLT may help to improve hydrogen atom transfer to free radicals but electron transfer property is slightly decreased. Anti-oxidant and protective effects of melatonin derivatives (AMLT and BMLT) on human gingival fibroblasts imply the potential use of these molecules as alternative therapeutics for chronic inflammatory oral diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytotoxic, Antiproliferative and Pro-Apoptotic Effects of 5-Hydroxyl-6,7,3′,4′,5′-Pentamethoxyflavone Isolated from Lantana ukambensis

Directory of Open Access Journals (Sweden)

Wamtinga Richard Sawadogo

2015-12-01

Full Text Available Lantana ukambensis (Vatke Verdc. is an African food and medicinal plant. Its red fruits are eaten and highly appreciated by the rural population. This plant was extensively used in African folk medicinal traditions to treat chronic wounds but also as anti-leishmanial or cytotoxic remedies, especially in Burkina Faso, Tanzania, Kenya, or Ethiopia. This study investigates the in vitro bioactivity of polymethoxyflavones extracted from a L. ukambensis as anti-proliferative and pro-apoptotic agents. We isolated two known polymethoxyflavones, 5,6,7,3′,4′,5′-hexamethoxyflavone (1 and 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 from the whole plant of L. ukambensis. Their chemical structures were determined by spectroscopic analysis and comparison with published data. These molecules were tested for the anti-proliferative, cytotoxic and pro-apoptotic effects on human cancer cells. Among them, 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 was selectively cytotoxic against monocytic lymphoma (U937, acute T cell leukemia (Jurkat, and chronic myelogenous leukemia (K562 cell lines, but not against peripheral blood mononuclear cells (PBMCs from healthy donors, at all tested concentrations. Moreover, this compound exhibited significant anti-proliferative and pro-apoptotic effects against U937 acute myelogenous leukemia cells. This study highlights the anti-proliferative and pro-apoptotic effects of 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 and provides a scientific basis of traditional use of L. ukambensis.

Oral JS-38, a metabolite from Xenorhabdus sp., has both anti-tumor activity and the ability to elevate peripheral neutrophils.

Science.gov (United States)

Liu, Min-Yu; Xiao, Lin; Chen, Geng-Hui; Wang, Yong-Xiang; Xiong, Wei-Xia; Li, Fei; Liu, Ying; Huang, Xiao-Ling; Deng, Yi-Fang; Zhang, Zhen; Sun, Hai-Yan; Liu, Quan-Hai; Yin, Ming

2014-10-01

JS-38 (mitothiolore), a synthetic version of a metabolite isolated from Xenorhabdus sp., was evaluated for its anti-tumor and white blood cell (WBC) elevating activities. These anti-proliferative activities were assessed in vitro using a panel of ten cell lines. The anti-tumor activities were tested in vivo using B16 allograft mouse models and xenograft models of A549 human lung carcinoma and QGY human hepatoma in nude mice. The anti-tumor interactions of JS-38 and cyclophosphamide (CTX) or 5-fluorouracil (5-Fu) were studied in a S180 sarcoma model in ICR mice. Specific stimulatory effects were determined on peripheral neutrophils in normal and CTX- and 5-Fu-induced neutropenic mice. The IC50 values ranged from 0.1 to 2.0 μmol·L(-1). JS-38 (1 μmol·L(-1)) caused an increase in A549 tumor cell apoptosis. Multi-daily gavage of JS-38 (15, 30, and 60 mg·kg(-1)·d(-1)) inhibited in vivo tumor progression without a significant effect on body weight. JS-38 additively enhanced the in vivo anti-tumor effects of CTX or 5-Fu. JS-38 increased peripheral neutrophil counts and neutrophil rates in normal BALB/c mice almost as effectively as granulocyte colony-stimulating factor (G-CSF). In mice with neutropenia induced by CTX or 5-Fu, JS-38 rapidly restored neutrophil counts. These results suggest that JS-38 has anti-tumor activity, and also has the ability to increase peripheral blood neutrophils. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Analgesic, anti-inflammatory, antipyretic and haematological effects of aethiopinone, an o-naphthoquinone diterpenoid from Salvia aethiopis roots and two hemisynthetic derivatives.

Science.gov (United States)

Hernández-Pérez, M; Rabanal, R M; de la Torre, M C; Rodríguez, B

1995-12-01

Aethiopinone (1), an o-naphthoquinone diterpene from Salvia aethiopis L. roots and two hemisynthetic derivatives 2 and 3 have been evaluated for toxicity, anti-inflammatory, analgesic, antipyretic, and haemostatic activities. The compounds tested showed low toxicity and a pharmacological profile similar to other NSAI substances on reducing the edema induced by carrageenan and contractions induced by phenyl-p-quinone; the most active compounds were 1 and 2. In the same way and as expected with these types of substances, the bleeding time increased. In the TPA-induced ear inflammation model, the three compounds showed a moderate reduction of edema, and 1 produced a significant increase in the reaction time against thermal painful stimuli in the tail immersion test. The results demonstrated strong anti-inflammatory, peripheral and central analgesic properties for 1, as well as antiedematose topical action and peripheral analgesic properties for 2 and 3.

Anti-solvent co-crystallization of carbamazepine and saccharin.

Science.gov (United States)

Wang, In-Chun; Lee, Min-Jeong; Sim, Sang-Jun; Kim, Woo-Sik; Chun, Nan-Hee; Choi, Guang J

2013-06-25

The co-crystal approach has been investigated extensively over the past decade as one of the most promising methods to enhance the dissolution properties of insoluble drug substances. Co-crystal powders are typically produced by mechanical grinding (neat or wet) or a solution method (evaporation or cooling). In this study, high-purity carbamazepine-saccharin (CBZ-SAC) co-crystals were manufactured by a novel method, anti-solvent addition. Among various solvents, methanol was found to perform well with water as the anti-solvent for the co-crystallization of CBZ and SAC. When water was added to the methanol solution of CBZ and SAC at room temperature under agitation, nucleation of CBZ-SAC co-crystals occurred within 2-3 min. Co-crystallization was complete after 30 min, giving a solid yield as high as 84.5% on a CBZ basis. The effects of initial concentrations, focusing on the SAC/CBZ ratio, were examined to establish optimal conditions. The whole anti-solvent co-crystallization process was monitored at-line via ATR-FTIR analysis of regularly sampled solutions. The nucleation and crystal growth of CBZ-SAC co-crystals were detected by a significant increase in absorption in the range of 2400-2260 cm(-1), associated with the formation of hydrogen bonds between the carbonyl group in CBZ and the N-H of SAC. When CBZ hydrates were formed as impurities during anti-solvent co-crystallization, the hydrogen bonding between methanol and water was reduced greatly, primarily due to the incorporation of water molecules into the CBZ crystal lattice. In conclusion, an anti-solvent approach can be used to produce highly pure CBZ-SAC co-crystal powders with a high solid yield. Copyright © 2013 Elsevier B.V. All rights reserved.

21 CFR 172.510 - Natural flavoring substances and natural substances used in conjunction with flavors.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Natural flavoring substances and natural substances used in conjunction with flavors. 172.510 Section 172.510 Food and Drugs FOOD AND DRUG ADMINISTRATION....510 Natural flavoring substances and natural substances used in conjunction with flavors. Natural...

MicroRNA-124 controls the proliferative, migratory, and inflammatory phenotype of pulmonary vascular fibroblasts.

Science.gov (United States)

Wang, Daren; Zhang, Hui; Li, Min; Frid, Maria G; Flockton, Amanda R; McKeon, B Alexandre; Yeager, Michael E; Fini, Mehdi A; Morrell, Nicholas W; Pullamsetti, Soni S; Velegala, Sivareddy; Seeger, Werner; McKinsey, Timothy A; Sucharov, Carmen C; Stenmark, Kurt R

2014-01-03

Pulmonary hypertensive remodeling is characterized by excessive proliferation, migration, and proinflammatory activation of adventitial fibroblasts. In culture, fibroblasts maintain a similar activated phenotype. The mechanisms responsible for generation/maintenance of this phenotype remain unknown. We hypothesized that aberrant expression of microRNA-124 (miR-124) regulates this activated fibroblast phenotype and sought to determine the signaling pathways through which miR-124 exerts effects. We detected significant decreases in miR-124 expression in fibroblasts isolated from calves and humans with severe pulmonary hypertension. Overexpression of miR-124 by mimic transfection significantly attenuated proliferation, migration, and monocyte chemotactic protein-1 expression of hypertensive fibroblasts, whereas anti-miR-124 treatment of control fibroblasts resulted in their increased proliferation, migration, and monocyte chemotactic protein-1 expression. Furthermore, the alternative splicing factor, polypyrimidine tract-binding protein 1, was shown to be a direct target of miR-124 and to be upregulated both in vivo and in vitro in bovine and human pulmonary hypertensive fibroblasts. The effects of miR-124 on fibroblast proliferation were mediated via direct binding to the 3' untranslated region of polypyrimidine tract-binding protein 1 and subsequent regulation of Notch1/phosphatase and tensin homolog/FOXO3/p21Cip1 and p27Kip1 signaling. We showed that miR-124 directly regulates monocyte chemotactic protein-1 expression in pulmonary hypertension/idiopathic pulmonary arterial hypertension fibroblasts. Furthermore, we demonstrated that miR-124 expression is suppressed by histone deacetylases and that treatment of hypertensive fibroblasts with histone deacetylase inhibitors increased miR-124 expression and decreased proliferation and monocyte chemotactic protein-1 production. Stable decreases in miR-124 expression contribute to an epigenetically reprogrammed, highly

Psychotoxic Substances

Science.gov (United States)

1964-11-16

halluci- nations , disturbances of body perception, depersonalization symptoms, and a "psychotic" status. Also with the derivatives, the individual...the substance had also local anesthetic properties. After clinical testing, ibogaine was then used as stimulans for neurasthenics and convalescents1 1 3...con- siderably disturbed by this group of substances. The optic halluci- nations consist to a small extent in scenic proceedings of actions, more

Improved PVDF membrane performance by doping extracellular polymeric substances of activated sludge.

Science.gov (United States)

Guan, Yan-Fang; Huang, Bao-Cheng; Qian, Chen; Wang, Long-Fei; Yu, Han-Qing

2017-04-15

Polyvinylidene fluoride (PVDF) membrane has been widely applied in water and wastewater treatment because of its high mechanical strength, thermal stability and chemical resistance. However, the hydrophobic nature of PVDF membrane makes it readily fouled, substantially reducing water flux and overall membrane rejection ability. In this work, an in-situ blending modifier, i.e., extracellular polymeric substances (EPS) from activated sludge, was used to enhance the anti-fouling ability of PVDF membrane. Results indicate that the pure water flux of the membrane and its anti-fouling performance were substantially improved by blending 8% EPS into the membrane. By introducing EPS, the membrane hydrophilicity was increased and the cross section morphology was changed when it interacted with polyvinl pyrrolidone, resulting in the formation of large cavities below the finger-like pores. In addition, the fraction of pores with a size of 100-500 nm increased, which was also beneficial to improving membrane performance. Surface thermodynamic calculations indicate the EPS-functionalized membrane had a higher cohesion free energy, implying its good pollutant rejection and anti-fouling ability. This work provides a simple, efficient and cost-effective method to improve membrane performance and also extends the applications of EPS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma

Science.gov (United States)

2011-01-01

Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis and metastasis. Curcumin has shown anti-proliferative effect in multiple cancers, and is an inhibitor of the transcription factor NF-κB and downstream gene products (including c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNF-α, interleukins and MMP-9). In addition, curcumin affects a variety of growth factor receptors and cell adhesion molecules involved in tumor growth, angiogenesis and metastasis. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and treatment protocols include disfiguring surgery, platinum-based chemotherapy and radiation, all of which may result in tremendous patient morbidity. As a result, there is significant interest in developing adjuvant chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent. PMID:21299897

Oridonin inhibits tumor growth and metastasis through anti-angiogenesis by blocking the Notch signaling.

Directory of Open Access Journals (Sweden)

Yanmin Dong

Full Text Available While significant progress has been made in understanding the anti-inflammatory and anti-proliferative effects of the natural diterpenoid component Oridonin on tumor cells, little is known about its effect on tumor angiogenesis or metastasis and on the underlying molecular mechanisms. In this study, Oridonin significantly suppressed human umbilical vascular endothelial cells (HUVECs proliferation, migration, and apillary-like structure formation in vitro. Using aortic ring assay and mouse corneal angiogenesis model, we found that Oridonin inhibited angiogenesis ex vivo and in vivo. In our animal experiments, Oridonin impeded tumor growth and metastasis. Immunohistochemistry analysis further revealed that the expression of CD31 and vWF protein in xenografts was remarkably decreased by the Oridonin. Furthermore, Oridonin reinforced endothelial cell-cell junction and impaired breast cancer cell transendothelial migration. Mechanistically, Oridonin not only down-regulated Jagged2 expression and Notch1 activity but also decreased the expression of their target genes. In conclusion, our results demonstrated an original role of Oridonin in inhibiting tumor angiogenesis and propose a mechanism. This study also provides new evidence supporting the central role of Notch in tumor angiogenesis and suggests that Oridonin could be a potential drug candidate for angiogenesis related diseases.

Substance Use Stigma: Reliability and validity of a theory-based scale for substance-using populations*

Science.gov (United States)

Smith, Laramie R.; Earnshaw, Valerie A.; Copenhaver, Michael M.; Cunningham, Chinazo O.

2016-01-01

Background Substance use disorders consistently rank among the most stigmatized conditions worldwide. Thus, substance use stigma fosters health inequities among persons with substance use disorders and remains a key barrier to successful screening and treatment efforts. Current efforts to measure substance use stigma are limited. This study aims to advance measurement efforts by drawing on stigma theory to develop and evaluate the Substance Use Stigma Mechanisms Scale (SU-SMS). The SU-SMS was designed to capture enacted, anticipated, and internalized substance use stigma mechanisms among persons with current and past substance use disorders, and distinguish between key stigma sources most likely to impact this target population. Methods This study was a cross-sectional evaluation of the validity, reliability, and generalizability of the SU-SMS across two independent samples with diverse substance use and treatment histories. Results Findings support the structural and construct validity of the SU-SMS, suggesting the scale was able to capture enacted, anticipated, and internalized stigma as distinct stigma experiences. It also further differentiated between two distinct stigma sources (family and healthcare providers). Analysis of these mechanisms and psychosocial metrics suggests that the scale is also associated with other health-related outcomes. Furthermore, the SU-SMS demonstrated high levels of internal reliability and generalizability across two independent samples of persons with diverse substance use disorders and treatment histories. Conclusion The SU-SMS may serve as a valuable tool for better understanding the processes through which substance use stigma serves to undermine key health behaviors and outcomes among persons with substance use disorders. PMID:26972790

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”.

Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti.

Science.gov (United States)

Zhou, Haonan; Zhang, Pengjie; Hou, Zhiguo; Xie, Jiabin; Wang, Yuming; Yang, Bin; Xu, Yanyan; Li, Yubo

2016-11-25

Radix Aconiti , a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity.

Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti

OpenAIRE

Haonan Zhou; Pengjie Zhang; Zhiguo Hou; Jiabin Xie; Yuming Wang; Bin Yang; Yanyan Xu; Yubo Li

2016-01-01

Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were availabl...

Anti-SEMA3A Antibody: A Novel Therapeutic Agent to Suppress GBM Tumor Growth.

Science.gov (United States)

Lee, Jaehyun; Shin, Yong Jae; Lee, Kyoungmin; Cho, Hee Jin; Sa, Jason K; Lee, Sang-Yun; Kim, Seok-Hyung; Lee, Jeongwu; Yoon, Yeup; Nam, Do-Hyun

2017-11-10

Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression. We employed public glioma datasets, Repository of Molecular Brain Neoplasia Data and The Cancer Genome Atlas, to analyze SEMA3A mRNA expression in human GBM specimens. We also evaluated for protein expression level of SEMA3A via tissue microarray (TMA) analysis. Cell migration and proliferation kinetics were assessed in various GBM patient-derived cells (PDCs) and U87-MG cell-line for SEMA3A antibody efficacy. GBM patient-derived xenograft (PDX) models were generated to evaluate tumor inhibitory effect of anti-SEMA3A antibody in vivo. By combining bioinformatics and TMA analysis, we discovered that SEMA3A is highly expressed in human GBM specimens compared to non-neoplastic tissues. We developed three different anti-SEMA3A antibodies, in fully human IgG form, through screening phage-displayed synthetic antibody library using a classical panning method. Neutralization of SEMA3A significantly reduced migration and proliferation capabilities of PDCs and U87-MG cell-line in vitro. In PDX models, treatment with anti-SEMA3A antibody exhibited notable tumor inhibitory effect through down-regulation of cellular proliferative kinetics and tumor-associated macrophages recruitment. In present study, we demonstrated tumor inhibitory effect of SEMA3A antibody in GBM progression and present its potential relevance as a therapeutic agent in a clinical framework.

Quercetin as an Emerging Anti-Melanoma Agent: A four-focus area therapeutic development strategy

Directory of Open Access Journals (Sweden)

Zoey Harris

2016-10-01

Full Text Available Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase -- a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes a feasible a target for polyphenol-based therapies. For example, quercetin (3,3′,4′,5,7-pentahydroxyflavone is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated anti-proliferative and pro-apoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anti-cancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review we explore the potential of Quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a four-focus area strategy to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to i modulate cellular bioreduction potential and associated signaling cascades, ii affect transcription of relevant genes, iii regulate epigenetic processes, and iv develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.

NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy.

Science.gov (United States)

Loukovaara, Sirpa; Piippo, Niina; Kinnunen, Kati; Hytti, Maria; Kaarniranta, Kai; Kauppinen, Anu

2017-12-01

Innate immunity and dysregulation of inflammatory processes play a role in vascular diseases like atherosclerosis or diabetes. Nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes are pro-inflammatory signalling complexes that were found in 2002. In addition to pathogens and other extracellular threats, they can be activated by various endogenous danger signals. The purpose of this study was to find out whether NLRP3 activation occurs in patients with sight-threatening forms of diabetic retinopathy (DR). Inflammasome components NLRP3 and caspase-1, inflammasome-related pro-inflammatory cytokines IL-1β and IL-18, vascular endothelial growth factor (VEGF), acute-phase cytokines TNF-α and IL-6, as well as adaptive immunity-related cytokine interferon gamma (IFN-γ) were measured from the vitreous samples of 15 non-proliferative diabetic retinopathy (non-PDR) and 23 proliferative diabetic retinopathy (PDR) patients using the enzyme-linked immunosorbent assay (ELISA) method. The adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) was determined using the Western blot technique. Inflammasome components were present in the vitreous of DR patients. Along with VEGF, the levels of caspase-1 and IL-18 were significantly increased, especially in PDR eyes. Interestingly, clearly higher levels of NLRP3 were found in the PDR eyes with tractional retinal detachment (TRD) than from PDR eyes with fully attached retina. There were no significant differences in the amounts of IL-1β, TNF-α, IL-6, and IFN-γ that were detectable in the vitreous of both non-PDR and PDR patients. Our results suggest that NLRP3 inflammasome activation can be associated especially with the pathogenesis of PDR. The lack of differences in TNF-α, IL-6, and IFN-γ also alludes that acute inflammation or T-cell-mediated responses do not dominate in PDR pathogenesis. © 2017 Acta Ophthalmologica Scandinavica Foundation

Phytochemical Analysis and Antimicrobial, Antinociceptive, and Anti-Inflammatory Activities of Two Chemotypes of Pimenta pseudocaryophyllus (Myrtaceae

Directory of Open Access Journals (Sweden)

Joelma Abadia Marciano de Paula

2012-01-01

Full Text Available Preparations from Pimenta pseudocaryophyllus (Gomes L.R. Landrum (Myrtaceae have been widely used in Brazilian folk medicine. This study aims to evaluate the antimicrobial activity of the crude ethanol extracts, fractions, semipurified substances, and essential oils obtained from leaves of two chemotypes of P. pseudocaryophyllus and to perform the antinociceptive and anti-inflammatory screening. The ethanol extracts were purified by column chromatography and main compounds were spectrally characterised (1D and 2D 1H and 13C NMR. The essential oils constituents were identified by GC/MS. The broth microdilution method was used for testing the antimicrobial activity. The abdominal contortions induced by acetic acid and the ear oedema induced by croton oil were used for screening of antinociceptive and anti-inflammatory activities, respectively. The phytochemical analysis resulted in the isolation of pentacyclic triterpenes, flavonoids, and phenol acids. The oleanolic acid showed the best profile of antibacterial activity for Gram-positive bacteria (31.2–125 μg mL−1, followed by the essential oil of the citral chemotype (62.5–250 μg mL−1. Among the semipurified substances, Ppm5, which contained gallic acid, was the most active for Candida spp. (31.2 μg mL−1 and Cryptococcus spp. (3.9–15.6 μg mL−1. The crude ethanol extract and fractions from citral chemotype showed antinociceptive and anti-inflammatory effects.

Screening for prenatal substance use: development of the Substance Use Risk Profile-Pregnancy scale.

Science.gov (United States)

Yonkers, Kimberly A; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B; Rounsaville, Bruce J

2010-10-01

To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into "training" (n=1,610) and "validation" (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike's Information Criterion=579.75, Nagelkerke R=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. III.

Pre-clinical assessment of A-674563 as an anti-melanoma agent

International Nuclear Information System (INIS)

Zou, Ying; Fan, Guobiao; Wang, Xuemin

2016-01-01

The present study aims to investigate the anti-melanoma activity by an Akt1 specific inhibitor A-674563. We showed that A-674563 was anti-proliferative and cytotoxic when added to human melanoma cells (A375, WM-115 and SK-Mel-2 lines). A-674563 induced caspase-dependent apoptotic death of human melanoma cells, and its cytotoxicity was inhibited with pre-treatment of caspase inhibitors. Further, A-674563 treatment blocked Akt and its downstream S6 Kinase 1 (S6K1) activation in A375 melanoma cells. Significantly, restoring Akt-S6K1 activation via introduction of constitutively-active Akt1 (ca-Akt1) only partially attenuated A-674563's cytotoxicity against A375 cells. Further, A-674563 induced pro-apoptotic ceramide production in A375 cells. Significantly, sphingosine-1-phosphate (S1P) inhibited A-674563-induced ceramide production and subsequent A375 cell apoptosis. On the other hand, co-treatment with the glucosylceramide synthase (GCS) inhibitor PDMP or the cell permeable short-chain ceramide (C6) potentiated A-674563's cytotoxicity against A375 cells. In vivo, A-674563 oral gavage inhibited A375 xenograft growth in severe combined immunodeficiency (scid) mice. Akt inactivation, caspase-3 activation and ceramide production were also observed in A-674563-treated A375 xenografts. Together, these results suggest that A-674563 exerts potent anti-melanoma activity, involving Akt-dependent and Akt-independent mechanisms. - Highlights: • A-674563 inhibits human melanoma cell survival and proliferation. • A-674563 induces melanoma cell apoptotic death, inhibited by caspase inhibitors. • A-674563 inhibits melanoma cells via Akt-dependent and -independent mechanisms. • A-674563 induces ceramide production in melanoma cells, independent of Akt inhibition. • A-674563 oral administration potently inhibits A375 xenograft growth in mice.

Pre-clinical assessment of A-674563 as an anti-melanoma agent

Energy Technology Data Exchange (ETDEWEB)

Zou, Ying; Fan, Guobiao; Wang, Xuemin, E-mail: wangxuemeidr@yeah.net

2016-08-12

The present study aims to investigate the anti-melanoma activity by an Akt1 specific inhibitor A-674563. We showed that A-674563 was anti-proliferative and cytotoxic when added to human melanoma cells (A375, WM-115 and SK-Mel-2 lines). A-674563 induced caspase-dependent apoptotic death of human melanoma cells, and its cytotoxicity was inhibited with pre-treatment of caspase inhibitors. Further, A-674563 treatment blocked Akt and its downstream S6 Kinase 1 (S6K1) activation in A375 melanoma cells. Significantly, restoring Akt-S6K1 activation via introduction of constitutively-active Akt1 (ca-Akt1) only partially attenuated A-674563's cytotoxicity against A375 cells. Further, A-674563 induced pro-apoptotic ceramide production in A375 cells. Significantly, sphingosine-1-phosphate (S1P) inhibited A-674563-induced ceramide production and subsequent A375 cell apoptosis. On the other hand, co-treatment with the glucosylceramide synthase (GCS) inhibitor PDMP or the cell permeable short-chain ceramide (C6) potentiated A-674563's cytotoxicity against A375 cells. In vivo, A-674563 oral gavage inhibited A375 xenograft growth in severe combined immunodeficiency (scid) mice. Akt inactivation, caspase-3 activation and ceramide production were also observed in A-674563-treated A375 xenografts. Together, these results suggest that A-674563 exerts potent anti-melanoma activity, involving Akt-dependent and Akt-independent mechanisms. - Highlights: • A-674563 inhibits human melanoma cell survival and proliferation. • A-674563 induces melanoma cell apoptotic death, inhibited by caspase inhibitors. • A-674563 inhibits melanoma cells via Akt-dependent and -independent mechanisms. • A-674563 induces ceramide production in melanoma cells, independent of Akt inhibition. • A-674563 oral administration potently inhibits A375 xenograft growth in mice.

N-acetyl-L-tryptophan, a substance-P receptor antagonist attenuates aluminum-induced spatial memory deficit in rats.

Science.gov (United States)

Fernandes, Joylee; Mudgal, Jayesh; Rao, Chamallamudi Mallikarjuna; Arora, Devinder; Basu Mallik, Sanchari; Pai, K S R; Nampoothiri, Madhavan

2018-06-01

Neuroinflammation plays an important role in the pathophysiology of Alzheimer's disease. Neurokinin substance P is a key mediator which modulates neuroinflammation through neurokinin receptor. Involvement of substance P in Alzheimer's disease is still plausible and various controversies exist in this hypothesis. Preventing the deleterious effects of substance P using N-acetyl-L-tryptophan, a substance P antagonist could be a promising therapeutic strategy. This study was aimed to evaluate the effect of N-acetyl-L-tryptophan on aluminum induced spatial memory alterations in rats. Memory impairment was induced using aluminum chloride (AlCl 3 ) at a dose of 10 mg/kg for 42 d. After induction of dementia, rats were exposed to 30 and 50 mg/kg of N-acetyl-L-tryptophan for 28 d. Spatial memory alterations were measured using Morris water maze. Acetylcholinesterase activity and antioxidant enzyme glutathione level were assessed in hippocampus, frontal cortex and striatum. The higher dose of N-acetyl-L-tryptophan (50 mg/kg) significantly improved the aluminum induced memory alterations. N-acetyl-L-tryptophan exposure resulted in significant increase in acetylcholinesterase activity and glutathione level in hippocampus. The neuroprotective effect of N-acetyl-L-tryptophan could be due to its ability to block substance P mediated neuroinflammation, reduction in oxidative stress and anti-apoptotic properties. To conclude, N-acetyl-L-tryptophan may be considered as a novel neuroprotective therapy in Alzheimer's disease.

[Analytic study of dot blotting for the detection of anti-Jo-1, anti-M2, anti-ribosomes and anti-LKM].

Science.gov (United States)

Huguet, S; Sghiri, R; Ballot, E; Johanet, C

2004-01-01

The Cyto-Dot 4 HM043 kit commercialised by BMD, has replaced the Cyto-Dot HM010 kit that allowed three auto-antibodies detection (anti-Jo-1, anti-M2 and anti-ribosomal protein). Detection of anti-LKM1 auto-antibody was added. These four auto-antibodies have in common only the intracytoplasmic localisation of their respective antigen. The aim of our study was to evaluate this new kit using 104 sera and to compare our results with reference techniques (indirect immunofluorescence IF for anti-M2, anti-ribosomal protein and anti-LKM1, double immunodiffusion ID for anti-Jo-1 and anti-LKM1, western blotting WB for anti-M2) and with Cyto-Dot HM010. The one hundred and four sera were divided into five groups: Group I (n = 12) with anti-Jo-1 detected by ID; Group II (n = 28) with 26 anti-M2 positive by IF and WB, 2 anti-M2 positive only by WB; Group III (n = 10) with anti-ribosomal protein detected by IF 5 of which precipitated by ID; Group IV (n = 32) with anti-LKM1 by IF and ID divided into 18 AIH2 and 14 HCV; Group V (n = 22) consisting of 14 healthy individuals and 8 patients with hypergammaglobulinemia. Results of this study are similar to those of Cyto-Dot HM010 for the three auto-antibodies already in use. Cyto-Dot 4 is a very good anti-LKM1 confirmation method as it is ID. Copyright John Libbey Eurotext 2003.

Carbon nanotubes as carriers of Panax ginseng metabolites and enhancers of ginsenosides Rb1 and Rg1 anti-cancer activity

Science.gov (United States)

Lahiani, Mohamed H.; Eassa, Souzan; Parnell, Charlette; Nima, Zeid; Ghosh, Anindya; Biris, Alexandru S.; Khodakovskaya, Mariya V.

2017-01-01

A major benefit to nanomaterial based-medicine is the ability to provide nanosized vehicles for sporadic metabolites. Here, we describe how the conjugation of valuable ginseng secondary metabolites (ginsenoside Rb1 or Rg1) with carbon nanotubes (CNT) can enhance their anti-proliferative and anti-cancer effects. Ginsenoside-CNT conjugate (Rb-CNT or Rg-CNT) permitted the ginsenosides to be used at a low dose, yet achieve a higher incidence of cancer killing. We were able to demonstrate that the ginsenoside-CNT conjugate can decrease cell viability up to 62% in breast cancer cells (MCF-7) and enhance antiproliferation of drug-resistant pancreatic cancer cells (PANC-1) by 61%. The interaction of the ginsenoside-CNT conjugate with breast cancer cells was studied using Raman Spectroscopy mapping. Total transcriptome profiling (Affymetrix platform) of MCF-7 cells treated with the ginsenoside-CNT conjugate shows that a number of cellular, apoptotic and response to stimulus processes were affected. Therefore, our data confirmed the potential use of CNT as a drug delivery system.

Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

International Nuclear Information System (INIS)

Li, Yi; Cui, Jiang-Tao

2016-01-01

Mammalian target of rapamycin (mTOR) is a therapeutic target for head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the activity of AZD-2014, a potent mTOR complex 1/2 (mTORC1/2) dual inhibitor, against HNSCC cells. We showed that AZD-2014 blocked mTORC1/2 activation in established and primary human HNSCC cells, where it was anti-proliferative and pro-apoptotic. Yet, AZD-2014 was non-cytotoxic to the human oral epithelial cells with low basal mTORC1/2 activation. In an effect to identify possible AZD-2014 resistance factors, we showed that the anti-apoptosis protein Bcl-2 was upregulated in AZD-2014-resistant SQ20B HNSCC cells. Inhibition of Bcl-2 by ABT-737 (a known Bcl-2 inhibitor) or Bcl-2 shRNA dramatically potentiated AZD-2014 lethality against HNSCC cells. On the other hand, exogenous overexpression of Bcl-2 largely attenuated AZD-2014’s activity against HNSCC cells. For the in vivo studies, we showed that oral gavage of AZD-2014 suppressed SQ20B xenograft growth in severe combined immunodeficient (SCID) mice. It also significantly improved mice survival. Importantly, AZD-2014’s anti-HNSCC activity in vivo was potentiated with co-administration of ABT-737. The preclinical results of this study suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. - Highlights: • AZD-2014 blocks mTORC1/2 activation in HNSCC cells. • AZD-2014 suppresses HNSCC cell proliferation. • AZD-2014 activates caspase-3 and apoptosis in HNSCC cells. • Bcl-2 is the key resistance factor of AZD-2014 in HNSCC cells. • ABT-737 sensitizes AZD-2014-induced anti-HNSCC activity in vivo.

Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

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Li, Yi; Cui, Jiang-Tao, E-mail: cuijingtaopaper@126.com

2016-09-02

Mammalian target of rapamycin (mTOR) is a therapeutic target for head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the activity of AZD-2014, a potent mTOR complex 1/2 (mTORC1/2) dual inhibitor, against HNSCC cells. We showed that AZD-2014 blocked mTORC1/2 activation in established and primary human HNSCC cells, where it was anti-proliferative and pro-apoptotic. Yet, AZD-2014 was non-cytotoxic to the human oral epithelial cells with low basal mTORC1/2 activation. In an effect to identify possible AZD-2014 resistance factors, we showed that the anti-apoptosis protein Bcl-2 was upregulated in AZD-2014-resistant SQ20B HNSCC cells. Inhibition of Bcl-2 by ABT-737 (a known Bcl-2 inhibitor) or Bcl-2 shRNA dramatically potentiated AZD-2014 lethality against HNSCC cells. On the other hand, exogenous overexpression of Bcl-2 largely attenuated AZD-2014’s activity against HNSCC cells. For the in vivo studies, we showed that oral gavage of AZD-2014 suppressed SQ20B xenograft growth in severe combined immunodeficient (SCID) mice. It also significantly improved mice survival. Importantly, AZD-2014’s anti-HNSCC activity in vivo was potentiated with co-administration of ABT-737. The preclinical results of this study suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. - Highlights: • AZD-2014 blocks mTORC1/2 activation in HNSCC cells. • AZD-2014 suppresses HNSCC cell proliferation. • AZD-2014 activates caspase-3 and apoptosis in HNSCC cells. • Bcl-2 is the key resistance factor of AZD-2014 in HNSCC cells. • ABT-737 sensitizes AZD-2014-induced anti-HNSCC activity in vivo.

Mecanismos de cardiotoxicidad: antineoplásicos, anti-inflamatorios no esteroideos, antipsicóticos, cocaetileno y simpaticomiméticos Mechanisms of cardiotoxicity: antineoplastics, nonsteroidal anti-inflammatory drugs, antipsychotics, cocaethylene and sympathomimetics

Directory of Open Access Journals (Sweden)

Lukas Salazar

2011-04-01

Full Text Available La interacción constante del organismo humano con diferentes sustancias, que incluso en muchas ocasiones se consideran inofensivas, tiene un alto impacto sobre todos los sistemas, siendo el cardiovascular uno de los más afectados. Por lo tanto, es vital reconocer los mecanismos por los cuales estas sustancias ejercen su efecto tóxico sobre este sistema, bien sea afectando la estabilidad de membrana y la función contráctil o generando disfunción de organelos intracelulares y estrés oxidativo. Numerosos estudios han descubierto efectos lesivos de sustancias, como la clozapina y las catecolaminas, que han tenido amplio uso durante largos años. En la actualidad aún se realizan investigaciones que buscan esclarecer los mecanismos cardiotóxicos de medicamentos de formulación común, entre ellos antineoplásicos y anti-inflamatorios no esteroideos (AINE, así como de sustancias de uso habitual que causan adicción, tales como alcohol, cocaína y cocaetileno, su metabolito activo.The constant interaction of the human body with different substances that are even in many cases considered harmless has a high impact on all systems, being the cardiovascular system one of the most affected. Therefore, it is vital to recognize the mechanisms by which these substances exert their toxic effect on this system, either affecting the membrane stability and the contractile function, or generating intracellular organelles dysfunction and oxidative stress. Numerous studies have found that drugs which have been widely used for many years such as clozapine and catecholamines, have harmful effects. Research is still being done seeking to clarify the cardiotoxic mechanisms of drugs commonly formulated, including anticancer and non steroidal anti-inflammatory drugs (NSAIDs, as well as commonly used substances that cause addiction, such as alcohol, cocaine and cocaethylene, its active metabolite.

Anti-inflammatory and anti-oxidant properties of Sida rhombifolia stems and roots in adjuvant induced arthritic rats.

Science.gov (United States)

Narendhirakannan, R T; Limmy, T P

2012-04-01

Free radical stress leads to tissue injury and progression of disease conditions such as arthritis, hemorrhagic shock, atherosclerosis, diabetes, hepatic injury, aging and ischemia, reperfusion injury of many tissues, gastritis, tumor promotion, neurodegenerative diseases and carcinogenesis. Safer anti-oxidants suitable for long term use are needed to prevent or stop the progression of free radical mediated disorders. Herbal medicine provides a foundation for various traditional medicine systems worldwide. The Sida species is one of the most important families of medicinal plants in India. Hence, the present study was aimed to investigate the possible anti-oxidant potential of Sida rhombifolia extracts for 30 days on adjuvant induced arthritis in experimental rats. The altered levels of hematological parameters were reverted to near normal levels, especially the elevated rate of erythrocyte sedimentation was significantly reduced by S. rhombifolia extracts in experimental rats. Oral administration of root and stem of S. rhombifolia extracts significantly increased the levels of thiobarbituric acid reactive substances and activities of catalase and glutathione peroxidase and decreased the levels of reduced glutathione and superoxide dismutase activity in arthritis induced rats. The free radical scavenging activity of the plant was further evidenced by histological and transmission electron microscopy observations made on the hind limb tissue.

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...

Sub-isotypic differences in the immunoglobulin G response to Lawsonia intracellularis in vaccinated, seropositive, and equine proliferative enteropathy-affected horses.

Science.gov (United States)

Page, Allen E; Stills, Harold F; Horohov, David W

2014-12-15

In the horse, Lawsonia intracellularis infection results in equine proliferative enteropathy (EPE). While upwards of 100% of weanlings on an endemic farm may seroconvert, only a small percentage (approximately 5%) will develop clinical disease. Cell-mediated immune mechanisms likely play a role in resistance to L. intracellularis and the absence of a L. intracellularis-specific IFN-γ response has been associated with the development of EPE. The goal of this study was to determine whether protection from clinical EPE is associated with the induction of a systemic IgG sub-isotypic response consistent with a Th1-type cytokine response. To describe their L. intracellularis/EPE status, horses enrolled in this study were placed into one of three categories: seropositive-only, vaccinated, and presumptive clinical EPE. An existing ELISA method was modified to detect L. intracellularis-specific IgG(a), IgG(b), and IgG(t) antibodies using the mouse anti-equine hybridomas CVS-48, CVS-39, and CVS-40, respectively. Additionally, the existing ELISA method was used to quantify total IgG antibodies specific for L. intracellularis for comparison between the groups. Total L. intracellularis-specific IgG was found to be significantly higher (pequine IgG sub-isotypes may provide additional information once these become commercially available. Copyright © 2014 Elsevier B.V. All rights reserved.

Antioxidant and apoptotic effects of an aqueous extract of Urtica dioica on the MCF-7 human breast cancer cell line.

Science.gov (United States)

Fattahi, Sadegh; Ardekani, Ali Motevalizadeh; Zabihi, Ebrahim; Abedian, Zeinab; Mostafazadeh, Amrollah; Pourbagher, Roghayeh; Akhavan-Niaki, Haleh

2013-01-01

Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of r(2)=0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an IC50 value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.

Report on achievements in fiscal 1998. Venture business growing type consortium - small business creating infrastructure (Development of simplified analysis system by using bio-markers of internal secretion disturbing substances - environmental hormone acting substances); 1998 nendo naibunpi kakuran busshitsu (kankyo hormone sayo busshitsu) no bio marker ni yoru kanben bunseki system no kaihatsu seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-03-01

Using the vitellogenin levels in male fishes as a parameter of pollution caused by internal secretion disturbing substances would allow collective measurement of compounding action of pollutants, acquisition of time averaged values, and large reduction in analysis cost. The present research and development works are intended to put such technological seeds into practical use, and promote its proliferation. The following subjects were implemented: (1) fabrication of effective anti-bodies, (2) their application to fresh water fishes, salmon, and trout, (3) their application to sea water fishes, (4) effects on mummichog and medaka, (5) correlation between spawning actions and vitellogenin manifestation in male fish, (6) discussions on chemical analysis methods and the correlativity therewith, and (7) establishment of methods for field investigation and evaluation. In Item (1), an ELISA system using vitellogenin anti-bodies of different fishes was established. A universal anti-body reacting commonly to all of fish vitellogenins was developed. In Items (2), (3) and (4), an evaluation system was established on actions of internal secretion disturbing substances on sea water fish and fresh water fish by using fish vitellogenins. In Item (5), effects on spawning of medaka, and effects on procreation activities (sterility) were evaluated by using vitellogenin. (NEDO)

Psychopathology in Substance Use Disorder Patients with and without Substance-Induced Psychosis

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Simon Zhornitsky

2015-01-01

Full Text Available Background. Substance-induced psychotic disorder (SIPD is a diagnosis constructed to distinguish substance-induced psychotic states from primary psychotic disorders. A number of studies have compared SIPD persons with primary psychotic patients, but there is little data on what differentiates substance use disorder (SUD individuals with and without SIPD. Here, we compared psychopathology, sociodemographic variables, and substance use characteristics between SUD patients with and without SIPD. Methods. A retrospective chart review was conducted on newly admitted patients at a rehabilitation centre between 2007 and 2012. Results. Of the 379 patients included in the study, 5% were diagnosed with SIPD n=19 and 95% were diagnosed with SUDs without SIPD n=360. More SIPD patients reported using cannabis and psychostimulants, and fewer SIPD patients reported using alcohol than SUDs patients without SIPD. SIPD patients scored higher on the “schizophrenia nuclear symptoms” dimension of the SCL-90R psychoticism scale and exhibited more ClusterB personality traits than SUD patients without SIPD. Discussion. These data are consistent with previous studies suggesting that psychopathology, substance type, and sociodemographic variables play important role in the development of SIPD. More importantly, the results highlight the need for paying greater attention to the types of self-reported psychotic symptoms during the assessment of psychotomimetic effects associated with psychoactive substances.

Mother-Child Interaction and Early Language Skills in Children Born to Mothers with Substance Abuse and Psychiatric Problems.

Science.gov (United States)

J Haabrekke, Kristin; Siqveland, Torill; Smith, Lars; Wentzel-Larsen, Tore; Walhovd, Kristine B; Moe, Vibeke

2015-10-01

This prospective, longitudinal study with data collected at four time points investigated how maternal psychiatric symptoms, substance abuse and maternal intrusiveness in interaction were related to early child language skills. Three groups of mothers were recruited during pregnancy: One from residential treatment institutions for substance abuse (n = 18), one from psychiatric outpatient treatment (n = 22) and one from well-baby clinics (n = 30). Maternal substance abuse and anti-social and borderline personality traits were assessed during pregnancy, postpartum depression at 3 months, maternal intrusiveness in interaction at 12 months, and child language skills at 2 years. Results showed that the mothers in the substance abuse group had the lowest level of education, they were younger and they were more likely to be single mothers than the mothers in the two other groups. There was a significant difference in expressive language between children born to mothers with substance abuse problems and those born to comparison mothers, however not when controlling for maternal age, education and single parenthood. No group differences in receptive language skills were detected. Results further showed that maternal intrusiveness observed in mother-child interaction at 12 months was significantly related to child expressive language at 2 years, also when controlling for socio-demographic risk factors. This suggests that in addition to addressing substance abuse and psychiatric problems, there is a need for applying treatment models promoting sensitive caregiving, in order to enhance child expressive language skills.

BIOPREPARATIONS USING IN THE ISCHEMIC HEART INJURY THERAPY

Directory of Open Access Journals (Sweden)

A. K. Gulevsky

2013-04-01

Full Text Available Possibility of biologically active substances using such as growth factors, cytomedines, natural antioxidants, substances contained in extracts from juvenile and fetal organs and animal tissues in the experiments and clinic of ischemic heart injury are discussed. Along with the well-studied and widely used in clinical practice biopreparations such as kordialin, actovegin, erbisol nesiritide, energostim, as promising tools for treatment of cardiovascular diseases, the extracts from the heart and low molecular weight fraction of cord blood are considered. It is shown that using of tissue reparative embriofetoplatsenta complex increases myocardial contractility. The main difference between these biopreparations and biogenic stimulants is that they have a balanced composition of biologically active substances, in particular different activators of regeneration and differentiation (fibroblast growth factors, nerve-stimulating factor and macrophage erythroid colonies and anti-proliferative cytokines preventing cellular and systemic hyperstimulation as well as other substances able to initiate a directed differentiation of stem cells and to affect regeneration of human myocardium, and hence to optimize the treatment of myocardial infarction. In addition, fetal cells and their associates are almost nonimmunogens. Thus, if the growth factors and differentiation capable to regulate the mitotic activity of cardiomyocytes are determined, it will be possible to initiate a process of stem cells directed differentiation and affect on the human myocardium regeneration, and hence to optimize the treatment of myocardial infarction.

Anti-allergic properties of Mangifera indica L. extract (Vimang) and contribution of its glucosylxanthone mangiferin.

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Rivera, Dagmar García; Balmaseda, Ivones Hernández; León, Alina Alvarez; Hernández, Belkis Cancio; Montiel, Lucía Márquez; Garrido, Gabino Garrido; Cuzzocrea, Salvatore; Hernández, René Delgado

2006-03-01

Vimang is the brand name of formulations containing an extract of Mangifera indica L., ethnopharmacologically used in Cuba for the treatment of some immunopathological disorders, including bronchial asthma, atopic dermatitis and other allergic diseases. However, the effects of Vimang on allergic response have not been reported until now. In this study, the effects of Vimang and mangiferin, a C-glucosylxanthone isolated from the extract, on different parameters of allergic response are reported. Vimang and mangiferin showed a significant dose-dependent inhibition of IgE production in mice and anaphylaxis reaction in rats, histamine-induced vascular permeability and the histamine release induced by compound 48/80 from rat mast cells, and of lymphocyte proliferative response as evidence of the reduction of the amount of B and T lymphocytes able to contribute to allergic response. In these experiments, ketotifen, promethazine and disodium cromoglicate were used as reference drugs. Furthermore, we demonstrated that Vimang had an effect on an in-vivo model of inflammatory allergy mediated by mast cells. These results constitute the first report of the anti-allergic properties of Vimang on allergic models, as well as suggesting that this natural extract could be successfully used in the treatment of allergic disorders. Mangiferin, the major compound of Vimang, contributes to the anti-allergic effects of the extract.

Toxic substances alert program

Science.gov (United States)

Junod, T. L.

1978-01-01

A toxicity profile is provided, of 187 toxic substances procured by NASA Lewis Research Center during a 3 1/2 year period, including 27 known or suspected carcinogens. The goal of the program is to assure that the center's health and safety personnel are aware of the procurement and use of toxic substances and to alert and inform the users of these materials as to the toxic characteristics and the control measures needed to ensure their safe use. The program also provides a continuing record of the toxic substances procured, who procured them, what other toxic substances the user has obtained in the past, and where similar materials have been used elsewhere at the center.

Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

Science.gov (United States)

de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra

2016-01-01

Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed. In addition, a critical evaluation of the recently emerged ligands fishing assays in complex mixtures is also discussed. PMID:27306095

Accounting for treatment delays when treating highly proliferative tumours

International Nuclear Information System (INIS)

Jones, L.; Metcalfe, P.; Hoban, P.

1999-01-01

This study was undertaken to investigate the possibility of increasing the dose per fraction or increasing the number of fractions to account for treatment delays occurring during radiotherapy treatments for highly proliferative tumours. The linear quadratic model with time was used to determine the difference in biological effective dose (BED) for the original schedule and the schedule including a treatment delay. Tables of extra fractions and extra dose per fraction required to account for a number of possible delays have been determined. It has been shown that for tumours with very short potential doubling times it is best to deliver the extra dose as an increase in dose per fraction rather than an increase in the number of fractions, while for tumours with moderately short potential doubling times (above 7 days) the reverse is true. The equivalent uninterrupted schedules, which would have delivered the same effects to the tumour, have also been determined. (author)

Inheritance of proliferative breast disease in breast cancer kindreds

International Nuclear Information System (INIS)

Skolnick, M.H.; Cannon-Albright, L.A.; Goldgar, D.E.; Ward, J.H.; Marshall, C.J.; Schumann, G.B.; Hogle, H.; McWhorter, W.P.; Wright, E.C.; Tran, T.D.; Bishop, D.T.; Kushner, J.P.; Eyre, H.J.

1990-01-01

Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer

Wingless promotes proliferative growth in a gradient-independent manner.

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Baena-Lopez, Luis Alberto; Franch-Marro, Xavier; Vincent, Jean-Paul

2009-10-06

Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during development depends on their graded distributions. Here, we describe an experimental test of this model for Wingless, one of the key organizers of wing development in Drosophila. Maximal Wingless signaling suppresses cellular proliferation. In contrast, we found that moderate and uniform amounts of exogenous Wingless, even in the absence of endogenous Wingless, stimulated proliferative growth. Beyond a few cell diameters from the source, Wingless was relatively constant in abundance and thus provided a homogeneous growth-promoting signal. Although morphogen signaling may act in combination with as yet uncharacterized graded growth-promoting pathways, we suggest that the graded nature of morphogen signaling is not required for proliferation, at least in the developing Drosophila wing, during the main period of growth.

Dimethyl sulfoxide-caused changes in pro- and anti-angiogenic factor levels could contribute to an anti-angiogenic response in HeLa cells.

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Şimşek, Ece; Aydemir, Esra Arslan; İmir, Nilüfer; Koçak, Orhan; Kuruoğlu, Aykut; Fışkın, Kayahan

2015-10-01

Dimethyl sulfoxide (DMSO) is widely used in biological research as a general solvent. While it has been previously demonstrated that DMSO possesses a wide range of pharmacological effects, there is no published work regarding the effects of DMSO on pro-angiogenic factor levels. This study was designed to investigate the possible effects of DMSO on the levels of three pro-angiogenic factors released from HeLa cells in vitro. Cells were treated with two different and previously determined concentrations of DMSO. The cytotoxic effects of DMSO concentrations on HeLa cells were determined via MTT. Survival rates of DMSO-treated cells were determined by Invitrogen live/dead viability/cytotoxicity kit and trypan blue exclusion assay. Changes in the pro-angiogenic levels in media were evaluated by Cayman's Substance P Enzyme Immunoassay ELISA kit. Vascular endothelial growth factor ELISA kit and interferon gamma ELISA kit for substance P, VEGF and IFNγ respectively. Changes in substance P levels were corrected by standard western blotting. Changes in VEGF and IFNγ levels were corrected both by western blot and real time PCR. Treatment with 1.4 μM DMSO caused a time-dependent inhibition of cell proliferation at 24, 48 and 72 h. 1.4 μM DMSO caused a significant reduction in VEGF levels at 72 h of incubation and sharp increases in IFNγ levels at both 48 and 72 h of incubation. According to real time PCR analyses, DMSO (1.4 μM) exhibited an inhibitory effect on VEGF but acted as an augmenter of IFNγ release on HeLa cells in vitro. This is the first report showing that the general solvent DMSO suppressed HeLa cell proliferation, decreased the levels of two pro-angiogenic factors (substance P and VEGF) and increased the release of an anti-angiogenic factor IFNγ in vitro. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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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.

Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling

International Nuclear Information System (INIS)

Meyer, J.S.; Sufrin, G.; Martin, S.A.

1982-01-01

The thymidine labeling index (TLI) was measured in vitro in the epithelium and stroma of benign prostate glands and seminal vesicles and in the epithelium of prostatic adenocarcinomas. The mean epithelial TLI of normal peripheral (posterior) prostatic zone was 0.12 per cent, and that of the normal central (deep) zone was 0.11 per cent. Mean normal stromal TLI's were 0.08 per cent and 0.06 per cent, respectively. The mean TLI of epithelium in nodular hyperplasia was 0.31 per cent, which differs significantly from normal epithelium, and the mean stromal TLI was also increased. The mean TLI of prostatic adenocarcinomas was 0.90 per cent (range 0.14 to 3.90 per cent) which was significantly higher than for either normal epithelium or epithelium of nodular hyperplasia. Trends of increasing TLI with increasing histologic grades and increasing nuclear size and numbers of nucleoli were not significant. The data support participation of both epithelial and stromal proliferation in nodular hyperplasia, and indicate a low basal proliferative rate in normal prostatic glands. The low TLI's of prostatic adenocarcinomas relative to other malignancies are consistent with their frequently slowly progressive course. The very low proliferative rate of seminal vesicular epithelium may account for the rarity of seminal vesicular carcinomas

Substance abuse and child maltreatment.

Science.gov (United States)

Wells, Kathryn

2009-04-01

Pediatricians and other medical providers caring for children need to be aware of the dynamics in the significant relationship between substance abuse and child maltreatment. A caregiver's use and abuse of alcohol, marijuana, heroin, cocaine, methamphetamine, and other drugs place the child at risk in multiple ways. Members of the medical community need to understand these risks because the medical community plays a unique and important role in identifying and caring for these children. Substance abuse includes the abuse of legal drugs as well as the use of illegal drugs. The abuse of legal substances may be just as detrimental to parental functioning as abuse of illicit substances. Many substance abusers are also polysubstance users and the compounded effect of the abuse of multiple substances may be difficult to measure. Often other interrelated social features, such as untreated mental illness, trauma history, and domestic violence, affect these families.

ABORTION AND VIOLENCE IN JANE MARTIN’S KEELY AND DU: PRO-CHOICE, PRO-LIFE, OR MERELY PROVOCATIVE?

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Eta Farmacelia Nurulhady

2017-04-01

Full Text Available Abortion and violence are global issues, yet different culture might respond to the issues somewhat differently. This study aims to reveal the abortion and violence issues in Jane Martin’s Keely and Du in terms of pro-choice and pro life movements and see how Indonesian students reading the play respond to the issues. In the United States of America, the discussion of abortion issue can be grouped into two major categories: the pro-life and pro-choice. In Indonesia, the majority of people would be against abortion when it is not for medical reasons. The students reading Keely and Du find the play challenging their beliefs as religious people still keeping hold of eastern values. Having discussed the nature of pro-life and pro-choice movements, it is difficult for them to decide whether they are proponent of either one. Keely and Du is successfully provocative in offering insight on how abortion and violence issues cannot be judged in a black and white manner.

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

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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. © 2014 S. Karger AG, Basel

When acute-stage psychosis and substance use co-occur: differentiating substance-induced and primary psychotic disorders.

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Caton, C L; Samet, S; Hasin, D S

2000-09-01

Substances such as alcohol, cocaine, amphetamine, and cannabis can produce psychotic reactions in individuals who are otherwise free of serious mental illness. However, persons with primary psychotic disorders, such as schizophrenia and bipolar disorder, who use these substances often present for treatment with signs and symptoms similar to those whose psychosis resulted from the use of drugs alone. While it is often difficult to distinguish substance-induced from primary psychoses, especially early in the course of treatment, this differential diagnosis has important implications for treatment planning. To help clinicians distinguish these two types of presentations, the authors first review the types of psychotic symptoms that can co-occur with substance use. They discuss the prevalence and patterns of substance use that have been found in patients with schizophrenia and other primary psychotic disorders and review the negative outcomes associated with substance use in this population. The prevalence of and types of symptoms and problems associated with psychotic symptoms that occur as a result of substance use alone are also reviewed. The authors describe assessment procedures for differentiating substance-induced and primary psychotic disorders. They stress the importance of accurately establishing the temporal relationship between the substance use and the onset and continuation of psychotic symptoms in making a differential diagnosis, as well as the importance of being familiar with the types of psychological symptoms that can occur with specific substances. The authors review the utility and limitations of a number of diagnostic instruments for assessing patients with co-occurring psychosis and substance use problems, including The Addiction Severity Index, The Michigan Alcohol Screening Test, and diagnostic interviews such as the Schedule for Affective Disorders and Schizophrenia and the Structured Clinical Interview for DSM. They then discuss the

Lymphocyte proliferative responses to mitogens in rats having an ancestry of a perinatal iodine-131 insult

International Nuclear Information System (INIS)

Stevens, R.H.; Cheng, H.F.

1987-01-01

The possible existence of a genealogical memory consisting of altered lymphocyte proliferative responses to a perinatal iodine-131 insult has been investigated in two generations of inbred Fischer F344 rat offspring. The studies which involved exposure to the radioiodine during late pregnancy with concentrations ranging from 1.85 MBq (50 μCi) to 7.4 MBq (200 μCi) revealed that only the peripheral blood T lymphocytes of the first generation male animals were significantly affected. These animals were found to possess T lymphocytes which exhibited increased proliferative responses expressed toward the mitogens concanavalin A and phytohemagglutin; however, no significant changes were noticeable in their B cell population following exposure to lipopolysaccharide. Neither the first generation females nor the male and female offspring of the second generation developed through sibling interbreeding seemed to be affected, this was unlike the cellular, humoral, and natural immunity which had previously been observed to be changed in both the second and third generation animals. These observations suggest that the effects of the radiation insult upon immunocompetency as measured by lymphocyte proliferation do not appear to be inherited

Anti-G with concomitant anti-C and anti-D: A case report in a pregnant woman.

Science.gov (United States)

Yousuf, Rabeya; Mustafa, Ahmad Nasirudin; Ho, Siew-Ling; Tang, Yee-Loong; Leong, Chooi-Fun

2017-01-01

The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG) when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women.

Anti-Cyclic Citrullinated Peptide (Anti-CCP and Anti-Mutated Citrullinated Vimentin (Anti-MCV Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

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Laura Gonzalez-Lopez

2014-01-01

Full Text Available We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP and anti-mutated citrullinated vimentin antibodies (anti-MCV with the presence of extra-articular (ExRA manifestations in 225 patients with rheumatoid arthritis (RA. Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P=0.40 and P=0.91, resp.. Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF; (P=0.01, anti-CCP (P=0.048, and anti-MCV (P=0.02. Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di (r=0.154, P=0.03, erythrocyte sedimentation rate (ESR; (r=0.155, P=0.03, and RF (P=0.254, P<0.001, whereas anti-MCV titres only correlated with RF (r=0.169, P=0.02. On adjusted analysis, ExRA was associated with longer age (P=0.015, longer disease duration (P=0.007, higher DAS-28 score (P=0.002, and higher HAQ-DI score (P=0.007, but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation.

[Effect of low-intensity electromagnetic fields of industrial frequency on the ultrastructure and proliferative activity of rat's thymus cells].

Science.gov (United States)

Zhitkevich, T I; Bokut', T B; Netukova, N I

2001-01-01

Effects of two types of low-intensity electromagnetic fields (EMF) of industrial frequency (50 Hz) on the fine structure and proliferative activity of thymic cells in white rats were studied. It was found that a weak EMF with a prevailing electrical component (380-480 V/m, 120-140 nT1) did not affect the DNA synthesis intensity. An EMF with a stronger magnetic induction (10-15 V/m, 800-1500 nT1) diminished the glucose-6-phosphate dehydrogenase activity and proliferative processes in cultured stimulated lymphocytes. Electron microscopic investigation of the thymus after both types of exposure revealed an accumulation of lymphocytes with pyknotic nuclei and electron-dense cytoplasm, as well as hypoplasia of the vascular endothelium. At the same time, EMF with a prevailing magnetic component produced a more marked negative effect on the ultrastructure of thymic cells, which indicated a lowered secretory activity of epitheliocytes.

Anti-G with concomitant anti-C and anti-D: A case report in a pregnant woman

Directory of Open Access Journals (Sweden)

Rabeya Yousuf

2017-01-01

Full Text Available The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women.

Playing video games while using or feeling the effects of substances: associations with substance use problems.

Science.gov (United States)

Ream, Geoffrey L; Elliott, Luther C; Dunlap, Eloise

2011-10-01

This study tested the hypothesis that playing video games while using or feeling the effects of a substance--referred to herein as "concurrent use"-is related to substance use problems after controlling for substance use frequency, video gaming as an enthusiastic hobby, and demographic factors. Data were drawn from a nationally representative online survey of adult video gamers conducted by Knowledge Networks, valid n = 2,885. Problem video game playing behavior was operationalized using Tejeiro Salguero and Bersabé Morán's 2002 problem video game play (PVP) measure, and measures for substance use problems were taken from the National Survey of Drug Use and Health (NSDUH). Separate structural equation modeling analyses were conducted for users of caffeine, tobacco, alcohol, and marijuana. In all four models, concurrent use was directly associated with substance use problems, but not with PVP. Video gaming as an enthusiastic hobby was associated with substance use problems via two indirect paths: through PVP for all substances, and through concurrent use for caffeine, tobacco, and alcohol only. Results illustrate the potential for "drug interaction" between self-reinforcing behaviors and addictive substances, with implications for the development of problem use.

Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti

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Haonan Zhou

2016-11-01

Full Text Available Radix Aconiti, a classic traditional Chinese medicine (TCM, has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA. Finally, the CCA results showed that LysoPC(22:5 is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity.

Influence of ecological factors on the production of active substances in the anti-cancer plant Sinopodophyllum hexandrum (Royle T.S. Ying.

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Wei Liu

Full Text Available The quality of traditional Chinese herbal medicine, which plays a very important role in the health system of China, is determined by the active substances produced by the plants. The type, content, and proportion of these substances may vary depending on ecological factors in areas where the plants are grown. Sinopodophyllum hexandrum (Royle T.S. Ying, an endangered plant species with great medical value, was investigated in eight production locations representative of its natural geographical distribution range in China. The correlation between the contents of the active ingredients extracted from the roots and rhizomes of S. hexandrum and the ecological factors were evaluated step-by-step using a series of computational biology methodologies. The results showed that ecological factors had significant effects on the contents but not on the types of the active ingredients in eight production locations. The primary ecological factors influencing the active substances included the annual average precipitation, July mean temperature, frost-free period, sunshine duration, soil pH, soil organic matter, and rapidly available potassium in the soil. The annual average precipitation was the most important determinant factor and was significantly and negatively correlated with the active ingredient contents (P < 0.001. In contrast, organic matter was the most important limiting factor and was significantly and positively correlated with the active substances. These ecological factors caused 98.13% of the total geographical variation of the active ingredient contents. The climate factors contributed more to the active ingredient contents than did the soil factors. It was concluded that from the view of the contents of the secondary metabolites and ecological factors of each growing location, in Jingyuan, Ningxia Province, and Yongdeng, Gansu Province, conditions were favorable to the production of podophyllotoxin and lignans, whereas in Shangri-La, Yunnan

The treatment of bronchial obstruction by beta/sub 2/-agonist and anti-cholinergic aerosol. Advantages of associating the two types of substance

Energy Technology Data Exchange (ETDEWEB)

Minette, A.; Marcq, M.

1980-01-01

The authors review the basic aspects of bronchodilatory treatment using beta/sub 2/-agonist and atropinic aerosols; present the results of a review of literature on the subject of the toxicity of various vector gases used in aerosols of this type; discuss the problems associated with the deposition disparity of aerosols in normal and pathological lungs; present and discuss the results of the prevalence of positive responses to atropine methyl-nitrate and to beta-agonist given in aerosol form to a group of subjects with reversible bronchial obstruction; discuss the advantages of oxitropium bromide, an atropic substance which has recently been discovered and which is apparently more interesting than ipratropium bromide, against the background of the ventilatory effects as observed for these 2 substances on 19 patients suffering from reversible bronchial obstruction; and discuss the advantages of associating atropinic and beta/sub 2/-agonist substances in the same aerosol on the bass of the effects of a recently-developed preparation which combines fenoterol and ipratropium bromide. 57 refs.

Model independent calculation of B(anti B0→D(*)+τ- anti ν)/B(anti B0→D(*)+e- anti ν)

International Nuclear Information System (INIS)

Hwang, D.S.

2000-01-01

Using the formulas for the dΓ/dq 2 distribution with non-zero lepton mass and experimentally determined form factors, we calculate the dΓ(D (*)+ l - anti ν)/dq 2 spectra and branching fractions for l=e,μ and τ. We obtain the results B(anti B 0 →D + τ - anti ν)/B(anti B 0 →D + e - anti ν)=0.278 +0.049 -0.035 and B(anti B 0 →D *+ τ - anti ν)/B(anti B 0 →D *+ e - anti ν)=0.256 +0.014 -0.013 . Since we used the experimentally measured form factors, these results are independent of theoretical models of the form factors. (orig.)

Reward deficiency and anti-reward in pain chronification.

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Borsook, D; Linnman, C; Faria, V; Strassman, A M; Becerra, L; Elman, I

2016-09-01

Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypodopaminergia, clinically manifested anhedonia, and diminished motivation for natural reinforcers. Anti-reward (AR) conversely pertains to a between-systems neuroadaptation involving over-recruitment of key limbic structures (e.g., the central and basolateral amygdala nuclei, the bed nucleus of the stria terminalis, the lateral tegmental noradrenergic nuclei of the brain stem, the hippocampus and the habenula) responsible for massive outpouring of stressogenic neurochemicals (e.g., norepinephrine, corticotropin releasing factor, vasopressin, hypocretin, and substance P) giving rise to such negative affective states as anxiety, fear and depression. We propose here the Combined Reward deficiency and Anti-reward Model (CReAM), in which biopsychosocial variables modulating brain reward, motivation and stress functions can interact in a 'downward spiral' fashion to exacerbate the intensity, chronicity and comorbidities of chronic pain syndromes (i.e., pain chronification). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

National substance use patterns on Twitter.

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Hsien-Wen Meng

Full Text Available We examined openly shared substance-related tweets to estimate prevalent sentiment around substance use and identify popular substance use activities. Additionally, we investigated associations between substance-related tweets and business characteristics and demographics at the zip code level.A total of 79,848,992 tweets were collected from 48 states in the continental United States from April 2015-March 2016 through the Twitter API, of which 688,757 were identified as being related to substance use. We implemented a machine learning algorithm (maximum entropy text classifier to estimate sentiment score for each tweet. Zip code level summaries of substance use tweets were created and merged with the 2013 Zip Code Business Patterns and 2010 US Census Data.Quality control analyses with a random subset of tweets yielded excellent agreement rates between computer generated and manually generated labels: 97%, 88%, 86%, 75% for underage engagement in substance use, alcohol, drug, and smoking tweets, respectively. Overall, 34.1% of all substance-related tweets were classified as happy. Alcohol was the most frequently tweeted substance, followed by marijuana. Regression results suggested more convenience stores in a zip code were associated with higher percentages of tweets about alcohol. Larger zip code population size and higher percentages of African Americans and Hispanics were associated with fewer tweets about substance use and underage engagement. Zip code economic disadvantage was associated with fewer alcohol tweets but more drug tweets.The patterns in substance use mentions on Twitter differ by zip code economic and demographic characteristics. Online discussions have great potential to glorify and normalize risky behaviors. Health promotion and underage substance prevention efforts may include interactive social media campaigns to counter the social modeling of risky behaviors.

What is it really? Anti-G or Anti-D plus Anti-C: Clinical Significance in Antenatal Mothers.