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Sample records for brain liver lung

  1. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

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    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Richardson, Jason R. [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States); Heck, Diane E. [Environmental Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY (United States); Laskin, Debra L. [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States)

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  2. Imaging Plasmodium immunobiology in the liver, brain, and lung.

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    Frevert, Ute; Nacer, Adéla; Cabrera, Mynthia; Movila, Alexandru; Leberl, Maike

    2014-02-01

    Plasmodium falciparum malaria is responsible for the deaths of over half a million African children annually. Until a decade ago, dynamic analysis of the malaria parasite was limited to in vitro systems with the typical limitations associated with 2D monocultures or entirely artificial surfaces. Due to extremely low parasite densities, the liver was considered a black box in terms of Plasmodium sporozoite invasion, liver stage development, and merozoite release into the blood. Further, nothing was known about the behavior of blood stage parasites in organs such as the brain where clinical signs manifest and the ensuing immune response of the host that may ultimately result in a fatal outcome. The advent of fluorescent parasites, advances in imaging technology, and availability of an ever-increasing number of cellular and molecular probes have helped illuminate many steps along the pathogenetic cascade of this deadly tropical parasite.

  3. Radioisotope scanning of brain, liver, lung and bone with a note on tumour localizing agents

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    Lavender, J. P.

    1973-01-01

    Radioisotopic scanning of brain, liver, lungs and the skeleton is briefly reviewed with a survey of recent developments of clinical significance. In brain scanning neoplasm detection rates of greater than 90% are claimed. The true figure is probably 70-80%. Autopsy data shows a number of false negatives, particularly with vascular lesions. Attempts to make scanning more specific in differentiating neoplasm from vascular lesions by rapid sequence blood flow studies are reviewed. In liver scanning by means of colloids again high success rate is claimed but small metastases are frequently missed and the false negative scan rate is probably quite high. Lung scanning still has its main place in investigating pulmonary embolic disease. Ventilation studies using Xenon 133 are useful, particularly combined with perfusion studies. The various radiopharmaceuticals for use in bone scanning are reviewed. The appearance of technetium labelled phosphate compounds will probably allow much wider use of total skeletal scanning. Research into tumour localizing agents continues, the most recent and interesting being Gallium citrate and labelled bleomycin. Neither agent is predictable however although Gallium may have a place in Hodgkins disease and bronchogenic neoplasm and both may have a place in the detection of cerebral tumours. ImagesFig. 1Fig. 2Fig. 3p452-bFig. 3bFig. 4Fig. 5Fig. 5bFig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 12c & 12dFig. 13Fig. 13 b,c,dFig. 14Fig. 14bFig. 15Fig. 15bFig. 16Fig. 17Fig. 18 PMID:4602127

  4. Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target

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    Elshenawy, Osama H.; Shoieb, Sherif M.; Mohamed, Anwar; El-Kadi, Ayman O.S.

    2017-01-01

    Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal ischemia/reperfusion (I/R) injury and polycystic kidney diseases. The role of 20-HETE in the liver is not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, and it is associated with liver cirrhotic ascites. In the respiratory system, 20-HETE plays a role in pulmonary cell survival, pulmonary vascular tone and tone of the airways. As for the brain, 20-HETE is involved in cerebral I/R injury. Moreover, 20-HETE has angiogenic and mitogenic properties and thus helps in tumor promotion. Several inhibitors and inducers of the synthesis of 20-HETE as well as 20-HETE analogues and antagonists are recently available and could be promising therapeutic options for the treatment of many disease states in the future. PMID:28230738

  5. Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target

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    Osama H. Elshenawy

    2017-02-01

    Full Text Available Cytochrome P450-mediated metabolism of arachidonic acid (AA is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal 19 ischemia/reperfusion (I/R injury and polycystic kidney diseases. The role of 20-HETE in the liver is not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, and it is associated with liver cirrhotic ascites. In the respiratory system, 20-HETE plays a role in pulmonary cell survival, pulmonary vascular tone and tone of the airways. As for the brain, 20-HETE is involved in cerebral I/R injury. Moreover, 20-HETE has angiogenic and mitogenic properties and thus helps in tumor promotion. Several inhibitors and inducers of the synthesis of 20-HETE as well as 20-HETE analogues and antagonists are recently available and could be promising therapeutic options for the treatment of many disease states in the future.

  6. [A Case of Brain Metastasis from Rectal Cancer with Synchronous Liver and Lung Metastases after Multimodality Treatment--A Case Report].

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    Udagawa, Masaru; Tominaga, Ben; Kobayashi, Daisuke; Ishikawa, Yuuya; Watanabe, Shuuichi; Adikrisna, Rama; Okamoto, Hiroyuki; Yabata, Eiichi

    2015-11-01

    We report a case of brain metastasis from rectal cancer a long time after the initial resection. A 62-year-old woman, diagnosed with lower rectal cancer with multiple synchronous liver and lung metastases, underwent abdominoperineal resection after preoperative radiochemotherapy (40 Gy at the pelvis, using the de Gramont regimen FL therapy: 1 kur). The histological diagnosis was a moderately differentiated adenocarcinoma. Various regimens of chemotherapy for unresectable and metastatic colorectal cancer were administered, and a partial response was obtained; thereby, the metastatic lesions became resectable. The patient underwent partial resection of the liver and lung metastases. Pathological findings confirmed that both the liver and lung lesions were metastases from the rectal cancer. A disease-free period occurred for several months; however, there were recurrences of the lung metastases, so we started another round of chemotherapy. After 8 months, she complained of vertigo and dizziness. A left cerebellar tumor about 3 cm in diameter was revealed by MRI and neurosurgical excision was performed. Pathological findings confirmed a cerebellar metastasis from the rectal cancer. Twenty months after resection of the brain tumor, the patient complained of a severe headache. A brain MRI showed hydrocephalia, and carcinomatous meningitis from rectal cancer was diagnosed by a spinal fluid cytology test. A ventriculo-peritoneal shunt was inserted, but the cerebrospinal pressure did not decreased and she died 20 months after the first surgery. Although brain metastasis from colorectal cancer is rare, the number of patients with brain metastasis is thought to increase in the near future. Chemotherapy for colorectal cancer is effective enough to prolong the survival period even if multiple metastases have occurred. However, after a long survival period with lung metastases such as in our case, there is a high probability of developing brain metastases.

  7. Development and Preclinical Application of an Immunocompetent Transplant Model of Basal Breast Cancer with Lung, Liver and Brain Metastases.

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    Olga Aprelikova

    Full Text Available Triple negative breast cancer (TNBC is an aggressive subtype of breast cancer that is associated with a poor prognosis and for which no targeted therapies currently exist. In order to improve preclinical testing for TNBC that relies primarily on using human xenografts in immunodeficient mice, we have developed a novel immunocompetent syngeneic murine tumor transplant model for basal-like triple-negative breast cancer. The C3(1/SV40-T/t-antigen (C3(1/Tag mouse mammary tumor model in the FVB/N background shares important similarities with human basal-like TNBC. However, these tumors or derived cell lines are rejected when transplanted into wt FVB/N mice, likely due to the expression of SV40 T-antigen. We have developed a sub-line of mice (designated REAR mice that carry only one copy of the C3(1/Tag-antigen transgene resulting from a spontaneous transgene rearrangement in the original founder line. Unlike the original C3(1/Tag mice, REAR mice do not develop mammary tumors or other phenotypes observed in the original C3(1/Tag transgenic mice. REAR mice are more immunologically tolerant to SV40 T-antigen driven tumors and cell lines in an FVB/N background (including prostate tumors from TRAMP mice, but are otherwise immunologically intact. This transplant model system offers the ability to synchronously implant the C3(1/Tag tumor-derived M6 cell line or individual C3(1/Tag tumors from various stages of tumor development into the mammary fat pads or tail veins of REAR mice. C3(1/Tag tumors or M6 cells implanted into the mammary fat pads spontaneously metastasize at a high frequency to the lung and liver. M6 cells injected by tail vein can form brain metastases. We demonstrate that irradiated M6 tumor cells or the same cells expressing GM-CSF can act as a vaccine to retard tumor growth of implanted tumor cells in the REAR model. Preclinical studies performed in animals with an intact immune system should more authentically replicate treatment

  8. MR ASSESSMENT OF LUNG DEVELOPMENT IN FETAL ANOMALIES USING RATIO OF LUNG TO LIVER SIGNAL INTENSITIES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To evaluate the monitoring and diagnostic potential of MR in fetal lung development using lung signal intensity changes in the fetus. Methods The lung-to-liver intensity ratio was calculated by means of region-of-interest analysis in all 35 fetuses including 7 bilateral urinary anomalies, 9 unilateral urinary anomalies, 5 pulmonary anomalies, and 14 others. Results All fetuses with urinary anomalies and pulmonary anomalies showed low ratio of lung-to-liver signal intensity. Conclusion Low ratio of lung-to-liver signal intensity on MR imaging indicates pulmonary hypoplasia after 22 weeks' gestation.

  9. HYDATID CYST IN LUNG AND LIVER

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    Mani

    2015-09-01

    Full Text Available Hydatid cyst is especially prevalent in parts of Eurasia, north and east Africa, Australia, South America. Hydatid disease is a zoonotic infection caused by adult or larval stages of the cestode Echinococcus granulosus and affects both humans and mammals. The infection is transmitted to dogs when they are fed on infected viscera of sheep or other ruminant during the home slaughter of animals. In the present case series four cases of hydatid cyst occurring at the lung and liver sites are discussed. The symptoms and signs may be caused by a toxic reaction to the parasite or by local and mechanical effects, depending on the location and nature of the cysts and the presence of complications. Early diagnosis and proper treatment will help to reduce the complication rate and prevent recurrence.

  10. The influence of brain death on liver function

    NARCIS (Netherlands)

    Olinga, Peter; Hoeven, Joost Alexander Boreas van der; Merema, M.T.; Freund, R.L.; Ploeg, R.J; Groothuis, Geny

    2005-01-01

    Background: In this study, we investigated the influence of brain death on inflammatory response and the effects of brain death on liver function both directly after explantation and after reoxygenation. Methods: The influence of brain death on liver function was studied in rats using a brain death

  11. Nitrofurantoin-induced immune-mediated lung and liver disease

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    Milić Rade

    2012-01-01

    Full Text Available Introduction. Nitrofurantoin, a furan derivative, introduced in the fifties has widely been used as an effective agent for the treatment and prevention of urinary tract infections (UTI. Spectrum of adverse reactions to nitrofurantoin is wide, ranging from eosinophilic interstitial lung disease, acute hepatitis and granulomatous reaction, to the chronic active hepatitis, a very rare adverse effect, that can lead to cirrhosis and death. Case report. We presented a 55-year-old female patient with eosinophilic interstitial lung disease, severe chronic active hepatitis and several other immune- mediated multisystemic manifestations of prolonged exposure to nitrofurantoin because of the recurrent UTI caused by Escherichia coli. We estimated typical radiographic and laboratory disturbances, also restrictive ventilatory changes, severe reduction of carbon monoxide diffusion capacity and abnormal liver function tests. Lymphocytic-eosinophylic alveolitis was consistent with druginduced reaction. Hepatitis was confirmed by liver biopsy. After withdrawal of nitrofurantoin and application of high dose of glicocorticosteroids, prompt clinical and laboratory recovery was achieved. Conclusion. Adverse drug reactions should be considered in patients with concomitant lung and liver disease. The mainstay of treatment is drug withdrawal and the use of immunosuppressive drugs in severe cases. Consideration should be given to monitor lung and liver function tests during long term nitrofurantoin therapy.

  12. Brain nodules with lung mass: are they always metastases?

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    Jorcano, Sandra; Farrús, Blanca; Pujol, Teresa; Verger, Eugenia; Marruecos, Jordi; Conill, Carlos

    2008-08-01

    In a smoking adult with a lung mass, brain masses are usually diagnosed as brain metastases of lung origin. Nevertheless, differential diagnosis between cerebral abscesses cannot be performed based on clinical symptoms or imaging technologies, and histological diagnosis is essential. This case illustrates the advisability of always obtaining histological diagnosis of the primary tumor and/or cerebral lesion before introducing any oncological treatment.

  13. Aerosolized 3-bromopyruvate inhibits lung tumorigenesis without causing liver toxicity.

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    Zhang, Qi; Pan, Jing; North, Paula E; Yang, Shoua; Lubet, Ronald A; Wang, Yian; You, Ming

    2012-05-01

    3-Bromopyruvate, an alkylating agent and a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. However, the chemopreventive effect of 3-bromopyruvate in lung tumorigenesis has not been tested. In this study, we investigated the chemopreventive activity of 3-bromopyruvate in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and 3-bromopyruvate was administered by oral gavage to female A/J mice. We found that 3-bromopyruvate significantly decreased tumor multiplicity and tumor load by 58% and 83%, respectively, at a dose of 20 mg/kg body weight by gavage. Due to the known liver toxicity of 3-bromopyruvate in animal models given large doses of 3-bromopyruvate, confirmed in this study, we decided to test the chemopreventive activity of aerosolized 3-bromopyruvate in the same lung tumor model. As expected, aerosolized 3-bromopyruvate similarly significantly decreased tumor multiplicity and tumor load by 49% and 80%, respectively, at a dose of 10 mg/mL by inhalation. Interestingly, the efficacy of aerosolized 3-bromopyruvate did not accompany any liver toxicity indicating that it is a safer route of administering this compound. Treatment with 3-bromopyruvate increased immunohistochemical staining for cleaved caspase-3, suggesting that the lung tumor inhibitory effects of 3-bromopyruvate were through induction of apoptosis. 3-Bromopyruvate also dissociated hexokinase II from mitochondria, reduced hexokinase activity, and blocked energy metabolism in cancer cells, finally triggered cancer cell death and induced apoptosis through caspase-3, and PARP in human lung cancer cell line. The ability of 3-bromopyruvate to inhibit mouse lung tumorigenesis, in part through induction of apoptosis, merits further investigation of this compound as a chemopreventive agent for human lung cancer.

  14. Desferrioxamine attenuates minor lung injury following surgical acute liver failure.

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    Kostopanagiotou, G G; Kalimeris, K A; Arkadopoulos, N P; Pafiti, A; Panagopoulos, D; Smyrniotis, V; Vlahakos, D; Routsi, C; Lekka, M E; Nakos, G

    2009-06-01

    Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study was to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF. 14 adult female domestic pigs were subjected to surgical devascularisation of the liver and were randomised to a study group (DFX group, n = 7), which received post-operative intravenous infusion of DFX (14.5 mg x kg(-1) x h(-1) for the first 6 h post-operatively and 2.4 mg x kg(-1) x h(-1) until completion of 24 h), and a control group (n = 7). Post-operative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis. DFX resulted in reduced BALF protein levels and tissue phospholipase (PL)A(2) activity. Plasma malondialdehyde and BALF nitrate and nitrite concentrations were lower, while catalase activity in the lung was higher after DFX treatment. PLA(2), platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocyte necrosis and total lung injury in the DFX-treated animals. DFX reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA(2) and the attenuation of pneumonocyte necrosis could represent beneficial mechanisms by which DFX improves alveolar-capillary membrane permeability and prevents alveolar space collapse.

  15. Brain death and marginal grafts in liver transplantation.

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    Jiménez-Castro, M B; Gracia-Sancho, J; Peralta, C

    2015-06-04

    It is well known that most organs for transplantation are currently procured from brain-dead donors; however, the presence of brain death is an important risk factor in liver transplantation. In addition, one of the mechanisms to avoid the shortage of liver grafts for transplant is the use of marginal livers, which may show higher risk of primary non-function or initial poor function. To our knowledge, very few reviews have focused in the field of liver transplantation using brain-dead donors; moreover, reviews that focused on both brain death and marginal grafts in liver transplantation, both being key risk factors in clinical practice, have not been published elsewhere. The present review aims to describe the recent findings and the state-of-the-art knowledge regarding the pathophysiological changes occurring during brain death, their effects on marginal liver grafts and summarize the more controversial topics of this pathology. We also review the therapeutic strategies designed to date to reduce the detrimental effects of brain death in both marginal and optimal livers, attempting to explain why such strategies have not solved the clinical problem of liver transplantation.

  16. Amniotic fluid embolism with involvement of the brain, lungs, adrenal glands, and heart.

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    Balazic, J; Rott, T; Jancigaj, T; Popović, M; Zajfert-Slabe, M; Svigelj, V

    2003-06-01

    The case of a healthy 31-year-old woman in the 40th week of second pregnancy is presented. During preparation for an emergency caesarean section, she developed an amniotic fluid embolism (AFE) with unusual and unique features. The acute onset of disease with cardiorespiratory failure with hypotension, tachycardia, cyanosis, respiratory disturbances and loss of consciousness, suggested at first a pulmonary thromboembolism, but the appearance of convulsions led to the diagnosis of AFE. The patient died after 5 days due to an untreatable brain edema. At autopsy, AFE with the usually associated disseminated intravascular coagulation was found in the lungs, brain, left adrenal gland, kidneys, liver and heart. Eosinophilic inflammatory infiltrates were found in the lungs, hepatic portal fields and especially in the heart, suggesting a specific hypersensitivity reaction to fetal antigens. Moreover, intravascular accumulation of macrophages in the lungs also favored a non-specific immune reaction to amniotic fluid constituents.

  17. Hippocampal-Sparing Whole-Brain Radiotherapy for Lung Cancer.

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    Zhao, Ren; Kong, Wei; Shang, Jun; Zhe, Hong; Wang, Yan-Yang

    2017-03-01

    Brain metastases occur in 20% to 40% of lung cancer patients. Whole-brain radiotherapy (WBRT) has long been considered the treatment of choice for many patients with lung cancer, because of its wide availability, ease of delivery, and effectiveness in prolonging survival. However, WBRT is also associated with several side effects, such as decline in memory and other cognitive functions. There exists significant preclinical and clinical evidence that radiation-induced injury to the hippocampus correlates with neurocognitive decline of patients who receive WBRT. Technological advances in treatment planning and delivery facilitate the use of hippocampal-sparing (HS) WBRT as prophylactic cranial irradiation or the primary treatment modality for lung cancer patients with brain metastases. In this review, we provide a detailed and comprehensive discussion of the safety profile, techniques for hippocampus-sparing, and the clinical evidence of HS-WBRT for lung cancer patients.

  18. Small vessel ischemic disease of the brain and brain metastases in lung cancer patients.

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    Peter J Mazzone

    Full Text Available BACKGROUND: Brain metastases occur commonly in patients with lung cancer. Small vessel ischemic disease is frequently found when imaging the brain to detect metastases. We aimed to determine if the presence of small vessel ischemic disease (SVID of the brain is protective against the development of brain metastases in lung cancer patients. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort of 523 patients with biopsy confirmed lung cancer who had received magnetic resonance imaging of the brain as part of their standard initial staging evaluation was reviewed. Information collected included demographics, comorbidities, details of the lung cancer, and the presence of SVID of the brain. A portion of the cohort had the degree of SVID graded. The primary outcome measure was the portion of study subjects with and without SVID of the brain who had evidence of brain metastases at the time of initial staging of their lung cancer.109 patients (20.8% had evidence of brain metastases at presentation and 345 (66.0% had evidence of SVID. 13.9% of those with SVID and 34.3% of those without SVID presented with brain metastases (p<0.0001. In a model including age, diabetes mellitus, hypertension, hyperlipidemia, and tobacco use, SVID of the brain was found to be the only protective factor against the development of brain metastases, with an OR of 0.31 (0.20, 0.48; p<0.001. The grade of SVID was higher in those without brain metastases. CONCLUSIONS/SIGNIFICANCE: These findings suggest that vascular changes in the brain are protective against the development of brain metastases in lung cancer patients.

  19. Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

    DEFF Research Database (Denmark)

    Fabian, Katalin; Gyulai, Marton; Furak, Jozsef;

    2016-01-01

    Background: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. Methods: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive...... lung cancer patients with brain metastases. Results: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p ... of peritumoral brain edema (p

  20. Brain MRI changes in chronic liver disease

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    Skehan, S. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Norris, S. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Hegarty, J. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Owens, A. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); MacErlaine, D. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland)

    1997-08-01

    Cirrhotic patients are known to have abnormally high signal principally in the globus pallidus on non-contrast T1-weighted MRI. The purpose of this study was to relate MR changes to clinical and pathological features of chronic liver disease. We confirmed abnormally high signal in the globus pallidus on T1-weighted images in 25 of 28 patients with chronic liver disease, showing that it also occurs in patients who have not yet progressed to cirrhosis. Changes were seen in patients both with and without clinical portosystemic shunting. This abnormality is not responsible for hepatic encephalopathy. Cholestatic disease was more likely to produce marked changes than non-cholestatic disease. No statistically significant correlation was demonstrated between the severity of liver disease and the degree of MR abnormality. However, marked improvement in MR appearances was seen after successful liver transplantation. (orig.). With 3 figs., 4 tabs.

  1. Genetics Home Reference: brain-lung-thyroid syndrome

    Science.gov (United States)

    ... Goizet C, Lacombe D, Moutard ML, Raybaud C, Raynaud-Ravni C, Romana S, Ythier H, Léger J, Polak M. Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case. Hum ...

  2. Oxidative metabolism of cocaine: comparison of brain and liver.

    Science.gov (United States)

    Benuck, M; Reith, M E; Sershen, H; Wiener, H L; Lajtha, A

    1989-01-01

    Norcocaine (NC) and N-hydroxynorcocaine (NHNC), products of the oxidative metabolism of cocaine, were examined in plasma, brain, and liver of mice injected intraperitoneally with cocaine. Plasma levels of NHNC were altered in vivo by inhibiting esterase activity with diazinon and chloral hydrate or activating esterase activity with phenobarbital, and activating the microsomal P-450 system with phenobarbital. Changes in plasma concentrations of NHNC resulted in similar changes in brain, which were often different from those in liver. After intracisternal administration of cocaine to mice, no appreciable amount of NC or NHNC could be detected in brain; the same results were obtained upon intracisternal and intraventricular administration to rats. Microsomal preparations from mouse brain were found to be considerably less active than those from liver in converting NC to NHNC. We conclude that the cerebral oxidative metabolism of cocaine is not appreciable and that most of the NC and NHNC found in the brain after systemic cocaine administration is derived from plasma rather than formed centrally by brain microsomal enzymes.

  3. Adenocarcinoma of the lung presenting with atypical cystic brain lesions

    Science.gov (United States)

    Costa, Ricardo; Costa, Rubens B; Bacchi, Carlos; Sarinho, Filipe

    2014-01-01

    Brain metastases occur in up to 10–30% of patients with cancer. Metastatic lesions are usually diagnosed as multiple mass lesions at the junction of the grey and white matter with associated perilesional vasogenic oedema. Cysticercosis is an endemic disease in underdeveloped countries of Africa, Central and South America and is the most common parasitic infection of the central nervous system. The classical radiological finding of neurocysticercosis is cystic lesions showing the scolex in the brain parenchyma. We report a case of metastatic adenocarcinoma of the lung presenting with cystic brain lesions mimicking neurocysticercosis. PMID:24717598

  4. Changes in the fatty acid profile of lung, liver and serum of rats intratracheally given silica

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    Eskelson, C.D.; Stiffel, V.; Owen, J.A.; Chvapil, M.; Vickers, A.; Brendel, K.

    1988-01-01

    The esterified (E) and nonesterified (NE) fatty acid level and profile in the lung, serum, and liver of rats are significantly altered after intratracheal administration of silica. The changes include a silica-specific increase of the total long chain (C/sub 16/-C/sub 20:4/) fatty acid content in the lung, and a decrease in the serum and liver of both groups of rats intratracheally given silica and/or saline. In the silicotic lung, arachidonate and palmitate accumulated at the highest rate. A heat-labile, high-molecular weight component from lung homogenates increases lipogenesis in isolated hepatocytes in vitro. These findings, taken together with evidence indicating increased lipogenesis in the liver of rats treated with silica under identical conditions, suggest a lung-liver communication mechanism which coordinates lipid uptake by the lung and lipid synthesis and release by the liver. The stimulatory factor identified in lung homogenates might play an important regulatory role for hepatic lipogenesis in rats developing silicotic lungs.

  5. Imaging findings of arteriovenous malformations involving lung and liver in hereditary hemorrhagic telangiectasia(Osler-weber-rendu disease): two cases report

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    Yi, Jeong Geun; Lee, Joo Hyuk; Seong, Su Ok [Cheongju St. Mary' s Hospital, Cheongju (Korea, Republic of)

    1999-09-01

    Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu disease is an autosomal dominant disorder characterized by repeated episodes of bleeding. Multiple telangiectases consisting of thin-walled, dilated vascular channels with arteriovenous communication may involve, for example, mucocutaneous tissue, the gastrointestinal tract, and the liver, lung, and brain. We report the imaging findings of two cases of HHT involving arteriovenous malformation of both the lungs and liver, a rare condition. Chest radiography revealed a round mass, while helical CT showed a feeding artery and draining vein with arteriovenous malformation in the lung. Color Doppler sonography revealed an enlarged and tortuous hepatic artery with high systolic velocity. CT demonstrated an enlarged hepatic artery, arteriovenous shunt, and early draining hepatic vein in the liver. Celiac angiography showed arteriovenous malformation.

  6. Expression of alcoholism-relevant genes in the liver are differently correlated to different parts of the brain.

    Science.gov (United States)

    Wang, Lishi; Huang, Yue; Jiao, Yan; Chen, Hong; Cao, Yanhong; Bennett, Beth; Wang, Yongjun; Gu, Weikuan

    2013-01-01

    The purpose of this study is to investigate whether expression profiles of alcoholism-relevant genes in different parts of the brain are correlated differently with those in the liver. Four experiments were conducted. First, we used gene expression profiles from five parts of the brain (striatum, prefrontal cortex, nucleus accumbens, hippocampus, and cerebellum) and from liver in a population of recombinant inbred mouse strains to examine the expression association of 10 alcoholism-relevant genes. Second, we conducted the same association analysis between brain structures and the lung. Third, using five randomly selected, nonalcoholism-relevant genes, we conducted the association analysis between brain and liver. Finally, we compared the expression of 10 alcoholism-relevant genes in hippocampus and cerebellum between an alcohol preference strain and a wild-type control. We observed a difference in correlation patterns in expression levels of 10 alcoholism-relevant genes between different parts of the brain with those of liver. We then examined the association of gene expression between alcohol dehydrogenases (Adh1, Adh2, Adh5, and Adh7) and different parts of the brain. The results were similar to those of the 10 genes. Then, we found that the association of those genes between brain structures and lung was different from that of liver. Next, we found that the association patterns of five alcoholism-nonrelevant genes were different from those of 10 alcoholism-relevant genes. Finally, we found that the expression level of 10 alcohol-relevant genes is influenced more in hippocampus than in cerebellum in the alcohol preference strain. Our results show that the expression of alcoholism-relevant genes in liver is differently associated with the expression of genes in different parts of the brain. Because different structural changes in different parts of the brain in alcoholism have been reported, it is important to investigate whether those structural differences in

  7. Diagnosis and significance of liver metastases in small cell carcinoma of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Mulshine, J.L.; Makuch, R.W.; Johnston-Early, A.; Matthews, M.J.; Carney, D.N.; Ihde, D.C.; Cohen, M.H.; Bates, H.R.; Dunnick, N.R.; Minna, J.D.

    1984-07-01

    One hundred fifty-seven consecutive patients with small cell lung cancer seen at the National Cancer Institute over a four-year period underwent a series of pretherapy liver staging procedures to determine optimal means of detection and prognostic implications of hepatic metastases. Liver evaluation included physical examination, liver function tests, and liver scan (radionuclide or computerized tomography (CT)), as well as percutaneous and/or peritoneoscopy-directed liver biopsy when possible (74%). Liver metastases were detected in 26% of patients. Peritoneoscopy was the most sensitive method of liver evaluation and increased the detection of liver metastases when done in a sequential fashion after percutaneous liver biopsy from 18 to a total of 27 patients. Of the noninvasive procedures, radionuclide and CT liver scan were the most accurate concurring with liver biopsy in 87% of patients but permitting correct discrimination of stage in excess of 96% of patients. The accuracy of this noninvasive procedure was enhanced by an algorithm combining the results of radionuclide liver scan with liver function tests to detect patients with high or low likelihood of liver involvement. The survival and response of patients with liver metastases was significantly worse than those without such metastases with no three-year disease-free survivors among patients with liver metastases.

  8. Brain and lung involvement of mycosis fungoides demonstrated by radionuclide imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, E.E.; DeLand, F.H.; Maruyama, Y.

    1979-03-01

    A patient with advanced mycosis fungoides developed neurologic and respiratory symptoms and signs following multiple courses of chemotherapy and radiotherapy. Various repeated diagnostic procedures - including cranial computerized tomography and fiberoptic bronchoscopy with transbronchial lung biopsy - failed to demonstrate an unusual involvement of the brain and lungs by myocosis fungoides. Radionuclide brain imaging and gallium imaging of the lungs demonstrated diffuse lesions confirmed at autopsy.

  9. Comparison of radiography and ultrasonography in the detection of lung and liver cysts in cattle and buffaloes

    Directory of Open Access Journals (Sweden)

    Ashwani Kumar

    2016-10-01

    Full Text Available Aim: Echinococcosis is the major cause of lung and liver cysts in ruminants. This study compared usefulness of radiography and ultrasonography (USG in the detection of lung and/or liver cysts in sick bovine animals. The study also worked out cooccurrence of lung and liver cysts, and whether these cysts were primary cause of sickness or not. Materials and Methods: This study was conducted on 45 sick bovine (37 buffaloes and 8 cattle suffering from lung and liver cysts. A complete history of illness and clinical examination was carried out. Lateral radiographs of chest and reticular region were taken. In radiographically positive or suspected cases of cysts, USG of the lung and liver region was done. Depending on the location of cyst and clinical manifestations of the animal, the cysts were categorized as primary or secondary causes of sickness. Results: Using either imaging technique, it was observed that 46.7% of the animals had both lung and liver cysts, whereas 33.3% had only lung and 20% had only liver cyst. Cysts were identified as primary cause of sickness in 31.1% animals only. For diagnosing lung cysts, radiography (71.1% and USG (62.2% had similar diagnostic utility. However, for detecting liver cysts, USG was the only imaging tool. Conclusion: The lung and liver cysts, depending on their number and size may be a primary cause of sickness in bovine. Radiography and USG are recommended, in combination, as screening tools to rule out echinococcosis.

  10. Diphenyl Ditelluride Intoxication Triggers Histological Changes in Liver, Kidney, and Lung of Mice

    Science.gov (United States)

    da Luz, Sônia Cristina Almeida; Daubermann, Melissa Falster; Thomé, Gustavo Roberto; dos Santos, Matheus Mülling; Ramos, Angelica; Torres Salazar, Gerson; da Rocha, João Batista Teixeira; Barbosa, Nilda Vargas

    2015-01-01

    Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe)2), an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 μmol/kg) or subchronically (one daily subcutaneous dose: 10 or 50 μmol/kg for 7 and 14 days) exposed to (PhTe)2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe)2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 μmol/kg (PhTe)2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe)2. Acute and subchronic intoxication with (PhTe)2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 μmol/kg (PhTe)2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe)2 did not cause histological changes in lungs. Our data show that (PhTe)2 may be considered a histotoxic agent for liver, kidney, and lung. PMID:26236579

  11. Diphenyl ditelluride intoxication triggers histological changes in liver, kidney, and lung of mice.

    Science.gov (United States)

    da Luz, Sônia Cristina Almeida; Daubermann, Melissa Falster; Thomé, Gustavo Roberto; Dos Santos, Matheus Mülling; Ramos, Angelica; Torres Salazar, Gerson; da Rocha, João Batista Teixeira; Barbosa, Nilda Vargas

    2015-01-01

    Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe)2), an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 μmol/kg) or subchronically (one daily subcutaneous dose: 10 or 50 μmol/kg for 7 and 14 days) exposed to (PhTe)2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe)2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 μmol/kg (PhTe)2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe)2. Acute and subchronic intoxication with (PhTe)2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 μmol/kg (PhTe)2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe)2 did not cause histological changes in lungs. Our data show that (PhTe)2 may be considered a histotoxic agent for liver, kidney, and lung.

  12. Diphenyl Ditelluride Intoxication Triggers Histological Changes in Liver, Kidney, and Lung of Mice

    Directory of Open Access Journals (Sweden)

    Sônia Cristina Almeida da Luz

    2015-01-01

    Full Text Available Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe2, an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 μmol/kg or subchronically (one daily subcutaneous dose: 10 or 50 μmol/kg for 7 and 14 days exposed to (PhTe2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 μmol/kg (PhTe2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe2. Acute and subchronic intoxication with (PhTe2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 μmol/kg (PhTe2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe2 did not cause histological changes in lungs. Our data show that (PhTe2 may be considered a histotoxic agent for liver, kidney, and lung.

  13. Flooded Lung Generates a Suitable Acoustic Pathway for Transthoracic Application of High Intensity Focused Ultrasound in Liver

    Science.gov (United States)

    Lesser, Thomas Günther; Boltze, Carsten; Schubert, Harald; Wolfram, Frank

    2016-01-01

    Background: In recent years, high intensity focused ultrasound (HIFU) has gained increasing clinical interest as a non-invasive method for local therapy of liver malignancies. HIFU treatment of tumours and metastases in the liver dome is limited due to the adjacent ultrasound blocking lung. One-lung flooding (OLF) enables complete sonography of lung and adjoining organs including liver. HIFU liver ablation passing through the flooded lung could enable a direct intercostal beam path and thus improve dose deposition in liver. In this study, we evaluate the feasibility of an ultrasound guided transthoracic, transpulmonary HIFU ablation of liver using OLF. Methods: After right-side lung flooding, ultrasound guided HIFU was applied transthoracic- transpulmonary into liver to create thermal lesions in three pigs. The HIFU beam was targeted five times into liver, two times at the liver surface and three times deeper into the tissue. During autopsy examinations of lung, diaphragm and liver located in the HIFU path were performed. The focal liver lesions and lung tissue out of the beam path were examined histologically. Results: Fifteen thermal liver lesions were generated by transpulmonary HIFU sonication in all targeted regions. The lesions appeared well-demarcated in grey color with a cigar-shaped configuration. The mean length and width of the superficial and deeper lesions were 15.8 mm (range: 13-18 mm) and 5.8 mm (range: 5-7 mm), and 10.9 mm (range: 9-13 mm) and 3.3 mm (range: 2-5 mm), respectively. Histopathological, all liver lesions revealed a homogeneous thermal necrosis lacking vitality. There were no signs of damage of the overlying diaphragm and lung tissue. Conclusions: Flooded lung is a suitable pathway for applying HIFU to the liver, thus enabling a transthoracic, transpulmonary approach. The enlarged acoustic window could enhance the ablation speed for targets in the hepatic dome. PMID:27766022

  14. Histopathology effects of nickel nanoparticles on lungs, liver, and spleen tissues in male mice

    Science.gov (United States)

    Ajdari, Marziyeh; Ziaee Ghahnavieh, Marziyeh

    2014-09-01

    Because of the classification of the nickel compounds as carcinogenic substances, there is a need for in vivo tests to nickel nanoparticles (NiNPs) for observing their effects on health experimentally. Spherical NiNPs with 10 nm in diameter and 75 ppm concentration were applied for investigating their toxicities within male albino mice as an in vivo model. We randomly made sham group, control group, and 75 ppm group (with five animals in each group). Then, the nanoparticles were injected into mice intraperitonealy for 7 days and after that their lungs, liver, and spleen were removed for histopathological observations. At the end of the test, section microscopic observations of liver, spleen, and lung in sham and control groups showed normal tissues but these tissues underwent significant abnormal effects in 75 ppm group. NiNPs can cause undesirable effects in lungs, liver, and spleen tissues with same condition of this study.

  15. [Interelement correlations in the lungs and the liver in alimentary obesity].

    Science.gov (United States)

    Churin, B V; Trunova, V A; Sidorina, A V; Zvereva, V V; Starkova, E V

    2014-01-01

    Using a high-fat diet in experiment on rats received model alimentary obesity (AO). Adding zinc to the diet did not affect the severity of the AO. The concentration of K, Ca, Mn, Fe, Cu, Zn, Se, Br, Rb, Sr in the liver and lungs of rats with obesity in both groups did not differ from that of healthy animals. As in the liver and lungs in rats of both groups with obesity has been a redistribution of interelement correlation (COP) and during physiological hunger and soon after consumption of pork fat. Redistribution of interelement COP in a state of physiological hunger reflects the strong changes of metabolic processes of the body. The nature of rearrangements of the COP in the liver and lungs were significantly different in each group of rats. Soon after intake of fatty foods in control rats and rats AO not receiving zinc, found an increase in the total number interelement COP in the lungs and major decline in the liver, which indirectly indicates the active participation of the lungs in the metabolism of dietary fat, over-expressed in control animals. In rats receiving more zinc, the increase in the total number of correlations after eating found in both bodies.

  16. Lung Dose Calculation With SPECT/CT for {sup 90}Yittrium Radioembolization of Liver Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Naichang, E-mail: yun@ccf.org [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Srinivas, Shaym M.; DiFilippo, Frank P.; Shrikanthan, Sankaran [Department of Nuclear Medicine, Cleveland Clinic, Cleveland, OH (United States); Levitin, Abraham; McLennan, Gordon; Spain, James [Department of Interventional Radiology, Cleveland Clinic, Cleveland, OH (United States); Xia, Ping; Wilkinson, Allan [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States)

    2013-03-01

    Purpose: To propose a new method to estimate lung mean dose (LMD) using technetium-99m labeled macroaggregated albumin ({sup 99m}Tc-MAA) single photon emission CT (SPECT)/CT for {sup 90}Yttrium radioembolization of liver tumors and to compare the LMD estimated using SPECT/CT with clinical estimates of LMD using planar gamma scintigraphy (PS). Methods and Materials: Images of 71 patients who had SPECT/CT and PS images of {sup 99m}Tc-MAA acquired before TheraSphere radioembolization of liver cancer were analyzed retrospectively. LMD was calculated from the PS-based lung shunt assuming a lung mass of 1 kg and 50 Gy per GBq of injected activity shunted to the lung. For the SPECT/CT-based estimate, the LMD was calculated with the activity concentration and lung volume derived from SPECT/CT. The effect of attenuation correction and the patient's breathing on the calculated LMD was studied with the SPECT/CT. With these effects correctly taken into account in a more rigorous fashion, we compared the LMD calculated with SPECT/CT with the LMD calculated with PS. Results: The mean dose to the central region of the lung leads to a more accurate estimate of LMD. Inclusion of the lung region around the diaphragm in the calculation leads to an overestimate of LMD due to the misregistration of the liver activity to the lung from the patient's breathing. LMD calculated based on PS is a poor predictor of the actual LMD. For the subpopulation with large lung shunt, the mean overestimation from the PS method for the lung shunt was 170%. Conclusions: A new method of calculating the LMD for TheraSphere and SIR-Spheres radioembolization of liver cancer based on {sup 99m}Tc-MAA SPECT/CT is presented. The new method provides a more accurate estimate of radiation risk to the lungs. For patients with a large lung shunt calculated from PS, a recalculation of LMD based on SPECT/CT is recommended.

  17. Mechanism of ethylbenzene-induced mouse-specific lung tumor: metabolism of ethylbenzene by rat, mouse, and human liver and lung microsomes.

    Science.gov (United States)

    Saghir, Shakil A; Rick, David L; McClymont, E L; Zhang, Fagen; Bartels, Michael J; Bus, James S

    2009-02-01

    This study was conducted to determine species differences in the metabolism of ethylbenzene (EB) in liver and lung. EB (0.22-7.0mM) was incubated with mouse, rat and human liver and lung microsomes and the formation of 1-phenylethanol (1PE), acetophenone (AcPh), 2-ethylphenol (2EP), 4-ethylphenol (4EP), 2,5-ethylquinone, and 3,4-ethylquinone were measured. Reactive metabolites (2,5-dihydroxyethylbenzene-GSH [2EP-GSH] and 3,4-dihydroxyethylbenzene-GSH [4EP-GSH]) were monitored via glutathione (GSH) trapping technique. None of the metabolites were formed at detectable levels in incubations with human lung microsomes. Percent conversion of EB to 1PE ranged from 1% (rat lung; 7.0mM EB) to 58% (mouse lung; 0.22 mM EB). More 1PE was formed in mouse lung than in mouse liver microsomes, although formation of 1PE by rat liver and lung microsomes was similar. Metabolism of EB to 1PE was in the order of mouse > rat > human. Formation of AcPh was roughly an order of magnitude lower than 1PE. Conversion of EB to ring-hydroxylated metabolites was much lower (0.0001% [4EP-GSH; rat lung] to 0.6% [2EP-GSH; mouse lung]); 2EP-GSH was typically 10-fold higher than 4EP-GSH. Formation of 2EP-GSH was higher by lung (highest by mouse lung) than liver microsomes and the formation of 2EP-GSH by mouse liver microsomes was higher than rat and human liver microsomes. Increasing concentrations of EB did lead to a decrease in amount of some formed metabolites. This may indicate some level of substrate- or metabolite-mediated inhibition. High concentrations of 2EP and 4EP were incubated with microsomes to further investigate their oxidation to ethylcatechol (ECat) and ethylhydroquinone (EHQ). Conversion of 2EP to EHQ ranged from 6% to 9% by liver (mouse > human > rat) and from 0.1% to 18% by lung microsomes (mouse > rat > human). Conversion of 4EP to ECat ranged from 2% to 4% by liver (mouse > human approximately rat) and from 0.3% to 7% by lung microsomes (mouse > rat > human). Although ring

  18. Brain metastasis as initial presentation of papillary adenocarcinoma of the lung: case report

    Energy Technology Data Exchange (ETDEWEB)

    Bispo, Irving Gabriel Araujo; Nascimento, Diego Teixeira; Ferreira, Karina Oliveira; Fakhouri, Ricardo; Godinho, Atilano Salvador; Ferrao, Thiago de Oliveira, E-mail: irvingbispo@yahoo.com.br [Universidade Federal de Sergipe (HU-UFS), Aracaju, SE (Brazil). Hospital Universitario

    2013-09-15

    The authors describe the case of a 33-year-old patient with history of seizures alone without any previous symptom, being diagnosed with brain metastases from primary papillary adenocarcinoma of the lung. Emphasis is given to the diagnostic investigation for brain metastasis and prognostic evaluation of papillary adenocarcinoma of the lung, and a brief literature review on such diseases is performed. (author)

  19. Clinical science workshop: targeting the gut-liver-brain axis.

    Science.gov (United States)

    Patel, Vishal C; White, Helen; Støy, Sidsel; Bajaj, Jasmohan S; Shawcross, Debbie L

    2016-12-01

    A clinical science workshop was held at the ISHEN meeting in London on Friday 11th September 2014 with the aim of thrashing out how we might translate what we know about the central role of the gut-liver-brain axis into targets which we can use in the treatment of hepatic encephalopathy (HE). This review summarises the integral role that inter-organ ammonia metabolism plays in the pathogenesis of HE with specific discussion of the roles that the small and large intestine, liver, brain, kidney and muscle assume in ammonia and glutamine metabolism. Most recently, the salivary and gut microbiome have been shown to underpin the pathophysiological changes which culminate in HE and patients with advanced cirrhosis present with enteric dysbiosis with small bowel bacterial overgrowth and translocation of bacteria and their products across a leaky gut epithelial barrier. Resident macrophages within the liver are able to sense bacterial degradation products initiating a pro-inflammatory response within the hepatic parenchyma and release of cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-8 into the systemic circulation. The endotoxemia and systemic inflammatory response that are generated predispose both to the development of infection as well as the manifestation of covert and overt HE. Co-morbidities such as diabetes and insulin resistance, which commonly accompany cirrhosis, may promote slow gut transit, promote bacterial overgrowth and increase glutaminase activity and may need to be acknowledged in HE risk stratification assessments and therapeutic regimens. Therapies are discussed which target ammonia production, utilisation or excretion at an individual organ level, or which reduce systemic inflammation and endotoxemia which are known to exacerbate the cerebral effects of ammonia in HE. The ideal therapeutic strategy would be to use an agent that can reduce hyperammonemia and reduce systemic inflammation or perhaps to adopt a combination of

  20. LUNG AND LIVER CHANGES DUE TO THE INDUCTION OF CIRRHOSIS IN TWO EXPERIMENTAL MODELS

    Directory of Open Access Journals (Sweden)

    Renata Salatti FERRARI

    2013-09-01

    Full Text Available Context To evaluate lung and liver changes in two experimental models using intraperitoneal carbon tetrachloride (CCl4 and bile duct ligation (BDL. Methods Twenty-four male Wistar rats were divided into a control group (CO and an experimental group (EX. We evaluated the liver transaminases (AST, ALT, AP, arterial blood gases (PaO2, PCO2 and SpO2 and lipid peroxidation by TBARS (substances that react to thiobarbituric acid and chemiluminescence. We also evaluated the antioxidant enzyme superoxide dismutase (SOD and histology of lung tissue and liver. Results There were significant differences in AST, ALT, ALP and PaO2 between CO group and EX group (P<0.05. The levels of TBARS, chemiluminescence and activity of enzyme superoxide dismutase were increased to different degrees in the CCl4 groups: CO and in the BDL -EX (P<0.05, respectively. In the lung histology, an increase in the wall thickness of the pulmonary artery and a diameter reduction in the CCl4 animal model were observed: comparing CO group with EX group, we observed a reduction in thickness and an increase in the diameter of the artery wall lung. Conclusion Both experimental models have caused liver damage and alterations in the artery wall that are associated with major changes in pulmonary gas exchange.

  1. Content of bioelements in the lungs and liver in rats with alimentary obesity.

    Science.gov (United States)

    Trunova, V A; Sidorina, A V; Zvereva, V V; Churin, B V; Starkova, E V; Sorokoletov, D S

    2016-01-01

    The synchrotron radiation X-ray fluorescence technique (SRXRF) was applied to the determination of K, Ca, Mn, Fe, Cu, Zn, Se, Br, Rb, and Sr concentrations in the liver and lungs in Wistar rats. The animals in the experiment included (1) healthy rats, (2) rats with alimentary obesity (AO), and (3) rats with alimentary obesity that were being given zinc sulphate with water for a long time (АО+Zn). Each group was divided into two subgroups. The experiment with the first subgroup was terminated with the animals in the state of physiological hunger and subsequent retrieval of liver and lung tissue, while the animals of the second subgroup were sacrificed two hours after ingestion of lard. The rats in physiological hunger manifested intergroup differences in the content of the bioelements (BEs) neither in the liver nor in the lungs. The rats with AO, as compared with the healthy animals, demonstrated in physiological hunger redistribution of inter-element correlations (IECs), which is an indirect reflection of sustained metabolic disorder. Additional zinc in the rats' ration did not affect their body weight and the concentration of the BEs (including zinc) in the liver and the lungs. However, the IECs in the tissues of these animals in physiological hunger also changed. This redistribution differed from that in the rats with AO. The IECs soon after ingestion of lard also changed, which also reflects sustained changes in the metabolism in the animals.

  2. Lung, liver and bone cancer mortality after plutonium exposure in beagle dogs and nuclear workers.

    Science.gov (United States)

    Wilson, Dulaney A; Mohr, Lawrence C; Frey, G Donald; Lackland, Daniel; Hoel, David G

    2010-01-01

    The Mayak Production Association (MPA) worker registry has shown evidence of plutonium-induced health effects. Workers were potentially exposed to plutonium nitrate [(239)Pu(NO(3))(4)] and plutonium dioxide ((239)PuO(2)). Studies of plutonium-induced health effects in animal models can complement human studies by providing more specific data than is possible in human observational studies. Lung, liver, and bone cancer mortality rate ratios in the MPA worker cohort were compared to those seen in beagle dogs, and models of the excess relative risk of lung, liver, and bone cancer mortality from the MPA worker cohort were applied to data from life-span studies of beagle dogs. The lung cancer mortality rate ratios in beagle dogs are similar to those seen in the MPA worker cohort. At cumulative doses less than 3 Gy, the liver cancer mortality rate ratios in the MPA worker cohort are statistically similar to those in beagle dogs. Bone cancer mortality only occurred in MPA workers with doses over 10 Gy. In dogs given (239)Pu, the adjusted excess relative risk of lung cancer mortality per Gy was 1.32 (95% CI 0.56-3.22). The liver cancer mortality adjusted excess relative risk per Gy was 55.3 (95% CI 23.0-133.1). The adjusted excess relative risk of bone cancer mortality per Gy(2) was 1,482 (95% CI 566.0-5686). Models of lung cancer mortality based on MPA worker data with additional covariates adequately described the beagle dog data, while the liver and bone cancer models were less successful.

  3. Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema

    DEFF Research Database (Denmark)

    Eefsen, Martin; Jelnes, Peter; Schmidt, Lars E;

    2010-01-01

    Cerebral edema is a feared complication to acute liver failure (ALF), but the pathogenesis is still poorly understood. The water channels Aquaporin-1 (Aqp1) and -4 (Aqp4) has been associated with brain edema formation in several neuropathological conditions, indicating a possible role of Aqp1 and....../or Aqp4 in ALF mediated brain edema. We induced acute liver injury and hyperammonemia in mice, to evaluate brain edema formation and the parallel expression of Aqp1 and Aqp4 in ALF. Liver injury and hyperammonemia were induced by +D-galactosamine (GLN) plus lipopolysaccharide (LPS) intraperitoneally......(6266) (p edema in mice with ALF....

  4. Surgical treatment of synchronous colorectal liver and lung metastases:the usefulness of thoracophrenolaparotomy for single stage resection

    Institute of Scientific and Technical Information of China (English)

    Daniele Del Fabbro; Marco Alloisio; Fabio Procopio; Matteo Cimino; Matteo Donadon; Angela Palmisano; Luca Viganò; Guido Torzilli

    2016-01-01

    When suitable, surgery still remains the therapeu-tic option to be preferred for patients carrier of colorectal liver and lung metastases. Since thoracophrenolaparotomy should be helpful during liver resection for some of these patients, si-multaneous removal of right lung metastases can be proposed through this approach. Eleven consecutive patients (median age of 53 years) carrier of colorectal liver and lung metastases, underwent single session surgical resection of both liver and right lung lesions by means of J-shaped thoracophrenolapa-rotomy. The median number of liver metastases removed was 5 (range 2-30) and of lung metastases removed was 2 (range 1-3). Lung metastases were located in the upper lobe in 1 pa-tient, in the middle lobe in 2, in the lower lobe in 6, and in the upper and lower lobe in 2. Mortality and major morbidity were nil. Two patients had a minor morbidity: one had wound infection and bile leakage treated conservatively and the other had transient fever. Mean overall survival was 24.4 months. An aggressive surgical approach should be undertaken for colorectal metastases: in case of multifocal liver disease with complex presentations, J-shaped thoracophrenolaparotomy could be considered as safe approach for combined liver and right lung metastasectomies.

  5. Alveolar echinococcosis localized in the liver, lung and brain

    Institute of Scientific and Technical Information of China (English)

    Seyit Mehmet Kayacan; Kutigin Turkmen; Fatih Yakar; Kerim Guier; Sezai Vatansever; Suleyman Temiz; Bora Uslu; Dilek Kayacan; Vakur Akkaya; Osman Erk; Büent Saka; Aytac Karadag

    2008-01-01

    @@ Echinococcosis is a parasitic disease caused by the larval forms of echinococci. It has two main forms as the unilocular cystic form that is more commonly seen and caused by E. granulosus and the alveolar form that is rarely seen and caused by E.

  6. Histological Changes in the Lung and Liver Tissues in Mice Exposed to Pyrethroid Inhalation

    Directory of Open Access Journals (Sweden)

    Nadeem SHEIKH

    2013-12-01

    Full Text Available Cypermethrin, a type II pyrethroid, is one of the most widely used insecticides in Pakistan. It is considered to be a safe pesticide; however, the possible health hazards of this pyrethroid have been ignored. Cypermethrin may become an air pollutant and adversely affect the health of non-target organisms, leading to acute or chronic disorders. The present work aims to investigate the effects of cypermethrin on lung and liver tissues due to inhalation exposure. The study is performed on 16 mature Swiss albino mice, including controls. The animals are divided into 4 groups (4 mice each and exposed to 0.5 % dilution of cypermethrin in an inhalation chamber (40×35×25 cm3 for different time periods, whereas control animals are not exposed to any insecticide. The histopathological changes in lungs and liver tissues reveal that cypermethrin exposure induces time dependent changes in the liver and in the lungs. It damages the normal organization of liver tissues, causing liver injury due to necrosis, significant decrease in number of cells, and widening of sinusoids and fibrosis. Inhalation exposure of cypermethrin results in significant hyperplasia, clumping of cells and necrosis in the lungs. It also induces pulmonary edema, alveolitis, and pulmonary fibrosis by the deposition of collagen. Taking these findings together, it may be concluded that cypermethrin and other pyrethroids cause hazardous effects in non-target organisms through inhalation exposure. Serious efforts and awareness are required to monitor and reduce the insecticide induced health hazards in third world countries.doi:10.14456/WJST.2014.67

  7. Liver transplant outcomes using ideal donation after circulatory death livers are superior to using older donation after brain death donor livers.

    Science.gov (United States)

    Scalea, Joseph R; Redfield, Robert R; Foley, David P

    2016-09-01

    Multiple reports have demonstrated that liver transplantation following donation after circulatory death (DCD) is associated with poorer outcomes when compared with liver transplantation from donation after brain death (DBD) donors. We hypothesized that carefully selected, underutilized DCD livers recovered from younger donors have excellent outcomes. We performed a retrospective study of the United Network for Organ Sharing database to determine graft survivals for patients who received liver transplants from DBD donors of age ≥ 60 years, DBD donors  60 years old. Careful donor organ and recipient selection can lead to excellent results, despite previous reports suggesting otherwise. Increased acceptance of these DCD livers would lead to shorter wait list times and increased national liver transplant rates. Liver Transplantation 22 1197-1204 2016 AASLD.

  8. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  9. Morphological Lesions in Mouse Liver and Lungs After Lung Exposure to Carbon Nanotubes

    DEFF Research Database (Denmark)

    Szarek, J.; Mortensen, Alicja; Jackson, P.;

    2013-01-01

    taken from six animals from each group for histopathological examination (haematoxylin and eosin staining) 6 weeks (A1, B1 group) and 4 months (A2, B2) after exposure. Results: Lungs in A1 mice showed bronchiolar subepithelial oedema and perivascular oedema and sporadic hyperaemia and the presence...

  10. Brain metastasis as initial presentation of papillary adenocarcinoma of the lung: case report

    Directory of Open Access Journals (Sweden)

    Irving Gabriel Araujo Bispo

    2013-09-01

    Full Text Available The authors describe the case of a 33-year-old patient with history of seizures alone without any previous symptom, being diagnosed with brain metastases from primary papillary adenocarcinoma of the lung. Emphasis is given to the diagnostic investigation for brain metastasis and prognostic evaluation of papillary adenocarcinoma of the lung, and a brief literature review on such diseases is performed.

  11. Traumatic Brain Injury in Rats Induces Lung Injury and Systemic Immune Suppression

    NARCIS (Netherlands)

    Vermeij, Jan-Dirk; Aslami, Hamid; Fluiter, Kees; Roelofs, Joris J.; van den Bergh, Walter M.; Juffermans, Nicole P.; Schultz, Marcus J.; Van der Sluijs, Koen; van de Beek, Diederik; van Westerloo, David J.

    2013-01-01

    Traumatic brain injury (TBI) is frequently complicated by acute lung injury, which is predictive for poor outcome. However, it is unclear whether lung injury develops independently or as a result of mechanical ventilation after TBI. Further, TBI is strongly associated with the development of pneumon

  12. Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria.

    Science.gov (United States)

    Cunha-Oliveira, Teresa; Silva, Lisbeth; Silva, Ana Maria; Moreno, António J; Oliveira, Catarina R; Santos, Maria S

    2013-06-07

    Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented. Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction. In this work, we compared the effects of cocaine and/or morphine on the bioenergetics of isolated brain and liver mitochondria, to understand their specific effects in each tissue. Upon energization with complex I substrates, cocaine decreased state-3 respiration in brain (but not in liver) mitochondria and decreased uncoupled respiration and mitochondrial potential in both tissues, through a direct effect on complex I. Morphine presented only slight effects on brain and liver mitochondria, and the combination cocaine+morphine had similar effects to cocaine alone, except for a greater decrease in state-3 respiration. Brain and liver mitochondrial respirations were differentially affected, and liver mitochondria were more prone to proton leak caused by the drugs or their combination. This was possibly related with a different dependence on complex I in mitochondrial populations from these tissues. In summary, cocaine and cocaine+morphine induce mitochondrial complex I dysfunction in isolated brain and liver mitochondria, with specific effects in each tissue.

  13. Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

    Directory of Open Access Journals (Sweden)

    RINI PUSPITANINGRUM

    2010-09-01

    Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxiatolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

  14. The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids

    Directory of Open Access Journals (Sweden)

    Suzanne M. de la Monte

    2009-07-01

    Full Text Available Alcohol abuse causes progressive toxicity and degeneration in liver and brain due to insulin resistance, which exacerbates oxidative stress and pro-inflammatory cytokine activation. Alcohol-induced steatohepatitis promotes synthesis and accumulation of ceramides and other toxic lipids that cause insulin resistance. Ceramides can readily cross the blood-brain barrier, and ceramide exposure causes neurodegeneration with insulin resistance and oxidative stress, similar to the effects of alcohol. Therefore, in addition to its direct neurotoxic effects, alcohol misuse establishes a liver-brain axis of neurodegeneration mediated by toxic lipid trafficking across the blood-brain barrier, leading to progressive white matter degeneration and cognitive impairment.

  15. Brain death is associated with endoplasmic reticulum stress and apoptosis in rat liver.

    Science.gov (United States)

    Cao, S; Wang, T; Yan, B; Lu, Y; Zhao, Y; Zhang, S

    2014-12-01

    Cell death pathways initiated by stress on the endoplasmic reticulum (ER) have been implicated in a variety of common diseases, such as ischemia/reperfusion injury, diabetes, heart disease, and neurodegenerative disorders. However, the contribution of ER stress to apoptosis and liver injury after brain death is not known. In the present study, we found that brain death induces a variety of signature ER stress markers, including ER stress-specific X box-binding protein 1 and up-regulation of glucose-regulated protein 78. Furthermore, brain death causes up-regulation of C/EBP homologous protein and caspase-12. Consistent with this, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling assay and transmission electron microscopy confirmed apoptosis in the liver after brain death. Taken together, the present study provides strong evidence supporting the presence and importance of ER stress and response in mediating brain death-induced apoptosis and liver injury.

  16. PRESENCE OF MYCOBACTERIA IN OTHER CELLS OF LUNG AND LIVER EXEPT IN MACROPHAGES

    Directory of Open Access Journals (Sweden)

    Dimitrina Kazachka

    2009-06-01

    Full Text Available Macrophages are the key cells for invading and replication of mycobacteria in the host and they play principal role in the pathogenesis of the tuberculosis. The aim of the present study was to reveal if mycobacterium invade other cells except these of immune defense and macrophages fi rst of all as a common feature. The results of ultrastructural studies of lungs of Mycobacterium bovis intraperitonealy infected rabbits and livers of Mycobacterium avium subcutaneously infected chickens showed the presence of mycobacteria into the cytoplasm of pneumocytes II type and capillary endothelial cells of rabbit lungs as well as in the cytoplasm of chicken liver parenchyma cells. On the base of these results and in particular invading of pneumocytes II type as a producers of the surfactant it was suggested that the surfactant or some of his components likely enhance phagocytosis of mycobacteria by macrophages. It could be a reason for mycobacterium affi nity to invade pneumocyte II type and to manipulate quality and quantity of the surfactant or some of his components. These results show that M. bovis invaded pneumocytes II type in vivo and it is an important step may be in the investigation of the possibility role of these cells in the pathogenesis of lung infection.

  17. Quantitative multivoxel H-1 MR spectroscopy of the brain in children with acute liver failure

    NARCIS (Netherlands)

    Sijens, Paul E.; Alkefaji, Heyder; Lunsing, Roelineke J.; van Spronsen, Francjan J.; Meiners, Linda C.; Oudkerk, Matthijs; Verkade, Henkjan J.

    2008-01-01

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) an

  18. A placebo-controlled, randomized phase II study of maintenance enzastaurin following whole brain radiation therapy in the treatment of brain metastases from lung cancer

    DEFF Research Database (Denmark)

    Grønberg, Bjørn H; Ciuleanu, Tudor; Fløtten, Øystein;

    2012-01-01

    Enzastaurin is a protein kinase C inhibitor with anti-tumor activity. This study was designed to determine if maintenance enzastaurin improved the outcome of whole brain radiotherapy (WBRT) in lung cancer (LC) patients with brain metastases (BMs).......Enzastaurin is a protein kinase C inhibitor with anti-tumor activity. This study was designed to determine if maintenance enzastaurin improved the outcome of whole brain radiotherapy (WBRT) in lung cancer (LC) patients with brain metastases (BMs)....

  19. Cytotoxicity of Marchantia convoluta leaf extracts to human liver and lung cancer cells

    Directory of Open Access Journals (Sweden)

    Xiao J.B.

    2006-01-01

    Full Text Available The cytotoxicity of three extracts (petroleum ether, ethyl acetate and n-butanol from a plant used in folk medicine, Marchantia convoluta, to human non-small cell lung carcinoma (H1299 and liver carcinoma (HepG2 cell lines was tested. After 72-h incubation of lung and liver cancer cell cultures with varying concentrations of extracts (15 to 200 µg/mL, cytotoxicity was determined by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay and reported in terms of cell viability. The extracts that showed a significant cytotoxicity were subjected to gas chromatography-mass spectrometry analysis to identify the components. The ethyl acetate, but not the petroleum ether or n-butanol extract, had a significant cytotoxicity against lung and liver carcinoma cells with IC50 values of 100 and 30 µg/mL, respectively. A high concentration of ethyl acetate extract (100 µg/mL rapidly reduced the number of H1299 cells. At lower concentrations of ethyl acetate extract (15, 30, and 40 µg/mL, the numbers of HepG2 cells started to decrease markedly. Gas chromatography-mass spectrometry analysis of the ethyl acetate extract revealed the presence of several compounds such as phytol (23.42%, 1,2,4-tripropylbenzene (13.09%, 9-cedranone (12.75%, ledene oxide (7.22%, caryophyllene (1.82%, and caryophyllene oxide (1.15%. HPLC analysis result showed that there were no flavonoids in ethyl acetate extract, but flavonoids are abundant in n-butanol extract. Further studies are needed regarding the identification, toxicity, and mechanism of action of active compounds.

  20. Brain and Liver Glutamine Synthetase of Rana catesbeiana and Rana cancrivora.

    Science.gov (United States)

    1983-07-01

    ammonia into urea in marine Chondrichthyes liver 7 Table 1--Liver and brain glutamine synthetase of urea-retaining and non-urea-retaining amphibians 8...for assimilation of ammonia into urea in marine Chondrichthyes liver (from Webb (15)) C1 klA IWE LO, AT? VH3 tLt TKATICAkMUIYL PUOSPULArL I CflALLLINE... elasmobranchii . Biol. Rev. Cambridge Philos. Soc. 11, 49-82. 15. Webb, J.T. 1979. "An assimilatory role of glutamine synthetase in the liver of urea

  1. Influence of sulfur dioxide on glycogenolysis in the lungs and liver

    Energy Technology Data Exchange (ETDEWEB)

    Vysocina, I.V.; Konstantinova, I.K.; Skvorcova, N.N.

    1974-04-01

    Report on research undertaken in white rats to determine the effect of sulfur dioxide (SO/sub 2/) inhalation on glycogenolysis. A concentration of 10mg/m/sup 3/ of SO/sub 2/ produced a dramatic fall in the pulmonary adenosine triphosphate level (to 3 times lower than the control value), while the lactic acid level was doubled. Anaerobic glycogenolysis in the lung homogenate tended to increase. No effect of SO/sub 2/ on anaerobic glycogenolysis in the liver tissue was observed at the concentration studied. The authors point to the carcinogenic effects of SO/sub 2/. (CIS Abstr.)

  2. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

    Science.gov (United States)

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-26

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

  3. A Phase I trial of dose escalation of topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaohui Ge; Wenyan Zhao; Xiaocang Ren; Yongqiang Wang; Zhigang Li; Yanqi Li; Yuee Liu; Qiang Lin

    2012-01-01

    Objective: The aim of this study was to define the maximum-tolerated dose (MTD) and observe the toxicity of escalating topotecan combined whole brain radiotherapy for brain metastasis in lung cancer. Methods: Patients with brain metastasis of lung cancer received conventional fractionation radiotherapy, with 5 daily fractions of 2 Gy per week, the total radiation dose was 40 Gy, while the larger lesions were boosted to 50-60 Gy. The initial dose of topotecan was 1.0 mg/m2. Escalation dose was 0.25 mg/m2. Every cohort contained at least 3 patients.If no dose-limiting toxicity (DLT) was observed,the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: Eighteen patients were recruited. Two cases of grade 3 leucopenia/neutropenia was observed as DLT at the level of topotecan 2.0 mg/m2. MTD of topotecan was defined as 1.75 mg/m2.The major side effects were leucopenia/neutropenia, nausea and vomiting. Conclusion: Topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer is well tolerated. Maximum-tolerated dose of topotecan is 1.75 mg/m2, once a week of a total of four.

  4. Effects of root and stem extracts of Asparagus cochinchinensis on biochemical indicators related to aging in the brain and liver of mice.

    Science.gov (United States)

    Xiong, Dasheng; Yu, Long-Xi; Yan, Xiao; Guo, Chunqiu; Xiong, Ying

    2011-01-01

    Asparagus cochinchinensis is a traditional Chinese medicine used for treating lung and spleen-related diseases. In this study, we compared the medicinal effects of A. cochinchinensis root and stem extracts on the activity of superoxide dismutase (SOD), the content of malonaldehyde (MDA) and total protein content in the brain, liver and plasma of mice. Polysaccharides and aqueous extracts of the roots significantly increased the spleen index and the SOD activity but reduced the MDA content and slowed down the aging process. In contrast, feeding with the stem extracts significantly reduced the SOD activity and increased the MDA accumulation in the brain and liver of mice, suggesting that the stem extracts may not be appropriate for treating aging-related diseases.

  5. Simulating Sleep Apnea by Exposure to Intermittent Hypoxia Induces Inflammation in the Lung and Liver

    Directory of Open Access Journals (Sweden)

    Darlan Pase da Rosa

    2012-01-01

    Full Text Available Sleep apnea is a breathing disorder that results from momentary and cyclic collapse of the upper airway, leading to intermittent hypoxia (IH. IH can lead to the formation of free radicals that increase oxidative stress, and this mechanism may explain the association between central sleep apnea and nonalcoholic steatohepatitis. We assessed the level of inflammation in the lung and liver tissue from animals subjected to intermittent hypoxia and simulated sleep apnea. A total of 12 C57BL/6 mice were divided into two groups and then exposed to IH (n=6 or a simulated IH (SIH (n=6 for 35 days. We observed an increase in oxidative damage and other changes to endogenous antioxidant enzymes in mice exposed to IH. Specifically, the expression of multiple transcription factors, including hypoxia inducible factor (HIF-1α, nuclear factor kappa B (NF-κB, and tumor necrosis factor (TNF-α, inducible NO synthase (iNOS, vascular endothelial growth factor (VEGF, and cleaved caspase 3 were shown to be increased in the IH group. Overall, we found that exposure to intermittent hypoxia for 35 days by simulating sleep apnea leads to oxidative stress, inflammation, and increased activity of caspase 3 in the liver and lung.

  6. Cholesterogenic genes expression in brain and liver of ganglioside-deficient mice.

    Science.gov (United States)

    Mlinac, Kristina; Fon Tacer, Klementina; Heffer, Marija; Rozman, Damjana; Bognar, Svjetlana Kalanj

    2012-10-01

    The aim of this study was to determine the effect of changed ganglioside profile on transcription of selected genes involved in cholesterol homeostasis. For that purpose, the expression of 11 genes related to cholesterol synthesis, regulation, and cholesterol transport was investigated in selected brain regions (frontal cortex, hippocampus, brain stem, cerebellum) and liver of St8sia1 knockout (KO) mice characterized by deficient synthesis of b- and c-series gangliosides and accumulation of a-series gangliosides. The expression of majority of the analyzed genes, as determined using quantitative real time PCR, was slightly higher in St8sia1 KO compared to wild-type (wt) controls. More prominent changes were observed in Hmgr, Cyp51, and Cyp46 expression in brain (hippocampus and brain stem) and Srebp1a, Insig2a, and Ldlr in liver. In addition, the expression of master transcriptional regulators, Srebp1a, Srebp1c, and Insig2a, as well as transporters Ldlr and Vldlr differed between liver and brain, and within brain regions in wt animals. Cyp46 expression was expectedly brain-specific, with brain region difference in both wt and St8sia1 KO. The established change in transcriptome of cholesterogenic genes is associated to specific alteration of ganglioside composition which indicates relationship between gangliosides and regulation of cholesterol metabolism.

  7. [Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis].

    Science.gov (United States)

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-08-20

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients' quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work.

  8. Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Qi SONG

    2016-08-01

    Full Text Available Brain metastasis, a common complication of non-small cell lung cancer (NSCLC with an incidence rate of 30%-50%, significantly affects the patients’ quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work.

  9. Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis

    OpenAIRE

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-01-01

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients’ quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approa...

  10. Protective effects of N-acetylcysteine on brain-dead rat liver

    Institute of Scientific and Technical Information of China (English)

    Shui-Jun Zhang; Ting-Wu Ma; Xiu-Xian Ma; Jian-Jun Gou; Ji-Hua Shi; Wen-Zhi Guo

    2006-01-01

    BACKGROUND: Brain-dead donors have been the main sources in organ transplantation. But many studies show that brain-death affects the organ's function after transplantation. This study was undertaken to investigate liver injury after brain-death in rats and the protective effects of N-acetyleysteine (NAC) on liver injury. METHODS: A total of 30 Wistar rats were randomized into 3 groups: normal control group (C), brain-dead group (B), and NAC pretreatment group (N). At 4 hours after the establishment of a brain-dead model, serum was collected to determine the levels of ALT, AST, TNF-α and hyaluronic acid (HA). Hepatic tissue was obtained for electron microscopic examination. RESULTS:At 4 hours, the levels of ALT, AST, TNF-α, and HA in group N were signiifcantly higher than those in group C, but these parameters were signiifcantly lower than those in group B. Electron microscopy showed activated Kupffer cells, denuded sinusoidal endothelial cells (SECs), and widened fenestration in group B, but eliminated activation of Kupffer cells and intact SECs in group N. CONCLUSION: Brain death can cause liver injury, and N-acetyleysteine can protect the liver from the injury.

  11. Endotoxin-induced lung alveolar cell injury causes brain cell damage

    Science.gov (United States)

    Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia RM; Pelosi, Paolo

    2015-01-01

    Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. PMID:25135986

  12. Effects of Liver × receptor agonist treatment on signal transduction pathways in acute lung inflammation

    Directory of Open Access Journals (Sweden)

    Bramanti Placido

    2010-02-01

    Full Text Available Abstract Background Liver × receptor α (LXRα and β (LXRβ are members of the nuclear receptor super family of ligand-activated transcription factors, a super family which includes the perhaps better known glucocorticoid receptor, estrogen receptor, thyroid receptor, and peroxisome proliferator-activated receptors. There is limited evidence that LXL activation may reduces acute lung inflammation. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse model of carrageenan-induced pleurisy. Methods Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs in the pleural cavity, infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx, tumor necrosis factor-α, (TNF-α and interleukin-1β (IL-1β. Furthermore, carrageenan induced the expression of iNOS, nitrotyrosine and PARP, as well as induced apoptosis (TUNEL staining and Bax and Bcl-2 expression in the lung tissues. Results Administration of T0901317, 30 min after the challenge with carrageenan, caused a significant reduction in a dose dependent manner of all the parameters of inflammation measured. Conclusions Thus, based on these findings we propose that LXR ligand such as T0901317, may be useful in the treatment of various inflammatory diseases.

  13. Gaucher's disease. Plain radiography, US, CT and MR diagnosis of lungs, bone and liver lesions

    Energy Technology Data Exchange (ETDEWEB)

    Hainaux, B.; Christophe, C.; Hanquinet, S.; Perlmutter, N. (Free Univ. of Brussels (Belgium). Dept. of Pediatric Radiology)

    1992-04-01

    We report our observations made by conventional radiography, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) on a 3 1/2-year-old girl with Gaucher's disease. The interest of the case consists in the exceptional lungs involvement, the demonstration by MRI of the bone marrow involvement and the necrosis and fibrosis of the liver, as shown by CT. This liver complication has been previously reported only once. (orig.).

  14. Brain death induces the alteration of liver protein expression profiles in rabbits.

    Science.gov (United States)

    Du, Bing; Li, Ling; Zhong, Zhibiao; Fan, Xiaoli; Qiao, Bingbing; He, Chongxiang; Fu, Zhen; Wang, Yanfeng; Ye, Qifa

    2014-08-01

    At present, there is no accurate method for evaluating the quality of liver transplant from a brain-dead donor. Proteomics are used to investigate the mechanisms involved in brain death‑induced liver injury and to identify sensitive biomarkers. In the present study, age‑ and gender‑matched rabbits were randomly divided into the brain death and sham groups. The sham served as the control. A brain‑death model was established using an intracranial progressive pressurized method. The differentially expressed proteins extracted from the liver tissues of rabbits that were brain‑dead for 6 h in the two groups were determined by two‑dimensional gel electrophoresis and matrix‑assisted laser desorption ionization time of flight mass spectrometry. Although there was no obvious functional and morphological difference in 2, 4 and 6 h after brain death, results of the proteomics analysis revealed 973±34 and 987±38 protein spots in the control and brain death groups, respectively. Ten proteins exhibited a ≥2‑fold alteration. The downregulated proteins were: aldehyde dehydrogenase, runt‑related transcription factor 1 (RUNX1), inorganic pyrophosphatase, glutamate‑cysteine ligase regulatory subunit and microsomal cytochrome B5. By contrast, the expression of dihydropyrimidinase-related protein 4, peroxiredoxin‑6, 3‑phosphoinositide‑dependent protein kinase‑1, 3-mercaptopyruvate and alcohol dehydrogenase were clearly upregulated. Immunohistochemistry and western blot analysis results revealed that the expression of RUNX1 was gradually increased in a time‑dependent manner in 2, 4, and 6 h after brain death. In conclusion, alteration of the liver protein expression profile induced by brain death indicated the occurrence of complex pathological changes even if no functional or morphological difference was identified. Thus, RUNX1 may be a sensitive predict factor for evaluating the quality of brain death donated liver.

  15. Quantification of DNA adducts formed in liver, lungs, and isolated lung cells of rats and mice exposed to (14)C-styrene by nose-only inhalation.

    Science.gov (United States)

    Boogaard, P J; de Kloe, K P; Wong, B A; Sumner, S C; Watson, W P; van Sittert, N J

    2000-10-01

    Bronchiolo-alveolar tumors were observed in mice exposed chronically to 160 ppm styrene, whereas no tumors were seen in rats up to concentrations of 1000 ppm. Clara cells, which are predominant in the bronchiolo-alveolar region in mouse lungs but less numerous in rat and human lung, contain various cytochrome P450s, which may oxidize styrene to the rodent carcinogen styrene-7,8-oxide (SO) and other reactive metabolites. Reactive metabolites may form specific DNA adducts and induce the tumors observed in mice. To determine DNA adducts in specific tissues and cell types, rats and mice were exposed to 160 ppm [ring-U-(14)C]styrene by nose-only inhalation for 6 h in a recirculating exposure system. Liver and lungs were isolated 0 and 42 h after exposure. Fractions enriched in Type II cells and Clara cells were isolated from rat and mouse lung, respectively. DNA adduct profiles differed quantitatively and qualitatively in liver, total lung, and enriched lung cell fractions. At 0 and 42 h after exposure, the two isomeric N:7-guanine adducts of SO (measured together, HPEG) were present in liver at 3.0 +/- 0.2 and 1.9 +/- 0.3 (rat) and 1.2 +/- 0.2 and 3.2 +/- 0.5 (mouse) per 10(8) bases. Several other, unidentified adducts were present at two to three times higher concentrations in mouse, but not in rat liver. In both rat and mouse lung, HPEG was the major adduct at approximately 1 per 10(8) bases at 0 h, and these levels halved at 42 h. In both rat Type II and non-Type II cells, HPEG was the major adduct and was about three times higher in Type II cells than in total lung. For mice, DNA adduct levels in Clara cells and non-Clara cells were similar to total lung. The hepatic covalent binding index (CBI) at 0 and 42 h was 0.19 +/- 0.06 and 0.14 +/- 0.03 (rat) and 0. 25 +/- 0.11 and 0.44 +/- 0.23 (mouse), respectively. The pulmonary CBIs, based on tissues combined for 0 and 42 h, were 0.17 +/- 0.04 (rat) and 0.24 +/- 0.04 (mouse). Compared with CBIs for other genotoxicants

  16. Effect of α-Ketoglutarate on Cyanide-induced Biochemical Alterations in Rat Brain and Liver

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the biochemical changes in rat brain and liver following acute exposure to a lethal dose of cyanide, and its response to treatment of α-ketoglutarate (α-KG) in the absence or presence of sodium thiosulfate (STS). Methods Female rats were administered 2.0 LD50 potassium cyanide (KCN; oral) in the absence or presence of pre-treatment (-10 min), simultaneous treatment (0 min) or post-treatment (+2-3 min) of α-KG (2.0 g/kg, oral) and/or STS (1.0 g/kg,intraperitoneal, -15 min, 0 min or + 2-3 min). At the time of onset of signs and symptoms of KCN toxicity (2-4 min) and at the time of death (5-15 min), various parameters particularly akin to oxidative stress viz. Cytochrome oxidase (CYTOX),superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH) and oxidized glutathione (GSSG) in brain, and CYTOX, sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP), GSH and GSSG in liver homogenate were measured. Results At both time intervals brain CYTOX, SOD, GPx, and GSH significantly reduced (percent inhibition compared to control) to 24%, 56%, 77%, and 65%, and 44%, 46%, 78%, and 57%, respectively. At the corresponding time points liver CYTOX and GSH reduced to 74% and 63%, and 44% and 68%, respectively. The levels of GSSG in the brain and liver, and hepatic ALP and SDH were unchanged. Pre-treatment and simultaneous treatment of α-KG alone or with STS conferred significant protection on above variables. Post-treatment was effective in restoring the changes in liver but failed to normalize the changes in the brain. Conclusions Oral treatment with α-KG alone or in combination with STS has protective effects on cyanide-induced biochemical alterations in rat brain and liver.

  17. Afatinib in Treatment-Naive Patients With EGFR-Mutated Lung Adenocarcinoma With Brain Metastasis: A Case Series.

    Science.gov (United States)

    Li, Shih-Hong; Hsieh, Meng-Heng; Fang, Yueh-Fu

    2015-10-01

    Tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) were previously the standard first-line treatments for lung cancers with activating EGFR mutations. The first-generation reversible EGFR TKIs, gefitinib and erlotinib, demonstrated substantial efficacy in the treatment of brain metastases from EGFR-mutated lung adenocarcinoma. However, the efficacy of afatinib, the second-generation irreversible EGFR TKI, as the first-line treatment in lung adenocarcinoma patients with brain metastasis has yet to be evaluated.Here, we report cases of 3 patients who received afatinib alone as the first-line treatment in combination with whole-brain radiotherapy or following surgical resection of brain metastases. All 3 patients had EGFR L858R mutation. The first patient had lung adenocarcinoma with brain metastasis and no neurologic symptoms. After consultation, she received afatinib as a first-line treatment. Chest computed tomography and brain magnetic resonance imaging (MRI) showed partial response. The second patient had lung adenocarcinoma accompanied with a metastatic brain lesion associated with seizures. This patient received whole-brain radiotherapy and afatinib treatment following brain MRI and subsequently showed significant regression of the brain metastasis. The third patient had strabismus of the right eye, and brain MRI showed a single tumor at the cerebellar pontine angle. This patient underwent surgical resection of the tumor followed by afatinib treatment. He refused adjuvant radiotherapy after surgery for brain metastasis. The brain MRI showed no recurrent brain metastasis, and the patient had relatively less neurologic deficiency.This series of 3 cases indicate that afatinib may be an appropriate first-line treatment alternative in patients having lung adenocarcinoma with EGFR mutations. Further retrospective analyses and prospective clinical trials are required to substantiate the efficacy of afatinib in the treatment of brain

  18. Lactate administration reproduces specific brain and liver exercise-related changes.

    Science.gov (United States)

    E, Lezi; Lu, Jianghua; Selfridge, J Eva; Burns, Jeffrey M; Swerdlow, Russell H

    2013-10-01

    The effects of exercise are not limited to muscle, and its ability to mitigate some chronic diseases is under study. A more complete understanding of how exercise impacts non-muscle tissues might facilitate design of clinical trials and exercise mimetics. Here, we focused on lactate's ability to mediate changes in liver and brain bioenergetic-associated parameters. In one group of experiments, C57BL/6 mice underwent 7 weeks of treadmill exercise sessions at intensities intended to exceed the lactate threshold. Over time, the mice dramatically increased their lactate threshold. To ensure that plasma lactate accumulated during the final week, the mice were run to exhaustion. In the liver, mRNA levels of gluconeogenesis-promoting genes increased. While peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1α) expression increased, there was a decrease in PGC-1β expression, and overall gene expression changes favored respiratory chain down-regulation. In the brain, PGC-1α and PGC-1β were unchanged, but PGC-1-related co-activator expression and mitochondrial DNA copy number increased. Brain tumor necrosis factor alpha expression fell, whereas vascular endothelial growth factor A expression rose. In another group of experiments, exogenously administered lactate was found to reproduce some but not all of these observed liver and brain changes. Our data suggest that lactate, an exercise byproduct, could mediate some of the effects exercise has on the liver and the brain, and that lactate itself can act as a partial exercise mimetic.

  19. Quantitative multivoxel {sup 1}H MR spectroscopy of the brain in children with acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs [University Medical Center Groningen and University of Groningen, Department of Radiology, Beatrix Children' s Hospital, Groningen (Netherlands); Lunsing, Roelineke J. [University Medical Center Groningen and University of Groningen, Department of Child Neurology, Beatrix Children' s Hospital, Groningen (Netherlands); Spronsen, Francjan J. van; Verkade, Henkjan J. [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Beatrix Children' s Hospital, Groningen (Netherlands)

    2008-11-15

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, {gamma}-glutamyl transpeptidase, alkaline phosphatase). (orig.)

  20. A Case of Lung Cancer with Brain Metastases Diagnosed After Epileptic Seizure

    Directory of Open Access Journals (Sweden)

    Hakan Simsek

    2016-04-01

    Full Text Available  LETTER TO THE EDITOR CONCERNING THE CASE REPORT “A case of lung cancer with brain metastases diagnosed after epileptic seizure” by M. Eroglu et al. J Clin Anal Med 2015; 6(3: 384-6

  1. Concurrent Low Brain and High Liver Uptake on FDG PET Are Associated with Cardiovascular Risk Factors

    Science.gov (United States)

    Nam, Hyun-Yeol; Jun, Sungmin; Pak, Kyoungjune

    2017-01-01

    Objective Concurrent low brain and high liver uptake are sometimes observed on fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We investigated the potential clinical significance of this uptake pattern related to metabolic syndrome (MS). Materials and Methods We retrospectively reviewed data from 264 consecutive males who had undergone general health check-ups, including FDG PET/CT scans. After an overnight fast, the men had their peripheral blood drawn and the levels of various laboratory parameters measured; an FDG PET/CT scan was performed on the same day. We measured the maximum standardized uptake values of the brain and liver from regions of interest manually placed over the frontal cortex at the level of the centrum semiovale and the right lobe of the liver parenchyma, respectively. Results Fasting blood glucose (FBG; odds ratio [OR] = 1.063, p < 0.001) and glycated hemoglobin (HbA1c; OR = 3.634, p = 0.010) were the strongest predictive factors for low brain FDG uptake, whereas waist circumference (OR = 1.200, p < 0.001) and γ-glutamyl transpeptidase (OR = 1.012, p = 0.001) were the strongest predictive factors for high liver uptake. Eleven subjects (4.2%) showed concurrent low brain and high liver FDG uptake, and all but one of these subjects (90.9%) had MS. Systolic blood pressure, waist circumference, FBG, triglyceride, alanine aminotransferase, insulin resistance (measured by homeostasis model assessment), insulin, HbA1c, and body mass index were higher in subjects with this FDG uptake pattern than in those without (all, p < 0.001). Conclusion Concurrent low brain and high liver FDG uptake were closely associated with MS. Moreover, subjects with this pattern had higher values for various cardiovascular risk factors than did those without. PMID:28246520

  2. Carbon monoxide inhalation ameliorates conditions of lung grafts from rat brain death donors

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hua-cheng; DING Wen-gang; CUI Xiao-guang; PAN Peng; ZHANG Bing; LI Wen-zhi

    2008-01-01

    Background Successful lung transplantation has been limited by the scarcity of donors. Brain death (BD) donors are major source of lung transplantation. Whereas BD process induces acute lung injury and aggravates lung ischemia reperfusion injury. Carbon monoxide (CO) inhalation at 50-500 parts per million (ppm) can ameliorate lung injury in several models. We examined in rats whether CO inhalation in BD donor would show favorable effects on lung grafts.Methods Rats were randomly divided into 4 groups. In sham group, donor rats received insertion of a balloon catheter into the cranial cavity, but the balloon was not inflated. In BD-only group, donor rats were ventilated with 40% oxygen after BD confirmation. In BD+CO250 and BD+CO500 groups, donor rats inhaled, after BD confirmation, 250 ppm or 500 ppm CO for 120 minutes prior to lung procurement, and orthotopic lung transplantation was performed. The rats were sacrificed 120 minutes after the lung transplantation by exsanguination, and their blood and lung graft samples were obtained. A total of 8 rats fulfilling the criteria were included in each group.Results The inhalation decreased the severity of lung injury in grafts from BD donors checked by histological examination. CO pretreatment reversed the aggravation of PaO2/FiO2 in recipients from BD donors. The CO inhalation down-regulated pro-inflammatory cytokines (TNF-α, IL-6) along with the increase of anti-inflammatory cytokine (IL-10) in recipient serum, and inhibited the activity of myeloperoxidase in grafts tissue. The inhalation significantly decreased cell apoptosis in lung grafts, inhibiting mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and caspase-3 in lung grafts. Further, the inhalation activated phosphorylation of p38 expression and inhibited phosphorylation of anti-extraceUular signal-regulated kinase (ERK) expression in lung grafts. The effects of CO at 500 ppm were greater than those at 250 ppm.Conclusions CO exerts

  3. The histological changes in the liver, lung and kidney after scorpion poisoning (Buthus quinquestriatus).

    Science.gov (United States)

    Nawar, N N; Shoukri, N A; Hanna, M M

    1979-06-01

    The effect of sublethal doses of Buthus quinquestriatus on the hepatic vascular bed and hepatic parenchyma were studied. The main effect of the venom was primarily on the vascular bed of the liver as manifested by dilatation of branches of the hepatic artery, portal vein together with intravascular thrombi and subcapsular haemorrhages. Apart from mild hydropic degeneration some cells of the hepatic parenchyma showed focal necrosis and Kupffer cells were frequently hypertrophied and contained pigment. In the lung, dilated thrombosed vessels were observed. In the kidney, the vessels showed the smae changes. The epithelial and endothelial cells of the glomeruli appeared normal except for slight swelling with intact basement membrane. The tubular cells were swollen with increased granularity and attenuation of their tubular lumen, a picture compatible with hydropic degeneration. The possible mechanisms in inducing such lesions were discussed.

  4. Isolation of Lymphocytes and Their Innate Immune Characterizations from Liver, Intestine, Lung and Uterus

    Institute of Scientific and Technical Information of China (English)

    Jianhong Zhang; Zhongjun Dong; Rongbin Zhou; Deming Luo; Haiming Wei; Zhigang Tian

    2005-01-01

    In steady-state conditions, the number and distribution of lymphocyte populations are under homeostatic control.New lymphocytes are continuously produced in primary and secondary lymphoid organs and then achieve immune-competence within different tissues, and they must challenge with resident cells for survival. The first step in the study of tissue lymphoid cells is their isolation in intact and viable form appropriate for establishment of in vitro culture systems. For reasons of simplicity, cell purity, cell yields and various purposes, lymphocytes obtained from different tissues in different labs were subjected to diverse protocols. To fully elucidate the nature of the local immune system as well as to adequately study the innate role of lymphocytes in liver, intestine, lung and uterus, we briefly reviewed the characterization of resident lymphocytes, and additional information on those cells from non-lymphoid tissues by using the recommended operation procedure was also presented.

  5. Preliminary Study of Brain Glucose Metabolism Changes in Patients with Lung Cancer of Different Histological Types

    Institute of Scientific and Technical Information of China (English)

    Wei-Ling Li; Chang Fu; Ang Xuan; Da-Peng Shi; Yong-Ju Gao; Jie Zhang; Jun-Ling Xu

    2015-01-01

    Background:Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors.This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types.Methods:One hundred and twenty patients with primary untreated lung cancer,who visited People's Hospital of Zhengzhou University from February 2012 to July 2013,were divided into three groups based on histological types confirmed by biopsy or surgical pathology,which included adenocarcinoma (52 cases),squamous cell carcinoma (43 cases),and small-cell carcinoma (25 cases).The whole body 18F-fluorodeoxyglucose (1 8F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied.The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software,with 50 age-matched and gender-matched healthy controls for comparison.Results:The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction.The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal,bilateral superior and middle temporal and inferior and middle temporal gyrus.Besides,the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group.The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292).Conclusions:The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  6. Similar liver transplantation survival with selected cardiac death donors and brain death donors

    NARCIS (Netherlands)

    Dubbeld, J.; Hoekstra, H.; Farid, W.; Ringers, J.; Porte, R. J.; Metselaar, H. J.; Baranski, A. G.; Kazemier, G.; van den Bere, A. P.; van Hoek, B.

    2010-01-01

    Background: The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive

  7. Mitochondrial oxidative stress and dysfunction induced by isoniazid : study on isolated rat liver and brain mitochondria

    NARCIS (Netherlands)

    Ahadpour, Morteza; Eskandari, Mohammad Reza; Mashayekhi, Vida; Hajmohammadebrahimtehrani, K.; Jafarian, Iman; Naserzadeh, Parvaneh; Hosseini, Mir-Jamal

    2015-01-01

    Isoniazid (INH or isonicotinic hydrazide) is used for the treatment and prophylaxis of tuberculosis. Liver and brain are two important target organs in INH toxicity. However, the exact mechanisms behind the INH hepatotoxicity or neurotoxicity have not yet been completely understood. Considering the

  8. Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages

    NARCIS (Netherlands)

    Huisman, M; Muskiet, FAJ; Van Der Paauw, CG; Essed, CE; Boersma, ER

    1998-01-01

    We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median (range) gestational ages and birth weights were 34 (17-40) wk and 2050 (162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos. 118

  9. Base-resolution DNA methylation landscape of zebrafish brain and liver

    Directory of Open Access Journals (Sweden)

    Aniruddha Chatterjee

    2014-12-01

    To our knowledge, these datasets are the only RRBS datasets and base-resolution DNA methylation data available at this time for zebrafish brain and liver. These datasets could serve as a resource for future studies to document the functional role of DNA methylation in zebrafish. In addition, these datasets could be used as controls while performing analysis on treated samples.

  10. Treatment for brain metastasis from lung cancer in the era of radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, Kazuhiro; Iwai, Yoshiyasu; Nakajima, Hideki [Osaka City General Hospital (Japan)] (and others)

    2001-07-01

    The treatment for brain metastasis has undergone remarkable changes since the development of radiosurgery. We investigated the results of treatment for brain metastasis from lung cancer since the initiation of gamma knife radiosurgery (GKRS) and we discuss the usefulness of GKRS combined with other treatments in cases with recurrence. We treated 142 patients with brain metastasis from lung cancer. Sixteen patients were treated surgically, 11 patients were treated with whole brain radiation therapy (WBRT), and 115 patients were treated with GKRS. Our treatment plan is to use GKRS in cases with less than 5 lesions and lesions less than 3 cm in mean diameter. We use WBRT in cases with 5 or more lesions, and surgery in cases with lesions 3 cm or larger. If new lesions or tumor regrowth appeared after the initial treatment, we retreated them with one of the methods mentioned above. Twice or three-time treatments were performed in 30 patients. Median survival including all cases was 10 months and the number of deaths due to local treatment failure was only 5 (6.5%) out of the total 77 deaths which occurred. We were able to carry out less invasive treatment for brain metastasis from lung cancer by utilizing GKRS. Though we have to consider the indications for other treatments, we can say that radiosurgery is usually the treatment of first choice for brain metastasis from lung caner. When new lesions appear in cases where a particular initial treatment was used, it is possible to maintain or improve the quality of life by retreatment, using a combination of GKRS, surgery or WBRT, to prolong the patient's life. (author)

  11. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  12. Surgery Versus Stereotactic Radiosurgery for Single Synchronous Brain Metastasis from Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Hui LI; Sheng-cai HOU; Bin HU; Tong LI; Yang Wang; Jin-bai Miao; Bin You; Yi-li Fu

    2009-01-01

    Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer.Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32(85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS.Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (N0), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P>0.05). In lymph node negative patients (N0), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1(2). The difference was significant (P0.05).Conclusion: Although the overall survival rate for

  13. Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice.

    Science.gov (United States)

    Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Morsy, Safaa M Youssef; Omara, Enayat A; Sleem, Amany A

    2014-05-01

    Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

  14. Gamma knife radiosurgery for multiple brain metastases from non-small cell lung cancer. Comparison with whole brain radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Serizawa, Toru; Ono, Junichi [Chiba Cardiovascular Center (Japan); Iuchi, Toshihiko; Osato, Katsunobu

    2001-04-01

    The purpose of this retrospective study is to compare the effectiveness of gamma knife radiosurgery (GKS) with that of whole-brain radiation therapy (WBRT) for multiple cerebral metastases from non-small cell lung cancer. Among 302 cases with cerebral metastases from non-small cell lung cancer treated at the Chiba Cardiovascular Center and Chiba Cancer Center between 1990 and 1999, 100 consecutive patients filling the following 4 entry criteria were analyzed in this study: Up to 10 multiple brain lesions at initial MRI study; No surgically inaccessible tumors with more than 30 mm in diameter; No carcinomatous meningitis; More than 3 months of life expectancy. The patients were divided into two groups: the GKS group (66 patients) and the WBRT group (34 patients). In the GKS group, large lesions ({>=}30mm) were removed microsurgically and all other small lesions (<30 mm) were treated by GKS. New distant lesions were treated by repeated GKS without prophylactic WBRT. In the WBRT group, the patients were treated by the traditional combined therapy of WBRT and surgery. In both groups, chemotherapy was administered according to the primary physician's protocol. The two groups did not differ in terms of age, gender, initial Karnofsky Performance Scale (KPS) score, pathology of lung caner, number, and size of brain lesion, systemic control, and chemotherapy. Overall survival (OS), neurological survival (NS) and qualitative survival (QS) of the GKS group were longer than those of the WBRT group according to Kaplan-Meier's method. In a multivariate analysis the WBRT group also had significant poor prognostic factors for OS, NS and QS. GKS without prophylactic WBRT could be a primary choice of treatment method for patients with as many as 10 cerebral metastases from non-small cell lung cancer. (author)

  15. Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin.

    Science.gov (United States)

    Bosch-Barrera, Joaquim; Sais, Elia; Cañete, Noemí; Marruecos, Jordi; Cuyàs, Elisabet; Izquierdo, Angel; Porta, Rut; Haro, Manel; Brunet, Joan; Pedraza, Salvador; Menendez, Javier A

    2016-05-31

    Despite multimodal treatment approaches, the prognosis of brain metastases (BM) from non-small cell lung cancer (NSCLC) remains poor. Untreated patients with BM have a median survival of about 1 month, with almost all patients dying from neurological causes. We herein present the first report describing the response of BM from NSCLC patients to an oral nutraceutical product containing silibinin, a flavonoid extracted from the seeds of the milk thistle. We present evidence of how the use of the silibinin-based nutraceutical Legasil® resulted in significant clinical and radiological improvement of BM from NSCLC patients with poor performance status that progressed after whole brain radiotherapy and chemotherapy. The suppressive effects of silibinin on progressive BM, which involved a marked reduction of the peritumoral brain edema, occurred without affecting the primary lung tumor outgrowth in NSCLC patients. Because BM patients have an impaired survival prognosis and are in need for an immediate tumor control, the combination of brain radiotherapy with silibinin-based nutraceuticals might not only alleviate BM edema but also prove local control and time for either classical chemotherapeutics with immunostimulatory effects or new immunotherapeutic agents such as checkpoint blockers to reveal their full therapeutic potential in NSCLC BM patients. New studies aimed to illuminate the mechanistic aspects underlying the regulatory effects of silibinin on the cellular and molecular pathobiology of BM might expedite the entry of new formulations of silibinin into clinical testing for progressive BM from lung cancer patients.

  16. Active targeting docetaxel-PLA nanoparticles eradicate circulating lung cancer stem-like cells and inhibit liver metastasis.

    Science.gov (United States)

    Yang, Nan; Jiang, Yao; Zhang, Huifeng; Sun, Bo; Hou, Chunying; Zheng, Ji; Liu, Yanyong; Zuo, Pingping

    2015-01-05

    Lung cancer is the major cause of cancer related lethality worldwide, and metastasis to distant organs is the pivotal cause of death for the vast majority of lung cancer patients. Accumulated evidence indicates that lung cancer stem-like cells (CSLCs) play important roles in metastagenesis, and these circulating CSLCs may be important targets to inhibit the subsequent metastasis. The present study was aimed at establishing CSLC-targeting polylactic acid (PLA) encapsulated docetaxel nanoparticles for antimetastatic therapy. Cyclic binding peptides were screened on CSLCs in vitro and the peptide CVKTPAQSC exhibiting high specific binding ability to pulmonary adenocarcinoma tissue was subsequently conjugated to the nanoparticles loaded with docetaxel (NDTX). Antimetastatic effect of CSLC-targeting nanoparticles loaded with docetaxel (TNDTX) was evaluated in a nude mouse model of liver metastasis. Results showed that, in the absence of targeting peptide, NDTX hardly exhibited any antimetastatic effect. However, TNDTX treatment significantly decreased the metastatic tumor area in the nude mouse liver. Histopathological and serological results also confirmed the antimetastatic efficacy of TNDTX. To our knowledge, this is the first report on establishing a CSLC-based strategy for lung cancer metastatic treatment, and we hope this will offer a potential therapeutic approach for management of metastatic lung cancer.

  17. Pathological characteristics of liver allografts from donation after brain death followed by cardiac death in pigs.

    Science.gov (United States)

    Ye, Hui; Wang, Dong-Ping; Zhang, Chuan-Zhao; Zhang, Long-Juan; Wang, Hao-Chen; Li, Zhuo-Hui; Chen, Zhen; Zhang, Tao; Cai, Chang-Jie; Ju, Wei-Qiang; Ma, Yi; Guo, Zhi-Yong; He, Xiao-Shun

    2014-10-01

    Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

  18. Brain-liver connections: role of the preautonomic PVN neurons.

    Science.gov (United States)

    O'Hare, James D; Zsombok, Andrea

    2016-02-01

    Diabetes mellitus and the coexisting conditions and complications, including hypo- and hyperglycemic events, obesity, high cholesterol levels, and many more, are devastating problems. Undoubtedly, there is a huge demand for treatment and prevention of these conditions that justifies the search for new approaches and concepts for better management of whole body metabolism. Emerging evidence demonstrates that the autonomic nervous system is largely involved in the regulation of glucose homeostasis; however, the underlying mechanisms are still under investigation. Within the hypothalamus, the paraventricular nucleus (PVN) is in a unique position to integrate neural and hormonal signals to command both the autonomic and neuroendocrine outflow. This minireview will provide a brief overview on the role of preautonomic PVN neurons and the importance of the PVN-liver pathway in the regulation of glucose homeostasis.

  19. Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine

    DEFF Research Database (Denmark)

    Artmann, Andreas; Petersen, Gitte; Hellgren, Lars

    2008-01-01

    acid in brain, jejunum and liver. The OA-diet increased brain levels of anandamide and oleoylethanolamide (not 2-arachidonoylglycerol) without changing tissue fatty acid composition. The same diet increased oleoylethanolamide in liver. All five dietary fats decreased oleoylethanolamide in jejunum...... (AA)) on tissue levels of 2-arachidonoylglycerol, anandamide, oleoylethanolamide, palmitoylethanolamide, stearoylethanolamide, linoleoylethanolamide, eicosapentaenoylethanolamide, docosahexaenoylethanolamide and tissue fatty acid composition. The LA-diet increased linoleoylethanolamide and linoleic...... without changing levels of anandamide, suggesting that dietary fat may have an orexigenic effect. The AA-diet increased anandamide and 2-arachidonoylglycerol in jejunum without effect on liver. The FO-diet decreased liver levels of all N-acylethanolamines (except eicosapentaenoylethanolamide...

  20. Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production.

    Science.gov (United States)

    Wang, Penny Y T; Caspi, Liora; Lam, Carol K L; Chari, Madhu; Li, Xiaosong; Light, Peter E; Gutierrez-Juarez, Roger; Ang, Michelle; Schwartz, Gary J; Lam, Tony K T

    2008-04-24

    Energy and glucose homeostasis are regulated by food intake and liver glucose production, respectively. The upper intestine has a critical role in nutrient digestion and absorption. However, studies indicate that upper intestinal lipids inhibit food intake as well in rodents and humans by the activation of an intestine-brain axis. In parallel, a brain-liver axis has recently been proposed to detect blood lipids to inhibit glucose production in rodents. Thus, we tested the hypothesis that upper intestinal lipids activate an intestine-brain-liver neural axis to regulate glucose homeostasis. Here we demonstrate that direct administration of lipids into the upper intestine increased upper intestinal long-chain fatty acyl-coenzyme A (LCFA-CoA) levels and suppressed glucose production. Co-infusion of the acyl-CoA synthase inhibitor triacsin C or the anaesthetic tetracaine with duodenal lipids abolished the inhibition of glucose production, indicating that upper intestinal LCFA-CoAs regulate glucose production in the preabsorptive state. Subdiaphragmatic vagotomy or gut vagal deafferentation interrupts the neural connection between the gut and the brain, and blocks the ability of upper intestinal lipids to inhibit glucose production. Direct administration of the N-methyl-d-aspartate ion channel blocker MK-801 into the fourth ventricle or the nucleus of the solitary tract where gut sensory fibres terminate abolished the upper-intestinal-lipid-induced inhibition of glucose production. Finally, hepatic vagotomy negated the inhibitory effects of upper intestinal lipids on glucose production. These findings indicate that upper intestinal lipids activate an intestine-brain-liver neural axis to inhibit glucose production, and thereby reveal a previously unappreciated pathway that regulates glucose homeostasis.

  1. Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

    Science.gov (United States)

    Johnson, Eric D.; Gulbahce, Evin; McNally, Joseph; Buys, Saundra S.

    2016-01-01

    Introduction Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported. PMID:28203179

  2. Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

    Directory of Open Access Journals (Sweden)

    Eric D. Johnson

    2016-12-01

    Full Text Available Introduction: Phyllodes tumors (PTs are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case: A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion: PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion: We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported.

  3. Boiling sheep liver or lung for 30 minutes is necessary and sufficient to kill Echinococcus granulosus protoscoleces in hydatid cysts

    Directory of Open Access Journals (Sweden)

    Li Jun

    2014-01-01

    Full Text Available Proper disposal of carcasses and offal after home slaughter is difficult in poor and remote communities and therefore dogs readily have access to hydatid cysts containing offal from livestock, thus completing the parasite cycle of Echinococcus granulosus and putting communities at risk of cystic echinococcosis. Boiling livers and lungs which contain hydatid cysts could be a simple, efficient and energy- and time-saving way to kill the infectious protoscoleces. The aim of this study was to provide precise practical recommendations to livestock owners. Our results show that boiling the whole sheep liver and/or lung, with single or multiple hydatid cysts, for 30 min is necessary and sufficient to kill E. granulosus protoscoleces in hydatid cysts. Advertising on this simple rule in at-risk communities would be an efficient and cheap complement to other veterinary public health operations to control cystic echinococcosis.

  4. The effect of induced liver, kidney and lung lesions on the toxicity of levamisole and diazinon in calves.

    Science.gov (United States)

    Abdelsalam, E B; Ford, E J

    1987-11-01

    Liver damage in calves, produced by the oral administration of the flukecide, carbon tetrachloride, increased the toxic effect of diazinon but not of levamisole, whereas the presence of a renal tubular lesion caused by mercuric chloride enhanced the toxicity of both commonly used anthelmintic compounds. The toxicity of diazinon was increased in calves with a lung lesion caused by oral dosing with tryptophan, an agent implicated in 'fog fever' of cattle.

  5. Angiotensin Converting Enzyme Activity in the Serum, Lung, Liver and Kidney in Streptozotocin -Induced Diabetic Rats and Diabetic Nephropathy

    OpenAIRE

    Üstündağ, Bilal

    2014-01-01

    To clarify the relationship between the alterations of the levels of angiotensin converting enzyme (ACE) and diabetic nephropathy, ACE activity in the lung, liver, kid-ney and serum were investigated in streptozotocin (STZ)-induced diabetic rats. The levels of serum ACE activity unchanged 3 days post STZ treatment but it was significantly an increase 12 and 30 days post STZ treatment in diabetic rats (p

  6. Thyroid hormone therapy and procurement of livers from brain-dead donors.

    Science.gov (United States)

    Novitzky, Dimitri; Mi, Zhibao; Videla, Luis A; Collins, Joseph F; Cooper, David K C

    2016-08-01

    Hormonal therapy to brain-dead potential organ donors remains controversial. A retrospective study was carried out of hormonal therapy on procurement of organs in 63,593 donors in whom information on T3/T4 therapy was available. In 40,124 donors, T3/T4 and all other hormonal therapy was recorded. The percentages of all organs procured, except livers, were greater in T3/T4-treated donors. Nevertheless, if T3/T4 therapy had been administered to the donor, liver transplantation was associated with significantly increased graft and recipient survival at 1 month and 12 months. The potential reasons for the lack of effect of T3/T4 therapy on the number of livers procured are discussed.

  7. Carboxylated nanodiamonds are neither cytotoxic nor genotoxic on liver, kidney, intestine and lung human cell lines.

    Science.gov (United States)

    Paget, V; Sergent, J A; Grall, R; Altmeyer-Morel, S; Girard, H A; Petit, T; Gesset, C; Mermoux, M; Bergonzo, P; Arnault, J C; Chevillard, S

    2014-08-01

    Although nanodiamonds (NDs) appear as one of the most promising nanocarbon materials available so far for biomedical applications, their risk for human health remains unknown. Our work was aimed at defining the cytotoxicity and genotoxicity of two sets of commercial carboxylated NDs with diameters below 20 and 100 nm, on six human cell lines chosen as representative of potential target organs: HepG2 and Hep3B (liver), Caki-1 and Hek-293 (kidney), HT29 (intestine) and A549 (lung). Cytotoxicity of NDs was assessed by measuring cell impedance (xCELLigence® system) and cell survival/death by flow cytometry while genotoxicity was assessed by γ-H2Ax foci detection, which is considered the most sensitive technique for studying DNA double-strand breaks. To validate and check the sensitivity of the techniques, aminated polystyrene nanobeads were used as positive control in all assays. Cell incorporation of NDs was also studied by flow cytometry and luminescent N-V center photoluminescence (confirmed by Raman microscopy), to ensure that nanoparticles entered the cells. Overall, we show that NDs effectively entered the cells but NDs do not induce any significant cytotoxic or genotoxic effects on the six cell lines up to an exposure dose of 250 µg/mL. Taken together these results strongly support the huge potential of NDs for human nanomedicine but also their potential as negative control in nanotoxicology studies.

  8. Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria.

    Science.gov (United States)

    Ahadpour, Morteza; Eskandari, Mohammad Reza; Mashayekhi, Vida; Haj Mohammad Ebrahim Tehrani, Kamaleddin; Jafarian, Iman; Naserzadeh, Parvaneh; Hosseini, Mir-Jamal

    2016-01-01

    Isoniazid (INH or isonicotinic hydrazide) is used for the treatment and prophylaxis of tuberculosis. Liver and brain are two important target organs in INH toxicity. However, the exact mechanisms behind the INH hepatotoxicity or neurotoxicity have not yet been completely understood. Considering the mitochondria as one of the possible molecular targets for INH toxicity, the aim of this study was to evaluate the mechanisms of INH mitochondrial toxicity on isolated mitochondria. Mitochondria were isolated by differential ultracentrifugation from male Sprague-Dawley rats and incubated with different concentrations of INH (25-2000 μM) for the investigation of mitochondrial parameters. The results indicated that INH could interact with mitochondrial respiratory chain and inhibit its activity. Our results showed an elevation in mitochondrial reactive oxygen species (ROS) formation, lipid peroxidation and mitochondrial membrane potential collapse after exposure of isolated liver mitochondria in INH. However, different results were obtained in brain mitochondria. Noteworthy, significant glutathione oxidation, adenosine triphosphate (ATP) depletion and lipid peroxidation were observed in higher concentration of INH, as compared to liver mitochondria. In conclusion, our results suggest that INH may initiate its toxicity in liver mitochondria through interaction with electron transfer chain, lipid peroxidation, mitochondrial membrane potential decline and cytochrome c expulsion which ultimately lead to cell death signaling.

  9. Evidence of oxidative stress in brain and liver of young rats submitted to experimental galactosemia.

    Science.gov (United States)

    Castro, Márcia B; Ferreira, Bruna K; Cararo, José Henrique; Chipindo, Adália E; Magenis, Marina L; Michels, Monique; Danielski, Lucinéia G; de Oliveira, Marcos R; Ferreira, Gustavo C; Streck, Emilio L; Petronilho, Fabricia; Schuck, Patrícia F

    2016-12-01

    Galactosemia is a disorder of galactose metabolism, leading to the accumulation of this carbohydrate. Galactosemic patients present brain and liver damage. For evaluated oxidative stress, 30-day-old males Wistar rats were divided into two groups: galactose group, that received a single injection of this carbohydrate (5 μmol/g), and control group, that received saline 0.9 % in the same conditions. One, twelve or twenty-four hours after the administration, animals were euthanized and cerebral cortex, cerebellum, and liver were isolated. After one hour, it was found a significant increase in TBA-RS levels, nitrate and nitrite and protein carbonyl contents in cerebral cortex, as well as protein carbonyl content in the cerebellum and in hepatic level of TBA-RS, and a significant decrease in nitrate and nitrite contents in cerebellum. TBA-RS levels were also found increased in all studied tissues, as well as nitrate and nitrite contents in cerebral cortex and cerebellum, that also present increased protein carbonyl content and impairments in the activity of antioxidant enzymes of rats euthanized at twelve hours. Finally, animals euthanized after twenty-four hours present an increase of TBA-RS levels in studied tissues, as well as the protein carbonyl content in cerebellum and liver. These animals also present an increased nitrate and nitrite content and impairment of antioxidant enzymes activities. Taken together, our data suggest that acute galactose administration impairs redox homeostasis in brain and liver of rats.

  10. Primary monophasic synovial sarcoma lung with brain metastasis diagnosed on transthoracic FNAC: Report of a case with literature review

    Directory of Open Access Journals (Sweden)

    Paras Nuwal

    2012-01-01

    Full Text Available Synovial sarcoma is highly malignant tumor of soft tissues, occurring chiefly in the extremities and limb girdle with a propensity for local recurrence and sometimes metastases to the lungs. Primary synovial sarcoma arising in the lungs is rare and brain metastasis as presentation is further uncommon. We report a case of primary monophasic synovial sarcoma lung presenting with brain metastasis in a 35-year-old male patient. The diagnosis was made on percutaneous transthoracic needle aspiration from left-sided pulmonary mass and later confirmed by immunohistochemistry. The utility of preoperative diagnosis by percutaneous aspiration cytology is also stressed.

  11. UPTAKE OF [3H]-COLCHICINE INTO BRAIN AND LIVER OF MOUSE, RAT, AND CHICK

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Edward L.; Alberti, Marie Hebert; Flood, James F.

    1980-07-01

    The uptake of [ring A-4-{sup 3}H] colchicine and [ring C-methoxy-{sup 3}H]colchicine has been compared in mice from 1 to 24 hr after administration. Less radioactivity was found in brain after administration of ring-labeled colchicine than after administration of the methoxy-labeled colchicine. Three hr after administration of ring-labeled colchicine, 5% of the label was in liver and about 0.01% of the label was present in brain. Forty percent of the brain radioactivity was bound to tubulin as determined by vinblastine precipitation. After 3 hr, an average of 8% of the radioactivity from methoxy-labeled colchicine was found in the liver and 0.16% in brain. However, less than 5% of the activity in brain was precipitated by vinblastine, and the colchicine equivalent was comparable to that found after administration of the ring-labeled colchicine. The amount of colchicine entering mouse brain after subcutaneous injection is comparable to the minimum behaviorally effective dose when administered to the caudate. The metabolism of [ring C-methoxy-{sup 3}H] and [ring A-{sup 3}H]colchicine was also studied in rats. the general pattern was similar to mice; less radioactivity was found in brain after administration of the ring-labeled alkoloid than after administration of methoxy-labeled colchicine. Again, 40-50% of ring-labeled colchicine was precipitated by vinblastine. A much smaller percentage of the methoxy-labeled drug was precipitated by vinblastine than of the ring A-labeled colchicine. These experiments, together with behavioral experiments [7], support the hypotheses that structural alteration in synapses by recently synthesized proteins which are transported down the axons and dendrites may be an essential process for long-term memory formation.

  12. Newcastle disease virus (NDV) induces protein oxidation and nitration in brain and liver of chicken: Ameliorative effect of vitamin E.

    Science.gov (United States)

    Venkata Subbaiah, Kadiam C; Valluru, Lokanatha; Rajendra, Wudayagiri; Ramamurthy, Chiteti; Thirunavukkarusu, Chinnasamy; Subramanyam, Rajagopal

    2015-07-01

    The present study was aimed at investigating the therapeutic efficacy of vitamin E on oxidative injury in brain and liver of Newcastle disease virus (NDV) challenged chickens. We have analyzed the xanthine oxidase (XOD) activity; uric acid (UA) levels and superoxide radical generation by using electron spin resonance spectroscopy. Further, protein oxidation, nitration and apoptosis were evaluated in the brain and liver of the control, NDV-infected and NDV+Vit. E treated groups. A significant elevation was observed in XOD activity and UA levels in brain (p<0.001) and liver (p<0.05) of NDV infected birds when compared to controls. Further, significant increase in the production of superoxides, enhanced intracellular protein carbonyls and nitrates were observed in the brain and liver of NDV-infected birds over healthy subjects. Apoptosis studies also suggested that a larger number of TUNEL positive cells were observed in brain and a moderately in liver of NDV-infected chickens. However, all these perturbations were significantly ameliorated in NDV+Vit. E treated chickens as compared to NDV-infected birds. Taken together, our results suggested that NDV-induced neuronal and hepatic damage at least in part mediates oxidative stress and on the other hand, supplementation of vitamin E mitigates NDV-induced oxidative damage thereby protects brain and liver of chickens. These findings could provide new insights into the understanding of NDV pathogenesis and therapeutic effects of dietary antioxidants.

  13. Mass Spectrometry Based Metabolomics Comparison of Liver Grafts from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD) Used in Human Orthotopic Liver Transplantation

    OpenAIRE

    Hrydziuszko, Olga; Perera, M. Thamara P. R; Laing, Richard; Kirwan, Jennifer; Silva, Michael A; Richards, Douglas A.; Murphy, Nick; Mirza, Darius F; Viant, Mark R.

    2016-01-01

    Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27...

  14. Effect of sulfur dioxide inhalation on CYP2B1/2 and CYP2E1 in rat liver and lung

    Energy Technology Data Exchange (ETDEWEB)

    Guohua Qin; Ziqiang Meng [Shanxi University, Taiyuan (China). Institute of Environmental Medicine and Toxicology

    2006-07-15

    Sulfur dioxide (SO{sub 2}) is a ubiquitous air pollutant, present in low concentrations in the urban air and in higher concentrations in the working environment. In this study, we investigated the effects of inhaled SO{sub 2} on the O-dealkylase of pentoxyresorufin (PROD) and p-nitrophenol hydroxylases (p-NP) activities and mRNA levels of CYP2B1/2 and CYP2E1 in the lung and liver of Wistar rats. Male Wistar rats were housed in exposure chambers and treated with 14.11 {+-}1.53, 28.36 {+-} 2.12, and 56.25 {+-} 4.28 mg /m{sup 3}SO{sub 2} for 6 h/day for 7 days, while control rats were exposed to filtered air in the same condition. The mRNAs of CYP2B1/2 and -2E1 were analyzed in livers and lungs by using reverse-transcription polymerase chain reaction (RT-PCR). Results showed that the PROD activities and mRNA of CYP2B1/2 were decreased in livers and lungs of rats exposed to SO{sub 2}. The p-NP activities and mRNA of CYP2E1 were decreased in lungs but not in livers of rats exposed to SO{sub 2}. Total liver microsomal cytochrome P-450 (CYP) contents were diminished in SO{sub 2} -exposed rats. These results lead to two conclusions: (1) SO{sub 2} exposure can suppress CYP2B1/2 and CYP2E1 in lungs and CYP2B1/2 in livers of rats, thus modifying the liver and lung toxication/detoxication potential, and (2) the total liver microsomal CYP contents were diminished, although the activity and mRNA expression of CYP2E1 in rat livers were not affected by SO{sub 2} exposure.

  15. Cryptococcus gattii fungemia: report of a case with lung and brain lesions mimicking radiological features of malignancy.

    Science.gov (United States)

    Oliveira, Flávio de Mattos; Severo, Cecília Bittencourt; Guazzelli, Luciana Silva; Severo, Luiz Carlos

    2007-01-01

    A 64-year-old apparently immunocompetent white man developed lung and brain lesions of disseminated cryptococcosis. The radiologic features mimicked those of lung cancer metastatic to the central nervous system. C. gattii was recovered from cultures of bronchoalveolar lavage fluid, brain biopsy, and blood. The same fungus was recovered from pulmonary and brain specimens at autopsy. Serum and cerebrospinal fluid cryptococcal antigen tests were diagnostic in our case and should be included in the diagnostic evaluation of unexplained pulmonary and cerebral lesions. A literature search showed few reports of fungemia by this species of Cryptococcus, contrasting to C. neoformans.

  16. New insights into the organ-specific adverse effects of fumonisin B1: comparison between lung and liver.

    Science.gov (United States)

    Loiseau, Nicolas; Polizzi, Arnaud; Dupuy, Aude; Therville, Nicole; Rakotonirainy, Mirindra; Loy, Jennifer; Viadere, Jean-Luc; Cossalter, Anne-Marie; Bailly, Jean-Denis; Puel, Olivier; Kolf-Clauw, Martine; Bertrand-Michel, Justine; Levade, Thierry; Guillou, Hervé; Oswald, Isabelle P

    2015-09-01

    Fumonisin B1 (FB1) is a well-known inhibitor of de novo sphingolipid biosynthesis, due to its ability to inhibit ceramide synthases (CerS) activity. In mammals, this toxin triggers broad clinical symptoms with multi-organ dysfunction such as hepatotoxicity or pulmonary edema. The molecular mechanism of CerS inhibition by FB1 remains unknown. Due to the existence of six mammalian CerS isoforms with a tissue-specific expression pattern, we postulated that the organ-specific adverse effects of FB1 might be due to different CerS isoforms. The sphingolipid contents of lung and liver were compared in normal and FB1-exposed piglets (gavage with 1.5 mg FB1/kg body weight daily for 9 days). The effect of the toxin on each CerS was deduced from the analysis of its effects on individual ceramide (Cer) and sphingomyelin (SM) species. As expected, the total Cer content decreased by half in the lungs of FB1-exposed piglets, while in contrast, total Cer increased 3.5-fold in the livers of FB1-exposed animals. Our data also indicated that FB1 is more prone to bind to CerS4 and CerS2 to deplete lung and to enrich liver in d18:1/C20:0 and d18:1/C22:0 ceramides. It also interact with CerS1 to enrich liver in d18:1/C18:0 ceramides. Cer levels were counterbalanced by those of SM. In conclusion, these results demonstrate that the specificity of the effects of FB1 on tissues and organs is due to the effects of the toxin on CerS4, CerS2, and CerS1.

  17. The antineoplastic antibiotic taurolidine promotes lung and liver metastasis in two syngeneic osteosarcoma mouse models and exhibits severe liver toxicity.

    Science.gov (United States)

    Arlt, Matthias J E; Walters, Denise K; Banke, Ingo J; Steinmann, Patrick; Puskas, Gabor J; Bertz, Josefine; Rentsch, Katharina M; Ehrensperger, Felix; Born, Walter; Fuchs, Bruno

    2012-09-01

    Osteosarcoma (OS) is the most frequent primary bone tumor. Despite multiagent neoadjuvant chemotherapy, patients with metastatic disease have a poor prognosis. Moreover, currently used chemotherapeutics have severe toxic side effects. Thus, novel agents with improved antimetastatic activity and reduced toxicity are needed. Taurolidine, a broad-spectrum antimicrobial, has recently been shown to have antineoplastic properties against a variety of tumors and low systemic toxicity. Consequently, we investigated in our study the antineoplastic potential of taurolidine against OS in two different mouse models. Although both OS cell lines, K7M2 and LM8, were sensitive for the compound in vitro, intraperitoneal application of taurolidine failed to inhibit primary tumor growth. Moreover, it enhanced the metastatic load in both models 1.7- to 20-fold and caused severe liver deformations and up to 40% mortality. Thus, systemic toxicity was further investigated in tumor-free mice histologically, by electron microscopy and by measurements of representative liver enzymes. Taurolidine dose-dependent fibrous thickening of the liver capsule and adhesions and atrophies of the liver lobes were comparable in healthy and tumor-bearing mice. Liver toxicity was further indicated by up to eightfold elevated levels of the liver enzymes alanine transaminase, aspartate transaminase and GLDH in the circulation. Ultrastructural analysis of affected liver tissue showed swollen mitochondria with cristolysis and numerous lipid vacuoles in the cytoplasm of hepatocytes. The findings of our study question the applicability of taurolidine for OS treatment and may suggest the need for caution regarding the widespread clinical use of taurolidine as an antineoplastic agent.

  18. Expression profiles of metastatic brain tumor from lung adenocarcinomas on cDNA microarray.

    Science.gov (United States)

    Kikuchi, Takefumi; Daigo, Yataro; Ishikawa, Nobuhisa; Katagiri, Toyomasa; Tsunoda, Tatsuhiko; Yoshida, Seiichi; Nakamura, Yusuke

    2006-04-01

    Distant metastasis is one of the crucial parameters determining the type of treatment and prognosis of patients. Previous studies discovered important factors involved in multiple steps of metastasis, the precise mechanisms of metastasis still remain to be clarified. To identify genes associated with this complicated biological feature of cancer, we analyzed expression profiles of 16 metastatic brain tumors derived from primary lung adenocarcinoma (ADC) using cDNA microarray representing 23,040 genes. We applied bioinformatic algorithm to compare the expression data of these 16 brain metastatic loci with those of 37 primary NSCLCs including 22 ADCs, and found that metastatic tumor cells has very different characteristics of gene expression patterns from primary ones. Two hundred and forty-four genes that showed significantly different expression levels between the two groups included plasma membrane bounding proteins, cellular antigens, and cytoskeletal proteins that might play important roles in altering cell-cell communication, attachment, and cell motility, and enhance the metastatic ability of cancer cells. Our results provide valuable information for development of predictive markers as well as novel therapeutic target molecules for metastatic brain tumor of ADC of the lung.

  19. Rapid reversal by naloxone of the chronic effects of morphine on rat liver and brain tryptophan metabolism.

    OpenAIRE

    Badawy, A. A.; Evans, M.

    1981-01-01

    The chronic morphine-induced inhibition of rat liver tryptophan pyrrolase activity and the resultant increases in tryptophan availability to the brain and brain 5-hydroxytryptamine (5-HT) synthesis are reversed within 10 min after naloxone administration. The possible involvement of hepatic tryptophan metabolism in morphine dependence is briefly discussed.

  20. Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Shi, Weiji [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Riely, Gregory J. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beal, Kathryn [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yu, Helena A. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wu, Abraham J., E-mail: wua@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-06-01

    Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.

  1. Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky-Molodkina model).

    Science.gov (United States)

    Venediktova, Natalya I; Gorbacheva, Olga S; Belosludtseva, Natalia V; Fedotova, Irina B; Surina, Natalia M; Poletaeva, Inga I; Kolomytkin, Oleg V; Mironova, Galina D

    2017-01-09

    The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats. The rate of H2O2 generation in brain mitochondria of КМ rats was twofold higher than in the control animals when using NAD-dependent substrates. This difference was less pronounced in liver mitochondria. In KM rats, the activity of mitochondrial ATP-dependent potassium channel was lower than in liver mitochondria of control rats. The comparative study of the mitochondria ability to retain calcium ions revealed that in the case of using the complex I and complex II substrates, permeability transition pore is easier to trigger in brain and liver mitochondria of KM and КМs rats than in the control ones. The role of the changes in the energetic, oxidative, and ionic exchange in the mechanism of audiogenic epilepsy generation in rats and the possible correction of the epilepsy seizures are discussed.

  2. Evaluation of 4-methylimidazole, in the Ames/Salmonella test using induced rodent liver and lung S9.

    Science.gov (United States)

    Beevers, Carol; Adamson, Richard H

    2016-01-01

    4-methylimidazole (4-MeI) is formed by the interaction of ammonia with reducing sugars and low levels have been identified as a by-product in coffee, soy sauce, wine, dark beers, soft drinks, and caramel colors. The 4-MeI has been reported to induce alveolar/bronchiolar tumors in mice but not rats. Its mechanism of action is unlikely to be due to genotoxicity as 4-MeI does not induce mutation in Salmonella typhimurium and does not induce micronuclei in rodent peripheral erythrocytes or bone marrow cells. However, the question of whether genetically reactive intermediates could be formed via lung-specific metabolism has not previously been addressed. The 4-MeI was tested for its ability to induce mutation in five standard Ames strains of S. typhimurium using induced rat (F344/N) and mouse (B6C3F1) liver and lung S9 as a source of exogenous metabolism. The chemicals were tested in an OECD 471-compliant bacterial reverse mutation assay, using both plate-incorporation and pre-incubation methodologies, together with 10% S-9 metabolic activation. No induction of mutation (as measured by an increase in revertant colonies) was observed and it was concluded that 4-MeI was not mutagenic in S. typhimurium using either rodent liver or lung S9 for exogenous metabolism.

  3. Accumulation of heavy metals and As in liver, hair, femur, and lung of Persian jird (Meriones persicus) in Darreh Zereshk copper mine, Iran.

    Science.gov (United States)

    Khazaee, Manoochehr; Hamidian, Amir Hossein; Alizadeh Shabani, Afshin; Ashrafi, Sohrab; Mirjalili, Seyyed Ali Ashghar; Esmaeilzadeh, Esmat

    2016-02-01

    Rodents frequently serve as bioindicator to monitor the quality of the environment. Concentrations of 11 elements (Cd, Co, Ti, Fe, Mn, Cu, Sb, As, Sr, Ni, and Cr) were investigated and compared in liver, hair, femur, and lung of the Persian jird (Meriones persicus) from Darreh Zereshk copper mine, Iran. Metals were determined in different tissues of 39 individuals of Persian jird, collected by snap trap in 2014 from five areas of Darreh Zereshk copper mine. Samples were prepared by wet digestion method, and the contents of elements were analyzed with ICP-OES (VARIAN, 725-ES) instrument. Cadmium, Sb, and Co were below the limit of detection, and Mn and As were found only in hair and liver tissues. We detected the highest concentration of Cu, As, Ti, Fe, Mn, Cr, and Ni in hair in comparison with other tissues. Significant higher levels of Ti in femur and hair; Fe in liver and hair; Mn in liver; As in hair; Sr in lung; Cr in lung, hair, femur, and liver; Cu in femur; and Ni in liver and lung tissues were observed in females. Nearly all element concentrations in the tissues of Persian jird from flotation site, Darreh Zereshk and Hasan Abad villages and leaching site (mining areas) were higher than those from tailing dump site (reference site). We found the highest concentrations of As in liver and hair; Ni and Cr in liver, hair, and lung; and Sr in lung and hair tissues of Persian jird in leaching site. We tried to specify the status of elements before fully exploitation of Darreh Zereshk copper mine by using bioindicator species. Based on our achievements, initial activities did not strongly pollute the surrounded environment of the mine. The high abundance of Persian jird as well as their several proper features makes them a suitable species for biomonitoring programs especially for further studies will be performed after full exploitation of Darreh Zereshk copper mine.

  4. Taurine treatment preserves brain and liver mitochondrial function in a rat model of fulminant hepatic failure and hyperammonemia.

    Science.gov (United States)

    Jamshidzadeh, Akram; Heidari, Reza; Abasvali, Mozhgan; Zarei, Mehdi; Ommati, Mohammad Mehdi; Abdoli, Narges; Khodaei, Forouzan; Yeganeh, Yasaman; Jafari, Faezeh; Zarei, Azita; Latifpour, Zahra; Mardani, Elnaz; Azarpira, Negar; Asadi, Behnam; Najibi, Asma

    2017-02-01

    Ammonia-induced mitochondrial dysfunction and energy crisis is known as a critical consequence of hepatic encephalopathy (HE). Hence, mitochondria are potential targets of therapy in HE. The current investigation was designed to evaluate the role of taurine treatment on the brain and liver mitochondrial function in a rat model of hepatic encephalopathy and hyperammonemia. The animals received thioacetamide (400mg/kg, i.p, for three consecutive days at 24-h intervals) as a model of acute liver failure and hyperammonemia. Several biochemical parameters were investigated in the serum, while the animals' cognitive function and locomotor activity were monitored. Mitochondria was isolated from the rats' brain and liver and several indices were assessed in isolated mitochondria. Liver failure led to cognitive dysfunction and impairment in locomotor activity in the rats. Plasma and brain ammonia was high and serum markers of liver injury were drastically elevated in the thioacetamide-treated group. An assessment of brain and liver mitochondrial function in the thioacetamide-treated animals revealed an inhibition of succinate dehydrogenase activity (SDA), collapsed mitochondrial membrane potential, mitochondrial swelling, and increased reactive oxygen species (ROS). Furthermore, a significant decrease in mitochondrial ATP was detected in the brain and liver mitochondria isolated from thioacetamide-treated animals. Taurine treatment (250, 500, and 1000mg/kg) decreased mitochondrial swelling, ROS, and LPO. Moreover, the administration of this amino acid restored brain and liver mitochondrial ATP. These data suggest taurine to be a potential protective agent with therapeutic capability against hepatic encephalopathy and hyperammonemia-induced mitochondrial dysfunction and energy crisis.

  5. Metallothionein (MT -I and MT-II expression are induced and cause zinc sequestration in the liver after brain injury.

    Directory of Open Access Journals (Sweden)

    Michael W Pankhurst

    Full Text Available UNLABELLED: Experiments with transgenic over-expressing, and null mutant mice have determined that metallothionein-I and -II (MT-I/II are protective after brain injury. MT-I/II is primarily a zinc-binding protein and it is not known how it provides neuroprotection to the injured brain or where MT-I/II acts to have its effects. MT-I/II is often expressed in the liver under stressful conditions but to date, measurement of MT-I/II expression after brain injury has focused primarily on the injured brain itself. In the present study we measured MT-I/II expression in the liver of mice after cryolesion brain injury by quantitative reverse-transcriptase PCR (RT-PCR and enzyme-linked immunosorbent assay (ELISA with the UC1MT antibody. Displacement curves constructed using MT-I/II knockout (MT-I/II(-/- mouse tissues were used to validate the ELISA. Hepatic MT-I and MT-II mRNA levels were significantly increased within 24 hours of brain injury but hepatic MT-I/II protein levels were not significantly increased until 3 days post injury (DPI and were maximal at the end of the experimental period, 7 DPI. Hepatic zinc content was measured by atomic absorption spectroscopy and was found to decrease at 1 and 3 DPI but returned to normal by 7DPI. Zinc in the livers of MT-I/II(-/- mice did not show a return to normal at 7 DPI which suggests that after brain injury, MT-I/II is responsible for sequestering elevated levels of zinc to the liver. CONCLUSION: MT-I/II is up-regulated in the liver after brain injury and modulates the amount of zinc that is sequestered to the liver.

  6. Rare Aggressive Behavior of MDM2-Amplified Retroperitoneal Dedifferentiated Liposarcoma, with Brain, Lung and Subcutaneous Metastases

    Science.gov (United States)

    Ben Salha, Imen; Zaidi, Shane; Noujaim, Jonathan; Miah, Aisha B.; Fisher, Cyril; Jones, Robin L.; Thway, Khin

    2016-01-01

    Dedifferentiated liposarcoma (DDL) is a histologically pleomorphic sarcoma, traditionally defined as well-differentiated liposarcoma with abrupt transition to high grade, non-lipogenic sarcoma. It can occur as part of recurrent well-differentiated liposarcoma, or may arise de novo. DDL most frequently occurs within the retroperitoneum, and while it is prone to local recurrence, it usually has a lower rate of metastasis than other pleomorphic sarcomas. We describe a case of retroperitoneal dedifferentiated liposarcoma in a 63-year-old male, who showed MDM2 amplification with fluorescence in situ hybridization, which displayed unusually aggressive behavior, with brain, lung and subcutaneous soft tissue metastases. As previous reports of metastatic liposarcoma have largely grouped DDL in with other (genetically and clinically distinct) liposarcoma subtypes, we highlight and discuss the rare occurrence of brain metastasis in MDM2-amplified retroperitoneal liposarcoma.

  7. Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography

    DEFF Research Database (Denmark)

    Lassen, U; Andersen, P; Daugaard, G

    1998-01-01

    for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor r......CMRglu, rCBF, and rCBV exerted a broad variability, but were higher than the corresponding values in white matter and higher than or similar to those of gray matter. Tumor rCMRglu and rCBF were highly correlated (P metabolic or hemodynamic parameters...... was not observed. Other methods for noninvasive in vivo analysis of tumor hemodynamics are needed, especially for discrimination between tumor necrosis and hypoxia....

  8. THE MANAGEMENT OF BRAIN METASTASES IN NON-SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Scott eOwen

    2014-09-01

    Full Text Available Brain metastases (BM are a common and lethal complication of non-small cell lung cancer (NSCLC which portend a poor prognosis. In addition, their management implies several challenges including preservation of neurological and neuro-cognitive function during surgery or radiation -therapy, minimizing iatrogenic complications of supportive medications, and optimizing drug delivery across the blood brain barrier (BBB. Despite these challenges, advancements in combined modality approaches can deliver hope of improved overall survival and quality of life for a subset of NSCLC patients with BM. Moreover, new drugs harnessing our greater understanding of tumour biology promise to build on this hope. In this mini-review, we revised the management of BM in NSCLC including advancements in neurosurgery, radiation therapy, as well as systemic and supportive therapy.

  9. Image guided respiratory gated hypofractionated Stereotactic Body Radiation Therapy (H-SBRT) for liver and lung tumors: Initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Wurm, R.E.; Gum, F.; Erbel, S. [Charite Campus Mitte, Berlin (Germany). Dept. of Radiation Oncology

    2006-09-15

    To evaluate our initial experience with image guided respiratory gated H-SBRT for liver and lung tumors. The system combines a stereoscopic x-ray imaging system (ExacTrac{sup R} X-Ray 6D) with a dedicated conformal stereotactic radiosurgery and radiotherapy linear accelerator (Novalis) and ExacTrac{sup R} Adaptive Gating for dynamic adaptive treatment. Moving targets are located and tracked by x-ray imaging of implanted fiducial markers defined in the treatment planning computed tomography (CT). The marker position is compared with the position in verification stereoscopic x-ray images, using fully automated marker detection software. The required shift for a correct, gated set-up is calculated and automatically applied. We present our acceptance testing and initial experience in patients with liver and lung tumors. For treatment planning CT and Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) as well as magnetic resonance imaging (MRI) taken at free breathing and expiration breath hold with internal and external fiducials present were used. Patients were treated with 8-11 consecutive fractions to a dose of 74.8-79.2 Gy. Phantom tests demonstrated targeting accuracy with a moving target to within {+-}1 mm. Inter- and intrafractional patient set-up displacements, as corrected by the gated set-up and not detectable by a conventional set-up, were up to 30 mm. Verification imaging to determine target location during treatment showed an average marker position deviation from the expected position of up to 4 mm on real patients. This initial evaluation shows the accuracy of the system and feasibility of image guided real-time respiratory gated H-SBRT for liver and lung tumors.

  10. The Analysis of Erlotinib on Brain Metastases in Patients with Non-small-cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Baohui HAN

    2009-12-01

    Full Text Available Background and objective Brain metastases are common in non-small-cell lung cancer (NSCLC and the prognosis is poor. Erlotinib is a specific inhibitor of the epidermal growth factor receptor-associated tyrosine kinase (EGFRTKI, which has been gradually used in the treatment for advanced NSCLC. The aim of this study is to evaluate the antitumor efficacy and its relevant factors of erlotinib in NSCLC patients with brain metastases. Methods The clinical data of 30 NSCLC patients with brain metastases were reviewed retrospectively. All of them were treated with erlotinib, given orally 150mg daily. These patients discontinued administration of erlotinib until disease progression, death or intolerable side effects. Results In terms of intracranial lesions, partial response (PR was observed in 2 patients (6.7%, with stable disease (SD in 17 patients (56.7%, for overall disease control rate (DCR of 63.4%. As for systemic disease, PR was observed in 2 patients (6.7%, with SD in 5 patients (16.7%, for overall DCR of 23.4%. There was no statistical difference in DCR among different subtypes of age, gender, smoking history, histology, PS score, the number of brain metastases, the onset of brain metastases, chemotherapy, brain radiotherapy and side effects. The median time to disease progression (MTTP and median survival time (MST was 2.4 months and 7.7 months respectively. The 1 and 2 year survival rate was 38.4% and 15.2%. The univariate analysis showed that the survival time was related to the patients’ PS score, smoking history, brain radiotherapy and chemotherapy. The multivariate analysis indicated that brain radiotherapy was the independent prognostic factor and the relationship between the survival time and smoking history was near to statistical significance. Conclusion The patients receiving brain radiotherapy may have better survival benefit. Non-smokers have a trend to survive longer than smokers. Erlotinib may be effective on brain metastases

  11. Membrane docosahexaenoate is supplied to the developing brain and retina by the liver.

    OpenAIRE

    Scott, B. L.; Bazan, N G

    1989-01-01

    Docosahexaenoic acid [22:6 omega 3; 22:6(4, 7, 10, 13, 16, 19)] is concentrated in phospholipids of cellular membranes from brain and retina. Although linolenic acid [18:3 omega 3; 18:3(9, 12, 15)] is the major omega 3 fatty acid of mouse dams' milk, 22:6 is the prevalent omega 3 fatty acid in serum and tissues. Intraperitoneal injection of [1-14C]18:3 into 3-day-old mouse pups resulted in liver and serum lipid labeling that was initially high, followed by a rapid decline. In contrast, labeli...

  12. [Disturbed brain bioelectric activity in patients with liver encephalopathy and cirrhosis].

    Science.gov (United States)

    Alekseeva, A S; Beloborodova, E I; Rachkovskiĭ, M I; Filippova, L P; Lambrova, E G

    2009-01-01

    Brain bioelectric activity in 52 patients with liver cirrhosis (LC) was measured with respect to the degree of hepatic encephalopathy (HE) from the results of background and reactive EEG using West Haven criteria. As the severity of LC increased, signs of HE on background EEG appeared, index frequency and a-rhythm decreased and its amplitude increased. Reactive EEG was indicative of reduced duration, intensity, and decrement rate of responses to orientational loading (visual, somatosensorial, and auditory evoked potentials). It is concluded that EEG studies permit to predict dynamics of LC clinical course and may be used as an additional diagnostic tool, especially at the preclinical stage of HE.

  13. Hot spot(s) of the lung in technetium-99m albumin colloid liver-spleen scintigraphy: case report

    Energy Technology Data Exchange (ETDEWEB)

    Shih, W.J.; Brandenburg, S.; Coupal, J.J.; Sullivan, J.D.; Beeler, J.A.; Magoun, S.; Ryo, U.Y.

    1988-06-01

    The authors replaced /sup 99m/Tc albumin colloid for /sup 99m/Tc sulfur colloid as a radiopharmaceutical for liver-spleen imaging and found two instances of hot spot(s) in the lung. The preparation procedure of albumin colloid is easier and more convenient as compared to that of sulfur colloid. Whereas replacement of /sup 99m/Tc sulfur colloid by /sup 99m/Tc albumin colloid is inevitable, it should be emphasized that one should avoid blood withdrawal in the syringe containing albumin colloid to prevent formation of clot(s) during the venous puncture for /sup 99m/Tc albumin colloid.

  14. Evaluation of reference genes for gene expression in red-tailed phascogale (Phascogale calura) liver, lung, small intestine and spleen

    Science.gov (United States)

    Ong, Oselyne T.W.; Young, Lauren J.

    2016-01-01

    Background Reference genes serve an important role as an endogenous control/standard for data normalisation in gene expression studies. Although reference genes have recently been suggested for marsupials, independent analysis of reference genes on different immune tissues is yet to be tested. Therefore, an assessment of reference genes is needed for the selection of stable, expressed genes across different marsupial tissues. Methods The study was conducted on red-tailed phascogales (Phascogale calura) using five juvenile and five adult males. The stability of five reference genes (glyceraldehyde-3-phosphate dehydrogenase, GAPDH; β-actin, ACTB; 18S rRNA, 18S; 28S rRNA, 28S; and ribosomal protein L13A, RPL13A) was investigated using SYBR Green and analysed with the geNorm application available in qBasePLUS software. Results Gene stability for juvenile and adult tissue samples combined show that GAPDH was most stable in liver and lung tissue, and 18S in small intestine and spleen. While all reference genes were suitable for small intestine and spleen tissues, all reference genes except 28S were stable for lung and only 18S and 28S were stable for liver tissue. Separating the two age groups, we found that two different reference genes were considered stable in juveniles (ACTB and GAPDH) and adults (18S and 28S), and RPL13A was not stable for juvenile small intestine tissue. Except for 28S, all reference genes were stable in juvenile and adult lungs, and all five reference genes were stable in spleen tissue. Discussion Based on expression stability, ACTB and GAPDH are suitable for all tissues when studying the expression of marsupials in two age groups, except for adult liver tissues. The expression stability between juvenile and adult liver tissue was most unstable, as the stable reference genes for juveniles and adults were different. Juvenile and adult lung, small intestine and spleen share similar stable reference genes, except for small intestine tissues where

  15. Excellent outcomes of liver transplantation using severely steatotic grafts from brain-dead donors.

    Science.gov (United States)

    Wong, Tiffany C L; Fung, James Y Y; Chok, Kenneth S H; Cheung, Tan To; Chan, Albert C Y; Sharr, William W; Dai, Wing Chiu; Chan, See Ching; Lo, Chung Mau

    2016-02-01

    Liver grafts with macrovesicular steatosis of > 60% are considered unsuitable for deceased donor liver transplantation (DDLT) because of the unacceptably high risk of primary nonfunction (PNF) and graft loss. This study reports our experience in using such grafts from brain-dead donors. Prospectively collected data of DDLT recipient outcomes from 1991 to 2013 were retrospectively analyzed. Macrovesicular steatosis > 60% at postperfusion graft biopsy was defined as severe steatosis. In total, 373 patients underwent DDLT. Nineteen patients received severely steatotic grafts (ie, macrovesicular steatosis > 60%), and 354 patients had grafts with ≤ 60% steatosis (control group). Baseline demographics were comparable except that recipient age was older in the severe steatosis group (51 versus 55 years; P = 0.03). Median Model for End-Stage Liver Disease (MELD) score was 20 in the severe steatosis group and 22 in the control group. Cold ischemia time (CIT) was 384 minutes in the severe steatosis group and 397.5 minutes in the control group (P = 0.66). The 2 groups were similar in duration of stay in the hospital and in the intensive care unit. Risk of early allograft dysfunction (0/19 [0%] versus 1/354 [0.3%]; P>0.99) and 30-day mortality (0/19 [0%] versus 11/354 [3.1%]; P = 0.93) were also similar between groups. No patient developed PNF. The 1-year and 3-year overall survival rates in the severe steatosis group were both 94.7%. The corresponding rates in the control group were 91.8% and 85.8% (P = 0.55). The use of severely steatotic liver grafts from low-risk donors was safe, and excellent outcomes were achieved; however, these grafts should be used with caution, especially in patients with high MELD score. Keeping a short CIT was crucial for the successful use of such grafts in liver transplantation.

  16. Optimization of the agar-gel method for isolation of migrating Ascaris suum larvae from the liver and lungs of pigs

    DEFF Research Database (Denmark)

    Saeed, I.; Roepstorff, A.; Rasmussen, T.;

    2001-01-01

    Experiments on use of an agar-gel method for recovery of migrating Ascaris suum larvae from the liver and lungs of pigs were conducted to obtain fast standardized methods. Subsamples of blended tissues of pig liver and lungs were mixed with agar to a final concentration of 1% agar and the larvae...... allowed to migrate out of the agar-gel into 0.9% NaCl at 38 degreesC. The results showed that within 3 h more than 88% of the recoverable larvae migrated out of the liver agar-gel and more than 83% of the obtained larvae migrated out of the lung agar-gel. The larvae were subsequently available in a very...

  17. Incorporation of radioactive polyunsaturated fatty acids into liver and brain of developing rat.

    Science.gov (United States)

    Sinclair, A J

    1975-03-01

    The incorporation of radioactivity from orally administered linoleic acid-1-14C, linolenic acid-1-14C, arachidonic acid-3H8, and docosahexaenoic acid-14C into the liver and brain lipids of suckling rats was studied. In both tissues, 22 hr after dosing, 2 distinct levels of incorporation were observed: a low uptake (from 18:2-1-14C and 18:3-1-14C) and a high uptake (from 20:4-3H8 and 22:6-14C). In adult rats, the incorporation of radioactivity into brain lipids from 18:2-1-14C and 20:4-3H was considerably lower than the incorporation into the brains of the young rats. In the livers of the suckling rats, the activity from the 18 carbon acids was associated mostly with the triglyceride fraction, whereas the activity from the 20:4-3H8 and 22:6-14C was concentrated in the phospholipid fraction. In the brain lipids, the activity from the different fatty apid fatty acids, some of the activity in the 18:2-1-14C and 18:3-1-14C experiments was associated with 20 and 22 carbon polyunsaturated fatty acids; however, radioactivity from orally administered 20:4-3H8 and 22:6-14C was incorporated intact into the tissue phospholipid to a much greater extent compared with the incorporation of radioactivity into 20:4 and 22:6 in the experiments where 18:2-1-14C and 18:3-1-14C, respectively, were administered. Possible reasons for these differences are discussed. Rat milk contains a wide spectrum of polyunsaturated fatty acids, including linoleate, linolenate, arachidonate, and docosahexaenoate. During the suckling period in the rat, there is a rapid deposition of 20:4 and 22:6 in the brain. The results of the present experiments suggested that dietary 20:4 and 22:6 were important sources of brain 20:4 and 22:6 in the developing rat.

  18. Lung, liver and lymph node metastases in follow-up MSCT. Comprehensive volumetric assessment of lesion size changes

    Energy Technology Data Exchange (ETDEWEB)

    Wulff, A.M.; Fischer, S.; Biederer, J.; Heller, M.; Fabel, M. [Universitaetsklinikum Schleswig-Holstein, Kiel (Germany). Klinik fuer Diagnostische Radiologie; Bolte, H. [Universitaetsklinikum Muenster (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Freitag-Wolf, S. [Universitaetsklinikum Schleswig-Holstein, Kiel (Germany). Inst. fuer Medizinische Informatik und Statistik; Soza, G.; Tietjen, C. [Siemens AG (Germany). Imaging and IT Div. Computed Tomography

    2012-09-15

    Purpose: To investigate measurement accuracy in terms of precision and inter-rater variability in the simultaneous volumetric assessment of lung, liver and lymph node metastasis size change over time in comparison to RECIST 1.1. Materials and Methods: Three independent readers evaluated multislice CT data from clinical follow-up studies (chest/abdomen) in 50 patients with metastases. A total of 117 lung, 77 liver and 97 lymph node metastases were assessed manually (RECIST 1.1) and by volumetry with semi-automated software. The quality of segmentation and need for manual adjustments were recorded. Volumes were converted to effective diameters to allow comparison to RECIST. For statistical assessment of precision and interobserver agreement, the Wilcoxon-signed rank test and Bland-Altman plots were utilized. Results: The quality of segmentation after manual correction was acceptable to excellent in 95 % of lesions and manual corrections were applied in 21 - 36 % of all lesions, most predominantly in lymph nodes. Mean precision was 2.6 - 6.3 % (manual) with 0.2 - 1.5 % (effective) relative measurement deviation (p <.001). Inter-reader median variation coefficients ranged from 9.4 - 12.8 % (manual) and 2.9 - 8.2 % (volumetric) for different lesion types (p <.001). The limits of agreement were {+-} 9.8 to {+-} 11.2 % for volumetric assessment. Conclusion: Superior precision and inter-rater variability of volumetric over manual measurement of lesion change over time was demonstrated in a whole body setting. (orig.)

  19. Postmortem changes in lungs in severe closed traumatic brain injury complicated by acute respiratory failure

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2013-08-01

    Full Text Available V.А. Tumanskіy, S.І. Ternishniy, L.M. Tumanskaya Pathological changes in the lungs were studied in the work of 42 patiens who died from severe closed intracranial injury (SCII. It was complicated with acute respiratory insufficient (ARI. The most modified subpleural areas were selected from every lobe of the lungs for pathological studies. Prepared histological sections were stained by means of hemotoxylin and eosin and by Van Giеson for light microscopy. The results of the investigation have shown absence of the significant difference of pathological changes in the lungs of patients who died from ARI because of severe brain injury and traumatic intracranial hemorrhage. Pathognomic pathological changes in the lungs as a result of acute lung injury syndrome (ALIS were found in deceased patients on the third day since the SCII (n=8. There was a significant bilateral interstitial edema and mild alveolar edema with the presence of red and blood cells in the alveoli, vascular plethora of the septum interalveolar and stasis of blood in the capillaries, the slight pericapillary leukocyte infiltration, subpleural hemorrhage and laminar pulmonary atelectasis. In deceased patients on 4-6 days after SCII that was complicated with ARI (n=14, morphological changes had been detected in the lungs. It was pathognomic for acute respiratory distress syndrome (ARDS with local pneumonic to be layered. A significant interstitial pulmonary edema was observed in the respiratory part of the lungs. The edema has spread from the walls of the alveoli into the interstitial spaces of the bronchioles and blood vessels, and also less marked serous-hemorrhagic alveolar edema with presence of the fibrin in the alveoli and macrophages. The ways of intrapleural lymphatic drainage were dilatated. Histopathological changes in the lungs of those who died on the 7-15th days after severe closed craniocerebral injury with ARI to be complicated (n=12 have been indicative of two

  20. A relevant exposure to a food matrix contaminated environmentally by polychlorinated biphenyls induces liver and brain disruption in rats.

    Science.gov (United States)

    Ounnas, Fayçal; Privé, Florence; Lamarche, Fréderic; Salen, Patricia; Favier-Hininger, Isabelle; Marchand, Philippe; Le Bizec, Bruno; Venisseau, Anais; Batandier, Cécile; Fontaine, Eric; de Lorgeril, Michel; Demeilliers, Christine

    2016-10-01

    Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants present in dietary fats. Most studies evaluating PCB effects have been conducted with a single compound or a mixture of PCBs given as a single acute dose. The purpose of this study was to evaluate in vivo PCB toxicity in a realistic model of exposure: a low daily dose of PCBs (twice the tolerable daily intake (TDI)), chronically administered (8 weeks) to rats in contaminated goat milk. Liver and brain PCB toxicities were investigated by evaluating oxidative stress status and mitochondrial function. PCB toxicity in the liver was also estimated by transaminase enzymatic activity. This study shows that even at low doses, chronic PCB exposure resulted in a statistically significant reduction of mitochondrial function in liver and brain. In the liver, oxygen consumption in the condition of adenosine triphosphate (ATP) production (state 3) decreased by 22-29% (p < 0.01), according to the respiratory substrates. In the brain, respiratory chain complexes II and III were reduced by 24% and 39%, respectively (p < 0.005). The exposed rats presented higher lipid peroxidation status (+20%, p < 0.05) and transaminase activity (+30%, p < 0.05) in the blood. Thus, our study showed that exposure of rats to a daily realistic dose of PCBs (twice the TDI in a food complex mixture of environmental origin) resulted in multiple disruptions in the liver and brain.

  1. A resected case of metachronous liver metastasis from lung cancer producing alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II).

    Science.gov (United States)

    Oshiro, Yukio; Takada, Yasutsugu; Enomoto, Tsuyoshi; Fukao, Katashi; Ishikawa, Shigemi; Iijima, Tatsuo

    2004-01-01

    A resected case of huge liver metastasis of hepatoid adenocarcinoma of the lung is described. A 77-year-old man who presented a solitary huge liver tumor was admitted to our hospital. He had undergone right lower lobectomy of the lung for lung cancer one year before. The view of imaging studies was not a typical one of hepatocellular carcinoma. Serum levels of AFP and PIVKA-II were 334,500ng/mL and 3,890mAU/mL, respectively, and the proportion of AFP L3 was 97.9%. It was thought that they were strongly diagnostic for hepatocellular carcinoma. Extended right lobectomy of the liver was performed. Microscopically, it was poorly differentiated adenocarcinoma and diagnosed as liver metastasis from the formerly resected lung cancer. The tumor was composed of cells with both sheet-like growth and tubule formation. The neoplastic cells, in the sheet-like growth resembled hepatocellular carcinoma cells. By immunohistochemical staining with anti-AFP and anti-PIVKA-II antibodies, cancer cells of both the primary and metastatic lesions were positive. The patient eventually died of multiple liver and bone metastasis 6 months after the operation.

  2. Comparison of erlotinib and pemetrexed as second-/third-line treatment for lung adenocarcinoma patients with asymptomatic brain metastases

    Directory of Open Access Journals (Sweden)

    He YY

    2016-04-01

    Full Text Available Yayi He,1,* Wenwen Sun,2,* Yan Wang,3,* Shengxiang Ren,1 Xuefei Li,3 Jiayu Li,3 Christopher J Rivard,4 Caicun Zhou,1 Fred R Hirsch4 1Department of Oncology, Shanghai Pulmonary Hospital, 2Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, 3Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, USA *These authors contributed equally to this work Objective: Brain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood–brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases.Methods: From January 2012 to June 2014, all lung adenocarcinoma patients with asymptomatic brain metastases who received treatment with erlotinib or pemetrexed as second-/third-line treatment were retrospectively reviewed. Chi-square and log-rank tests were used to perform statistical analysis.Results: The study enrolled 99 patients, of which 44 were positive for EGFR mutation. Median progression-free survival (PFS in months was not significantly different between the erlotinib- and pemetrexed-treated groups (4.2 vs 3.4 months; 95% confidence interval [CI]: 2.01–6.40 vs 2.80–5.00, respectively; P=0.635. Median PFS was found to be significantly longer in EGFR mutation–positive patients in the erlotinib-treated group (8.0 months; 95% CI 5.85–10.15 compared to the pemetrexed group (3.9 months; 95% CI: 1.25–6.55; P=0.032. The most common treatment-related side effect was mild-to-moderate rash and the most common drug-related side

  3. [Deceased organ donors, legal regulations governing diagnosis of brain death, overview of donors and liver transplants in the Czech Republic].

    Science.gov (United States)

    Pokorná, E

    2013-08-01

    The key restriction of transplantation medicine globally, as well as in the Czech Republic, concerns the lack of organs. The number of deceased donors, and thus the availability of organ transplants, has been stagnating in our country. The paper describes current legal regulations governing the dia-gnosis of brain death and primary legal and medical criteria for the contraindication of the deceased for organ explantation, gives an overview of the number of liver transplants, age structure, and diagnosis resulting in brain death of the deceased liver donors in the Czech Republic.

  4. Time course of arsenic species in the brain and liver of mice after oral administration of arsenate

    Energy Technology Data Exchange (ETDEWEB)

    Juarez-Reyes, Amida; Jimenez-Capdeville, Maria E.; Delgado, Juan M.; Ortiz-Perez, Deogracias [Universidad Autonoma de San Luis Potosi, Departamento de Bioquimica, Facultad de Medicina, San Luis Potosi (Mexico)

    2009-06-15

    The understanding of the biomethylation process of arsenic is essential to uncover the mechanisms of arsenic toxicity. This work analyzes the time course of arsenic species in the brain and liver of adult mice, after a single oral administration of three arsenate doses [2.5, 5.0 and 10 mg As(V)/kg]. Quantification of arsenic species was performed by means of liquid chromatography coupled to atomic fluorescence 2, 5, 8, 12 and 24 h after administration. The results show that 2 h after arsenate administration inorganic arsenic arrives to the liver and its concentration diminishes gradually until becoming non-detectable at 12 h. Arsenic takes longer to appear in the brain and it is present only as dimethyl arsinic acid. Since arsenic concentration decreases in liver while it increases in the brain, this suggests that the arsenic metabolite reaches the brain after formation in the liver. Importantly, the fact that dimethyl arsinic acid is no longer present after 24 h suggests the existence of a mechanism to clear this metabolite from brain tissue. (orig.)

  5. Cement Dust Exposure and Perturbations in Some Elements and Lung and Liver Functions of Cement Factory Workers

    Directory of Open Access Journals (Sweden)

    Egbe Edmund Richard

    2016-01-01

    Full Text Available Background. Cement dust inhalation is associated with deleterious health effects. The impact of cement dust exposure on the peak expiratory flow rate (PEFR, liver function, and some serum elements in workers and residents near cement factory were assessed. Methods. Two hundred and ten subjects (50 workers, 60 residents, and 100 controls aged 18–60 years were studied. PEFR, liver function {aspartate and alanine transaminases (AST and ALT and total and conjugated bilirubin (TB and CB}, and serum elements {lead (Pb, copper (Cu, manganese (Mn, iron (Fe, cadmium (Cd, selenium (Se, chromium (Cr, zinc (Zn, and arsenic (As} were determined using peak flow meter, colorimetry, and atomic absorption spectrometry, respectively. Data were analysed using ANOVA and correlation at p=0.05. Results. The ALT, TB, CB, Pb, As, Cd, Cr, Se, Mn, and Cu were significantly higher and PEFR, Fe, and Zn lower in workers and residents compared to controls (p<0.05. Higher levels of ALT, AST, and Fe and lower levels of Pb, Cd, Cr, Se, Mn, and Cu were seen in cement workers compared to residents (p<0.05. Negative correlation was observed between duration of exposure and PEFR (r=-0.416, p=0.016 in cement workers. Conclusions. Cement dust inhalation may be associated with alterations in serum elements levels and lung and liver functions while long term exposure lowers peak expiratory flow rate.

  6. SC1, an immunoglobulin-superfamily cell adhesion molecule, is involved in the brain metastatic activity of lung cancer cells

    Science.gov (United States)

    KUBOTA, YUKA; KIRIMURA, NAOKI; SHIBA, HATSUKI; ADACHI, KAZUHIDE; TSUKAMOTO, YASUHIRO

    2015-01-01

    SC1 is a cell adhesion molecule that belongs to the immunoglobulin superfamily; this molecule was initially purified from the chick embryonic nervous system and was reported to exhibit homophilic adhesion activity. SC1 is transiently expressed in various organs during development and has been identified in numerous neoplastic tissues, including lung cancer and colorectal carcinomas. The present study focused on the encephalic metastasis of lung cancer cells with respect to the potential function of SC1, as this molecule is known to be consistently expressed in the central nervous system as well as lung cancers. SC1 complementary DNA was introduced into A549 cells, a human lung cancer-derived cell line. The stable overexpression of the SC1 protein in A549 cells was demonstrated to enhance the self-aggregation of the cells. In addition, the SC1 transfectants enhanced the metastatic and invasive potential to the encephalic parenchyma following implantation into nude mice. In conclusion, the results of the present study demonstrated that cell adhesion due interactions between SC1 on brain tissue and SC1 on lung cancer cells was involved in the malignant aspects of lung cancer, including invasion and metastasis to the brain. PMID:26622821

  7. IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain

    Directory of Open Access Journals (Sweden)

    Mami Noda

    2012-12-01

    Full Text Available In the animal model of brain metastasis using human lung squamous cell carcinoma-derived cells (HARA-B inoculated into the left ventricle of the heart of nude mice, metastasized tumor cells and brain resident cells interact with each other. Among them, tumor cells and astrocytes have been reported to stimulate each other, releasing soluble factors from both sides, subsequently promoting tumor growth significantly. Among the receptors for soluble factors released from astrocytes, only IL-6 receptor (IL-6R on tumor cells was up-regulated during the activation with astrocytes. Application of monoclonal antibody against human IL-6R (tocilizumab to the activated HARA-B cells, the growth of HARA-B cells stimulated by the conditioned medium of HARA-B/astrocytes was significantly inhibited. Injecting tocilizumab to animal models of brain metastasis starting at three weeks of inoculation of HARA-B cells, two times a week for three weeks, significantly inhibited the size of the metastasized tumor foci. The up-regulated expression of IL-6R on metastasized lung tumor cells was also observed in the tissue from postmortem patients. These results suggest that IL-6R on metastasized lung tumor cells would be a therapeutic target to inhibit the growth of the metastasized lung tumor cells in the brain.

  8. Prolonging in utero-like oxygenation after birth diminishes oxidative stress in the lung and brain of mice pups

    Directory of Open Access Journals (Sweden)

    Javier Escobar

    2013-01-01

    Conclusions: Delaying the increase in tissue oxygenation to occur after birth reduces short-and-long-term oxidative stress in the lung. Similar yet more subtle effects were found in the brain. Apparently, the fetal-to-neonatal transition under hypoxic conditions appears to have protective qualities.

  9. Oxidative stress of brain and liver is increased by Wi-Fi (2.45GHz) exposure of rats during pregnancy and the development of newborns.

    Science.gov (United States)

    Çelik, Ömer; Kahya, Mehmet Cemal; Nazıroğlu, Mustafa

    2016-09-01

    An excessive production of reactive oxygen substances (ROS) and reduced antioxidant defence systems resulting from electromagnetic radiation (EMR) exposure may lead to oxidative brain and liver damage and degradation of membranes during pregnancy and development of rat pups. We aimed to investigate the effects of Wi-Fi-induced EMR on the brain and liver antioxidant redox systems in the rat during pregnancy and development. Sixteen pregnant rats and their 48 newborns were equally divided into control and EMR groups. The EMR groups were exposed to 2.45GHz EMR (1h/day for 5 days/week) from pregnancy to 3 weeks of age. Brain cortex and liver samples were taken from the newborns between the first and third weeks. In the EMR groups, lipid peroxidation levels in the brain and liver were increased following EMR exposure; however, the glutathione peroxidase (GSH-Px) activity, and vitamin A, vitamin E and β-carotene concentrations were decreased in the brain and liver. Glutathione (GSH) and vitamin C concentrations in the brain were also lower in the EMR groups than in the controls; however, their concentrations did not change in the liver. In conclusion, Wi-Fi-induced oxidative stress in the brain and liver of developing rats was the result of reduced GSH-Px, GSH and antioxidant vitamin concentrations. Moreover, the brain seemed to be more sensitive to oxidative injury compared to the liver in the development of newborns.

  10. Gestational age dependent changes of the fetal brain, liver and adipose tissue fatty acid compositions in a population with high fish intakes

    NARCIS (Netherlands)

    Kuipers, Remko S.; Luxwolda, Martine F.; Offringa, Pieter J.; Boersma, E. Rudy; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    2012-01-01

    Introduction: There are no data on the intrauterine fatty acid (FA) compositions of brain, liver and adipose tissue of infants born to women with high fish intakes. Subjects and methods: We analyzed the brain (n = 18), liver (n = 14) and adipose tissue (n = 11) FA compositions of 20 stillborn infant

  11. Propolis attenuates oxidative injury in brain and lung of nitric oxide synthase inhibited rats

    Directory of Open Access Journals (Sweden)

    Zeliha Selamoglu-Talas

    2015-10-01

    Full Text Available Background: The blocking of nitric oxide synthase (NOS activity may reason vasoconstriction with formation of reactive oxygen species. Propolis has biological and pharmacological properties, such as antioxidant. The aim of this study was to examine the antioxidant effects of propolis which natural product on biochemical parameters in brain and lung tissues of acute nitric oxide synthase inhibited rats by Nω-nitro-L-arginine methyl ester (L-NAME.Methods: Rats have been received L-NAME (40 mg/kg, intraperitoneally, NOS inhibitor for 15 days to produce hypertension and propolis (200mg/kg, by gavage the lastest 5 of 15 days.Results: There  were  the  increase  (P<0.001  in  the  malondialdehyde  levels  in  the  L-NAME treatment groups when compared to control rats, but the decrease (P<0.001 in the catalase activities in both brain and lung tissues. There were statistically changes (P<0.001 in these parameters of L-NAME+propolis treated rats as compared with L-NAME-treated group.Conclusion: The application of L-NAME to the Wistar rats resulted in well developed oxidative stress. Also, propolis may influence endothelial NO production. Identification of such compounds and characterisation of their cellular actions may increase our knowledge of the regulation of endothelial NO production and could provide valuable clues for the prevention or treatment of hypertensive diseases and oxidative stress.

  12. Protective Effects of Salubrinal on Liver Injury in Rat Models of Brain Death

    Institute of Scientific and Technical Information of China (English)

    Tao Wang; Shui-Jun Zhang; Sheng-Li Cao; Wen-Zhi Guo; Bing Yan; Hong-Bo Fang

    2015-01-01

    Background:Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead (BD) rats.In this study,we observed the effect ofsalubrinal (Sal,Sigma,USA) on liver cells in BD rats and explored its relevant mechanisms.Methods:Thirty Sprague-Dawley rats were equally randomized into three groups:BD group,Sal group,and DMSO group.The BD models were established by increasing intracranial pressure in a modified,slow,and intermittent way.In the drug groups,Sal was administered l h before the induction of BD.After modeling was completed,the blood and liver samples were harvested.CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction.PKR-like ER kinase (PERK),P-eukaryotic translation initiation factor 2α (eIF2α),eIF2α,CHOP and caspase-12 expression was detected using western blotting (WB).CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry (IHC).Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer.Hepatic cell apoptosis was detected using TUNEL.The results were analyzed using Quantity-one v4.62 software (Bio-Rad,USA).Results:CHOP and caspase-12 expression and PERK,eIF2α,and P-eIF2α protein expression showed no significant difference between BD group and DMSO group.Compared with BD group,Sal group had a significantly higher P-eIF2C level and a lower P-PERK level 2 h and 6 h after BD (P < 0.05).However,eIF2α expression showed no significant difference (P > 0.05).After the Sal treatment,CHOP and caspase-12 mRNA expression significantly decreased 4 h after BD (P < 0.05).WB and IHC indicated that CHOP and caspase-12 expression also significantly decreased after Sal treatment.Sal was associated with improved liver function and decreased hepatic cell apoptosis.Conclusions:Sal can significantly reduce apoptosis in hepatic cells of BD rats

  13. Optical pathology of human brain metastasis of lung cancer using combined resonance Raman and spatial frequency spectroscopies

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-hui; Pu, Yang; Cheng, Gangge; Zhou, Lixin; Chen, Jun; Zhu, Ke; Alfano, Robert R.

    2016-03-01

    Raman spectroscopy has become widely used for diagnostic purpose of breast, lung and brain cancers. This report introduced a new approach based on spatial frequency spectra analysis of the underlying tissue structure at different stages of brain tumor. Combined spatial frequency spectroscopy (SFS), Resonance Raman (RR) spectroscopic method is used to discriminate human brain metastasis of lung cancer from normal tissues for the first time. A total number of thirty-one label-free micrographic images of normal and metastatic brain cancer tissues obtained from a confocal micro- Raman spectroscopic system synchronously with examined RR spectra of the corresponding samples were collected from the identical site of tissue. The difference of the randomness of tissue structures between the micrograph images of metastatic brain tumor tissues and normal tissues can be recognized by analyzing spatial frequency. By fitting the distribution of the spatial frequency spectra of human brain tissues as a Gaussian function, the standard deviation, σ, can be obtained, which was used to generate a criterion to differentiate human brain cancerous tissues from the normal ones using Support Vector Machine (SVM) classifier. This SFS-SVM analysis on micrograph images presents good results with sensitivity (85%), specificity (75%) in comparison with gold standard reports of pathology and immunology. The dual-modal advantages of SFS combined with RR spectroscopy method may open a new way in the neuropathology applications.

  14. Impact of CT/MRI Image Registration on Target Delineation of Radiotherapy for Lung Cancer with Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Yang LI

    2012-08-01

    Full Text Available Background and objective Accurate target delineation in radiation therapy is a key component of the treatment regimen for brain metastasis for which CT/MRI fusion technology provides a feasible method. The aim of this study is to explore the role of CT/MRI image registration in target delineation for lung cancer with brain metastasis. Methods The image data of 31 patients were processed using Oncentra MasterPlan. The GTVs were delineated on CT and CT/MRI images, and their differences were compared to analyze the impact of the maximum average error and tumor edema on target delineation. Results The GTVs delineated on CT/MRI images were markedly smaller than those delineated on CT images. Target delineation was clearly influenced by edema. Conclusion The technology of CT/MRI image registration can improve the accuracy of target delineation for lung cancer with brain metastasis.

  15. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

    DEFF Research Database (Denmark)

    Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.;

    1999-01-01

    Organochlorines are persistent lipophilic compounds that accumulate in Inuit people living in circumpolar countries. Organochlorines accumulate as a result of the Inuits' large consumption of sea mammal fat; however, available data are limited to blood lipids, milk fat, and adipose tissue. We...... report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high......-resolution gas chromatography with electron capture detection. Mean concentrations of polychlorinated biphenyls, 2, 2'-bis(4-chlorophenyl)-1,1-dichloroethylene, ss-hexachlorocyclohexane, hexachlorobenzene, mirex, trans-nonachlor, and oxychlordane in adipose tissue samples from Greenlanders were 3-34-fold higher...

  16. Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens; Trueba, Gilberto Perez; Poulsen, Henrik E;

    2007-01-01

    Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency...

  17. In vivo formation of natural HgSe nanoparticles in the liver and brain of pilot whales

    DEFF Research Database (Denmark)

    Gajdosechova, Z.; Lawan, M. M.; Urgast, D. S.

    2016-01-01

    Se) nanoparticles in the liver and brain of long-finned pilot whales are attached to Se-rich structures and possibly act as a nucleation point for the formation of large Se-Hg clusters, which can grow with age to over 5 μm in size. The detoxification mechanism is fully developed from the early age of the animals...

  18. Weak mitochondrial targeting sequence determines tissue-specific subcellular localization of glutamine synthetase in liver and brain cells.

    NARCIS (Netherlands)

    Matthews, G.D.; Gur, N.; Koopman, W.J.H.; Pines, O.; Vardimon, L.

    2010-01-01

    Evolution of the uricotelic system for ammonia detoxification required a mechanism for tissue-specific subcellular localization of glutamine synthetase (GS). In uricotelic vertebrates, GS is mitochondrial in liver cells and cytoplasmic in brain. Because these species contain a single copy of the GS

  19. Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney.

    Science.gov (United States)

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh; Samini, Fariborz

    2017-03-01

    Restraint stress has been indicated to induce oxidative damage in tissues. Several investigations have reported that curcumin (CUR) may have a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CUR on restraint stress induced oxidative stress damage in the brain, liver and kidneys. For chronic restraint stress, rats were kept in the restrainers for 1h every day, for 21 consecutive days. The animals received systemic administrations of CUR daily for 21days. In order to evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), as well as antioxidant enzyme activities superoxide dismutase (SOD) glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were measured in the brain, liver and kidney of rats after the end of restraint stress. The restraint stress significantly increased MDA level, but decreased the level of GSH and activists of SOD, GPx, GR, and CAT the brain, liver and kidney of rats in comparison to the normal rats (Poxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in the tissues versus the control group (Pstress-induced oxidative damage in the brain, liver and kidney of rats and propose that CUR may be useful agents against oxidative stress in the tissues.

  20. Organochlorine contaminants in the muscle, liver and brain of seabirds (Larus) from the coastal area of the Southern Baltic.

    Science.gov (United States)

    Falkowska, Lucyna; Reindl, Andrzej R; Grajewska, Agnieszka; Lewandowska, Anita U

    2016-11-01

    The presence of persistent organic pollutants in the environment manifests itself most strongly in the marine trophic chain, where the highest link is comprised of seabirds. At the same time, seabirds are excellent indicators of contamination in their habitat. The present study concentrates on toxic substances: polychlorinated dibenzo-p-dioxin (PCDDs), polychlorinated dibenzofurans (PCDFs) and chlorinated organic pesticides (OCPs) accumulated in the livers, pectoral muscles and brains of dead gulls collected along the Polish coast of the Baltic Sea in the years 2010-12. The highest toxic equivalence was determined in the livers of Larus argentatus (TEQ(birds TEF)-28.3pgg(-1) ww) and Larus marinus (TEQ(birds TEF)-29.9pgg(-1) ww.). However, the toxic equivalence of muscles was lower and amounted to 3.9pgg(-1) ww. and 7.8pgg(-1) ww. respectively for the two species. The lowest toxic equivalence was found in the brains of birds, where only one, the most toxic, 2,3,7,8 TCDD congener was found (TEQ(birds TEF) 0.87pgg(-1) ww). The highest concentration of chloroorganic pesticides was determined in the brains of the birds (total OCP 167.8pgg(-1) ww.), lower concentrations were found in the livers (total OCP 92.1pgg(-1) ww.) and muscles (total OCP 43.1pgg(-1) ww.). With regard to pesticides, the highest proportion in the total OCP content was constituted by DDT and its isomers (liver 81%, muscles 77% and brain 55%). High concentrations of the studied pollutants in the livers of gulls found dead on the coast of the Southern Baltic could have been effected by levels of contamination in the birds' last meals, which resulted in a seven-fold increase of the liver's toxic equivalence and a two-fold increase in OCP concentration in relation to muscles.

  1. Encephalitozoon cuniculi: Grading the Histological Lesions in Brain, Kidney, and Liver during Primoinfection Outbreak in Rabbits

    Directory of Open Access Journals (Sweden)

    Luis E. Rodríguez-Tovar

    2016-01-01

    Full Text Available This is the first confirmed report of Encephalitozoon cuniculi (E. cuniculi in farm meat rabbits located in Northern Mexico. Eighty young rabbits exhibited clinical signs of this zoonotic emerging disease, like torticollis, ataxia, paresis, circling, and rolling. Samples of brain, kidney, and liver were examined for histology lesions. For the first time the lesions caused by E. cuniculi were graded according to their severity (I, II, and III and the size of the granulomas (Types A, B, and C. The main cerebral injuries were Grade III, coinciding with the presence of Type C granulomas. The cerebral lesions were located in the cortex, brain stem, and medulla. The renal lesions were also Grade III distributed throughout cortex and renal medulla, with no granuloma formation. The involvement of hypersensitivity Types III and IV is suggested. All of the rabbits were seropositive to E. cuniculi by CIA testing, suggesting that this zoonotic and emerging pathogen is widely distributed among animals intended for human consumption. We believe this work could be used as a guide when examining E. cuniculi and will provide direction to confirm the diagnosis of this pathogen.

  2. Encephalitozoon cuniculi: Grading the Histological Lesions in Brain, Kidney, and Liver during Primoinfection Outbreak in Rabbits

    Science.gov (United States)

    Rodríguez-Tovar, Luis E.; Nevárez-Garza, Alicia M.; Trejo-Chávez, Armando; Hernández-Martínez, Carlos A.; Zarate-Ramos, Juan J.; Castillo-Velázquez, Uziel

    2016-01-01

    This is the first confirmed report of Encephalitozoon cuniculi (E. cuniculi) in farm meat rabbits located in Northern Mexico. Eighty young rabbits exhibited clinical signs of this zoonotic emerging disease, like torticollis, ataxia, paresis, circling, and rolling. Samples of brain, kidney, and liver were examined for histology lesions. For the first time the lesions caused by E. cuniculi were graded according to their severity (I, II, and III) and the size of the granulomas (Types A, B, and C). The main cerebral injuries were Grade III, coinciding with the presence of Type C granulomas. The cerebral lesions were located in the cortex, brain stem, and medulla. The renal lesions were also Grade III distributed throughout cortex and renal medulla, with no granuloma formation. The involvement of hypersensitivity Types III and IV is suggested. All of the rabbits were seropositive to E. cuniculi by CIA testing, suggesting that this zoonotic and emerging pathogen is widely distributed among animals intended for human consumption. We believe this work could be used as a guide when examining E. cuniculi and will provide direction to confirm the diagnosis of this pathogen. PMID:27022485

  3. Comparative evaluation of the effects of short-term inhalation exposure to diesel engine exhaust on rat lung and brain

    Energy Technology Data Exchange (ETDEWEB)

    Berlo, Damien van; Albrecht, Catrin; Krutmann, Jean; Schins, Roel P.F. [Institut fuer Umweltmedizinische Forschung (IUF) an der Heinrich-Heine-Universitaet Duesseldorf GmbH, Duesseldorf (Germany); Knaapen, Ad M.; Schooten, Frederik-Jan van [Maastricht University, Department of Health Risk Analysis and Toxicology, Maastricht (Netherlands); Cassee, Flemming R.; Gerlofs-Nijland, Miriam E.; Kooter, Ingeborg M. [National Institute for Public Health and the Environment (RIVM), Centre for Environmental Health, Bilthoven (Netherlands); Palomero-Gallagher, Nicola [Research Center Juelich, Institute of Neurosciences and Medicine (INM-2), Juelich (Germany); Bidmon, Hans-Juergen [Heinrich-Heine-University, C and O Vogt Institute for Brain Research, Duesseldorf (Germany)

    2010-07-15

    Combustion-derived nanoparticles, such as diesel engine exhaust particles, have been implicated in the adverse health effects of particulate air pollution. Recent studies suggest that inhaled nanoparticles may also reach and/or affect the brain. The aim of our study was to comparatively evaluate the effects of short-term diesel engine exhaust (DEE) inhalation exposure on rat brain and lung. After 4 or 18 h recovery from a 2 h nose-only exposure to DEE (1.9 mg/m{sup 3}), the mRNA expressions of heme oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and cytochrome P450 1A1 (CYP1A1) were investigated in lung as well as in pituitary gland, hypothalamus, olfactory bulb, olfactory tubercles, cerebral cortex, and cerebellum. HO-1 protein expression in brain was investigated by immunohistochemistry and ELISA. In the lung, 4 h post-exposure, CYP1A1 and iNOS mRNA levels were increased, while 18 h post-exposure HO-1 was increased. In the pituitary at 4 h post-exposure, both CYP1A1 and HO-1 were increased; HO-1 was also elevated in the olfactory tuberculum at this time point. At 18 h post-exposure, increased expression of HO-1 and COX-2 was observed in cerebral cortex and cerebellum, respectively. Induction of HO-1 protein was not observed after DEE exposure. Bronchoalveolar lavage analysis of inflammatory cell influx, TNF-{alpha}, and IL-6 indicated that the mRNA expression changes occurred in the absence of lung inflammation. Our study shows that a single, short-term inhalation exposure to DEE triggers region-specific gene expression changes in rat brain to an extent comparable to those observed in the lung. (orig.)

  4. Absceso hepático asociado a absceso pulmonar y endoftalmitis Liver abscess associated to lung abscess and endophthalmitis

    Directory of Open Access Journals (Sweden)

    Jairo Cordero-Chen

    2013-03-01

    Full Text Available El absceso hepático piógeno producido por Klebsiella pneumoniae es relativamente raro y puede complicarse con lesiones sépticas a distancia. Esto se relaciona con características propias del germen que incluyen el genotipo K1, resistencia a la fagocitosis y la presencia del gen mag-A. Tales metástasis sépticas contemplan absceso pulmonar, meningitis, endocarditis bacteriana y, muy especialmente, endoftalmitis. Esta última ocurre con mayor frecuencia en pacientes diabéticos, y puede causar ceguera. Se reporta caso de absceso hepático por K. pneumoniae asociado a absceso pulmonar y endoftalmitis, y se revisa epidemiología, fisiopatología, diagnóstico y tratamiento de la entidad.The pyogenic liver abscess due to Klebsiella pneumoniae is relatively rare and can be complicated by distant septic metastases. This can be related to specific bacterial properties including genotype K1, resistance to phagocytosis and the presence of the gene mag-A. The septic metastases include lung abscess, meningitis, infective endocarditis and specially endophtalmitis. The latter is more frequent in diabetic patients and can result in blindness. We report a case of liver abscess produced by K. pneumoniae associated to pulmonary abscess and endophtalmitis, and review the epidemiology, pathophysiology, diagnosis and treatment of this disease.

  5. Therapy for non-small-cell lung cancer patients with brain metastasis Therapy for non-small-cell lung cancer patients with brain metastasis

    Institute of Scientific and Technical Information of China (English)

    Bing Li; Yuchen Bao Co-first author; Bin Chen; Songwen Zhou

    2014-01-01

    Brain metastasis is a major cause of poor prognosis and high mortality for non-smal celllung cancer patients. The prognosis of non-smal-celllung cancer (NSCLC) patients with brain metastasis is generaly poor and more efective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.

  6. Metastatic tumor to the iris and ciliary body as an initial sign of lung cancer: a case report

    Institute of Scientific and Technical Information of China (English)

    SUI Rui-fang; ZHAO Jia-liang; ZHANG Shun-hua; FENG Rui-e; CHENG Gang-wei; MA Jian-min; MAO Jin

    2005-01-01

    @@ The most common sites of lung cancer metastases are pleura, bone, brain, pericardium and liver.1 Tumor metastasis to the eye is a rare complication of lung cancer. Metastatic cancer to the ocular region most often involves the uveal tract, however, most uveal metastases occur in the posterior uvea, and iris metastases are relatively rare. We describe a patient with adenocarcinoma of the lung metastatic to the iris as the first clinical sign without symptoms of lung cancer.

  7. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

    Science.gov (United States)

    Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2014-06-01

    Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

  8. Crizotinib Treatment Combined with Resection and Whole-brain Radiation Therapy 
in A ROS1 Rearranged Lung Adenocarcinoma with Brain Metastasis: 
Case Report and Literature Review

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    Min ZHANG

    2016-08-01

    Full Text Available Background and objective Lung cancer with brain metastasis had poor prognosis. Crizotinib had been confirmed to be used in ROS1 (C-ros oncogene 1 receptor tyrosine kinase rearranged lung adenocarcinoma, but its efficacy in lung cancer with brain metastasis was poor due to the blood brain barrier. In the present study, we reported one case of ROS1 fusion lung adenocarcinoma with symptomatic brain matastasis, who was treated with brain metastases resection, crizotinib, and whole brain radiotherapy plus boost to residual brain metastasis. The safety and efficacy was summarized. Methods At first, surgical resection was used to relive mass effect and to biopsy. Then crizotinib (250 mg, bid was chosen for the existence of ROS1 fusion gene. Whole brain radiotherapy plus boost to residual brain metastasis were used after surgery. Objective response was evaluated by Response Evaluation Criteriation in Solid Tumours (RECIST v1.1 and brain metastasis were evaluated by computer tomography (CT/magnetic resonance imaging (MRI image. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTC AE v4.0. Results After taking crizotinib for 3 months, the lung lesions were close to complete response (CR, the brain metastasis were partial response (PR, the abdomen metastasis were CR and the symptom of blurred vision relieved. Conclusion Crizotinib combined with palliative operation and radiation therapy (WBRT plus boost to residual brain metastasis in the treatment of ROS1 fusion gene positive lung adenocarcinoma with symptomatic brain metastases, can effectively control intracranial lesions with good tolerance.

  9. Prognostic predictors for non-small cell lung cancer patients with brain metastasis after radiotherapy

    Directory of Open Access Journals (Sweden)

    Qiuhong FAN

    2008-06-01

    Full Text Available Background and objective Brain metastasis (BM is often found in the patients with lung cancer. Radiotherapy is regular and effective means of therapy and it aims at palliating symptoms and prolonging survival time. However, now there are different viewpoints on protocols of radiotherapy and prognostic factors. A retrospective analysis is used to evaluate the results of treatment for 82 cases with brain metastasis from non-small cell lung cancer (NSCLC and explore the prognostic factors to establish a prognostic index (PI model. Methods From Feb.1995 to Oct. 2006, 82 patients irradiated for BM from NSCLC, with both complete medical charts and follow-up data available, were eligible for this retrospective analysis. A number of potential factors which might affect prognosis after irradiation were evaluated. The significance of prognostic variables in the survival resulted from both univariate analysis by Kaplan-Meier combining with log-rank test and multivariate Cox regression model. The prognostic index (PI was established based on Cox regression analysis and subgrouping values. Results The follow-up time was 1-120 months. For the entire cohort, the median survival from the start of radiation for BM was 10.5 months, and the actuarial overall survival rate was 50.8%, 23.7% and 5.1% at 0.5, 1 and 2 years respectively. Univariate analysis showed KPS, control of primary tumor, interval from the beginning of diagnostic to BM, extracranial systemic metastasis, counts of lymphocyte and solitary BM were predictors of prognosis. However, in the Cox multivariate analysis, only KPS, control of primary tumor, interval from the beginning of diagnostic to BM and solitary BM were significant prognostic factors. The prognostic index was established based on Cox regression analysis and 82 patients were stratified good, intermediate and poor prognostic sub-groups. The difference of survival rate among 3 subgroups is significant (P<0.001. Conclusion Radiotherapy is

  10. The Gut-Liver-Lung Axis. Modulation of the Innate Immune Response and Its Possible Role in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Young, Robert P; Hopkins, Raewyn J; Marsland, Benjamin

    2016-02-01

    Evidence from epidemiological studies suggests that a diet high in fiber is associated with better lung function and reduced risk of chronic obstructive pulmonary disease (COPD). The mechanism for this benefit remains unknown, but, as fiber is not absorbed by the gut, this finding suggests that the gut may play an active role in pathogenic pathways underlying COPD. There is a growing awareness that aberrant activity of the innate immune system, characterized by increased neutrophil and macrophage activation, may contribute to the development or progression of COPD. Innate immunity is modulated in large part by the liver, where hepatic cells function in immune surveillance of the portal circulation, as well as providing a rich source of systemic inflammatory cytokines and immune mediators (notably, IL-6 and C-reactive protein). We believe that the beneficial effect of dietary fiber on lung function is through modulation of innate immunity and subsequent attenuation of the pulmonary response to inflammatory stimuli, most apparent in current or former smokers. We propose that the "gut-liver-lung axis" may play a modifying role in the pathogenesis of COPD. In this review, we summarize lines of evidence that include animal models, large prospective observational studies, and clinical trials, supporting the hypothesis that the gut-liver-lung axis plays an integral part in the pathogenic mechanisms underlying the pathogenesis of COPD.

  11. Brain-lung-thyroid disease: clinical features of a kindred with a novel thyroid transcription factor 1 mutation.

    Science.gov (United States)

    Ferrara, Joseph M; Adam, Octavian R; Kirwin, Susan M; Houghton, David J; Shepherd, Casey; Vinette, Kathy M B; Litvan, Irene

    2012-01-01

    Brain-lung-thyroid disease is a rare familial disorder caused by mutations in thyroid transcription factor 1, a gene that regulates neuronal migration. We report the clinical features of ten patients from a single family with a novel gene mutation, including observations regarding treatment. Neurologic features of the kindred included developmental delay, learning difficulties, psychosis, chorea, and dystonia. Three patients had a history of seizure, which has not been previously reported in genetically confirmed cases. Low-dose dopamine-receptor blocking drugs were poorly tolerated in 2 patients who received this therapy, levodopa improved chorea in 3 of 4 children, and diazepam was markedly effective in a single adult patient. Chorea related to brain-lung-thyroid disease appears to respond paradoxically to antidopaminergic drugs. The unusual therapeutic response seen in our patients and others may help elucidate how disease-related migratory deficits affect neural pathways associated with motor control.

  12. Studying the Risks of Cotton Cooking Oil Fumes on the Lung and Liver of Rats and the Protective Role of (Vitamin E Alphatocopherol

    Directory of Open Access Journals (Sweden)

    Fahmy GAD GAD ELsaid

    2005-12-01

    Full Text Available Fumes emitted from edible vegetable cooking oils during stir- and deep-frying are important contributors to indoor air pollution. Indoor air pollution may be increase the lung and liver cancer in Egypt in 2005. Therefore, the present study was undertaken to investigate the effects of Egyptian cotton cooking oil fumes on rats. The exposed rats for 30 and 60 days to cotton oil fumes showed a significant increase in the lung and liver malondialdehyde levels which accompanied with a significant decrease in glutathione content. Also, there was a significant decrease in lung and liver superoxide dismutase, catalase, glutathione s-transferase activities. As well as, there was a significant decrease in serum amino acids levels, lung and liver nucleic acids and total proteins. These changes were obviously after 60 days than that of 30 days of exposure. DNA change was clear in the lungs of rats after cotton oil fumes exposed as showed by the differential display technique, P53 primer which used to study the expression of the p35 gene as well as to confirm and amplify these changes after oil fumes exposure. Band with different molecular weights were observed after the exposure and in protected groups but not presented in the control. More characterization for the changes had been carried out in the animal on two levels, one the DNA using RAPD-PCR and the other on the protein level using SDS-PAGE techniques. Also, vitamin E ameliorates these abnormalities to extent limit in all cases in this work.

  13. Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer

    OpenAIRE

    H Billur Engin; Emre Guney; Ozlem Keskin; Baldo Oliva; Attila Gursoy

    2013-01-01

    Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer H. Billur Engin1, Emre Guney2, Ozlem Keskin1, Baldo Oliva2, Attila Gursoy1* 1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Istanbul, Turkey, 2 Structural Bioinformatics Group (GRIB), Universitat Pompeu Fabra Abstract Blocking specific protein interactions can lead to human diseases. Accordingly, protein i...

  14. A Comprehensive MicroRNA Expression Profile of Liver and Lung Metastases of Colorectal Cancer with Their Corresponding Host Tissue and Its Prognostic Impact on Survival

    Science.gov (United States)

    Pecqueux, Mathieu; Liebetrau, Isabell; Werft, Wiebke; Dienemann, Hendrik; Muley, Thomas; Pfannschmidt, Joachim; Müssle, Benjamin; Rahbari, Nuh; Schölch, Sebastian; Büchler, Markus W.; Weitz, Jürgen; Reissfelder, Christoph; Kahlert, Christoph

    2016-01-01

    MicroRNAs are small non-coding RNAs with a length of 18–25 nucleotides. They can regulate tumor invasion and metastasis by changing the expression and translation of their target mRNAs. Their expression is substantially altered in colorectal cancer cells as well as in the adjacent tumor-associated stroma. Both of these compartments have a mutual influence on tumor progression. In the development of metastases, cancer cells initially interact with the host tissue. Therefore, compartment-specific expression signatures of these three locations—tumor, associated stroma, and host tissue—can provide new insights into the complex tumor biology of colorectal cancer. Frozen tissue samples of colorectal liver (n = 25) and lung metastases (n = 24) were laser microdissected to separate tumor cells and the adjacent tumor-associated stroma cells. Additionally, normal lung and liver tissue was collected from the same patients. We performed a microarray analysis in four randomly selected liver metastases and four randomly selected lung metastases, analyzing a total of 939 human miRNAs. miRNAs with a significant change >2-fold between the tumor, tumor stroma, and host tissue were analyzed in all samples using RT-qPCR (11 miRNAs) and correlated with the clinical data. We found a differential expression of several miRNAs between the tumor, the tumor-associated stroma, and the host tissue compartment. When comparing liver and lung metastases, miR-194 showed a 1.5-fold; miR-125, miR-127, and miR-192 showed a 2.5-fold; miR-19 and miR-215 a 3-fold; miR-145, miR-199-3, and miR-429 a 5-fold; miR-21 a 7-fold; and, finally, miR-199-5 a 12.5-fold downregulation in liver metastases compared to lung metastases. Furthermore miR-19, miR-125, miR-127, miR-192, miR-194, miR-199-5, and miR-215 showed a significant upregulation in the normal liver tissue compared to the normal lung tissue. Univariate analysis identified an association of poor survival with the expression of miR-125 (p = 0

  15. Branched chain amino acid transaminase and branched chain alpha-ketoacid dehydrogenase activity in the brain, liver and skele­tal muscle of acute hepatic failure rats

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    Takei,Nobuyuki

    1985-02-01

    Full Text Available Branched chain amino acid (BCAA transaminase activity increased in both the mitochondrial and supernatant fractions of brain from hepatic failure rats, in which a partial hepatectomy was performed 24h following carbon tetrachloride (CCl4 administration, although the activity of liver and skeletal muscle was the same as in control rats. The elevation of mitochondrial BCAA transaminase activity in liver-injured rats was partly due to increased activity of brain specific Type III isozyme. Branched chain alpha-ketoacid (BCKA dehydrogenase in the brain homogenates was not significantly altered in acute hepatic failure rats, while the liver enzyme activity was markedly diminished. BCKA dehydrogenase activity in the brain homogenates was inhibited by adding ATP to the assay system, and was activated in vitro by preincubating the brain homogenate at 37 degrees C for 15 min. These findings suggest that brain BCAA catabolism is accelerated in acute hepatic failure rats.

  16.  Liver transplantation in the critically ill: donation after cardiac death compared to donation after brain death grafts.

    Science.gov (United States)

    Taner, C Burcin; Bulatao, Ilynn G; Arasi, Lisa C; Perry, Dana K; Willingham, Darrin L; Sibulesky, Lena; Rosser, Barry G; Canabal, Juan M; Nguyen, Justin H; Kramer, David J

    2012-01-01

     Patients with end stage liver disease may become critically ill prior to LT requiring admission to the intensive care unit (ICU). The high acuity patients may be thought too ill to transplant; however, often LT is the only therapeutic option. Choosing the correct liver allograft for these patients is often difficult and it is imperative that the allograft work immediately. Donation after cardiac death (DCD) donors provide an important source of livers, however, DCD graft allocation remains a controversial topic, in critically ill patients. Between January 2003-December 2008, 1215 LTs were performed: 85 patients at the time of LT were in the ICU. Twelve patients received DCD grafts and 73 received donation after brain dead (DBD) grafts. After retransplant cases and multiorgan transplants were excluded, 8 recipients of DCD grafts and 42 recipients of DBD grafts were included in this study. Post-transplant outcomes of DCD and DBD liver grafts were compared. While there were differences in graft and survival between DCD and DBD groups at 4 month and 1 year time points, the differences did not reach statistical significance. The graft and patient survival rates were similar among the groups at 3-year time point. There is need for other large liver transplant programs to report their outcomes using liver grafts from DCD and DBD donors. We believe that the experience of the surgical, medical and critical care team is important for successfully using DCD grafts for critically ill patients.

  17. Kinetics of eicosapentaenoic acid in brain, heart and liver of conscious rats fed a high n-3 PUFA containing diet.

    Science.gov (United States)

    Igarashi, Miki; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I

    2013-01-01

    Eicosapentaenoic acid (EPA, 20:5n-3), a precursor of docosahexaenoic acid (DHA), may benefit cardiovascular and brain health. Quantifying EPA's in vivo kinetics might elucidate these effects. [1-(14)C]EPA was infused i.v. for 5min in unanesthetized male rats fed a standard EPA-DHA diet. Plasma and microwaved tissue were analyzed. Kinetic parameters were calculated using our compartmental model. At 5min, 31-48% of labeled EPA in brain and heart was oxidized, 7% in liver. EPA incorporation rates from brain and liver precursor EPA-CoA pools into lipids, mainly phospholipids, were 36 and 2529nmol/s/g×10(-4), insignificant for heart. Deacylation-reacylation half-lives were 22h and 38-128min. Conversion rates to DHA equaled 0.65 and 25.1nmol/s/g×10(-4), respectively. The low brain concentration and incorporation rate and high oxidation of EPA suggest that, if EPA has a beneficial effect in brain, it might result from its suppression of peripheral inflammation and hepatic conversion to bioactive DHA.

  18. Liver and brain abscess caused by Aggregatibacter paraphrophilus in association with a large patent foramen ovale: a case report

    Directory of Open Access Journals (Sweden)

    Carmichael Andrew

    2010-02-01

    Full Text Available Abstract Introduction Aggregatibacter paraphrophilus (former name Haemophilus paraphrophilus is a normal commensal of the oral flora. It is a rare cause of hepatobiliary or intracerebral abscesses. Case presentation We report a case of a 53-year-old Caucasian man with a liver abscess and subsequent brain abscesses caused by Aggregatibacter paraphrophilus. The probable source of the infection was the oral flora of our patient following ingestion of a dental filling. The presence of a large patent foramen ovale was a predisposing factor for multifocal abscesses. Conclusion In this case report, we describe an unusual case of a patient with both liver and brain abscesses caused by an oral commensal Aggregatibacter paraphrophilus that can occasionally show significant pathogenic potential.

  19. Effects of aluminum sulfate on delta-aminolevulinate dehydratase from kidney, brain, and liver of adult mice

    Directory of Open Access Journals (Sweden)

    Schetinger M.R.C.

    1999-01-01

    Full Text Available The purpose of the present study was to investigate the in vitro and in vivo effects of aluminum sulfate on delta-aminolevulinic acid dehydratase (ALA-D activity from the brain, liver and kidney of adult mice (Swiss albine. In vitro experiments showed that the aluminum sulfate concentration needed to inhibit the enzyme activity was 1.0-5.0 mM (N = 3 in brain, 4.0-5.0 mM (N = 3 in liver and 0.0-5.0 mM (N = 3 in kidney. The in vivo experiments were performed on three groups for one month: 1 control animals (N = 8; 2 animals treated with 1 g% (34 mM sodium citrate (N = 8 and 3 animals treated with 1 g% (34 mM sodium citrate plus 3.3 g% (49.5 mM aluminum sulfate (N = 8. Exposure to aluminum sulfate in drinking water inhibited ALA-D activity in kidney (23.3 ± 3.7%, mean ± SEM, P<0.05 compared to control, but enhanced it in liver (31.2 ± 15.0%, mean ± SEM, P<0.05. The concentrations of aluminum in the brain, liver and kidney of adult mice were determined by graphite furnace atomic absorption spectrometry. The aluminum concentrations increased significantly in the liver (527 ± 3.9%, mean ± SEM, P<0.05 and kidney (283 ± 1.7%, mean ± SEM, P<0.05 but did not change in the brain of aluminum-exposed mice. One of the most important and striking observations was the increase in hepatic aluminum concentration in the mice treated only with 1 g% sodium citrate (34 mM (217 ± 1.5%, mean ± SEM, P<0.05 compared to control. These results show that aluminum interferes with delta-aminolevulinate dehydratase activity in vitro and in vivo. The accumulation of this element was in the order: liver > kidney > brain. Furthermore, aluminum had only inhibitory properties in vitro, while in vivo it inhibited or stimulated the enzyme depending on the organ studied.

  20. Brain and Liver Headspace Aldehyde Concentration Following Dietary Supplementation with n-3 Polyunsaturated Fatty Acids.

    Science.gov (United States)

    Ross, Brian M; Babay, Slim; Malik, Imran

    2015-11-01

    Reactive oxygen species react with unsaturated fatty acids to form a variety of metabolites including aldehydes. Many aldehydes are volatile enough to be detected in headspace gases of blood or cultured cells and in exhaled breath, in particular propanal and hexanal which are derived from omega-3 and omega-6 polyunsaturated fatty acids, respectively. Aldehydes are therefore potential non-invasive biomarkers of oxidative stress and of various diseases in which oxidative stress is thought to play a role including cancer, cardiovascular disease and diabetes. It is unclear, however, how changes in the abundance of the fatty acid precursors, for example by altered dietary intake, affect aldehyde concentrations. We therefore fed male Wistar rats diets supplemented with either palm oil or a combination of palm oil plus an n-3 fatty acid (alpha-linolenic, eicosapentaenoic, or docosahexaenoic acids) for 4 weeks. Fatty acid analysis revealed large changes in the abundance of both n-3 and n-6 fatty acids in the liver with smaller changes observed in the brain. Despite the altered fatty acid abundance, headspace concentrations of C1-C8 aldehydes, and tissue concentrations of thiobarbituric acid reactive substances, did not differ between the 4 dietary groups. Our data suggest that tissue aldehyde concentrations are independent of fatty acid abundance, and further support their use as volatile biomarkers of oxidative stress.

  1. The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation.

    Science.gov (United States)

    Kalisvaart, Marit; de Haan, Jubi E; Hesselink, Dennis A; Polak, Wojciech G; Hansen, Bettina E; IJzermans, Jan N M; Gommers, Diederik; Metselaar, Herold J; de Jonge, Jeroen

    2016-11-19

    Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06-4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.

  2. Protective effects of ω-3 PUFA on the second liver injury in rats with traumatic brain injury and hemorrhagic shock

    Institute of Scientific and Technical Information of China (English)

    许会彬

    2014-01-01

    Objective To investigate the effects of preconditioning withω-3 polyunsaturated fatty acid(ω-3 PUFA)on the second liver injury in rats with traumatic brain injury and hemorrhagic shock(TBIS)and explore the underlying mechanism.Methods Total of 36 male Wistar rats were assigned randomly(random number)into 3 groups(n=12 in each):sham

  3. Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation.

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    Elizabeth Osterndorff-Kahanek

    Full Text Available Chronically available alcohol escalates drinking in mice and a single injection of the immune activator lipopolysaccharide can mimic this effect and result in a persistent increase in alcohol consumption. We hypothesized that chronic alcohol drinking and lipopolysaccharide injections will produce some similar molecular changes that play a role in regulation of alcohol intake. We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We identified similar patterns of transcriptional changes among four groups of animals, three consuming alcohol (vs water in different consumption tests and one injected with lipopolysaccharide (vs. vehicle. The three tests of alcohol consumption are the continuous chronic two bottle choice (Chronic, two bottle choice available every other day (Chronic Intermittent and limited access to one bottle of ethanol (Drinking in the Dark. Gene expression changes were more numerous and marked in liver than in prefrontal cortex for the alcohol treatments and similar in the two tissues for lipopolysaccharide. Many of the changes were unique to each treatment, but there was significant overlap in prefrontal cortex for Chronic-Chronic Intermittent and for Chronic Intermittent-lipopolysaccharide and in liver all pairs showed overlap. In silico cell-type analysis indicated that lipopolysaccharide had strongest effects on brain microglia and liver Kupffer cells. Pathway analysis detected a prefrontal cortex-based dopamine-related (PPP1R1B, DRD1, DRD2, FOSB, PDNY network that was highly over-represented in the Chronic Intermittent group, with several genes from the network being also regulated in the Chronic and lipopolysaccharide (but not Drinking in the Dark groups. Liver showed a CYP and GST centered metabolic network shared in part by all four treatments. We demonstrate common consequences of chronic alcohol

  4. Soluble CD163 Predicts Incident Chronic Lung, Kidney and Liver Disease in HIV Infection

    DEFF Research Database (Denmark)

    Kirkegaard-Klitbo, Ditte M.; Mejer, Niels; Knudsen, Troels Bygum

    2017-01-01

    OBJECTIVE:: To examine if monocyte and macrophage activity may be on the mechanistic pathway to non-AIDS comorbidity by investigating the associations between plasma soluble CD163 (sCD163) and incident non-AIDS comorbidities in well-treated HIV-infected individuals. DESIGN:: Prospective single......-center cohort study. METHODS:: Plasma sCD163 was quantified by ELISA technique at study entry in 2004/05 and non-AIDS comorbidity was identified by International Classification of Disease Tenth revision (ICD-10) diagnosis codes and registry linkage in 2014/2015. Associations between sCD163 and incident...... comorbidity was examined using multivariable Cox proportional hazards models adjusted for pertinent covariates. RESULTS:: In HIV-1 infected individuals (n=799), the highest quartile of plasma sCD163 was associated with incident chronic lung disease (adjusted hazard ratio (aHR), 3.2; 95% confidence interval...

  5. Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz; Farkhondeh, Tahereh

    2016-04-01

    Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.

  6. Up-regulation of nucleotide excision repair in mouse lung and liver following chronic exposure to aflatoxin B{sub 1} and its dependence on p53 genotype

    Energy Technology Data Exchange (ETDEWEB)

    Mulder, Jeanne E. [Pharmacology and Toxicology Graduate Program, Department of Biomedical and Molecular Sciences, Queen' s University Kingston, Ontario K7L 3N6 (Canada); Bondy, Genevieve S.; Mehta, Rekha [Toxicology Research Division, 2202D, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Massey, Thomas E., E-mail: masseyt@queensu.ca [Pharmacology and Toxicology Graduate Program, Department of Biomedical and Molecular Sciences, Queen' s University Kingston, Ontario K7L 3N6 (Canada)

    2014-03-01

    Aflatoxin B{sub 1} (AFB{sub 1}) is biotransformed in vivo into an epoxide metabolite that forms DNA adducts that may induce cancer if not repaired. p53 is a tumor suppressor gene implicated in the regulation of global nucleotide excision repair (NER). Male heterozygous p53 knockout (B6.129-Trp53{sup tm1Brd}N5, Taconic) and wild-type mice were exposed to 0, 0.2 or 1.0 ppm AFB{sub 1} for 26 weeks. NER activity was assessed with an in vitro assay, using AFB{sub 1}-epoxide adducted plasmid DNA as a substrate. For wild-type mice, repair of AFB{sub 1}–N7-Gua adducts was 124% and 96% greater in lung extracts from mice exposed to 0.2 ppm and 1.0 ppm AFB{sub 1} respectively, and 224% greater in liver extracts from mice exposed to 0.2 ppm AFB{sub 1} (p < 0.05). In heterozygous p53 knockout mice, repair of AFB{sub 1}–N7-Gua was only 45% greater in lung extracts from mice exposed to 0.2 ppm AFB{sub 1} (p < 0.05), and no effect was observed in lung extracts from mice treated with 1.0 ppm AFB{sub 1} or in liver extracts from mice treated with either AFB{sub 1} concentration. p53 genotype did not affect basal levels of repair. AFB{sub 1} exposure did not alter repair of AFB{sub 1}-derived formamidopyrimidine adducts in lung or liver extracts of either mouse genotype nor did it affect XPA or XPB protein levels. In summary, chronic exposure to AFB{sub 1} increased NER activity in wild-type mice, and this response was diminished in heterozygous p53 knockout mice, indicating that loss of one allele of p53 limits the ability of NER to be up-regulated in response to DNA damage. - Highlights: • Mice are chronically exposed to low doses of the mycotoxin aflatoxin B{sub 1} (AFB{sub 1}). • The effects of AFB{sub 1} and p53 status on nucleotide excision repair are investigated. • AFB{sub 1} increases nucleotide excision repair in wild type mouse lung and liver. • This increase is attenuated in p53 heterozygous mouse lung and liver. • Results portray the role of p53 in

  7. Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development.

    Directory of Open Access Journals (Sweden)

    Keith M Godfrey

    Full Text Available Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001 and at age 4 years (r = 0.16, P = 0.02. In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02. This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04. We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.

  8. Cystic echinococcosis of the liver and lung treated by radiofrequency thermal ablation: An ex-vivo pilot experimental study in animal models

    Institute of Scientific and Technical Information of China (English)

    Vincenzo Lamonaca; Antonino Virga; Marta Ida Minervini; Roberta Di Stefano; Alessio Provenzani; Pietro Tagliareni; Giovanna Fleres; Angelo Luca; Giovanni Vizzini; Ugo Palazzo; Bruno Gridelli

    2009-01-01

    AIM: To evaluate radiofrequency thermal ablation (RTA) for treatment of cystic echinococcosis in animal models (explanted organs). METHODS: Infected livers and lungs from slaughtered animals, 10 bovine and two ovine, were collected. Cysts were photographed, and their volume, cyst content, germinal layer adhesion status, wall calcification and presence of daughter or adjacent cysts were evaluated by ultrasound. Some cysts were treated with RTA at 150 W, 80℃, 7 min. Temperature was monitored inside and outside the cyst. A second needle was placed inside the cyst for pressure stabilization. After treatment, all cysts were sectioned and examined by histology. Cysts were defined as alive if a preserved germinal layer at histology was evident, and as successfully treated if the germinal layer was necrotic. RESULTS: The subjects of the study were 17 cysts (nine hepatic and eight pulmonary), who were treated with RTA. Pathology showed 100% success rate in both hepatic (9/9) and lung cysts (8/8); immediate volume reduction of at least 65%; layer of host tissue necrosis outside the cyst, with average extension of 0.64 cm for liver and 1.57 cm for lung; and endocyst attached to the pericystium both in hepatic and lung cysts with small and focal de novo endocyst detachment in just 3/9 hepatic cysts.CONCLUSION: RTA appears to be very effective in killing hydatid cysts of explanted liver and lung.Bile duct and bronchial wall necrosis, persistence of endocyst attached to pericystium, should help avoid or greatly decrease in vivo post-treatment fistula occurrence and consequent overlapping complications that are common after surgery or percutaneous aspiration,injection and reaspiration. In vivo studies are required to confirm and validate this new therapeutic approach.

  9. Comparison of computed tomography and radionuclide scanning for detection of brain metastases in small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Crane, J.M.; Nelson, M.J.; Ihde, D.C.; Makuch, R.W.; Glatstein, E.; Zabell, A.; Johnston-Early, A.; Bates, H.R.; Saini, N.; Cohen, M.H.

    1984-09-01

    Neurologic history and examination, radionuclide brain scans (RN), and computed tomographic brain scans (CT) were performed at diagnosis and sequentially in 153 consecutive patients with small cell lung cancer (SCLC) to assess the sensitivity and accuracy of these screening methods and to determine whether the early detection of brain metastases influences survival. CT scans (sensitivity, 98%; positive predictive accuracy, 98%) were superior to RN scans (sensitivity, 71%; positive predictive accuracy, 86%) in patients with or without neurologic signs or symptoms. However, CT scans were positive in only 6% of asymptomatic patients at diagnosis and 13% of asymptomatic patients after systemic therapy. Brain metastases detected by CT scan were the sole site of extensive-stage disease in 6% of patients at diagnosis. Despite the enhanced ability of CT scans to detect asymptomatic lesions, survival after therapeutic cranial irradiation was similar for asymptomatic and symptomatic patients. The results suggest that CT brain scans should be used routinely in SCLC patients with neurologic signs or symptoms, at diagnosis (when treatment decisions are based on stage), and at six-month intervals in patients with prior brain metastases and in whom erratic follow-up is likely.

  10. Mass Spectrometry Based Metabolomics Comparison of Liver Grafts from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD) Used in Human Orthotopic Liver Transplantation.

    Science.gov (United States)

    Hrydziuszko, Olga; Perera, M Thamara P R; Laing, Richard; Kirwan, Jennifer; Silva, Michael A; Richards, Douglas A; Murphy, Nick; Mirza, Darius F; Viant, Mark R

    2016-01-01

    Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations.

  11. Mass Spectrometry Based Metabolomics Comparison of Liver Grafts from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD) Used in Human Orthotopic Liver Transplantation

    Science.gov (United States)

    Laing, Richard; Kirwan, Jennifer; Silva, Michael A.; Richards, Douglas A.; Murphy, Nick; Mirza, Darius F.; Viant, Mark R.

    2016-01-01

    Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations. PMID:27835640

  12. The porcine systemic response to pleuropneumonia studied by transcriptional profiling of liver and tracheobronchial lung lymph nodes using multiplexed mRNA-Seq

    DEFF Research Database (Denmark)

    Hedegaard, Jakob; Schou, Kirstine Klitgaard; Skovgaard, Kerstin

    2010-01-01

    Actinobacillus pleuropneumoniae (Ap) is a gram-negative bacterium that causes porcine pleuropneumonia, which is a widespread, highly contagious and often fatal respiratory disease in swine. A total of 44 pigs were experimentally inoculated with Ap serotype 2 or 6 and samples of liver and tracheob......Actinobacillus pleuropneumoniae (Ap) is a gram-negative bacterium that causes porcine pleuropneumonia, which is a widespread, highly contagious and often fatal respiratory disease in swine. A total of 44 pigs were experimentally inoculated with Ap serotype 2 or 6 and samples of liver...... and tracheobronchial lung lymph nodes were collected 6, 12, 24 and 48 hours after experimental inoculation, as well as from six non-inoculated control pigs. Transcriptional profiles of the liver samples have been generated by preparation of 12-plexed mRNA-Seq libraries followed by sequencing on an Illumina GAIIx (51...

  13. Systemic treatments for brain metastases from breast cancer, non-small cell lung cancer, melanoma and renal cell carcinoma: an overview of the literature.

    Science.gov (United States)

    Lombardi, Giuseppe; Di Stefano, Anna Luisa; Farina, Patrizia; Zagonel, Vittorina; Tabouret, Emeline

    2014-09-01

    The frequency of metastatic brain tumors has increased over recent years; the primary tumors most involved are breast cancer, lung cancer, melanoma and renal cell carcinoma. While radiation therapy and surgery remain the mainstay treatment in selected patients, new molecular drugs have been developed for brain metastases. Studies so far report interesting results. This review focuses on systemic cytotoxic drugs and, in particular, on new targeted therapies and their clinically relevant activities in brain metastases from solid tumors in adults.

  14. Surgical resection of synchronous and metachronous lung and liver metastases of colorectal cancers

    Science.gov (United States)

    Jeong, Shinseok; Park, Jin Young; Choi, Dong Wook; Choi, Seong Ho

    2017-01-01

    Purpose Surgical resection of isolated hepatic or pulmonary metastases of colorectal cancer is an established procedure, with a 5-year survival rate of about 50%. However, the role of surgical resections in patients with both hepatic and pulmonary metastases is not well established. We aimed to analyze overall survival of these patients and associated factors. Methods Data retrospectively collected from 66 patients who underwent both hepatic and pulmonary metastasectomy after colorectal cancer surgery from August 2002 through August 2013 were analyzed. In univariate analysis, the log-rank test compared patient survival between groups. P < 0.1 was considered indicative of significance. Multivariate analysis of the significance data using a Cox proportional hazard model identified factors associated with overall survival. The synchronous group (n = 57) was defined as patients who had metastasectomy within 3 months from primary colorectal cancer surgery. The remaining nine patients constituted the metachronous group. Results Median follow-up was 126 months from the primary colorectal cancer surgery. The 5-year survival was 73.4%. There was no difference in overall survival between the synchronous and metachronous groups, consistent with previous studies. Distribution (involving one hemiliver or both, P = 0.010 in multivariate analysis) of liver metastases and multiplicity of the pulmonary metastasis (P = 0.039) were predictors of poor prognosis. Conclusion Sequential or simultaneous resection of both hepatic and pulmonary metastasis of colorectal cancer resulted in good long-term survival in selected patients. Thus, an aggressive surgical approach and multidisciplinary decision making with surgeons seems to be justified. PMID:28203555

  15. Lung endothelial cells strengthen, but brain endothelial cells weaken barrier properties of a human alveolar epithelium cell culture model.

    Science.gov (United States)

    Neuhaus, Winfried; Samwer, Fabian; Kunzmann, Steffen; Muellenbach, Ralf M; Wirth, Michael; Speer, Christian P; Roewer, Norbert; Förster, Carola Y

    2012-11-01

    The blood-air barrier in the lung consists of the alveolar epithelium, the underlying capillary endothelium, their basement membranes and the interstitial space between the cell layers. Little is known about the interactions between the alveolar and the blood compartment. The aim of the present study was to gain first insights into the possible interplay between these two neighbored cell layers. We established an in vitro Transwell model of the alveolar epithelium based on human cell line H441 and investigated the influence of conditioned medium obtained from human lung endothelial cell line HPMEC-ST1.6R on the barrier properties of the H441 layers. As control for tissue specificity H441 layers were exposed to conditioned medium from human brain endothelial cell line hCMEC/D3. Addition of dexamethasone was necessary to obtain stable H441 cell layers. Moreover, dexamethasone increased expression of cell type I markers (caveolin-1, RAGE) and cell type II marker SP-B, whereas decreased the transepithelial electrical resistance (TEER) in a concentration dependent manner. Soluble factors obtained from the lung endothelial cell line increased the barrier significantly proven by TEER values and fluorescein permeability on the functional level and by the differential expression of tight junctional proteins on the molecular level. In contrast to this, soluble factors derived from brain endothelial cells weakened the barrier significantly. In conclusion, soluble factors from lung endothelial cells can strengthen the alveolar epithelium barrier in vitro, which suggests communication between endothelial and epithelial cells regulating the integrity of the blood-air barrier.

  16. In vivo Brain Delivery of v-myc Overproduced Human Neural Stem Cells via the Intranasal Pathway: Tumor Characteristics in the Lung of a Nude Mouse

    Directory of Open Access Journals (Sweden)

    Eun Seong Lee

    2015-01-01

    Full Text Available We aimed to monitor the successful brain delivery of stem cells via the intranasal route and to observe the long-term consequence of the immortalized human neural stem cells in the lungs of a nude mouse model. Stably immortalized HB1.F3 human neural stem cells with firefly luciferase gene (F3-effluc were intranasally delivered to BALB/c nude mice. Bioluminescence images were serially acquired until 41 days in vivo and at 4 hours and 41 days ex vivo after intranasal delivery. Lungs were evaluated by histopathology. After intranasal delivery of F3-effluc cells, the intense in vivo signals were detected in the nasal area, migrated toward the brain areas at 4 hours (4 of 13, 30.8%, and gradually decreased for 2 days. The brain signals were confirmed by ex vivo imaging (2 of 4, 50%. In the mice with initial lung signals (4 of 9, 44.4%, the lung signals disappeared for 5 days but reappeared 2 weeks later. The intense lung signals were confirmed to originate from the tumors in the lungs formed by F3-effluc cells by ex vivo imaging and histopathology. We propose that intranasal delivery of immortalized stem cells should be monitored for their successful delivery to the brain and their tumorigenicity longitudinally.

  17. Long-term effects of a novel phosphorothionate (RPR-II) on detoxifying enzymes in brain, lung, and kidney rats.

    Science.gov (United States)

    Mahboob, M; Siddiqui, M K J

    2002-11-01

    The effects of a phosphorothionate, 2-butenoic acid-3-(diethoxyphosphinothioyl) methyl ester (RPR-II), on the activities of glutathione S-transferase (GST) and UDP-glucuronyltransferase (UDPGT) and the level of glutathione (GSH) were evaluated in rats after administration of RPR-II at 0.014 (low), 0.028 (medium), and 0.042 (high) mgkg(-1)day(-1) for 90 days and also at 28 days (withdrawal) after stopping treatment. Brain GST activity and GSH level decreased significantly at the high dose on the 45th and 90th days of treatment. Dose- and time-dependent decreases in GST activity and GSH was level were observed in lung at medium and high doses and in kidneys at all three doses on both the 45th and 90th days. UDPGT activity increased significantly in kidneys at the medium and high doses at 45 and 90 days. Brain and lung did not display any significant variations in UDPGT activity when compared with the control. Interestingly, the withdrawal study revealed that the effect was reversible within 28 days of cessation of treatment, when enzyme activity reverted to levels close to those of controls. The study revealed that RPR-II affected the GSH- and GST-dependent detoxification system of the treated tissues of rat and its potential to modulate the enzymes is in the order kidneys>lung>brain. The present subacute study suggests that RPR-II may bring about physiological upsets by altering GSH- and GST-dependent events in different tissues of exposed organisms.

  18. Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core.

    Science.gov (United States)

    Tice, Colin M; Noto, Paul B; Fan, Kristi Yi; Zhao, Wei; Lotesta, Stephen D; Dong, Chengguo; Marcus, Andrew P; Zheng, Ya-Jun; Chen, Guozhou; Wu, Zhongren; Van Orden, Rebecca; Zhou, Jing; Bukhtiyarov, Yuri; Zhao, Yi; Lipinski, Kerri; Howard, Lamont; Guo, Joan; Kandpal, Geeta; Meng, Shi; Hardy, Andrew; Krosky, Paula; Gregg, Richard E; Leftheris, Katerina; McKeever, Brian M; Singh, Suresh B; Lala, Deepak; McGeehan, Gerard M; Zhuang, Linghang; Claremon, David A

    2016-10-15

    Liver X receptor (LXR) agonists have been reported to lower brain amyloid beta (Aβ) and thus to have potential for the treatment of Alzheimer's disease. Structure and property based design led to the discovery of a series of orally bioavailable, brain penetrant LXR agonists. Oral administration of compound 18 to rats resulted in significant upregulation of the expression of the LXR target gene ABCA1 in brain tissue, but no significant effect on Aβ levels was detected.

  19. Effects of vitamin A pretreatment on nickel-induced lipid peroxidation and concentration of essential metals in liver, kidney and lung of mice

    Energy Technology Data Exchange (ETDEWEB)

    Chen Changyu [Graduate Institute of Medicine and School of Technology for Medical Sciences, Kaohsiung Medical College, Kaohsiung, Taiwan 807 (Taiwan, Province of China)]|[Department of Medical Technology, Foo-Yin Institute of Technology, Kaohsiung, Taiwan (Taiwan, Province of China); Huang Yeoulih; Lin Tehsien [Graduate Institute of Medicine and School of Technology for Medical Sciences, Kaohsiung Medical College, Kaohsiung, Taiwan 807 (Taiwan, Province of China)

    1998-05-01

    In the present study we report the effects of pretreatment with large doses of vitamin A (Vit A, retinol) on hepatic, renal and pulmonary lipid peroxidation, and Ni and essential metal (Fe, Cu, Zn and Ca) concentrations in mice acutely exposed to nickel. Vitamin A (250 000 IU/kg per day) was administered by oral gavage to ICR mice for 7 days. On the 8th day, NiCl{sub 2} (5 mg Ni/kg body wt.) was injected i.p. to Vit A- or vehicle-pretreated mice. Vitamin A pretreatment alone did not alter lipid peroxidation in liver, kidney and lung. Lipid peroxidation in liver, kidney and lung was increased after treatment with NiCl{sub 2} alone. The extent of lipid peroxidation levels in Vit A+Ni treated mice was enhanced in liver, but reduced in kidney and lung. The Ni concentration in these three organs was below the detection limit (0.09 {mu}g/g) in control and Vit A-pretreated mice. The accumulation of Ni in Vit A+Ni treated mice was increased in liver, but decreased in kidney and lung compared to Ni-treated mice. The concentrations of Fe, Cu, Zn and Ca in these organs were significantly increased in Ni-treated mice. In Vit A+Ni treated mice, compared to Ni-treated mice, hepatic Fe was significantly increased while Cu, Zn and Ca levels were reduced, but still higher than those of control and Vit A-treated mice. In the kidney of Vit A+Ni treated mice, the increase of Cu, Fe, and Zn but not Ca, was reduced and not significantly different from control and Vit A-treated mice. Pretreatment with Vit A reduced the increased Fe, Cu, Zn and Ca concentration in the lung caused by Ni injection. We therefore conclude that the effect of Vit A pretreatment on Ni toxicity is organ-dependent. (orig.) With 3 figs., 4 tabs., 35 refs.

  20. Inhibition of the thioredoxin system in the brain and liver of zebra-seabreams exposed to waterborne methylmercury.

    Science.gov (United States)

    Branco, Vasco; Canário, João; Holmgren, Arne; Carvalho, Cristina

    2011-03-01

    Mercury compounds were recently found to interact in vitro with the thioredoxin system, inhibiting both Thioredoxin (Trx) and Thioredoxin reductase (TrxR). In order to evaluate if Trx and TrxR are affected in vivo by methylmercury (MeHg), we exposed juvenile zebra-seabreams to different concentrations of this toxicant in water for 28days followed by a 14-day depuration period. Methylmercury accumulated to a larger extent in the kidney and liver of fishes, but decreased significantly during the depuration. During the exposure, MeHg percentage in the liver reached levels above 90% of total mercury (HgT) decreasing to 60% of HgT by the end of the depuration period. In the kidney, MeHg accounted for 50-70% of HgT. In the brain and muscle, mercury accumulated throughout the exposure with all mercury being MeHg. The total mercury kept increasing in these organs during the depuration period. However, in the brain, this increase in HgT was accompanied by a decrease in the MeHg percentage (~10%). In the liver, both Trx and TrxR activities were significantly reduced (TrxR--40%; Trx--70%) by the end of the exposure, but recovered to control levels (100%) during the depuration. In the brain, both enzymes where inhibited during the depuration period (TrxR--75%; Trx--70%) when some production of inorganic mercury was detected. Activity of glutathione reductase showed increased levels when TrxR activity was low, suggesting complementarity between both systems. These results indicate that in vivo the thioredoxin system is a toxicological target for MeHg with TrxR being particularly affected.

  1. Prerecovery liver biopsy in the brain-dead donor: a case-control study of logistics, safety, precision, and utility.

    Science.gov (United States)

    Oliver, Joseph Benton; Peters, Stephen; Bongu, Advaith; Beidas, Abdel-Kareem; Dikdan, George; Brown, Lloyd; Koneru, Baburao

    2014-02-01

    Prerecovery liver biopsy (PLB) can potentially to decrease futile recovery and increase utilization of marginal brain-dead donor (BDD) livers. A case-control study was conducted to examine the logistics, safety, histological precision, and liver utilization associated with PLB in BDDs. Twenty-three cases between January 2008 and January 2013 were compared to 2 groups: 48 sequential and 69 clinically matched controls. Compared to the sequential controls, the cases were older (53 versus 46 years), heavier (30.2 versus 25.8 kg/m2), had higher prevalences of hypertension (78.3% versus 44.7%) and alcohol use (56.5% versus 23.4%), and a lower United Network for Organ Sharing expected organ yield (0.73 versus 0.81 livers/donor; P < 0.05 for all). Baseline characteristics were similar between cases and clinical controls. Donor management time was longer for the cases (22.4 hours) versus sequential controls (16.5 hours, P = 0.01) and clinical controls (15.9 hours, P = 0.01). Complications for cases (8.7%) were not different from either group of controls (18.8% for sequential controls, P = 0.46; 17.4% for clinical controls, P = 0.50). The agreement between the donor hospital and study pathologists was substantial regarding evaluation of steatosis (κ = 0.623) and fibrosis (κ = 0.627) and moderate regarding inflammation (κ = 0.495). The proportions of livers that were transplanted were similar for the cases and the clinical controls (60.9% versus 59.4%). In contrast, the proportion of donors for whom liver recovery was not attempted was higher (30.4% versus 8.7%), and the proportion of attempted liver recoveries that did not result in transplantation was lower (8.7% versus 31.9%). These differences were significant at P = 0.009. Overall, PLB is logistically feasible with only a minimal delay and is safe, its interpretation at donor hospitals is reproducible, and it appears to decrease futile liver recovery.

  2. Brain choline acetyltransferase and muscarinic receptor sites, brain and liver cholinesterases in precocial Acomys cahirinus and altricial rat during post-natal development.

    Science.gov (United States)

    Michalek, H; Pintor, A; Fortuna, S; Bisso, G M

    1988-01-01

    Brain choline acetyltransferase, acetylcholinesterase with its molecular forms, and muscarinic receptor sites, as well as liver total cholinesterases were evaluated during the first postnatal month in pups of a precocial (Acomys cahirinus) and altricial (rat) murid species. At birth the levels of brain cholinergic markers were higher in the Acomys than in the rat, but in adulthood the differences were smaller or even reversed. The postnatal increase up in the markers to weaning was considerably more pronounced in the rat. However, substantial variations in the patterns of development of the three cholinergic markers within and between species were observed. Liver cholinesterases were considerably higher in Acomys than in rats at all ages investigated. These and literature data are discussed in relation to postnatal, post-conception and post-organogenesis age of pups belonging to the two species. The variability of the ontogenetic patterns between the enzymes suggests that there is some biological control of individual rates of maturation and that it is necessary to be careful in broadly interpreting growth patterns across organs within the same species and across species.

  3. IMPACT OF SEVOFLURANE AND ACETYLCYSTEINE ON ISCHEMIA-REPERFUSION INJURY OF THE LIVER FROM BRAIN-DEAD DONOR

    Directory of Open Access Journals (Sweden)

    A. E. Shcherba

    2013-01-01

    Full Text Available Aim. The purpose of our work was to estimate the impact of preconditioning with acetylcysteine and sevoflurane on ischemia-reperfusion injury of cadaveric donor liver with marginal features. Methods and results. In this prospective randomized controlled trial we recruited 21 heart beating donors with brain death. We assigned 11 donors to the study group, and 10 donors to the control group. Morphological characteristics of ischemia- reperfusion injury in both groups were analyzed. Conclusion. Use of pharmacological preconditioning with acetylcysteine and sevoflurane resulted in necrosis and hepatocyte apoptosis reduction as compared to the control group, thereby had a protective effect against ischemia-reperfusion injury. 

  4. Miliary brain metastases from adenocarcinoma of the lung: MR imaging findings with clinical and post-mortem histopathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Iguchi, Yohei; Mano, Kazuo; Goto, Yoji; Nakano, Tomonobu [Japanese Red Cross Nagoya First Hospital, Department of Neurology Medicine, Nagoya, Aichi (Japan); Nomura, Fumio; Shimokata, Tomoya [Japanese Red Cross Nagoya First Hospital, Department of Respiratory Medicine, Nagoya, Aichi (Japan); Iwamizu-Watanabe, Sachiko [Nagoya University Graduate School of Medicine, Department of Pathology of Molecular Diagnosis, Nagoya (Japan); Hashizume, Yoshio [Aichi Medical University, Institute for Medical Science of Aging, Nagakute, Aichi (Japan)

    2007-01-15

    Miliary dissemination is a rare form of brain metastasis. The clinical and pathologic features of this form are unclear. We report a 66-year-old man with miliary brain metastases from adenocarcinoma of the lung, describing MRI and neuropathologic findings in the context of previously reported cases. Initial disorientation progressed to an apallic state within 6 months. Although, CT with administration of contrast agent failed to demonstrate any lesions, MRI with Gd-DTPA administration showed multiple enhancing miliary nodules in the cerebral cortex, basal ganglia, thalamus, cerebellum, and brainstem. Some of those nodules also could be seen on T2-weighted imaging without Gd-DTPA, but were difficult to identify conclusively. A histopathologic examination at autopsy disclosed diffusely distributed miliary tumor nodules in a perivascular distribution without surrounding focal edema or reactive gliosis. Notably, this patient with miliary brain metastases developed disorientation followed by unconsciousness, which overshadowed other focal neurologic signs at that time. We should consider this pattern of brain dissemination when a cancer is associated with unexplained disturbance of consciousness. (orig.)

  5. Gene expression patterns of spleen, lung and brain with different radiosensitivity in C57BL6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Majumder, Zahidur Rahman; Lee, Woo Jung; Bae, Sang Woo; Lee, Yun Sil [Laboratory of Radiation Effect, Seoul (Korea, Republic of); Lee, Su Jae [Laboratory of Radiation Experimental Therapeutics, Seoul (Korea, Republic of)

    2005-12-15

    Although little information is available on the underlying mechanisms, various genetic factors have been associated with tissue-specific responses to radiation. In the present study, we explored the possibility whether organ specific gene expression is associated with radiosensitivity using samples from brain, lung and spleen. We examined intrinsic expression pattern of 23 genes in the organs by semi-quantitative RT-PCR method using both male and female C57BL/6 mice. Expression of p53 and p21, well known factors for governing sensitivity to radiation or chemotherapeutic agents, was not different among the organ types. Both higher expression of sialyltransferase, delta7-sterol reductase, leptin receptor splice variant form 12.1, and Cu/Zn SuperOxide Dismutase (SOD) and lower expression of alphaB crystalline were specific for spleen tissue. Expression level of glutathione peroxidase and APO-1 cell surface antigen gene in lung tissue was high, while that of Na, K-ATPase alpha-subunit, Cu/ZnSOD, and cyclin G was low. Brain, radioresistant organ, showed higher expression of Na, K-ATPase-subunit, cyclin G, and nucleolar protein hNop56 and lower expression of delta7-sterol reductase. The result revealed a potential correlation between gene expression patterns and organ sensitivity, and identified genes which might be responsible for organ sensitivity.

  6. Determination of endocrine disrupting compounds in fish liver, brain, and muscle using focused ultrasound solid-liquid extraction and dispersive solid phase extraction as clean-up strategy.

    Science.gov (United States)

    Ros, Oihana; Vallejo, Asier; Olivares, Maitane; Etxebarria, Nestor; Prieto, Ailette

    2016-08-01

    This study describes a new method for the simultaneous extraction of several endocrine disrupting compounds, including alkylphenols (APs), estrogen, bisphenol-A (BPA) and one phthalate metabolite (mono-2-ethylhexyl ester, MEHP) in fish liver, brain, and muscle. Parameters affecting the extraction (extraction solvent and temperature) and the clean-up (dispersive phase nature and amount) steps were evaluated. The extraction was performed by means of focused ultrasound solid-liquid extraction (FUSLE) using 10 mL of n-hexane:acetone (50:50, v/v) for 5 min at ~0 °C, and the clean-up was done by means of dispersive solid phase extraction (dSPE) using 100 mg of ENVI-CARB and 100 mg of MgSO4 for the cleaning of brain and muscle extracts together with 100 mg of PSA in the case of liver extracts. Good apparent recoveries were obtained in the case of liver (62-132 %), brain (66-120 %), and muscle (74-129 %), relative standard deviation (RSD%) was always below 26 %, and the method detection limits (MDLs) were at low ng/g level. The developed method was applied to fish captured in Urdaibai estuary (Bay of Biscay) in December 2015, and the concentrations obtained were in the range MDL-1115 ng/g in brain, MDL-962 ng/g in muscle, and MDL-672 ng/g in liver. In general, the highest concentrations were measured in liver, followed by brain and muscle. In addition, diethylstilbestrol was only detected in fish brain. Graphical Abstract MS method scheme for the/MS method scheme for the determination of EDCs in fish liver, brain and muscle.

  7. Streptococcus pneumoniae-induced pneumonia and Citrobacter rodentium-induced gut infection differentially alter vitamin A concentrations in the lung and liver of mice.

    Science.gov (United States)

    Restori, Katherine H; McDaniel, Kaitlin L; Wray, Amanda E; Cantorna, Margherita T; Ross, A Catharine

    2014-03-01

    In the developing world, vitamin A (VA) deficiency is endemic in populations that are also at great risk of morbidity and mortality because of pneumococcal pneumonia and enteric infections. To better understand how lung and gastrointestinal pathogens affect VA status, we assessed VA concentrations in serum, lung, and liver during an invasive pneumonia infection induced by Streptococcus pneumoniae serotype 3, and a noninvasive gut infection induced by Citrobacter rodentium, in vitamin A-adequate (VAA) and vitamin A-deficient (VAD) mice. For pneumonia infection, mice were immunized with pneumococcal polysaccharide serotype 3 (PPS3), or not (infected-control), 5 d prior to intranasal inoculation with S. pneumoniae. Two days post-inoculation, immunization was protective against systemic infection regardless of VA status as PPS3 immunization decreased bacteremia compared with infected-control mice (P pneumonia had less effect on VA status than gastrointestinal infection, predominantly owing to reduced hepatic VA storage at the peak of gut infection.

  8. Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948-2008.

    Directory of Open Access Journals (Sweden)

    Mikhail Sokolnikov

    Full Text Available Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948-2008. The cohort of Mayak Production Association (PA workers in Russia offers a unique opportunity to study the effects of prolonged low dose rate external gamma exposures and exposure to plutonium in a working age population. We examined radiation effects on the risk of mortality from solid cancers excluding sites of primary plutonium deposition (lung, liver, and bone surface among 25,757 workers who were first employed in 1948-1982. During the period 1948-2008, there were 1,825 deaths from cancers other than lung, liver and bone. Using colon dose as a representative external dose, a linear dose response model described the data well. The excess relative risk per Gray for external gamma exposure was 0.16 (95% CI: 0.07 - 0.26 when unadjusted for plutonium exposure and 0.12 (95% CI 0.03 - 0.21 when adjusted for plutonium dose and monitoring status. There was no significant effect modification by sex or attained age. Plutonium exposure was not significantly associated with the group of cancers analyzed after adjusting for monitoring status. Site-specific risks were uncertainly estimated but positive for 13 of the 15 sites evaluated with a statistically significant estimate only for esophageal cancer. Comparison with estimates based on the acute exposures in atomic bomb survivors suggests that the excess relative risk per Gray for prolonged external exposure in Mayak workers may be lower than that for acute exposure but, given the uncertainties, the possibility of equal effects cannot be dismissed.

  9. Comparative protective effects of royal jelly and cod liver oil against neurotoxic impact of tartrazine on male rat pups brain.

    Science.gov (United States)

    Mohamed, Amany Abdel-Rahman; Galal, Azza A A; Elewa, Yaser H A

    2015-09-01

    This study is aimed to evaluate the possible neurotoxic effect of tartrazine (T), an extensively used synthetic azo dye, as well as to determine the potential modulatory role of cod liver oil (CLO) or royal jelly (RJ) against such effects. For this purpose, thirty-six male rat pups were allocated into six groups. The 1st group received distilled water (control group), the 2nd group was given 300 mg RJ/kg bw (RJ group), the 3rd group was given 0.4 ml CLO/kg bw (CLO group), the 4th was given 500 mg T/kg bw (T group). The 5th group was given T concurrently with RJ (TRJ group) and the 6th group was given T concurrently with CLO (TCLO group), at the same doses as the former groups. All treatments were given orally for 30 consecutive days. The concentrations of different brain neurotransmitters, gamma amino butyric acid (GABA), dopamine (DA) and serotonin (5HT) as well as the antioxidant and oxidative stress biomarkers were measured in the brain homogenates. An immunohistochemical staining of the cerebral cortex was applied with the anti-ssDNA antibody (an apoptotic cell marker) to reveal the changes in brain structure. The T group revealed a significant decrease in the concentration of the brain neurotransmitters, a sharp shortage in the level of antioxidant biomarkers (super oxide dismutase, catalase and the reduced glutathione), a marked increase in malondialdehyde levels, and numerous apoptotic cells in the brain cortex compared with the other groups. Interestingly, all the previously mentioned parameters were almost retrieved in both the TRJ and TCLO groups compared to the T group. These results conclusively demonstrate that RJ and CLO administration provides sufficient protection against the ruinous effects of T on rat pups brain tissue function and structure.

  10. Polyamine Metabolites Profiling for Characterization of Lung and Liver Cancer Using an LC-Tandem MS Method with Multiple Statistical Data Mining Strategies: Discovering Potential Cancer Biomarkers in Human Plasma and Urine

    Directory of Open Access Journals (Sweden)

    Huarong Xu

    2016-08-01

    Full Text Available Polyamines, one of the most important kind of biomarkers in cancer research, were investigated in order to characterize different cancer types. An integrative approach which combined ultra-high performance liquid chromatography—tandem mass spectrometry detection and multiple statistical data processing strategies including outlier elimination, binary logistic regression analysis and cluster analysis had been developed to discover the characteristic biomarkers of lung and liver cancer. The concentrations of 14 polyamine metabolites in biosamples from lung (n = 50 and liver cancer patients (n = 50 were detected by a validated UHPLC-MS/MS method. Then the concentrations were converted into independent variables to characterize patients of lung and liver cancer by binary logic regression analysis. Significant independent variables were regarded as the potential biomarkers. Cluster analysis was engaged for further verifying. As a result, two values was discovered to identify lung and liver cancer, which were the product of the plasma concentration of putrescine and spermidine; and the ratio of the urine concentration of S-adenosyl-l-methionine and N-acetylspermidine. Results indicated that the established advanced method could be successfully applied to characterize lung and liver cancer, and may also enable a new way of discovering cancer biomarkers and characterizing other types of cancer.

  11. Polyamine Metabolites Profiling for Characterization of Lung and Liver Cancer Using an LC-Tandem MS Method with Multiple Statistical Data Mining Strategies: Discovering Potential Cancer Biomarkers in Human Plasma and Urine.

    Science.gov (United States)

    Xu, Huarong; Liu, Ran; He, Bosai; Bi, Cathy Wenchuan; Bi, Kaishun; Li, Qing

    2016-08-10

    Polyamines, one of the most important kind of biomarkers in cancer research, were investigated in order to characterize different cancer types. An integrative approach which combined ultra-high performance liquid chromatography-tandem mass spectrometry detection and multiple statistical data processing strategies including outlier elimination, binary logistic regression analysis and cluster analysis had been developed to discover the characteristic biomarkers of lung and liver cancer. The concentrations of 14 polyamine metabolites in biosamples from lung (n = 50) and liver cancer patients (n = 50) were detected by a validated UHPLC-MS/MS method. Then the concentrations were converted into independent variables to characterize patients of lung and liver cancer by binary logic regression analysis. Significant independent variables were regarded as the potential biomarkers. Cluster analysis was engaged for further verifying. As a result, two values was discovered to identify lung and liver cancer, which were the product of the plasma concentration of putrescine and spermidine; and the ratio of the urine concentration of S-adenosyl-l-methionine and N-acetylspermidine. Results indicated that the established advanced method could be successfully applied to characterize lung and liver cancer, and may also enable a new way of discovering cancer biomarkers and characterizing other types of cancer.

  12. Effects of Feiji Decoction for Soothing the Liver Combined with Psychotherapy 
on Quality of Life in Primary Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Yilin YAO

    2012-01-01

    Full Text Available Background and objective Primary lung cancer is one of the most common malignant tumors. It causes great pain and mood disorders to patients, and significantly reduces their quality of life. The aim of the current study is to evaluate the effect of Feiji Decoction for soothing the liver combined with psychotherapy on quality of life (QoL and physical status of patients with primary lung cancer. Methods A total of 118 patients with primary non-small cell lung cancer were randomly divided into two groups. The 57 patients in the combined therapy group were treated with Feiji Decoction for soothing the liver and psychotherapy combined with chemotherapy, whereas the 61 patients in the control group were treated with chemotherapy only. Both groups were observed for the two treatment courses. The European Organization for Research and Treatment of Cancer QoL Questionnaire LC-43 (EORTC QLQ-LC43 was used to assess the QoL of every patient in both groups before and after treatment scales. At the same time, physical status was assessed using the Karnofsky performance status (KPS and East Cooperative Oncology Group performance status (ECOG. Results The scores of physiology function, role function, emotion function, cognize function, society function, and general health in the therapy group were higher than that of the control group. The therapy group also showed better QoL results than the contol group. Significant differences were observed between the two groups (P<0.01. Meanwhile, the scores of fatigue, vomit, pain, polypnea, insomnia, anorexia, constipation, and specific manifestation of lung cancer in the therapy group were obviously lower than that of the control group; more patients were observed to be relieved. Significant differences between the two groups were observed (P<0.01. The KPS and ECOG scores of the patients were observed to have improved and stabilized in the therapy group than that of the control group; the differences were statistically

  13. Effects of an Agaricus blazei Aqueous Extract Pretreatment on Paracetamol-Induced Brain and Liver Injury in Rats

    Directory of Open Access Journals (Sweden)

    Andréia A. Soares

    2013-01-01

    Full Text Available The action of an Agaricus blazei aqueous extract pretreatment on paracetamol injury in rats was examined not only in terms of the classical indicators (e.g., levels of hepatic enzymes in the plasma but also in terms of functional and metabolic parameters (e.g., gluconeogenesis. Considering solely the classical indicators for tissue damage, the results can be regarded as an indication that the A. blazei extract is able to provide a reasonable degree of protection against the paracetamol injury in both the hepatic and brain tissues. The A. blazei pretreatment largely prevented the increased levels of hepatic enzymes in the plasma (ASP, ALT, LDH, and ALP and practically normalized the TBARS levels in both liver and brain tissues. With respect to the functional and metabolic parameters of the liver, however, the extract provided little or no protection. This includes morphological signs of inflammation and the especially important functional parameter gluconeogenesis, which was impaired by paracetamol. Considering these results and the long list of extracts and substances that are said to have hepatoprotective effects, it would be useful to incorporate evaluations of functional parameters into the experimental protocols of studies aiming to attribute or refute effective hepatoprotective actions to natural products.

  14. Evaluating the significance of density, localization, and PD-1/PD-L1 immunopositivity of mononuclear cells in the clinical course of lung adenocarcinoma patients with brain metastasis

    DEFF Research Database (Denmark)

    Téglási, Vanda; Reiniger, Lilla; Fabian, Katalin

    2017-01-01

    therapeutic strategies with these agents. The aim of this study was to characterize the distribution of ICs and determine the expression of the checkpoint molecules programmed death protein 1 (PD-1) and its ligand, PD-L1, in brain metastasis of lung adenocarcinoma (LUAD) patients and to analyze......Background. Management of lung cancer patients who suffer from brain metastases represents a major challenge. Considering the promising results with immune checkpoint inhibitor treatment, evaluating the status of immune cell (IC) infiltrates in the prognosis of brain metastasis may lead to better...... their clinicopathological correlations. Methods. We determined the presence of peritumoral mononuclear cells (mononuclear ring) and the density of intratumoral stromal mononuclear cells on brain metastasis tissue sections of 208 LUAD patients. PD-L1/PD-1 expressions were analyzed by immunohistochemistry. Results...

  15. Effect of electromagnetic radiofrequency radiation on the rats' brain, liver and kidney cells measured by comet assay.

    Science.gov (United States)

    Trosić, Ivancica; Pavicić, Ivan; Milković-Kraus, Sanja; Mladinić, Marin; Zeljezić, Davor

    2011-12-01

    The goal of study was to evaluate DNA damage in rat's renal, liver and brain cells after in vivo exposure to radiofrequency/microwave (Rf/Mw) radiation of cellular phone frequencies range. To determine DNA damage, a single cell gel electrophoresis/comet assay was used. Wistar rats (male, 12 week old, approximate body weight 350 g) (N = 9) were exposed to the carrier frequency of 915 MHz with Global System Mobile signal modulation (GSM), power density of 2.4 W/m2, whole body average specific absorption rate SAR of 0.6 W/kg. The animals were irradiated for one hour/day, seven days/week during two weeks period. The exposure set-up was Gigahertz Transversal Electromagnetic Mode Cell (GTEM--cell). Sham irradiated controls (N = 9) were apart of the study. The body temperature was measured before and after exposure. There were no differences in temperature in between control and treated animals. Comet assay parameters such as the tail length and tail intensity were evaluated. In comparison with tail length in controls (13.5 +/- 0.7 microm), the tail was slightly elongated in brain cells of irradiated animals (14.0 +/- 0.3 microm). The tail length obtained for liver (14.5 +/- 0.3 microm) and kidney (13.9 +/- 0.5 microm) homogenates notably differs in comparison with matched sham controls (13.6 +/- 0.3 microm) and (12.9 +/- 0.9 microm). Differences in tail intensity between control and exposed animals were not significant. The results of this study suggest that, under the experimental conditions applied, repeated 915 MHz irradiation could be a cause of DNA breaks in renal and liver cells, but not affect the cell genome at the higher extent compared to the basal damage.

  16. EGFR mutations are associated with favorable intracranial response and progression-free survival following brain irradiation in non-small cell lung cancer patients with brain metastases

    Science.gov (United States)

    2012-01-01

    Background The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro. However, the results from clinical studies regarding the radiosensitivity in NSCLC with mutant EGFR are inconclusive. We retrospectively analyzed our NSCLC patients who had been regularly followed up by imaging studies after irradiation for brain metastases, and investigated the impact of EGFR mutations on radiotherapy (RT). Methods Forty-three patients with brain metastases treated with RT, together with EGFR mutation status, demographics, smoking history, performance status, recursive partitioning analysis (RPA) class, tumor characteristics, and treatment modalities, were included. Radiological images were taken at 1 to 3 months after RT, and 3 to 6 months thereafter. Radiographic response was evaluated by RECIST criteria version 1.1 according to the intracranial images before and after RT. Log-rank test and Cox regression model were used to correlate EGFR mutation status and other clinical features with intracranial radiological progression-free survival (RPFS) and overall survival (OS). Results The median follow-up duration was 15 months. Patients with mutant EGFR had higher response rates to brain RT than those with wild-type EGFR (80% vs. 46%; p = 0.037). Logistic regression analysis showed that EGFR mutation status is the only predictor for treatment response (p = 0.032). The median intracranial RPFS was 18 months (95% CI = 8.33-27.68 months). In Cox regression analysis, mutant EGFR (p = 0.025) and lower RPA class (p = 0.026) were associated with longer intracranial RPFS. EGFR mutation status (p = 0.061) and performance status (p = 0.076) had a trend to predict OS. Conclusions Mutant EGFR in NSCLC patients is an independent prognostic factor for better treatment response and longer intracranial RPFS following RT for brain metastases. PMID:23110940

  17. Disposition of 14C-mescaline by rabbit lung.

    Science.gov (United States)

    Roth, R A; Roth, J A; Gillis, C N

    1977-02-01

    Metabolism of mescaline by several rabbit tissues was examined in vitro. Mescaline-oxidizing activity (micromoles per milligram of protein/15 min) of lung homogenates was 4 times greater than that of either liver or kidney. Brain and plasma each had comparatively little capacity to metabolize mescaline. Mescaline metabolism in vitro was sensitive to inhibition by semicarbazide. Removal of mescaline from the medium perfusing the isolated rabbit lung was explained by intrapulmonary metabolism. Semicarbazide (10(-3) M pargyline. Semicarbazide-treated lungs accumulated more mescaline than did untreated lungs. Mescaline efflux from lung was slower than that of its metabolite. These results indicate that the intact lung removes perfused mescaline and may be important in the disposition of circulating mescaline in vivo.

  18. Influence of electromagnetic field (1800 MHz on lipid peroxidation in brain, blood, liver and kidney in rats

    Directory of Open Access Journals (Sweden)

    Paweł Bodera

    2015-08-01

    Full Text Available Objectives: The aim of this study is the evaluation of the influence of repeated (5 times for 15 min exposure to electromagnetic field (EMF of 1800 MHz frequency on tissue lipid peroxidation (LPO both in normal and inflammatory state, combined with analgesic treatment. Material and Methods: The concentration of malondialdehyde (MDA as the end-product of the lipid peroxidation (LPO was estimated in blood, liver, kidneys, and brain of Wistar rats, both healthy and those with complete Freund’s adjuvant (CFA-induced persistent paw inflammation. Results: The slightly elevated levels of the MDA in blood, kidney, and brain were observed among healthy rats in electromagnetic field (EMF-exposed groups, treated with tramadol (TRAM/EMF and exposed to the EMF. The malondialdehyde remained at the same level in the liver in all investigated groups: the control group (CON, the exposed group (EMF, treated with tramadol (TRAM as well as exposed to and treated with tramadol (TRAM/EMF. In the group of animals treated with the complete Freund’s adjuvant (CFA we also observed slightly increased values of the MDA in the case of the control group (CON and the exposed groups (EMF and TRAM/EMF. The MDA values concerning kidneys remained at the same levels in the control, exposed, and not-exposed group treated with tramadol. Results for healthy rats and animals with inflammation did not differ significantly. Conclusions: The electromagnetic field exposure (EMF, applied in the repeated manner together with opioid drug tramadol (TRAM, slightly enhanced lipid peroxidation level in brain, blood, and kidneys.

  19. Brain metastases from lung cancer show increased expression of DVL1, DVL3 and beta-catenin and down-regulation of E-cadherin.

    Science.gov (United States)

    Kafka, Anja; Tomas, Davor; Beroš, Vili; Pećina, Hrvoje Ivan; Zeljko, Martina; Pećina-Šlaus, Nives

    2014-06-13

    The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1), Dishevelled-3 (DVL3), E-cadherin (CDH1) and beta-catenin (CTNNB1). Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR)/loss of heterozygosity (LOH). Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p=0.0001). Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC) were significantly associated to CDH1 LOH (p=0.001). Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

  20. Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

    Directory of Open Access Journals (Sweden)

    Anja Kafka

    2014-06-01

    Full Text Available The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1, Dishevelled-3 (DVL3, E-cadherin (CDH1 and beta-catenin (CTNNB1. Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR/loss of heterozygosity (LOH. Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001. Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC were significantly associated to CDH1 LOH (p = 0.001. Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

  1. Extra corporeal membrane oxygenation in newborns : implications for brain and lung

    NARCIS (Netherlands)

    Heijst, Adrianus Franciscus Jacobus van

    2004-01-01

    Extracorporeal membrane oxygenation (ECMO) is a rescue treatment for newborns with severe respiratory insufficiency. In veno-arterial ECMO, venous blood is drained from the right atrium, oxygenated in an artificial lung and reinfused in the aorta. For vascular access the right internal jugular vein

  2. Heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of deleted in malignant brain tumor 1

    DEFF Research Database (Denmark)

    Bisgaard, Hanne Cathrine; Holmskov, Uffe; Santoni-Rugiu, Eric

    2002-01-01

    DNA library screening approach, we identified 48 enriched, nonredundant gene products associated with liver injury and oval cell proliferation in the adult rat liver. Of these, only two, namely alpha-fetoprotein and a novel transcript with high homology to human DMBT1 (deleted in malignant brain tumor 1......), were specifically associated with the emergence of ductular (oval) cell populations in injured liver. Subsequent cloning and characterization of the rat DMBT1 homologue revealed a highly inducible expression in ductular reactions composed of transit-amplifying ductular (oval) cells, but not in ductular...

  3. Low concentration toxic metal mixture interactions: Effects on essential and non-essential metals in brain, liver, and kidneys of mice on sub-chronic exposure.

    Science.gov (United States)

    Cobbina, Samuel J; Chen, Yao; Zhou, Zhaoxiang; Wu, Xueshan; Feng, Weiwei; Wang, Wei; Mao, Guanghua; Xu, Hai; Zhang, Zhen; Wu, Xiangyang; Yang, Liuqing

    2015-08-01

    The deleterious effects of long term exposure to individual toxic metals in low doses are well documented. There is however, a paucity of information on interaction of low dose toxic metal mixtures with toxic and essential metals. This study reports on interactions between low dose mixtures of lead (Pb), mercury (Hg), arsenic (As) and cadmium (Cd) and toxic and essential metals. For 120d, six groups of forty mice each were exposed to metal mixtures, however, the control group was given distilled water. Exposure to Pb+Cd increased brain Pb by 479% in 30d, whiles Pb+Hg+As+Cd reduced liver Hg by 46.5%, but increased kidney As by 130% in 30d. Brain Cu, increased by 221% on Pb+Hg+As+Cd exposure, however, liver Ca reduced by 36.1% on Pb+Hg exposure in 60-d. Interactions within metal mixtures were largely synergistic. Principal component analysis (PCA) showed that low dose metal exposures influenced greatly levels of Hg (in brain and liver) and As (brain). The influence exerted on essential metals was highest in liver (PC1) followed by kidney (PC2) and brain (PC3). Exposure to low dose metal mixtures affected homeostasis of toxic and essential metals in tissues of mice.

  4. Changes of biochemical indices in brain, liver tissue and serum in mice with Alzheimer disease after Chinese medicine treatment

    Institute of Scientific and Technical Information of China (English)

    Xiangyang Wang; Lili Zhang; Haode Huang; Qiang Qin; Guimei Luo; Chaogan Li; Shuqiu Zhang

    2007-01-01

    BACKGROUND: Alzheimer disease is a main type of dementia, and the important clinical characteristic is the rapid declines of memory and cognitive ability.OBJECTIVE: To study changes of biochemical indices in brain, liver tissue and serum, as well as memory of mice with Alzheimer disease after Chinese medicine treatment. DESIGN: A comparative animal experimental observation. SETTING: Haierfu Research Center of Youjiang Medical College for Nationalities.MATERIALS: Forty-eight healthy Kunming mice (24 males and 24 females), 3 months old, were provided by the animal room of Youjiang Medical College for Nationalities. The animals were divided into four groups according to sex and body mass: control group, model group, Wuyuan Buxue treated group, Haierfu treated group, and 12 mice in each group. Wuyuan Buxue oral liquid was extracted from Polygonum multiflorum Thunb (red, radix) and longan meat (country medicine quasi- word B20020828). Haierfu oral liquid was extracted from Yinhua, poriacocos, licorice, etc (Q/452600RYYLC01-92). METHODS: The experiment was completed in Haierfu Research Center and Institute of Heavy Metal and Fluorosis-Arsenism of Youjiang Medical College for Nationalities from May 2006 to December 2006. ①All animals except those in the control group were given feed which was mixed with AlC3 (12 g/L), and they could freely drink 3 g/L Al(NO3)3. The mice in the control group were given normal feed. Wuyuan Buxue oral liquid and Haierfu oral liquid were distilled by distilled water for one time respectively. Five months after model establishment, mice in the Wuyuan Buxue treated group and Haierfu treated group were given intrapastric perfusion of Wuyuan Buxue oral liquid and Haierfu oral liquid respectively, and those in the model group and control group were given intrapastric perfusion of distilled water of the same volume. All the mice were treated for 45 days. ②The swimming time (s) and error times were determined with Y-shape water maze before and

  5. Effects of glucocorticoid dexamethasone on serum nitric oxide synthase activity and nitric oxide levels in a rat model of lung disease-induced brain injury

    Institute of Scientific and Technical Information of China (English)

    Huajun Li; Ligang Jiang; Meng Xia; Haiping Li; Fanhua Meng; Wei Li; Lifeng Liu; Zhaohui Wang

    2011-01-01

    In this study, we investigated the effects of dexamethasone, pertussis toxin (a Gi protein inhibitor), and actinomycin (a transcription inhibitor) on serum nitric oxide synthase activity and nitric oxide content in a rat model of lung disease-induced brain injury. High-dose dexamethasone (13 mg/kg) and dexamethasone + actinomycin reduced lung water content, increased serum nitric oxide synthase activity and nitric oxide content, diminished inflammatory cell infiltration in pulmonary alveolar interstitium, attenuated meningeal vascular hyperemia, reduced glial cell infiltration, and decreased cerebral edema. These results demonstrate that high-dose glucocorticoid treatment can reduce the severity of lung disease-induced brain injury by increasing nitric oxide synthase activity and nitric oxide levels.

  6. The brain in acute liver failure. A tortuous path from hyperammonemia to cerebral edema

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Eefsen, Martin; Hansen, Bent Adel

    2008-01-01

    Acute liver failure (ALF) is a condition with an unfavourable prognosis. Multiorgan failure and circulatory collapse are frequent causes of death, but cerebral edema and intracranial hypertension (ICH) are also common complications with a high risk of fatal outcome. The underlying pathogenesis has...

  7. Prevention and management of brain edema in patients with acute liver failure

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

    ) and an increase in cerebral blood flow while the cerebrospinal fluid volume remains constant. 3. The development of intracranial hypertension in patients with acute liver failure may be controlled by manipulation of the position, body temperature, plasma tonicity, arterial carbon dioxide tension, and arterial...

  8. Metal accumulation in human tissues. Vol. 6. Chromium, nickel, lead, cadmium, and zinc in liver, lungs, spleen, and kidneys. Metallanreicherungen in Humangeweben. Bd. 6. Chrom, Nickel, Blei, Cadmium und Zink in Lunge, Leber, Milz und Niere

    Energy Technology Data Exchange (ETDEWEB)

    Kollmeier, H.; Seemann, J.; Wittig, P.; Witting, C.; Rothe, G.

    1985-01-01

    This paper presents the results of the analytical determination of Cr, Ni, Pb, Cd, and Zn in human lungs, livers, spleens, and kidneys by means of flameless atomic absorption spectrometry, and this on an individual and on a group basis; individually as a combined record which contains the trace metal concentrations of the investigated tissues and the post-mortem findings obtained by autopsy. The retrieval of the findings in case of certain diseases is realized by an index. The tissue concentrations of those metals depend upon many endogenous and exogenous variables, especially as regards time and place. Thus, often interpretations are only possible on an individual basis. For example, we measured an increased tissue concentration of lead in a cadaver which perinatally died of severe vasal malformations. On the other hand, we found a highly positive correlation between age and chromium and nickel content of lungs, which might be interesting in regard to occupational lung cancer. In relation to our results we tried to establish reference levels. However, the interpretation of the measurements remains difficult. Within the scientific literature the results of such studies are very different, and this both in regard to the analytical method used and to the year of publication. This fact is demonstrated by tabular overviews of the investigated metals and tissues. Furthermore, problems of organisation of getting samples, of avoiding sample contamination, of quality assurance etc. are discussed.

  9. The effects of montelukast on antioxidant enzymes and proinflammatory cytokines on the heart, liver, lungs, and kidneys in a rat model of cecal ligation and puncture-induced sepsis.

    Science.gov (United States)

    Coskun, Ali Kagan; Yigiter, Murat; Oral, Akgun; Odabasoglu, Fehmi; Halici, Zekai; Mentes, Oner; Cadirci, Elif; Atalay, Fadime; Suleyman, Halis

    2011-07-07

    We investigated the potential protective effects of montelukast (MLK) on cecal ligation and puncture (CLP)-induced tissue injury in vital organs - liver, heart, kidneys, and especially lungs - through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS) in rats. The rat groups were (1) a 10-mg/kg MLK-treated CLP group; (2) a 20-mg/kg MLK-treated CLP group; (3) a 20-mg/kg MLK-treated, sham-operated group; (4) a CLP control group; and (5) a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6) cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure.

  10. The Effects of Montelukast on Antioxidant Enzymes and Proinflammatory Cytokines on the Heart, Liver, Lungs, and Kidneys in a Rat Model of Cecal Ligation and Puncture–Induced Sepsis

    Directory of Open Access Journals (Sweden)

    Ali Kagan Coskun

    2011-01-01

    Full Text Available We investigated the potential protective effects of montelukast (MLK on cecal ligation and puncture (CLP–induced tissue injury in vital organs — liver, heart, kidneys, and especially lungs — through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS in rats. The rat groups were (1 a 10-mg/kg MLK-treated CLP group; (2 a 20-mg/kg MLK-treated CLP group; (3 a 20-mg/kg MLK-treated, sham-operated group; (4 a CLP control group; and (5 a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6 cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure.

  11. Scintigraphic evaluation of brain death

    Energy Technology Data Exchange (ETDEWEB)

    Park, C. H.; Bai, M. S.; Cho, K. K.; Kim, S. J.; Yoon, S. N.; Cho, C. W. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1997-07-01

    A law recognizing brain death is a life saving legal measure in patients suffering from badly diseased organs such as kidney, liver, heart, and lung. Such law is being discussed for legalization at the Korean National Assembly. There are various criteria used for brain death in western world and brain scintiscan is one of them. However, the scintiscan is not considered in establishing brain death in the draft of the law. The purpose of this report is to spread this technique in nuclear medicine society as well as in other medical societies. We evaluated 7 patients with clinical suspicion of brain death by various causes. The patient's age ranged from 5 to 39 years. We used 5-20mCi {sup 99m}Tc-HMPAO (d.1-hexamethyl propylene amine oxime) or ECD (Ethyl Cysteinate Dimer), lipophilic agents that cross BBB (blood brain barrier). A dynamic study followed by static or SPECT (single photon emission tomography) was performed. Interpretive criteria used for brain death were 1) no intracranial circulation 2) no brain uptake. The second criteria is heavily used. Five of 7 patients were scintigraphically brain dead and the remaining 2 had some brain uptake excluding the diagnosis of scintigraphic brain death. In conclusion, cerebral perfusion study using a lipophilic brain tracer offers a noninvasive, rapid, easy, accurate and reliable mean in the diagnosis of brain death. We believe that this modality should be included in the criteria of brain death in the draft of the proposed Korean law.

  12. Acute onset of brain atrophy and dementia in a patient with small cell lung cancer: a case report.

    Science.gov (United States)

    Asano, Michiko; Fujimoto, Nobukazu; Gemba, Kenichi; Wada, Sae; Ono, Katsuichiro; Ozaki, Shinji; Adachi, Yoshiaki; Yamamoto, Hiromichi; Kishimoto, Takumi

    2011-03-01

    A 59-year-old man who was diagnosed with small cell lung cancer (SCLC), achieved a complete response to the induction chemoradiotherapy and received prophylactic cranial irradiation (PCI) (25 Gy at 250 cGy per fraction) in October 2008. Three months later, he complained of anorexia, weight loss, fatigue, and short-term memory loss and developed dementia and systemic muscle weakness. Magnetic resonance imaging in April and July 2009 revealed the progression of the diffuse brain atrophy without evidence of the metastasis of SCLC. Paraneoplastic neurological syndrome was suspected because anti-Hu antibody was detected in his serum and cerebrospinal fluid, but the adverse effects of chemotherapy and/or radiotherapy were also suspected as the cause of his neurological disorder.

  13. Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart.

    Science.gov (United States)

    Vrhovac, Ivana; Balen Eror, Daniela; Klessen, Dirk; Burger, Christa; Breljak, Davorka; Kraus, Ognjen; Radović, Nikola; Jadrijević, Stipe; Aleksic, Ivan; Walles, Thorsten; Sauvant, Christoph; Sabolić, Ivan; Koepsell, Hermann

    2015-09-01

    Novel affinity-purified antibodies against human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) were used to localize hSGLT2 in human kidney and hSGLT1 in human kidney, small intestine, liver, lung, and heart. The renal locations of both transporters largely resembled those in rats and mice; hSGLT2 and SGLT1 were localized to the brush border membrane (BBM) of proximal tubule S1/S2 and S3 segments, respectively. Different to rodents, the renal expression of hSGLT1 was absent in thick ascending limb of Henle (TALH) and macula densa, and the expression of both hSGLTs was sex-independent. In small intestinal enterocytes, hSGLT1 was localized to the BBM and subapical vesicles. Performing double labeling with glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP), hSGLT1 was localized to GLP-1-secreting L cells and GIP-secreting K cells as has been shown in mice. In liver, hSGLT1 was localized to biliary duct cells as has been shown in rats. In lung, hSGLT1 was localized to alveolar epithelial type 2 cells and to bronchiolar Clara cells. Expression of hSGLT1 in Clara cells was verified by double labeling with the Clara cell secretory protein CC10. Double labeling of human heart with aquaporin 1 immunolocalized the hSGLT1 protein in heart capillaries rather than in previously assumed myocyte sarcolemma. The newly identified locations of hSGLT1 implicate several extra renal functions of this transporter, such as fluid absorption in the lung, energy supply to Clara cells, regulation of enteroendocrine cells secretion, and release of glucose from heart capillaries. These functions may be blocked by reversible SGLT1 inhibitors which are under development.

  14. Whole brain radiotherapy plus concurrent chemotherapy in non-small cell lung cancer patients with brain metastases: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hong Qin

    Full Text Available The aim of the present meta-analysis is to evaluate the response rate, median survival time (MST and toxicity in patients with brain metastases (BM originating from non-small cell lung cancer (NSCLC and who were treated using either whole brain radiotherapy (WBRT plus concurrent chemotherapy or WBRT alone.PubMed, EMBASE, Web of Science, The Cochrane Library, clinical trials and current controlled trials were searched to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using Stata11.0 software.In total, six randomized controlled trials (RCT involving 910 participants were included in the meta-analysis. The results of the analysis indicate that WBRT plus concurrent chemotherapy was more effective at improving response rate (RR = 2.06, 95% CI [1.13, 3.77]; P = 0.019 than WBRT alone. However, WBRT plus concurrent chemotherapy did not improve median survival time (MST (HR = 1.09, 95%CI [0.94, 1.26]; P = 0.233 or time of neurological progression (CNS-TTP (HR = 0.93, 95%CI [0.75, 1.16]; P = 0.543, and increased adverse events (Grade≥3 (RR = 2.59, 95% CI [1.88, 3.58]; P = 0.000. There were no significant differences in Grade 3-5 neurological or hematological toxicity between two patient groups (RR = 1.08, 95%CI [0.23, 5.1]; P = 0.92.The combination of chemotherapy plus WBRT in patients with BM originating from NSCLC may increase treatment response rates of brain metastases with limited toxicity. Although the therapy schedule did not prolong MST or CNS-TTP, further assessment is warranted.

  15. Simultaneous alterations of brain and plasma serotonin concentrations and liver cytochrome P450 in rats fed on a tryptophan-free diet.

    Science.gov (United States)

    Kot, Marta; Pilc, Andrzej; Daniel, Władysława A

    2012-10-01

    Our previous study suggested involvement of the brain serotonergic system in the regulation of liver cytochrome P450 (CYP). The aim of the present study was to demonstrate simultaneous responsiveness of liver CYP and the peripheral and brain serotonergic systems to a tryptophan deficient diet during three days and one or three weeks of ingestion. The concentrations of serotonin, noradrenaline, dopamine and their metabolites were measured in blood plasma, the hypothalamus and brain stem of male rats. The enzyme activity and protein levels in the liver were determined for isoforms CYP1A, CYP2A, CYP2B, CYP2C6, CYP2C11, CYP2D and CYP3A. A three-day tryptophan-free diet increased serotonin content in the hypothalamus (but not in the brain stem or plasma). After one week, the level of serotonin was not changed in the brain, but was markedly increased in the plasma. A three week tryptophan restriction significantly reduced the concentration of serotonin in the brain and plasma. Changes in CYP2C6 and CYP2C11 (an increase and a decrease, respectively) were maintained throughout the experiment, while those found in other CYP isoforms varied, which usually resulted in a gradual increase in the enzyme activity within three weeks. The observed alterations in liver CYPs suggest involvement of both central and peripheral serotonin in the regulation of liver CYP expression whose mechanism is discussed. In conclusion, a deficit in tryptophan in the diet may be responsible for very serious food-cytochrome P450 and food-drug metabolism interactions. Interactions of this type may also refer to drugs acting via serotonergic system.

  16. Efficacy and Potential MicroRNA Mechanism for Computed Tomography-Guided Percutaneous Radiofrequency Ablation of Primary Lung Cancer and Lung Metastasis from Liver Cancer

    Directory of Open Access Journals (Sweden)

    Xun Hu

    2014-04-01

    Full Text Available Background: The aim of this study was to evaluate comparatively the effectiveness of computed tomography-guided percutaneous radiofrequency ablation (CT-PRFA for primary non-small cell lung cancer (NSCLC and lung metastases from hepatocellular carcinoma (HCC and to explore the potential miRNA mechanisms for the efficacy of CT-PRFA. Methods: 14 patients pathologically diagnosed with NSCLC and 12 patients with lung metastases from HCC were enrolled in the study and underwent CT-PRFA. Clinical outcomes were compiled on the basis of review of medical records, imaging follow-up reports, and any biopsy-proved residual or recurrent disease. Real-time RT-PCR was used to quantify the selected miRNAs known to be play key roles in lung cancer. Results: A total of 21 tumors were treated with umbrella-tip electrodes and spiral-tip electrodes were used for the remaining 8 tumors. The median follow-up was 13.5 months (range, 3-30 months and no patient was lost to follow-up. The rate of technique efficacy for primary tumors was ∼93% (13 of 14. Treatment was successful in 11 out of 12 (91.7% lung metastases patients. Overall survival rate was 80.8% at 2 years, and cancer-specific survival rate was 100% at 2 years. The tumor-free survival was 69.2% at 1 year and 26.9% at 2 years. Before PRFA, tumor suppressor let-7a and miR-34a were downregulated whereas oncomiR miR-21 was upregulated in primary tumors, and let-7a and miR-126 levels were downregulated whereas oncomiRs miR-21, miR-155 and miR-17-5p/miR-20b levels were upregulated in secondary tumors. This abnormal expression was normalized by CT-PRFA. Most notably, CT-PRFA failed to normalize the deregulated miRNAs in the non-survivors. Conclusions: CT-PRFA is a effective treatment for primary NSCLCs and secondary lung tumors from HCC and the efficacy may be related to its ability to normalize deregulated expression of miRNAs: upregulating tumor suppressor miRNAs and downregulating oncomiRs.

  17. Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China

    Institute of Scientific and Technical Information of China (English)

    Xu-Ying Luo; Ying-Hong Hu; Xiang-Yuan Cao; Yan Kang; Li-Ping Liu; Shou-Hong Wang; Rong-Guo Yu

    2016-01-01

    Background:Over the years,the mechanical ventilation (MV) strategy has changed worldwide.The aim of the present study was to describe the ventilation practices,particularly lung-protective ventilation (LPV),among brain-injured patients in China.Methods:This study was a multicenter,1-day,cross-sectional study in 47 Intensive Care Units (ICUs) across China.Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study,including traumatic brain injury,stroke,postoperation with intracranial tumor,hypoxic-ischemic encephalopathy,intracranial infection,and idiopathic epilepsy,were enrolled.Demographic data,primary diagnoses,indications for MV,MV modes and settings,and prognoses on the 60th day were collected.Multivariable logistic analysis was used to assess factors that might affect the use of LPV.Results:A total of 104 patients were enrolled in the present study,87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale <8 points.Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode,accounting for 46.2% of the entire cohort.The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR],7.0-8.9 ml/kg) of the predicted body weight;50 (48.1%) patients received LPV.The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR,5-6 cmH2O).No PEEP values were higher than 10 cmH2O.Compared with partially mandatory ventilation,supportive and spontaneous ventilation practices were associated with LPV.There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not.Conclusions:Among brain-injured patients in China,SIMV was the most frequent ventilation mode.Nearly one-half of the brain-injured patients received LPV.Patients under supportive and spontaneous ventilation were more likely to receive LPV.

  18. Pediatric respiratory and systemic effects of chronic air pollution exposure: nose, lung, heart, and brain pathology.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Torres-Jardón, Ricardo; Henriquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Valencia-Salazar, Gildardo; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderón, Rafael; Reed, William

    2007-01-01

    Exposures to particulate matter and gaseous air pollutants have been associated with respiratory tract inflammation, disruption of the nasal respiratory and olfactory barriers, systemic inflammation, production of mediators of inflammation capable of reaching the brain and systemic circulation of particulate matter. Mexico City (MC) residents are exposed to significant amounts of ozone, particulate matter and associated lipopolysaccharides. MC dogs exhibit brain inflammation and an acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by air pollutants. MC children, adolescents and adults have a significant upregulation of cyclooxygenase-2 (COX2) and interleukin-1beta (IL-1beta) in olfactory bulb and frontal cortex, as well as neuronal and astrocytic accumulation of the 42 amino acid form of beta -amyloid peptide (Abeta 42), including diffuse amyloid plaques in frontal cortex. The pathogenesis of Alzheimer's disease (AD) is characterized by brain inflammation and the accumulation of Abeta 42, which precede the appearance of neuritic plaques and neurofibrillary tangles, the pathological hallmarks of AD. Our findings of nasal barrier disruption, systemic inflammation, and the upregulation of COX2 and IL-1beta expression and Abeta 42 accumulation in brain suggests that sustained exposures to significant concentrations of air pollutants such as particulate matter could be a risk factor for AD and other neurodegenerative diseases.

  19. Semiautomatic technique for defining the internal gross tumor volume of lung tumors close to liver/spleen cupola by 4D-CT

    Energy Technology Data Exchange (ETDEWEB)

    Mancosu, Pietro; Sghedoni, Roberto; Bettinardi, Valentino; Aquilina, Mark Anthony; Navarria, Piera; Cattaneo, Giovanni Mauro; Di Muzio, Nadia; Cozzi, Luca; Scorsetti, Marta [Department of Radiotherapy, IRCCS Istituto Clinico Humanitas, Rozzano, 20089 Milano (Italy); Department of Medical Physics, Arcispedale S. Maria Nuova, Reggio, 42100 Emilia (Italy); Department of Nuclear Medicine, Scientific Institute H. S. Raffaele, 20089 Milan (Italy); Department of Radiotherapy, IRCCS Istituto Clinico Humanitas, 20089 Rozzano, Milano (Italy); Department of Medical Physics, San Raffaele Scientific Institute, 20133 Milan (Italy); Department of Radiotherapy, San Raffaele Scientific Institute, 20133 Milan (Italy); Medical Physics Unit, Oncology Institute of Southern Switzerland, 6504 Bellinzona (Switzerland); Department of Radiotherapy, IRCCS Istituto Clinico Humanitas, 20089 Rozzano, Milano (Italy)

    2010-09-15

    Purpose: It has been shown that in cases of lung tumors close to the liver cupola, the four dimensional (4D)-CT postprocessing maximum intensity projection (MIP) algorithm does not fully recover the radiotherapy internal gross tumor volume (IGTV). In this work, a semiautomatic technique was evaluated by which the residual IGTV that was not included into the IGTV by MIP algorithm was actually added. Methods: A moving phantom and five selected patients were considered. The various IGTVs produced by the semiautomatic approach were compared to those generated by 4D-CT manual contouring. Results: In all cases, the radiation oncologist qualitatively concurred with the semiautomatic IGTV. A quantitative difference in volume of 2.6% was found in the phantom study, whereas a mean difference of 0.1{+-}4.6% was obtained in the patient studies. Conclusions: A semiautomatic technique to include the residual part of IGTV covered by liver/spleen cupola when using MIP algorithm was validated on phantom and on selected patients, revealing the possibility of defining the IGTV for patients with lesions located near liver/spleen cupola by performing only the contours on the MIP series.

  20. In vivo field dependence of proton relaxation times in human brain, liver and skeletal muscle: a multicenter study

    DEFF Research Database (Denmark)

    Henriksen, O; de Certaines, J D; Spisni, A;

    1993-01-01

    T1 and T2 relaxation times are fundamental parameters for signal contrast behaviour in MRI. A number of ex vivo relaxometry studies have dealt with the magnetic field dispersion of T1. By means of multicenter study within the frame of the COMAC BME Concerted Action on Tissue Characterization by MRI...... and MRS, the in vivo field dispersion of T1 and T2 has been measured in order to evaluate whether ex vivo data are representative for the in vivo situation. Brain, skeletal muscle, and liver of healthy human volunteers were studied. Fifteen MR units with a field strength ranging from 0.08 T to 1.5 T took...... part in the trial, which comprised 218 volunteers. All the MR systems were tested for measurement accuracy using the Eurospin TO5 test object. The measured relaxation data were subsequently corrected according to the obtained calibration curves. The results showed a clear field dispersion of T1...

  1. Genotoxicity of styrene-acrylonitrile trimer in brain, liver, and blood cells of weanling F344 rats.

    Science.gov (United States)

    Hobbs, Cheryl A; Chhabra, Rajendra S; Recio, Leslie; Streicker, Michael; Witt, Kristine L

    2012-04-01

    Styrene-acrylonitrile Trimer (SAN Trimer), a by-product in production of acrylonitrile styrene plastics, was identified at a Superfund site in Dover Township, NJ, where childhood cancer incidence rates were elevated for a period of several years. SAN Trimer was therefore tested by the National Toxicology Program in a 2-year perinatal carcinogenicity study in F344/N rats and a bacterial mutagenicity assay; both studies gave negative results. To further characterize its genotoxicity, SAN Trimer was subsequently evaluated in a combined micronucleus (MN)/Comet assay in juvenile male and female F344 rats. SAN Trimer (37.5, 75, 150, or 300 mg/kg/day) was administered by gavage once daily for 4 days. Micronucleated reticulocyte (MN-RET) frequencies in blood were determined by flow cytometry, and DNA damage in blood, liver, and brain cells was assessed using the Comet assay. Highly significant dose-related increases (P exposure to SAN Trimer.

  2. Genotoxicity of Styrene–Acrylonitrile Trimer in Brain, Liver, and Blood Cells of Weanling F344 Rats

    Science.gov (United States)

    Hobbs, Cheryl A.; Chhabra, Rajendra S.; Recio, Leslie; Streicker, Michael; Witt, Kristine L.

    2012-01-01

    Styrene–acrylonitrile Trimer (SAN Trimer), a by-product in production of acrylonitrile styrene plastics, was identified at a Superfund site in Dover Township, NJ, where childhood cancer incidence rates were elevated for a period of several years. SAN Trimer was therefore tested by the National Toxicology Program in a 2-year perinatal carcinogenicity study in F344/N rats and a bacterial mutagenicity assay; both studies gave negative results. To further characterize its genotoxicity, SAN Trimer was subsequently evaluated in a combined micronucleus (MN)/Comet assay in juvenile male and female F344 rats. SAN Trimer (37.5, 75, 150, or 300 mg/kg/day) was administered by gavage once daily for 4 days. Micronucleated reticulocyte (MN-RET) frequencies in blood were determined by flow cytometry, and DNA damage in blood, liver, and brain cells was assessed using the Comet assay. Highly significant dose-related increases (P exposure to SAN Trimer. PMID:22351108

  3. Alcohol,inflammation,and gut-liver-brain interactions in tissue damage and disease development

    Institute of Scientific and Technical Information of China (English)

    H; Joe; Wang; Samir; Zakhari; M; Katherine; Jung

    2010-01-01

    Chronic inflammation is often associated with alcoholrelated medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous syst...

  4. Prednisolone has a positive effect on the kidney but not on the liver of brain dead rats : a potencial role in complement activation

    NARCIS (Netherlands)

    Rebolledo Acevedo, Rolando; Liu, Bo; Akhtar, Mohammed Z.; Ottens, Petra J.; Zhang, Jian-ning; Ploeg, Rutger J.; Leuvenink, Henri G. D.

    2014-01-01

    Background: Contradictory evidence has been published on the effects of steroid treatments on the outcomes of kidney and liver transplantation from brain dead (BD) donors. Our study aimed to evaluate this disparity by investigating the effect of prednisolone administration on BD rats. Methods: BD in

  5. Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

    Science.gov (United States)

    Yu, Nanyang; Wei, Si; Li, Meiying; Yang, Jingping; Li, Kan; Jin, Ling; Xie, Yuwei; Giesy, John P.; Zhang, Xiaowei; Yu, Hongxia

    2016-04-01

    Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.

  6. Prognostic factors to predict survival in non-small-cell lung cancer with brain metastasis

    Institute of Scientific and Technical Information of China (English)

    Tiantian Li; Xuezhen Ma; Yuan Yao

    2014-01-01

    Objective:The purpose of the study was to assess prognostic factors to predict overal survival (OS) and progres-sion-free survival (PFS) in non-smal-celllung cancer (NSCLC) with brain metastasis (BM). Methods:From November 2011 to March 2013, the clinical data of 31 NSCLC cases with BM treated with multiple modalities including brain radiotherapy alone, systemic chemotherapy, whole brain radiotherapy (WBRT) combined with tyrosine kinase inhibitor (TKIs). The ef icacy and adverse reaction were evaluated after treatment. Results:In terms of intracranial lesions, the objective response rate (ORR) and the disease control rate (DCR) were 22.6%and 90.3%, respectively. As for systemic disease, ORR and DCR were 32.3%and 93.5%, respectively. The median time to progression-free survival (PFS) was 298 days (95%CI:258.624-337.376 days), whereas in the epidermal growth factor receptor (EGFR) mutation patients was 331 days. Patients who received EGFR-TKIs combined with brain radiation had better response rate (RR) than those only brain radiation. Univariate analysis showed that the EGFR-mutations could predictive factors for PFS, and not to other clinical pathological features. The most common toxici-ties were rash and diarrhea, but al were wel-tolerated. Conclusion:EGFR-mutations is the independent prognostic factors af ecting the survival rates of NSCLC patients with BM. Through the clinical observation, icotinib combined with WBRT may be ef ective on brain metastases in NSCLC patients, and toxicities are tolerable, which worth further study.

  7. Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

    Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

  8. N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reper fusion injur y in mice

    Institute of Scientific and Technical Information of China (English)

    Xin Jin; Lin Wang; He-Shui Wu; Lei Zhang; Chun-You Wang; Yuan Tian; Jing-Hui Zhang

    2007-01-01

    BACKGROUND: Toll-like receptor 2 and 4 (TLR2/4) may play important roles in ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the generation of reactive oxygen species (ROS) induced by I/R injury. This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment. METHODS:BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group (SH), a hepatic ischemia/reperfusion group (I/R) or a NAC pretreated, hepatic I/R group (I/R-NAC). The levels of TNF-α in the portal vein and plasma alanine aminotransferase (ALT) were measured at 1 and 3 hours after reperfusion. The lung wet-to-dry ratio was measured, and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points. RESULTS: Compared with the I/R group, the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P CONCLUSIONS:TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury. NAC inhibited the activation of TLR2/4 and the induction of TNF-αresulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.

  9. Cerebral Alveolar Echinococcosis Concomitant with Liver and Lung Lesions in a Young Adult Patient: Case Report and Literature Review.

    Science.gov (United States)

    Batçık, Osman Ersegun; Öğrenci, Ahmet; Koban, Orkun; Ekşi, Murat Şakir; Bilge, Turgay

    2016-09-01

    We present the case of a 25-year-old male harboring multiple brain lesions mimicking tumor metastasis that were revealed to be caused by Echinococcus multilocularis. Cerebral echinococcosis with multiple lesions is rare and might be confused with a brain abscess, tuberculoma, or metastatic tumor disease. Brain magnetic resonance imaging and serological studies are helpful in the differential diagnosis. In case of E. multilocularis, cerebral invasion is the late stage of the disease that necessitates an aggressive treatment protocol.

  10. Respiratory Deleted in Malignant Brain Tumours 1 (DMBT1) levels increase during lung maturation and infection

    DEFF Research Database (Denmark)

    Müller, H; End, C; Weiss, C;

    2007-01-01

    Deleted in Malignant Brain Tumours 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds and aggregates various bacteria and viruses in vitro. Studies in adults have shown that DMBT1 is expressed mainly by mucosal epithelia and glands, in particular within the respiratory...

  11. Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Shank, B.; Natale, R.B.; Hilaris, B.S.; Wittes, R.E.

    1981-04-01

    Survival of patients with small cell carcinoma of lung, treated on a new combined radiotherapy-chemotherapy protocol, compares favorably with other regimens in the literature and our own previous combined approaches. Radiation, given after induction chemotherapy, consisted of whole brain prophylaxis in all 44 evaluable patients. Patients with limited disease were also treated to the primary and mediastinum to a high dose (5000 rad equivalent) using multiple fields. The new chemotherapy regimen consisted of induction with cyclophosphamide, doxorubicin, and vincristine alternated with cis-platinum and VP-16 (an epipodophyllotoxin) for two cycles, followed by consolidation with low dose cyclophosphamide and vincristine concurrent with irradiation. Patients with limited disease who achieved less than complete response, and all patients with extensive disease were not continued on maintenance chemotherapy. Out of 24 evaluable patients with limited disease, there was 73% survival at 1 year by life-table analysis, measured from treatment initiation. After induction, 16/24 of these limited disease patients were CR (complete responders): 20/24 were CR at completion of their irradiation. Out of 20 evaluable patients with extensive disease, there was 59% survival at 1 year by life-table analysis. Only 4/44 (9%) brain parenchymal relapses occurred, one at 3 months and one at 6 months after local failure and two in patients who did not become CRs, implicating a possible re-seeding mechanism. Five patients had central nervous system relapses outside of brain parenchyma (spinal epidural and leptomeningeal); in three patients this was the initial site of failure. Significant complications included leukopenia (50%) and thrombocytopenia (24%) primarily during induction, and chronic pulmonary fibrosis (25%), possibly contributing to two deaths.

  12. Whole brain radiotherapy in management of non-small-cell lung carcinoma associated leptomeningeal carcinomatosis: evaluation of prognostic factors.

    Science.gov (United States)

    Ozdemir, Yurday; Yildirim, Berna Akkus; Topkan, Erkan

    2016-09-01

    To assess the efficacy of whole-brain radiotherapy (WBRT) and prognostic factors in leptomeningeal carcinomatosis (LMC) of non-small-cell lung cancer (NSCLC) patients. WBRT records of 51 LMC patients confined to brain were reviewed. Eligible patients had squamous-cell carcinoma (SCC) or adenocarcinoma, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-3. The WBRT was either 20 or 30 Gray. The primary and secondary objectives were to determine overall survival (OS) and prognostic factors for improved treatment response, respectively. Median age was 53 years (range 39-68), 58.8 % had SCC, 74.5 % had ECOG PS 1-2, and 70.6 % had LMC accompanied by parenchymal brain metastases (BM). The median follow-up was 4.1 months (range 0.7-14.4); all patients died due to disease progression. Median OS was 3.9 months (95 % CI 3.3-4.5) with 6 and 12 month estimates of 19.6 and 5.9 %, respectively. Evaluation of prognostic factors revealed that patients with ECOG 1, longer time to LMC (TT-LMC) from NSCLC diagnosis (>11.3 months), and absence of parenchymal BM had significantly superior OS than those patients with ECOG 2 (p = 0.01) or 3 (p  11.3 months, and no BM as independent prognosticators for better response to WBRT in NSCLC patients with LMC.

  13. Sparteine monooxygenase in brain and liver: Identified by the dopamine uptake blocker ( sup 3 H)GBR-12935

    Energy Technology Data Exchange (ETDEWEB)

    Kalow, W.; Tyndale, R.F.; Niznik, H.B.; Inaba, T. (Univ. of Toronto, Ontario (Canada))

    1990-02-26

    P450IID6 (human sparteine monooxygenase) metabolizes many drugs including neuroleptics, antidepressants, and beta-blockers. The P450IID6 exists in human, bovine, rat and canine brains, but in very low quantities causing methodological difficulties in its assessment. Work with ({sup 3}H)GBR-12935; 1-(2-(diphenylmethoxy) ethyl)-4-(3-phenyl propyl) piperazine has shown that it binds a neuronal/hepatic protein with high affinity ({approximately}7nM) and a rank order of inhibitory potency suggesting that the binding protein is cytochrome P450IID6. The binding was used to predict that d-amphetamine and methamphetamine would interact with P450IID6. Inhibition studies indicated that these compounds were competitive inhibitors of P450IID6. Haloperidol (HAL) and it's metabolite hydroxy-haloperidol (RHAL) are both competitive inhibitors of P450IID6 activity and were found to inhibit ({sup 3}H)GBR-12935 binding. K{sub i} values of twelve compounds (known to interact with the DA transporter or P450IID6) for ({sup 3}H)GRB-12935 binding and P450IID6 activity. The techniques are now available for measurements of cytochrome P450IID6 in healthy and diseased brain/liver tissue using radio-receptor binding assay techniques with ({sup 3}H)GBR-12935.

  14. Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Mao-hua Zheng

    2016-01-01

    Full Text Available Background. To comprehensively assess the efficacy and safety of whole-brain radiotherapy (WBRT combined with gefitinib/erlotinib for treatment of brain metastases (BM from non-small-cell lung cancer (NSCLC. Methods. Databases including PubMed, EMBASE.com, Web of Science, and Cochrane Library were searched from inception to April 12, 2015. Studies on randomized controlled trials (RCTs and case-control trials comparing WBRT combined with gefitinib/erlotinib versus WBRT alone for BM from NSCLC were included. Literature selection, data extraction, and quality assessment were performed independently by two trained reviewers. RevMan 5.3 software was used to analyze data. Results. A total of 7 trials involving 622 patients were included. Compared with WBRT alone or WBRT plus chemotherapy, WBRT plus gefitinib/erlotinib could significantly improve response rate (OR = 2.16, 95% CI: 1.35–3.47; P=0.001, remission rate of central nervous system (OR = 6.06, 95% CI: 2.57–14.29; P<0.0001, disease control rate (OR = 3.34, 95% CI: 1.84–6.07; P<0.0001, overall survival (HR = 0.72, 95% CI: 0.58–0.89; P=0.002, and 1-year survival rate (OR = 2.43, 95% CI: 1.51–3.91; P=0.0002. In adverse events (III-IV, statistically significant differences were not found, except for rash (OR = 7.96, 95% CI: 2.02–31.34; P=0.003 and myelosuppression (OR = 0.19, 95% CI: 0.07–0.51; P=0.0010. Conclusions. WBRT plus gefitinib/erlotinib was superior to WBRT alone and well tolerated in patients with BM from NSCLC.

  15. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages.

  16. EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer

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    Pascale Tomasini

    2016-12-01

    Full Text Available Background: Lung cancer is the leading cause of brain metastases (BM. The identification of driver oncogenes and matched targeted therapies has improved outcome in non-small cell lung cancer (NSCLC patients; however, a better understanding of BM molecular biology is needed to further drive the process in this field. Methods: In this observational study, stage IV NSCLC patients tested for EGFR and KRAS mutations were selected, and BM incidence, recurrence and patients’ outcome were assessed. Results: A total of 144 patients (142 Caucasian and two Asian were selected, including 11.27% with EGFR-mutant and 33.10% with KRAS-mutant tumors, and 57.04% patients had developed BM. BM incidence was more frequent in patients with EGFR mutation according to multivariate analyses (MVA (Odds ratio OR = 8.745 [1.743–43.881], p = 0.008. Among patients with treated BM, recurrence after local treatment was less frequent in patients with KRAS mutation (OR = 0.234 [0.078–0.699], p = 0.009. Among patients with untreated BM, overall survival (OS was shorter for patients with KRAS mutation according to univariate analysis (OR = 7.130 [1.240–41.012], p = 0.028, but not MVA. Conclusions: EGFR and KRAS mutations have a predictive role on BM incidence, recurrence and outcome in Caucasian NSCLC patients. These results may impact the routine management of disease in these patients. Further studies are required to assess the influence of other biomarkers on NSCLC BM.

  17. EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer

    Science.gov (United States)

    Tomasini, Pascale; Serdjebi, Cindy; Khobta, Nataliya; Metellus, Philippe; Ouafik, L’Houcine; Nanni, Isabelle; Greillier, Laurent; Loundou, Anderson; Fina, Frederic; Mascaux, Celine; Barlesi, Fabrice

    2016-01-01

    Background: Lung cancer is the leading cause of brain metastases (BM). The identification of driver oncogenes and matched targeted therapies has improved outcome in non-small cell lung cancer (NSCLC) patients; however, a better understanding of BM molecular biology is needed to further drive the process in this field. Methods: In this observational study, stage IV NSCLC patients tested for EGFR and KRAS mutations were selected, and BM incidence, recurrence and patients’ outcome were assessed. Results: A total of 144 patients (142 Caucasian and two Asian) were selected, including 11.27% with EGFR-mutant and 33.10% with KRAS-mutant tumors, and 57.04% patients had developed BM. BM incidence was more frequent in patients with EGFR mutation according to multivariate analyses (MVA) (Odds ratio OR = 8.745 [1.743–43.881], p = 0.008). Among patients with treated BM, recurrence after local treatment was less frequent in patients with KRAS mutation (OR = 0.234 [0.078–0.699], p = 0.009). Among patients with untreated BM, overall survival (OS) was shorter for patients with KRAS mutation according to univariate analysis (OR = 7.130 [1.240–41.012], p = 0.028), but not MVA. Conclusions: EGFR and KRAS mutations have a predictive role on BM incidence, recurrence and outcome in Caucasian NSCLC patients. These results may impact the routine management of disease in these patients. Further studies are required to assess the influence of other biomarkers on NSCLC BM. PMID:27999344

  18. Outcome of surgical resection for brain metastases and radical treatment of the primary tumor in Chinese non–small-cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Li Z

    2015-04-01

    Full Text Available Zhenye Li,1,3,* Xiangheng Zhang,1,* Xiaobing Jiang,1 Chengcheng Guo,1 Ke Sai,1 Qunying Yang,1 Zhenqiang He,1 Yang Wang,1 Zhongping Chen,1 Wei Li,2 Yonggao Mou1 1Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China *These authors have contributed equally to this work Purpose: Brain metastasis is the most common complication of brain cancer; nevertheless, primary lung cancer accounts for approximately 20%–40% of brain metastases cases. Surgical resection is the preferred treatment for brain metastases. However, no studies have reported the outcome of surgical resection of brain metastases from non–small-cell lung cancer (NSCLC in the People’s Republic of China. Moreover, the optimal treatment for primary NSCLC in patients with synchronous brain metastases is hitherto controversial. Patients and methods: We retrospectively analyzed the cases of NSCLC patients with brain metastases who underwent neurosurgical resection at the Sun Yat-sen University Cancer Center, and assessed the efficacy of surgical resection and the necessity of aggressive treatment for primary NSCLC in synchronous brain metastases patients. Results: A total of 62 patients, including 47 men and 15 women, with brain metastases from NSCLC were enrolled in the study. The median age at the time of craniotomy was 54 years (range 29–76 years. At the final follow-up evaluation, 50 patients had died. The median OS time was 15.1 months, and the survival rates were 70% and 37% at 1 and 2 years, respectively. The median OS

  19. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua, E-mail: wlhwq@yahoo.com

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  20. Afatinib-refractory brain metastases from EGFR-mutant non-small-cell lung cancer successfully controlled with erlotinib: a case report.

    Science.gov (United States)

    Nonagase, Yoshikane; Okamoto, Kunio; Iwasa, Tsutomu; Yoshida, Takeshi; Tanaka, Kaoru; Takeda, Masayuki; Kaneda, Hiroyasu; Shimizu, Toshio; Tsurutani, Junji; Nakagawa, Kazuhiko

    2016-03-01

    Both afatinib and erlotinib are tyrosine kinase inhibitors that inhibit aberrant epidermal growth factor receptor (EGFR) signals in non-small-cell lung cancer (NSCLC). Afatinib is an irreversible inhibitor directed against EGFR, ErbB-2, and ErbB-4, whereas erlotinib is a reversible inhibitor directed against EGFR only. Although afatinib has been shown to be effective in the treatment for erlotinib-refractory and/or gefitinib-refractory central nervous system metastases from NSCLC, little is known about the efficacy of erlotinib for afatinib-refractory central nervous system metastases. In the present report we describe a case of EGFR mutation-positive NSCLC in which brain metastases developed during first-line afatinib treatment. Whole-brain radiation therapy and substitution of erlotinib for afatinib led to successful shrinkage of the brain metastases. Our report highlights the potential benefit of erlotinib for the management of brain metastases refractory over afatinib in patients with NSCLC.

  1. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

    Directory of Open Access Journals (Sweden)

    Junhwan Kim

    2016-01-01

    Full Text Available Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  2. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

    Science.gov (United States)

    Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

    2016-01-01

    Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  3. Absence of O sup 6 -alkylguanine-DNA alkyltransferase induction in chick embryo liver and brain following X-irradiation or treatment with bleomycin

    Energy Technology Data Exchange (ETDEWEB)

    Stammberger, I.; Tempel, K. (Munich Univ. (Germany). Faculty of Veterinary Medicine)

    1991-01-01

    The presence of O{sup 6}-alkylguanine-DNA alkyltransferase (AT) in liver and brain of chick embryos, chicks and hens was demonstrated. An induction of AT activity has only been found in the liver of chicks and hens 48 h after X-irradiation. The administration of methylmethanesulphonate to the chick embryo resulted 3-24 hr later in strong inhibition of AT activity accompanied by DNA alkylation. Under the same conditions, X-irradiation, dimethylnitrosamine and bleomycin exhibited no effect. The results are compared with those obtained in mouse, rat and human foetal tissues. (author).

  4. Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2017-01-01

    Full Text Available CeO2 nanoparticles (CeO2 NPs which are used as a diesel fuel additive are emitted in the particulate phase in the exhaust, posing a health concern. However, limited information exists regarding the in vivo acute toxicity of CeO2 NPs on multiple organs. Presently, we investigated the acute (24 h effects of intratracheally instilled CeO2 NPs in mice (0.5 mg/kg on oxidative stress, inflammation, and DNA damage in major organs including lung, heart, liver, kidneys, spleen, and brain. Lipid peroxidation measured by malondialdehyde production was increased in the lungs only, and reactive oxygen species were increased in the lung, heart, kidney, and brain. Superoxide dismutase activity was decreased in the lung, liver, and kidney, whereas glutathione increased in lung but it decreased in the kidney. Total nitric oxide was increased in the lung and spleen but it decreased in the heart. Tumour necrosis factor-α increased in all organs studied. Interleukin- (IL- 6 increased in the lung, heart, liver, kidney, and spleen. IL-1β augmented in the lung, heart, kidney, and spleen. Moreover, CeO2 NPs induced DNA damage, assessed by COMET assay, in all organs studied. Collectively, these findings indicate that pulmonary exposure to CeO2 NPs causes oxidative stress, inflammation, and DNA damage in multiple organs.

  5. Overexpression of adenylate cyclase-associated protein 1 may predict brain metastasis in non-small cell lung cancer.

    Science.gov (United States)

    Xie, Shuan-Shuan; Tan, Min; Lin, Hai-Yan; Xu, Lei; Shen, Chang-Xing; Yuan, Qing; Song, Xiao-Lian; Wang, Chang-Hui

    2015-01-01

    This study was designed to establish a biomarker risk model for predicting brain metastasis (BM) in non-small cell lung cancer (NSCLC). The model comprises 120 cases of NSCLC that were treated and followed up for 4 years. The patients were divided into the BM (n=50) and non-BM (other visceral metastasis and those without recurrence) (n=70) groups. Immunohistochemical and western blot analyses were performed in metastatic tissues of NSCLC. Multivariate regression analysis was performed to correlate the immunoreactive cyclase-associated protein 1 (CAP1) signal with BM. Survival analyses were performed by using the Kaplan-Meier method. CAP1 protein content and immunoreactivity were significantly increased in BM specimens compared to other-metastatic specimens. The survival analysis revealed that CAP1 overexpression was significantly associated with survival (P<0.05). The ROC test suggested that the area under the curve was 73.33% (P<0.001; 95% CI, 63.5-83.2%). When P=0.466, the sensitivity and specificity reached 79.5 and 67.1%, respectively. These findings suggested that CAP1 is involved in the BM of NSCLC, and that elevated levels of CAP1 expression may indicate a poor prognosis for patients with BM. The CAP1 molecular model may be useful in the prediction of the risk of BM in NSCLC.

  6. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

    Science.gov (United States)

    Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P brain (P brain, liver, and kidney (all P brain (all P brain (P drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences.

  7. Solitary brain metastasis of an occult and stable small-cell lung cancer in a schizophrenic patient: a 3-year control.

    Science.gov (United States)

    Jesien-Lewandowicz, Emilia; Spych, Michal; Fijuth, Jacek; Kordek, Radzislaw

    2010-08-01

    Small-cell lung cancer is a highly aggressive carcinoma, with poorer prognosis in patients with brain metastases. We present the case of a 49-year-old woman diagnosed with a cerebellar tumour which, following surgery, was revealed to be a metastatic small-cell lung carcinoma. Subsequent CT and PET scanning showed a small, isolated 8 mm nodule in the upper lobe of the right lung. The patient was suffering from schizophrenia and has been treated with clozapine for 17 years. Because of the unusual presentation, there was no therapy given for the primary tumour at the time, and systemic therapy or surgery was discussed. However, 18 months later, the nodule was slightly larger (14 mm), and surgery was performed. On pathology examination, the tumour was presented as a typical small-cell carcinoma. Standard chest irradiation with systemic chemotherapy was given. At the time of writing, 39 months after diagnosis of metastatic small-cell carcinoma, the patient is disease free. However, this case is unusual in that a long-term observation of a small stable primary tumour in the lung took place without any therapy being given. This case strongly supports the thesis that small-cell lung cancer may comprise a heterogeneous group of tumours with different biological properties. The proapoptotic effect of clozapine may be also taken into account.

  8. The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer.

    Science.gov (United States)

    Lee, Dong-Soo; Kim, Yeon-Sil; Jung, So-Lyoung; Lee, Kyo-Young; Kang, Jin-Hyoung; Park, Sarah; Kim, Young-Kyoon; Yoo, Ie-Ryung; Choi, Byung-Ock; Jang, Hong-Seok; Yoon, Sei-Chul

    2012-08-01

    Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1-3) and high total metastatic score group (score 4-7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.

  9. Incorporation in polymeric nanocapsules improves the antioxidant effect of melatonin against lipid peroxidation in mice brain and liver.

    Science.gov (United States)

    Schaffazick, Scheila R; Siqueira, Ionara R; Badejo, Alessandra S; Jornada, Denise S; Pohlmann, Adriana R; Netto, Carlos Alexandre; Guterres, Sílvia S

    2008-05-01

    It has been recently shown that the association of melatonin with polymeric nanoparticles causes a significant increase of the in vitro effect against lipid peroxidation. Hence, the aim of the present study was to compare the in vivo acute antioxidant effect of intraperitoneal administration of melatonin-loaded polysorbate 80-coated nanocapsules with that of melatonin aqueous solution in mice brain (frontal cortex and hippocampus) and liver. The lipid peroxidation through thiobarbituric acid reactive substance levels, the total antioxidant reactivity (luminol-enhanced chemiluminescence) and the free radical levels (formed dichlorofluorescein) has been carried out. Our results show that a single melatonin aqueous solution injection exerted no antioxidant activity in the evaluated range, while the administration of the melatonin-loaded polysorbate 80-coated nanocapsules caused a marked reduction on lipid peroxidation levels in all studied tissues. No differences on free radical content were found in the tissues. The melatonin-loaded nanocapsules also increased the total antioxidant reactivity in the hippocampus. These in vivo results are in accordance with our previous in vitro findings and confirm the hypothesis that polymeric nanocapsules improve the antioxidant effect of melatonin against lipid peroxidation.

  10. In vivo formation of natural HgSe nanoparticles in the liver and brain of pilot whales

    Science.gov (United States)

    Gajdosechova, Zuzana; Lawan, Mohammed M.; Urgast, Dagmar S.; Raab, Andrea; Scheckel, Kirk G.; Lombi, Enzo; Kopittke, Peter M.; Loeschner, Katrin; Larsen, Erik H.; Woods, Glenn; Brownlow, Andrew; Read, Fiona L.; Feldmann, Jörg; Krupp, Eva M.

    2016-09-01

    To understand the biochemistry of methylmercury (MeHg) that leads to the formation of mercury-selenium (Hg-Se) clusters is a long outstanding challenge that promises to deepen our knowledge of MeHg detoxification and the role Se plays in this process. Here, we show that mercury selenide (HgSe) nanoparticles in the liver and brain of long-finned pilot whales are attached to Se-rich structures and possibly act as a nucleation point for the formation of large Se-Hg clusters, which can grow with age to over 5 μm in size. The detoxification mechanism is fully developed from the early age of the animals, with particulate Hg found already in juvenile tissues. As a consequence of MeHg detoxification, Se-methionine, the selenium pool in the system is depleted in the efforts to maintain essential levels of Se-cysteine. This study provides evidence of so far unreported depletion of the bioavailable Se pool, a plausible driving mechanism of demonstrated neurotoxic effects of MeHg in the organism affected by its high dietary intake.

  11. In vivo formation of natural HgSe nanoparticles in the liver and brain of pilot whales

    Science.gov (United States)

    Gajdosechova, Zuzana; Lawan, Mohammed M.; Urgast, Dagmar S.; Raab, Andrea; Scheckel, Kirk G.; Lombi, Enzo; Kopittke, Peter M.; Loeschner, Katrin; Larsen, Erik H.; Woods, Glenn; Brownlow, Andrew; Read, Fiona L.; Feldmann, Jörg; Krupp, Eva M.

    2016-01-01

    To understand the biochemistry of methylmercury (MeHg) that leads to the formation of mercury-selenium (Hg-Se) clusters is a long outstanding challenge that promises to deepen our knowledge of MeHg detoxification and the role Se plays in this process. Here, we show that mercury selenide (HgSe) nanoparticles in the liver and brain of long-finned pilot whales are attached to Se-rich structures and possibly act as a nucleation point for the formation of large Se-Hg clusters, which can grow with age to over 5 μm in size. The detoxification mechanism is fully developed from the early age of the animals, with particulate Hg found already in juvenile tissues. As a consequence of MeHg detoxification, Se-methionine, the selenium pool in the system is depleted in the efforts to maintain essential levels of Se-cysteine. This study provides evidence of so far unreported depletion of the bioavailable Se pool, a plausible driving mechanism of demonstrated neurotoxic effects of MeHg in the organism affected by its high dietary intake. PMID:27678068

  12. Functional Coupling of Human Microphysiology Systems: Intestine, Liver, Kidney Proximal Tubule, Blood-Brain Barrier and Skeletal Muscle

    Science.gov (United States)

    Vernetti, Lawrence; Gough, Albert; Baetz, Nicholas; Blutt, Sarah; Broughman, James R.; Brown, Jacquelyn A.; Foulke-Abel, Jennifer; Hasan, Nesrin; In, Julie; Kelly, Edward; Kovbasnjuk, Olga; Repper, Jonathan; Senutovitch, Nina; Stabb, Janet; Yeung, Catherine; Zachos, Nick C.; Donowitz, Mark; Estes, Mary; Himmelfarb, Jonathan; Truskey, George; Wikswo, John P.; Taylor, D. Lansing

    2017-01-01

    Organ interactions resulting from drug, metabolite or xenobiotic transport between organs are key components of human metabolism that impact therapeutic action and toxic side effects. Preclinical animal testing often fails to predict adverse outcomes arising from sequential, multi-organ metabolism of drugs and xenobiotics. Human microphysiological systems (MPS) can model these interactions and are predicted to dramatically improve the efficiency of the drug development process. In this study, five human MPS models were evaluated for functional coupling, defined as the determination of organ interactions via an in vivo-like sequential, organ-to-organ transfer of media. MPS models representing the major absorption, metabolism and clearance organs (the jejunum, liver and kidney) were evaluated, along with skeletal muscle and neurovascular models. Three compounds were evaluated for organ-specific processing: terfenadine for pharmacokinetics (PK) and toxicity; trimethylamine (TMA) as a potentially toxic microbiome metabolite; and vitamin D3. We show that the organ-specific processing of these compounds was consistent with clinical data, and discovered that trimethylamine-N-oxide (TMAO) crosses the blood-brain barrier. These studies demonstrate the potential of human MPS for multi-organ toxicity and absorption, distribution, metabolism and excretion (ADME), provide guidance for physically coupling MPS, and offer an approach to coupling MPS with distinct media and perfusion requirements. PMID:28176881

  13. Effects of an n-3-deficient diet on brain, retina, and liver fatty acyl composition in artificially reared rats.

    Science.gov (United States)

    Moriguchi, Toru; Lim, Sun-Young; Greiner, Rebecca; Lefkowitz, William; Loewke, James; Hoshiba, Junji; Salem, Norman

    2004-08-01

    Rat pups born to dams fed a diet with 3.1% of total fatty acids as alpha-linolenic acid (LNA) were fed, using an artificial rearing system, either an n-3-deficient (n-3-Def) or an n-3-adequate (n-3-Adq) diet. Both diets contained 17.1% linoleic acid, but the n-3-Adq diet also contained 3.1% LNA. The percentage of brain docosahexaenoic acid (DHA) continuously decreased (71%) with time over the 29 days of the experiment, with concomitant increases in docosapentaenoic acid (DPAn-6). In the retina, the percentage of DHA rose in the n-3-Adq group, with an apparent increased rate around the time of eye opening. However, there was a flat curve for the percentage of DHA in the n-3-Def group and a rising DPAn-6 with time. Liver DHA was highest at the time of birth in the n-3-Adq group but fell off somewhat over the course of 29 days. This decrease was more pronounced in the n-3-Def group, and the DPAn-6 rose considerably during the second half of the experiment. This method presents a first-generation model for n-3 deficiency that is more similar to the case of human nutrition than is the commonly employed two-generation model.

  14. Paracetamol (acetaminophen) decreases hydrogen sulfide tissue concentration in brain but increases it in the heart, liver and kidney in mice.

    Science.gov (United States)

    Wiliński, Bogdan; Wiliński, Jerzy; Somogyi, Eugeniusz; Góralska, Marta; Piotrowska, Joanna

    2011-01-01

    The biological action ofN-acetyl-p-aminophenol - paracetamol (acetaminophen) has been demonstrated to involve different mechanisms and is still not clear. Hydrogen sulfide (H2S) has been shown to play an important role in many physiological and pathological processes including nociception. The interaction between acetaminophen and endogenous H2S is unknown. Twenty four female CBA strain mice were administered intraperitoneal injections of N-acetyl-p-aminophenol solution: paracetemol in doses of 30 mg/kg b.w. per day (group D1, n = 8) or 100 mg/kg b.w. per day (group D2, n = 8).. The control group (n = 8) received physiological saline in portions of the same volume--0.2 ml. The measurements of tissue H2S concentration were performed with the Siegel spectrophotometric modified method. In the brain, the H2S tissue level decreased, but more significantly in the lower drug dose group. Conversely, there was a significant rise in the H2S tissue concentration in D1 and D2 groups in heart and kidney with the increase more pronounced in the group with the lower paracetamol dose. In the liver only the higher acetaminophen dose elicited a change in H2S concentration, increasing after administration of acetaminophen at 100 mg/kg. Our study demonstrates that paracetamol induces H2S tissue concentration changes in different mouse organs.

  15. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    Energy Technology Data Exchange (ETDEWEB)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian [Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, and Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Wang Ping, E-mail: Doctorwang66@yahoo.cn [Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, and Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin (China)

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  16. Accumulation of mercury, selenium and PCBs in domestic duck brain, liver and egg from a contaminated area with an investigation of their redox responses.

    Science.gov (United States)

    Cheng, Jinping; Zhao, Wenchang; Wang, Qian; Liu, Xiaojie; Wang, Wenhua

    2013-05-01

    PCBs and methylmercury (MeHg) are two of the most ubiquitous contaminants in the Qingzhen (QZ) area of Guizhou province. The estimated tolerable daily intakes (TDIs) of total mercury (T-Hg), MeHg, PCBs and Se from contaminated rice, eggs and fish by Chinese people in QZ showed that both MeHg and PCBs exceeded the corresponding safety limits. Pearson's correlation analyses of mercury and Se in all duck tissues showed that there were high correlations with T-Hg or MeHg and Se in QZ samples. However, the molar ratio between T-Hg and Se in brain tissues was close to 1, suggesting that Se is antagonistic to mercury toxicity only in brain tissues. Biochemical analyses showed that both superoxide dismutase and glutathione peroxidase increased in the brain, whereas in the liver and egg these enzymes decreased. However, lipid peroxidation and H2O2 generation in liver and egg tissues showed contrary responses, where significant increases in these tissues were seen relative to controls. Mercury and PCBs co-accumulation in liver and egg tissues gave rise to large numbers of free radicals as well as aggravated alkyl free radicals, superoxide radical and nitric oxide, thereby resulting in oxidative stress in these tissues. It can be concluded that an adaptive response of the redox defense system is present in brain tissues, as opposed to a general break down of the redox defense system in liver and egg. The results obtained in this study will provide basic information on exposure and risk assessment in local residents.

  17. Induction of CYP1A1, CYP1A2, CYP1B1, increased oxidative stress and inflammation in the lung and liver tissues of rats exposed to incense smoke.

    Science.gov (United States)

    Hussain, Tajamul; Al-Attas, Omar S; Al-Daghri, Nasser M; Mohammed, Arif A; De Rosas, Edgard; Ibrahim, Shebl; Vinodson, Benjamin; Ansari, Mohammed G; El-Din, Khaled I Alam

    2014-06-01

    Incense smoke is increasingly being recognized as a potential environmental contaminant and is linked to malignant and non-malignant respiratory diseases. The detoxification of environmental contaminants including polycyclic aromatic hydrocarbons (PAHs) involves the induction of cytochrome P-450 family enzymes (CYPs) by PAHs. However, the detoxification of PAHs also results in the generation of reactive and unstable intermediary metabolites which are implicated in the oxidative stress, DNA damage, and inflammation. It is unclear whether CYPs are similarly induced by incense smoke, which incidentally contains substantial amounts of PAHs. Here, we examined the impact of long-term incense smoke exposure on the induction of CYPs in male Wister Albino rats. Incense smoke exposure significantly induced the expression of CYP1A1, CYP1A2, and CYP1B1 mRNAs in both lung and liver tissues. The extent of CYP1A1 and CYP1B1 induction was significantly higher in the liver compared to that in the lung, while that of CYP1A2 was greater in the lung than in liver. Incense smoke exposure also increased malondialdehyde and reduced glutathione levels in lung and liver tissues, and the catalase activity in the liver tissues to significant levels. Furthermore incense smoke exposure led to a marked increase in TNF-α and IL-4 levels. The data demonstrate for the first time the capacity of incense smoke to induce CYP1 family enzymes in the target and non-target tissues. Induction of CYPs increased oxidative stress and inflammation appear to be intimately linked to promote the carcinogenesis and health complications in people chronically exposed to incense smoke.

  18. Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain, kidney and liver oxidative stress and some biochemical parameters in male rats.

    Science.gov (United States)

    Ragy, Merhan Mamdouh

    2015-01-01

    Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1 h/d for 60 d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1 h/d for 60 d then left for 30 d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levels in brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p electromagnetic field emitting from mobile phone might produce impairments in some biochemicals changes and oxidative stress in brain, liver and renal tissue of albino rats. These alterations were corrected by withdrawal.

  19. Activity of pemetrexed and high-dose gefitinib in an EGFR-mutated lung adenocarcinoma with brain and leptomeningeal metastasis after response to gefitinib

    Directory of Open Access Journals (Sweden)

    Yuan Ying

    2012-11-01

    Full Text Available Abstract About 20% to 40% of patients with non-small cell lung cancer (NSCLC will develop brain metastases during the natural course of their disease. The prognosis for such patients is very poor with limited survival. In addition to the standard whole brain radiation therapy (WBRT, some studies have shown that chemotherapy drugs and/or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI can improve the outcome of these patients. Here, we report a stage IIIA patient who developed multiple brain metastases one year after operation. Oral gefitinib with concurrent WBRT were given as first-line therapy. Complete response and a 50-month progression-free survival (PFS were obtained. Double dosage of gefitinib (500 mg per day together with pemetrexed were given as the second-line therapy after the patient developed new brain lesions and leptomeningeal metastasis during the maintenance therapy of gefitinib. The PFS for the second-line therapy was six months. In total, the patient obtained an overall survival of 59 months since the first diagnosis of brain metastases. Mutational analysis showed a 15-nucleotide deletion and a missense mutation in exon 19 of the EGFR gene, and a missense mutation at codon 12 of the K-ras gene. These underlying genetic changes might partially explain the long-term survival of this patient after brain metastases when treated with concurrent or sequential therapies of EGFR-TKI, radiotherapy and chemotherapy.

  20. Hypofractionated stereotactic radiotherapy for brain metastases from lung cancer. Evaluation of indications and predictors of local control

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, Takeaki [Kobe University Graduate School of Medicine, Division of Radiation Oncology, Hyogo (Japan); Seirei Mikatahara General Hospital, Department of Radiation Oncology, Shizuoka (Japan); Yamada, Kazunari; Isogai, Kenta; Tonosaki, Yoshihiro [Seirei Mikatahara General Hospital, Department of Radiation Oncology, Shizuoka (Japan); Harada, Aya [Kobe Minimum Invasive Cancer Medical Center, Department of Radiation Oncology, Hyogo (Japan); Demizu, Yusuke [Hyogo Ion Beam Medical Center, Department of Radiology, Hyogo (Japan); Miyawaki, Daisuke; Yoshida, Kenji; Ejima, Yasuo; Sasaki, Ryohei [Kobe University Graduate School of Medicine, Division of Radiation Oncology, Hyogo (Japan)

    2016-06-15

    To evaluate the efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) for brain metastases (BMs) from lung cancer, and to explore prognostic factors associated with local control (LC) and indication. We evaluated patients who were treated with linac-based HSRT for BMs from lung cancer. Lesions treated with stereotactic radiosurgery (SRS) in the same patients during the same periods were analysed and compared with HSRT in terms of LC or toxicity. There were 53 patients with 214 lesions selected for this analysis (HSRT: 76 lesions, SRS: 138 lesions). For HSRT, the median prescribed dose was 35 Gy in 5 fractions. The 1-year LC rate was 83.6 % in HSRT; on multivariate analysis, a planning target volume (PTV) of <4 cm{sup 3}, biologically effective dose (BED{sub 10}) of ≥51 Gy, and adenocarcinoma were significantly associated with better LC. Moreover, in PTVs ≥ 4 cm{sup 3}, there was a significant difference in LC between BED{sub 10} < 51 Gy and ≥ 51 Gy (p = 0.024). On the other hand, in PTVs < 4 cm{sup 3}, both HSRT and SRS had good LC with no significant difference (p = 0.195). Radiation necrosis emerged in 5 of 76 lesions (6.6 %) treated with HSRT and 21 of 138 (15.2 %) lesions treated with SRS (p = 0.064). Linac-based HSRT was safe and effective for BMs from lung cancer, and hence might be particularly useful in or near an eloquent area. PTV, BED{sub 10}, and pathological type were significant prognostic factors. Furthermore, in BMs ≥ 4 cm{sup 3}, a dose of BED ≥ 51 Gy should be considered. (orig.) [German] Beurteilung von Wirksamkeit und Toxizitaet einer hypofraktionierten stereotaktischen Strahlentherapie (HSRT) zur Behandlung von Hirnmetastasen (HM) eines Lungenkarzinoms und Erforschung von mit der lokalen Kontrolle (LK) und der Indikation assoziierten Prognosefaktoren. Analysiert wurden Daten von Patienten (n = 53), die sich einer Linearbeschleuniger-basierten HSRT unterzogen (mit HSRT behandelte Laesionen n = 76; Median der

  1. Minimal hepatic encephalopathy in children with liver cirrhosis: diffusion-weighted MR imaging and proton MR spectroscopy of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Abdel Razek, Ahmed Abdel Khalek; Ezzat, Amany [Mansoura University Hospital, Department of Diagnostic Radiology, Mansoura Faculty of Medicine, Mansoura (Egypt); Abdalla, Ahmed; Megahed, Ahmed; Barakat, Tarek [Mansoura Children Hospital, Gastroenterology and Hepatology Unit, Mansoura Faculty of Medicine, Mansoura (Egypt)

    2014-10-15

    The aim of this work was to detect minimal hepatic encephalopathy (minHE) in children with diffusion-weighted MR imaging (DWI) and proton magnetic resonance spectroscopy ({sup 1}H-MRS) of the brain. Prospective study conducted upon 30 consecutive children (age range 6-16 years, 21 boys and 9 girls) with liver cirrhosis and 15 age- and sex-matched healthy control children. Patients with minHE (n = 17) and with no minHE (n = 13) groups and control group underwent DWI, {sup 1}H-MRS, and neuropsychological tests (NPTs). The glutamate or glutamine (Glx), myoinositol (mI), choline (Cho), and creatine (Cr) at the right ganglionic region were determined at {sup 1}H-MRS. The apparent diffusion coefficient (ADC) value and metabolic ratios of Glx/Cr, mI/Cr, and Cho/Cr were calculated. There was elevated ADC value and Glx/Cr and decreased mI/CI and Ch/Cr in patients with minHE compared to no minHE and control group. There was significant difference between minHE, no minHE, and control group in the ADC value (P = 0.001 for all groups), GLx/Cr (P = 0.001 for all groups), mI/Cr (P = 0.004, 0.001, and 0.001, respectively), Ch/Cr (P = 0.001 for all groups), and full-scale IQ of NPT (P = 0.001, 0.001, and 0.143, respectively). The NPT of minHE had negative correlation with ADC value (r = -0.872, P = 0.001) and GLx/Cr (r = -0.812, P = 0.001) and positive correlation with mI/Cr (r = 0.732, P = 0.001). DWI and {sup 1}H-MRS are imaging modalities that can detect minHE in children with liver cirrhosis and correlate well with parameters of NPT. (orig.)

  2. Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow,heart,liver,muscle,lung,derma,kidney,and fat

    Institute of Scientific and Technical Information of China (English)

    FANG Baijun; SONG Yongping; ZHAO Chunhua; SHI Mingxia; LIN Quande

    2007-01-01

    Previously,we reported that a cell population derived from human fetal bone marrow fBM),termed here Flk1+CD34-postembryonic pluripotent stem cells(PPSCs)that have the characteristics of mesenchymal stem cells (MSCs),could difierentiate into ectodermal,endodermal and mesodermal celI types at the single cell level in vitro,and that these cells could also difierentiate into the epithelium of liver,lung,gut,as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient(NOD/SCID) mice.In this study,we further isolated pluripotent stem cells from human fetal heart,liver,muscle,lung,derma,kidney,and fat and then analyzed the characteristics and function of these stem cells.It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1+CD34-PPSCs.i.e.Flk1 and CD44 positive,GlyA,CD34,CD45,class I-HLA and HLA-DR negative.Morphologically,these cells were fibroblast-like and the doubling time was about 30 h.More importantly,culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes,osteocytes,neurons,gilal cells and hepatocytes.These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1+CD34-PPSCs can be selected and cultured from tissues other than the BM.This phenomenon may help explain the"stem cell plasticity"found in multiple human tissues.In addition,as fetal BM-derived Flk1+CD34-PPSCs,these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage difierentiation even after being expanded for more than 40 population doublings in vitro.Thus,they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.

  3. The role of microRNA-21 in predicting brain metastases from non-small cell lung cancer

    Science.gov (United States)

    Dong, Jing; Zhang, Zhi; Gu, Tao; Xu, Shu-Feng; Dong, Li-Xin; Li, Xin; Fu, Bao-Hong; Fu, Zhan-Zhao

    2017-01-01

    Objective This study aimed at exploring the role of microRNA-21 (miR-21) in predicting brain metastases (BM) from non-small cell lung cancer (NSCLC). Methods A total of 132 NSCLC patients, including 68 patients with BM and 64 patients without BM, were included in the study. NSCLC cells were collected and assigned to the inhibitor (IN) group, the mock group, and the negative control (NC) group. The quantitative real-time polymerase chain reaction assay was used to detect the miR-21 expression. Cell proliferation, migration, invasion, and apoptosis were detected by colony-forming assay, MTT assay, transwell assay, and flow cytometry, respectively. Angiogenesis was measured by endothelial cell tube formation assay. Results The miR-21 expression was higher in NSCLC patients with BM than in those without BM. The miR-21 expression in the IN group was lower than that in the NC and mock groups. Compared with the NC and mock groups, the values of optical density (OD) and the colony-forming number decreased in the IN group. Compared with the NC and mock groups, cell invasion and migration abilities significantly reduced in the IN group. The IN group had higher apoptosis rate than the NC and mock groups. The tube length was shorter and the number of junction points was less in the IN group in comparison to the NC and mock groups. Conclusion miR-21 might be a potential biomarker for the development of BM in NSCLC patients and could promote the proliferation, migration, invasion, and angiogenesis of NSCLC cells.

  4. Borate-aided anion exchange high-performance liquid chromatography of uridine diphosphate-sugars in brain, heart, adipose and liver tissues.

    Science.gov (United States)

    Oikari, Sanna; Venäläinen, Tuula; Tammi, Markku

    2014-01-03

    In this paper we describe a method optimized for the purification of uridine diphosphate (UDP)-sugars from liver, adipose tissue, brain, and heart, with highly reproducible up to 85% recoveries. Rapid tissue homogenization in cold ethanol, lipid removal by butanol extraction, and purification with a graphitized carbon column resulted in isolation of picomolar quantities of the UDP-sugars from 10 to 30mg of tissue. The UDP-sugars were baseline separated from each other, and from all major nucleotides using a CarboPac PA1 anion exchange column eluted with a gradient of acetate and borate buffers. The extraction and purification protocol produced samples with few unidentified peaks. UDP-N-acetylglucosamine was a dominant UDP-sugar in all the rat tissues studied. However, brain and adipose tissue showed high UDP-glucose levels, equal to that of UDP-N-acetylglucosamine. The UDP-N-acetylglucosamine showed 2.3-2.7 times higher levels than UDP-N-acetylgalactosamine in all tissues, and about the same ratio was found between UDP-glucose and UDP-galactose in adipose tissue and brain (2.6 and 2.8, respectively). Interestingly, the UDP-glucose/UDP-galactose ratio was markedly lower in liver (1.1) and heart (1.7). The UDP-N-acetylglucosamine/UDP-glucuronic acid ratio was also constant, between 9.7 and 7.7, except in liver with the ratio as low as 1.8. The distinct UDP-glucose/galactose ratio, and the abundance of UDP-glucuronic acid may reflect the specific role of liver in glycogen synthesis, and metabolism of hormones and xenobiotics, respectively, using these UDP-sugars as substrates.

  5. Effects of oil pollution and persistent organic pollutants (POPs) on glycerophospholipids in liver and brain of male Atlantic cod (Gadus morhua).

    Science.gov (United States)

    Bratberg, Mari; Olsvik, Pål A; Edvardsen, Rolf B; Brekken, Hans Kristian; Vadla, Reidun; Meier, Sonnich

    2013-02-01

    Fish in the North Sea are exposed to relatively high levels of halogenated compounds in addition to the pollutants released by oil production activities. In this study male Atlantic cod (Gadus morhua) were orally exposed to environmental realistic levels (low and high) of weathered crude oil and/or a mixture of POPs for 4weeks. Lipid composition in brain and in liver extracts were analysed in order to assess the effects of the various pollutants on membrane lipid composition and fatty acid profiles. Transcriptional effects in the liver were studied by microarray and quantitative real-time RT-PCR. Chemical analyses confirmed uptake of polychlorinated biphenyls (PCBs) and chlorinated pesticides, polybrominated diphenyl ethers (PBDEs) and perfluorooctanesulfonate (PFOS) in the liver and excretion of metabolites of polyaromatic hydrocarbons (PAHs) in the bile. Treatment with POPs and/or crude oil did not induce significant changes in lipid composition in cod liver. Only a few minor changes were observed in the fatty acid profile of the brain and the lipid classes in the liver. The hypothesis that pollution from oil or POPs at environmental realistic levels alters the lipid composition in marine fish was therefore not confirmed in this study. However, the transcriptional data suggest that the fish were affected by the treatment at the mRNA level. This study suggests that a combination of oil and POPs induce the CYP1a detoxification system and gives an increase in the metabolism and clearing rate of PAHs and POPs, but with no effects on membrane lipids in male Atlantic cod.

  6. DANCE in developing and injured lung.

    Science.gov (United States)

    Jean, Jyh-Chang; Eruchalu, Ifeanyi; Cao, Yu Xia; Joyce-Brady, Martin

    2002-01-01

    We identified rat developing arteries and neural crest derivatives with multiple epidermal growth factor-like domains (DANCE) as a developmentally regulated gene using suppression-subtractive hybridization. Northern analysis confirmed a fivefold induction of this mRNA transcript between fetal day 18 and 20 that persisted through postnatal day 17. The level was declining at postnatal day 21 and was similar in adult lung to that at fetal day 18. In adults DANCE mRNA abundance was highest in lung, kidney, and spleen, lower in heart, skeletal muscle, and brain, but absent from liver and thymus. It was abundant in pulmonary artery endothelium and a lung epithelial type 2 cell line, barely detectable in vascular smooth muscle, and absent in fibroblasts. In situ hybridization revealed a regulated pattern of expression in endothelial cells of fetal, postnatal, and adult lung. Because DANCE mRNA was inducible in systemic arteries during recovery from injury, we searched for induction in lung injured by hyperoxia. Mouse DANCE mRNA abundance was unchanged during an acute 3-day exposure period, induced threefold 5 days into the recovery phase, and returned to baseline at days 8, 11, and 14. In situ hybridization at day 5 suggested a diffuse pattern of induction. DANCE may play a role in lung endothelial cell biology during development repair after injury.

  7. Rice Germosprout Extract Protects Erythrocytes from Hemolysis and the Aorta, Brain, Heart, and Liver Tissues from Oxidative Stress In Vitro

    Science.gov (United States)

    Hussain, Jakir; Islam, Saiful

    2016-01-01

    Identifying dietary alternatives for artificial antioxidants capable of boosting antihemolytic and antioxidative defense has been an important endeavor in improving human health. In the present study, we studied antihemolytic and antioxidative effects of germosprout (i.e., the germ part along with sprouted stems plus roots) extract prepared from the pregerminated rice. The extract contained considerable amounts of antioxidant β-carotene (414 ± 12 ng/g of extract) and phytochemicals such as total polyphenols (12.0 ± 1.1 mg gallic acid equivalent/g of extract) and flavonoids (11.0 ± 1.4 mg catechin equivalent/g of extract). The antioxidant potential of the extract was assessed by its DPPH- (2,2-diphenyl-1-picrylhydrazyl-) free radical scavenging activity where we observed that germosprout extract had considerable antioxidative potentials. To evaluate antihemolytic effect of the extract, freshly prepared erythrocytes were incubated with either peroxynitrite or Fenton's reagent in the absence or presence of the extract. We observed that erythrocytes pretreated with the extract exhibited reduced degree of in vitro hemolysis. To support the proposition that germosprout extract could act as a good antioxidative agent, we also induced in vitro oxidative stress in erythrocyte membranes and in the aorta, brain, heart, and liver tissue homogenates in the presence of the extract. As expected, germosprout extract decreased oxidative stress almost to the same extent as that of vitamin E, as measured by lipid peroxide levels, in all the mentioned tissues. We conclude that rice germosprout extract could be a good natural source of antioxidants to reduce oxidative stress-induced hemolysis and damage of blood vessels and other tissues. PMID:27413391

  8. Rice Germosprout Extract Protects Erythrocytes from Hemolysis and the Aorta, Brain, Heart, and Liver Tissues from Oxidative Stress In Vitro

    Directory of Open Access Journals (Sweden)

    Shahdat Hossain

    2016-01-01

    Full Text Available Identifying dietary alternatives for artificial antioxidants capable of boosting antihemolytic and antioxidative defense has been an important endeavor in improving human health. In the present study, we studied antihemolytic and antioxidative effects of germosprout (i.e., the germ part along with sprouted stems plus roots extract prepared from the pregerminated rice. The extract contained considerable amounts of antioxidant β-carotene (414±12 ng/g of extract and phytochemicals such as total polyphenols (12.0±1.1 mg gallic acid equivalent/g of extract and flavonoids (11.0±1.4 mg catechin equivalent/g of extract. The antioxidant potential of the extract was assessed by its DPPH- (2,2-diphenyl-1-picrylhydrazyl- free radical scavenging activity where we observed that germosprout extract had considerable antioxidative potentials. To evaluate antihemolytic effect of the extract, freshly prepared erythrocytes were incubated with either peroxynitrite or Fenton’s reagent in the absence or presence of the extract. We observed that erythrocytes pretreated with the extract exhibited reduced degree of in vitro hemolysis. To support the proposition that germosprout extract could act as a good antioxidative agent, we also induced in vitro oxidative stress in erythrocyte membranes and in the aorta, brain, heart, and liver tissue homogenates in the presence of the extract. As expected, germosprout extract decreased oxidative stress almost to the same extent as that of vitamin E, as measured by lipid peroxide levels, in all the mentioned tissues. We conclude that rice germosprout extract could be a good natural source of antioxidants to reduce oxidative stress-induced hemolysis and damage of blood vessels and other tissues.

  9. Mössbauer study of exogenous iron redistribution between the brain and the liver after administration of {sup 57}Fe{sub 3}O{sub 4} ferrofluid in the ventricle of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Polikarpov, Dmitry, E-mail: polikarpov.imp@gmail.com [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Russian National Research Medical University named after N.I.Pirogov, Moscow (Russian Federation); Gabbasov, Raul; Cherepanov, Valery [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Loginova, Natalia; Loseva, Elena [Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow (Russian Federation); Nikitin, Maxim [Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow (Russian Federation); Yurenia, Anton; Panchenko, Vladislav [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Lomonosov Moscow State University, Moscow (Russian Federation)

    2015-04-15

    Iron clearance pathways after the injection of {sup 57}Fe{sub 3}O{sub 4}-based ferrofluid into the brain ventricles were studied histologically and by Mössbauer spectroscopy. It was found that the dextran coated initial nanobeads of the ferrofluid disintegrated in the brain into separate superparamagnetic nanoparticles within a week after the injection. The exogenous iron completely exited all ventricular cavities of the brain within a week after the injection but remained in the white matter for months. Kupffer cells with the exogenous iron appeared in the rat liver 2 hours after the injection. Their concentration reached its maximum on the third day and dropped to zero within a week. The exogenous iron appeared in the spleen a week after the injection and remained in the spleen for months.

  10. Monoclonal Gammopathy of Undetermined Significance with Amyloid Deposition in the Lung and Non-Amyloid Eosinophilic Deposition in the Brain: A Case Report

    Directory of Open Access Journals (Sweden)

    Francois Abi-Fadel

    2010-01-01

    Full Text Available Background. Monoclonal gammopathy of undetermined significance (MGUS is rarely complicated by amyloidosis. Case. A 66-year-old white male presented to the emergency room (ER after an unwitnessed fall and change in mental status. Patient was awake and alert but not oriented. There was no focal deficit on neurological exam. Past medical history (PMH included hypertension, hypercholesterolemia, aortic valve replacement (nonmetallic, incomplete heart block controlled by a pacemaker and IgG- IgA type Monoclonal Gammopathy of Undetermined Significance. The MGUS was diagnosed 9 months ago on serum protein electrophoresis (SPEP as patient was referred to the outpatient clinic for hyperglobulinemia on routine blood work. In ER, a head-computed tomography (CT revealed multiple parenchymal hemorrhagic lesions suspicious for metastases. A CT chest, abdomen and pelvis revealed numerous ground-glass and solid nodules in the lungs. Lower extremity duplex and transesophageal echocardiogram were negative. Serial blood cultures and serologies for cryptococcus and histoplasmosis, antineutrophil cytoplasmic antibody (ANCA, antinuclear antibody (ANA, rheumatoid factor (RF, cryoglobulin, and antiglomerular basement membrane (anti-GBM antibodies were all negative. CT guided lung biopsy was positive for Thioflavin T amyloid deposits. Brain biopsy was positive for eosinophilic material (similar to the lungs but negative for Thioflavin T stain. The patient's clinical status continued to deteriorate with cold cyanotic fingers developing on day 12 and a health care acquired pneumonia, respiratory failure, and fungemia on day 18. On day 29, family withdrew life support and denied any autopsies. Conclusion. Described is an atypical course of MGUS complicated by amyloidosis of the lung and nonamyloid eosinophilic deposition in the brain. As MGUS might be complicated by diseases such as amyloidosis and multiple myeloma, a scheduled follow-up of these patients is always

  11. The Impact of Ischemia/Reperfusion Injury on Liver Allografts from Deceased after Cardiac Death versus Deceased after Brain Death Donors.

    Directory of Open Access Journals (Sweden)

    Jin Xu

    Full Text Available The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD. The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD, we aimed to understand how ischemia/reperfusion (I/R injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration.Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13 and DBD (n = 10 livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22 and DBD (n = 13 livers.When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05 and C22 ceramide (p<0.05 were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST of DCD allografts had significantly increased.These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation.

  12. MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation

    Directory of Open Access Journals (Sweden)

    McKiernan Patrick J

    2011-05-01

    Full Text Available Abstract Background Propionic acidaemia (PA results from deficiency of Propionyl CoA carboxylase, the commonest form presenting in the neonatal period. Despite best current management, PA is associated with severe neurological sequelae, in particular movement disorders resulting from basal ganglia infarction, although the pathogenesis remains poorly understood. The role of liver transplantation remains controversial but may confer some neuro-protection. The present study utilises quantitative magnetic resonance spectroscopy (MRS to investigate brain metabolite alterations in propionic acidaemia during metabolic stability and acute encephalopathic episodes. Methods Quantitative MRS was used to evaluate brain metabolites in eight children with neonatal onset propionic acidaemia, with six elective studies acquired during metabolic stability and five studies during acute encephalopathic episodes. MRS studies were acquired concurrently with clinically indicated MR imaging studies at 1.5 Tesla. LCModel software was used to provide metabolite quantification. Comparison was made with a dataset of MRS metabolite concentrations from a cohort of children with normal appearing MR imaging. Results MRI findings confirm the vulnerability of basal ganglia to infarction during acute encephalopathy. We identified statistically significant decreases in basal ganglia glutamate+glutamine and N-Acetylaspartate, and increase in lactate, during encephalopathic episodes. In white matter lactate was significantly elevated but other metabolites not significantly altered. Metabolite data from two children who had received liver transplantation were not significantly different from the comparator group. Conclusions The metabolite alterations seen in propionic acidaemia in the basal ganglia during acute encephalopathy reflect loss of viable neurons, and a switch to anaerobic respiration. The decrease in glutamine + glutamate supports the hypothesis that they are consumed to

  13. cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca(2+) homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency.

    Science.gov (United States)

    Amaral, Alexandre Umpierrez; Cecatto, Cristiane; da Silva, Janaína Camacho; Wajner, Alessandro; Godoy, Kálita Dos Santos; Ribeiro, Rafael Teixeira; Wajner, Moacir

    2016-09-01

    Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is biochemically characterized by tissue accumulation of octanoic (OA), decanoic (DA) and cis-4-decenoic (cDA) acids, as well as by their carnitine by-products. Untreated patients present episodic encephalopathic crises and biochemical liver alterations, whose pathophysiology is poorly known. We investigated the effects of OA, DA, cDA, octanoylcarnitine (OC) and decanoylcarnitine (DC) on critical mitochondrial functions in rat brain and liver. DA and cDA increased resting respiration and diminished ADP- and CCCP-stimulated respiration and complexes II-III and IV activities in both tissues. The data indicate that these compounds behave as uncouplers and metabolic inhibitors of oxidative phosphorylation. Noteworthy, metabolic inhibition was more evident in brain as compared to liver. DA and cDA also markedly decreased mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded brain and liver mitochondria. The reduction of Ca(2+) retention capacity was more pronounced in liver and totally prevented by cyclosporine A and ADP, as well as by ruthenium red, demonstrating the involvement of mitochondrial permeability transition (mPT) and Ca(2+). Furthermore, cDA induced lipid peroxidation in brain and liver mitochondria and increased hydrogen peroxide formation in brain, suggesting the participation of oxidative damage in cDA-induced alterations. Interestingly, OA, OC and DC did not alter the evaluated parameters, implying lower toxicity for these compounds. Our results suggest that DA and cDA, in contrast to OA and medium-chain acylcarnitines, disturb important mitochondrial functions in brain and liver by multiple mechanisms that are possibly involved in the neuropathology and liver alterations observed in MCAD deficiency.

  14. Oxidative stress response of Forster's terns (Sterna forsteri) and Caspian terns (Hydroprogne caspia) to mercury and selenium bioaccumulation in liver, kidney, and brain

    Science.gov (United States)

    Hoffman, David J.; Eagles-Smith, Collin A.; Ackerman, Joshua T.; Adelsbach, Terrence L.; Stebbins, Katherine R.

    2011-01-01

    Bioindicators of oxidative stress were examined in prebreeding and breeding adult and chick Forster's terns (Sterna forsteri) and in prebreeding adult Caspian terns (Hydroprogne caspia) in San Francisco Bay, California. Highest total mercury (THg) concentrations (mean±standard error;μg/g dry wt) in liver (17.7±1.7), kidney (20.5±1.9), and brain (3.0±0.3) occurred in breeding adult Forster's terns. The THg concentrations in liver were significantly correlated with hepatic depletion of reduced glutathione (GSH), increased oxidized glutathione (GSSG):GSH ratio, and decreased hepatic gamma-glutamyl transferase (GGT) activity in adults of both tern species. Prefledging Forster's tern chicks with one-fourth the hepatic THg concentration of breeding adults exhibited effects similar to adults. Total mercury-related renal GSSG increased in adults and chicks. In brains of prebreeding adults, THg was correlated with a small increase in glucose-6-phosphate dehydrogenase (G-6-PDH) activity, suggestive of a compensatory response. Brain THg concentrations were highest in breeding adult Forster's terns and brain tissue exhibited increased lipid peroxidation as thiobarbituric acid-reactive substances, loss of protein bound thiols (PBSH), and decreased activity of antioxidant enzymes, GSSG reductase (GSSGrd), and G-6-PDH. In brains of Forster's tern chicks there was a decrease in total reduced thiols and PBSH. Multiple indicator responses also pointed to greater oxidative stress in breeding Forster's terns relative to prebreeding terns, attributable to the physiological stress of reproduction. Some biondicators also were related to age and species, including thiol concentrations. Enzymes GGT, G-6-PDH, and GSSGred activities were related to species. Our results indicate that THg concentrations induced oxidative stress in terns, and suggest that histopathological, immunological, and behavioral effects may occur in terns as reported in other species.

  15. Dietary Omega-3 Fatty Acids Do Not Change Resistance of Rat Brain or Liver Mitochondria to Ca2+ and/or Prooxidants

    Directory of Open Access Journals (Sweden)

    Irina G. Stavrovskaya

    2012-01-01

    Full Text Available Omega-3 polyunsaturated fatty acids (n-3 PUFAs block apoptotic neuronal cell death and are strongly neuroprotective in acute and chronic neurodegeneration. Theoretical considerations, indirect data, and consideration of parsimony lead to the hypothesis that modulation of mitochondrial pathway(s underlies at least some of the neuroprotective effects of n-3 PUFAs. We therefore systematically tested this hypothesis on healthy male FBFN1 rats fed for four weeks with isocaloric, 10% fat-containing diets supplemented with 1, 3, or 10% fish oil (FO. High resolution mass spectrometric analysis confirmed expected diet-driven increases in docosahexaenoic acid (DHA, 22:6, n-3 and eicosapentaenoic acid (EPA, 20:5, n-3 in sera, liver and nonsynaptosomal brain mitochondria. We further evaluated the resistance of brain and liver mitochondria to Ca2+ overload and prooxidants. Under these conditions, neither mitochondrial resistance to Ca2+ overload and prooxidants nor mitochondrial physiology is altered by diet, despite the expected incorporation of DHA and EPA in mitochondrial membranes and plasma. Collectively, the data eliminate one of the previously proposed mechanism(s that n-3 PUFA induced augmentation of mitochondrial resistance to the oxidant/calcium-driven dysfunction. These data furthermore allow us to define a specific series of follow-up experiments to test related hypotheses about the effect of n-3 PUFAs on brain mitochondria.

  16. Electron spin resonance study of free radicals produced from ethanol and acetaldehyde after exposure to a Fenton system or to brain and liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Gonthier, B.; Jeunet, A.; Barret, L. (Departement de Toxicologie, C.H.R.U. de Grenoble, (France))

    1991-09-01

    Free radical formation from ethanol and acetaldehyde was studied in the presence of a spin-trap and a NADPH generating system with a chemical model, Fenton's reagent, or by enzymatic oxidation of these solvents by rat liver and brain microsomes. The free radicals were detected by electron spin resonance spectroscopy (E.S.R.), using the spin-trapping agent, alpha-(4-pyridyl l-oxide)-N-tertbutyl-nitrone (POBN). Under such conditions, the hydroxyethyl radical derived from ethanol was obtained after both incubation in liver and brain microsomes as well as after exposure to the Fenton system. Enzymatic inhibition and activation showed that the mixed function oxidase system plays an important role in the generation of such a radical, even in the brain. Under all the experimental conditions acetaldehyde could also generate a free radical deriving directly from the parent molecule and modified by enzymatic activation or inhibition. A second, longer lasting radical was also observed in the presence of acetaldehyde. On the basis of a comparative study to a known process causing lipoperoxidation, its lipidic origin was suggested.

  17. Different early effect of irradiation in brain and small cell lung cancer examined by in vivo 31P-magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Kristjansen, P E; Pedersen, A G; Quistorff, B

    1992-01-01

    Early effects of irradiation were evaluated by non-invasive in vivo 31P-magnetic resonance spectroscopy (31P-MRS) of two small cell lung cancer (SCLC) tumor lines CPH SCCL 54A and 54B, in nude mice. The tumors were originally derived from the same patient and have similar morphology and growth...... characteristics, but a different radiosensitivity. The 54A tumors are twice as radiosensitive as the 54B's. In the present study the tumors were treated with 2.5, 10, and 40 Gy. For comparison, nude mice were given cranial irradiation at the same three doses, and the effect was evaluated by in vivo 31P-MRS...... in ATP/Pi. The differential effect on tumors and brain might be relevant for monitoring irradiation effects by in vivo 31P-MRS in patients with brain metastases....

  18. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

    Directory of Open Access Journals (Sweden)

    Moch Holger

    2009-07-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP are involved in the intracellular transport of fatty acids (FA. We examined the level of brain-type (B and liver-type (L FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Methods Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative RT-PCR, immunohistochemistry and western blotting were used to determine B- and L-FABP in tumor and normal tissues. The tissue microarray (TMA contained 272 clinico-pathologically characterized renal cell carcinomas of the clear cell, papillary and chromophobe subtype. SPSS 17.0 was used to apply crosstables (χ2-test, correlations and survival analyses. Results B-FABP mRNA was significantly up-regulated in renal cell carcinoma. In normal tissue B-FABP mRNA was very low or often not detectable. RCC with a high tumor grading (G3 + G4 showed significantly lower B-FABP mRNA compared with those with a low grading (G1 + G2. Western blotting analysis detected B-FABP in 78% of the cases with a very strong band but in the corresponding normal tissue it was weak or not detectable. L-FABP showed an inverse relationship for mRNA quantification and western blotting. A strong B-FABP staining was present in 52% of the tumor tissues contained in the TMA. In normal renal tissue, L-FABP showed a moderate to strong immunoreactivity in proximal tubuli. L-FABP was expressed at lower rates compared with the normal tissues in 30.5% of all tumors. There was no correlation between patient survival times and the staining intensity of both FABPs. Conclusion While B-FABP is over expressed in renal cell carcinoma in comparison to normal renal tissues L-FABP appears to be reduced in tumor tissue. Although the expression behavior was not related to the survival outcome of the RCC patients

  19. Dose and time dependent effects of morphine on the incorporation of (3H)valine into soluble brain and liver proteins

    Energy Technology Data Exchange (ETDEWEB)

    Roennbaeck, L.; Hansson, E.; Cupello, A.

    1983-03-01

    Morphine (10(-6)-10(-5) M) causes an increase in incorporation of (/sup 3/H)valine into soluble proteins during 4 hr in rat brain cortical slices, liver slices and cultivated astroglial cells. The effects are dose-dependent. They are neither cell specific nor strictly related to classical opiate receptors. Pulse-labeling with (/sup 3/H)valine for 60 min after incubation in 10(-6)-10(-5) M morphine, resolves time-dependent changes in incorporation, with both increases and decreases in protein metabolism.

  20. The impact of different dietary sources of marine polyunsaturated fatty acids on the fatty acid composition of rat brain, liver and red blood cells.

    OpenAIRE

    2005-01-01

    There is a general consensus that the physiological activity of fish oil can be ascribable to eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). However, the form in which they are introduced in diet might affect the rate of incorporation in tissue. The aim of this study was to examine the effects of n-3 polyunsaturated fatty acids (PUFA) of different marine origin and the incorporation of EPA and DHA in rat brain, liver and red blood cells (RBC). ...

  1. High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases.

    Science.gov (United States)

    Zhu, Jian-Fei; Cai, Ling; Zhang, Xue-Wen; Wen, Yin-Sheng; Su, Xiao-Dong; Rong, Tie-Hua; Zhang, Lan-Jun

    2014-02-01

    High expression of fibrinogen and platelets are often observed in non-small cell lung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months; P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698, P high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

  2. [Effect of ATP and glutaminic acid on carbohydrate-energy and nitrogen metabolism in the rat brain and liver under the effect of pulsed electromagnetic field].

    Science.gov (United States)

    Mishchenko, L I; Kolodub, F A

    1975-01-01

    Oxidative phosphorylation, content of lactate, creatine phosphate, ammonia and glutamine were studied as affected by ATP and glutaminic acid in the brain and liver of rat subjected to the action of the pulsed electromagnetic field of 7 kHz frequency (72 kA/m, 15 seances). ATP (1 mg per 100 g of weight) was found to have a normalizing effect on the processes of nitrogen metabolism in the rat brain, ATP increasing the intenstiy of the oxidative phosphorylation in the tissues of intact rats, has no analogous influence on the irradiated animals. With administration of glutaminic acid (5 mg per 100 g of weight) the processes of oxidative phosphorylation and nitrogen metabolism, disturbed under the effect of the pulsed electromagnetic field are normalized.

  3. Age and heat exposure-dependent changes in antioxidant enzymes activities in rat's liver and brain mitochondria: role of alpha-tocopherol.

    Science.gov (United States)

    Stojkovski, V; Hadzi-Petrushev, N; Ilieski, V; Sopi, R; Gjorgoski, I; Mitrov, D; Jankulovski, N; Mladenov, M

    2013-01-01

    To investigate the role of mitochondrial antioxidant capacity during increased susceptibility to heat accompanied by the aging, young and aged Wistar rats were exposed on heat for 60 min. After heat exposure, hepatic and brain mitochondria were isolated. Our results revealed changes in antioxidant enzyme activities in liver and brain mitochondria from young and to a greater extent in aged rats. Our measurements of MnSOD, GPx and GR activity indicate greater reactive oxygen species production from the mitochondria of aged heat exposed in comparison to young heat exposed rats. Also in the aged rats, the effect of alpha-tocopherol treatment in the prevention of oxidative stress occurred as a result of heat exposure, is less pronounced. Taken together, our data suggest that mitochondria in aged rats are more vulnerable and less able to prevent oxidative changes that occur in response to acute heat exposure.

  4. Relation of benzodiazepine use to the risk of selected cancers: breast, large bowel, malignant melanoma, lung, endometrium, ovary, non-Hodgkin's lymphoma, testis, Hodgkin's disease, thyroid, and liver.

    Science.gov (United States)

    Rosenberg, L; Palmer, J R; Zauber, A G; Warshauer, M E; Strom, B L; Harlap, S; Shapiro, S

    1995-06-15

    Some animal data have raised the possibility that benzodiazepines influence the risk of selected cancers. With data collected in 1977-1991 in a US hospital-based study, the authors assessed the relation of benzodiazepine use to the risk of 11 cancers: breast (6,056 patients), large bowel (2,203), malignant melanoma (1,457), lung (1,365), endometrium (812), ovary (767), non-Hodgkin's lymphoma (382), testis (314), Hodgkin's disease (299), thyroid (111), and liver (37). Cases were compared with cancer controls (3,777 patients with other cancers) and noncancer controls (1,919 patients admitted for acute nonmalignant disorders). Relative risks were estimated for benzodiazepine use at least 4 days a week for at least 1 month, initiated at least 2 years before admission (sustained use) by multiple logistic regression with control for confounding factors. Results derived with noncancer controls were similar to those derived with cancer controls. For sustained benzodiazepine use relative to no use, relative risk estimates for all 11 cancers were compatible with 1.0 at the 0.05 level of significance. Relative risk estimates for durations of at least 5 years were also compatible with 1.0, with the exceptions of an increased estimate, of borderline statistical significance, for endometrial cancer, and a decreased estimate for ovarian cancer. Relative risk estimates both for sustained use that continued into the 2-year period before admission and for sustained use that ended up to > or = 10 years previously were compatible with 1.0, suggesting a lack of tumor promotion and no increase in the risk after a latent interval. Results were also null for diazepam, chlordiazepoxide, and other benzodiazepines considered separately. The results suggest absence of association between benzodiazepine use and the cancers considered, with the evidence stronger for the cancers with larger numbers of subjects. The similarity of results derived with cancer and noncancer controls suggests that

  5. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  6. Differential regulation of glutathione S—transferase Yb1 mRNA levels in rat prostate,liver and brain by androgen

    Institute of Scientific and Technical Information of China (English)

    ZHANGYUAN; CHAWNSHANGCHANG; 等

    1995-01-01

    Northern blot analysis of glutathione S-transferase (GST)Yb1 mRNA in different tissues of male and female rate revealed that its tissue-specific transcription patterns were highly sex hormone related.Although the GST Yb1 mRNA could be detected in most of the tissues examined at various levels,the highest abundance was observed in the ventral prostate,uterus and liver,which were the main the ventral prostate,uterus and liver,which were the main target tissue for androgen,estrogen and glucocorticoid respectively.The effect of androgen on the transcription of GST YB1 was also tissue-specific.Since androgen with drawal by castration caused the up-regulation of GST Yb1 mRNA in the ventral prostate but down-regulation in the liver and no effect in the brain,evalution of this system for studying the regulation mechanisms of gene expression by which androgen exerts its differential effects has been discussed.

  7. 从肝肺组织病理改变及细胞超微结构变化探讨慢性阻塞性肺疾病中肺肝的相关性%Research on the Correlation between the Lung and Liver in the State of Chronic Obstructive Pulmonary Disease(COPD) through Pathological Changes of the Liver and Lung Tissue and Cellular Ultrastructural Changes

    Institute of Scientific and Technical Information of China (English)

    张伟; 孙璐璐; 韩佳; 姚玉强; 谷明明

    2012-01-01

    To observe the changes of the γ - GCSmRNA expression level in the lung and liver tissue,the content of MMP -9 in the pulmonary homogenate, pathological and cellular ultrastructural changes of liver and lung tissue, we discussed the correlation between the two organs under the state of COPD. The Wistar rats were divided into four groups randomly: the blank group ( A) , the COPD group (B) ,the pure liver damaged group (C) and the COPD with liver damaged group (D) ,with 8 rats in each group. Then the model of the COPD by the improved passive smoking with LPS dropped into the trachea was establised, the model of liver injury with subcutaneous injection CC14. Then γ - GCSmRNA expression level with the RT - PCR assay was detected, the content of MMP - 9 by ELISA methods was tested,pathological and cellular ultrastructural changes of live and lung tissue were observed. Compared with the group A, in the group B and D, the content of MMP - 9 was significantly higher (P <0. 01) ;in the group C, we also found it higher( P < 0. 05 ) , which was significant in contrast with the group D and B (P < 0.05). Compared with the group A, in the group B and D, the γ - GC-SmRNA expression level in the lung tissue increased obviously ( P < 0. 01) ; in the group C, It was also higher( P < 0. 05 ) . The expression level in the group D also increased significantly in contrast to the group B ( P < 0.01). In the group B, the γ - GCSmRNA expression level in the liver tissue had no statistical significance,which in the group D and group C was obviously higher (P <0. 01) ,especially in the group D(P<0.01). The damage degree of the liver and lung tissue was the heaviest under the light microscope and transmission electron microscopy in the group D. In contrast with group B,the damaged degree of lung tissue was more serious. Compared with group D,the damage degree of liver tissue was more serious too. In the state of COPD.the lung damage can bring different degrees of the liver damage

  8. Protein kinase CK2: evidence for a protein kinase CK2beta subunit fraction, devoid of the catalytic CK2alpha subunit, in mouse brain and testicles

    DEFF Research Database (Denmark)

    Guerra, B; Siemer, S; Boldyreff, B;

    1999-01-01

    The highest CK2 activity was found in mouse testicles and brain, followed by spleen, liver, lung, kidney and heart. The activity values were directly correlated with the protein expression level of the CK2 subunits alpha (catalytic) and beta (regulatory). The alpha' subunit was only detected...... found for testicles and brain. The amount of CK2beta protein in brain in comparison to the other organs (except testicles) was estimated to be ca. 2-3-fold higher whereas the ratio of CK2beta between testicles and brain was estimated to be 3-4-fold. Results from the immunoprecipitation experiments...... support the notion for the existence of free CK2beta population and/or CK2beta in complex with other protein(s) present in brain and testicles. In all other mouse organs investigated, i.e. heart, lung, liver, kidney and spleen, no comparable amount of free CK2beta was observed. This is the first...

  9. Comparative study of activities in reactive oxygen species production/defense system in mitochondria of rat brain and liver, and their susceptibility to methylmercury toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mori, N.; Hirayama, K. [Kumamoto University, School of Health Science, Kumamoto (Japan); Yasutake, A. [National Institute for Minamata Disease, Minamata (Japan)

    2007-11-15

    The involvement of oxidative stress has been suggested as a mechanism for neurotoxicity caused by methylmercury (MeHg), but the mechanism for MeHg selective toxicity in the central nervous system is still unclear. In this research, to clarify the mechanism of selective neurotoxicity caused by MeHg, the oxygen consumption levels, the reactive oxygen species (ROS) production rates and several antioxidant levels in mitochondria were compared among the cerebrum, cerebellum and liver of male Wistar rats. In addition, the alterations of these indexes were examined in MeHg-intoxicated rats (oral administration of 10 mg/kg day, for 5 days). Although the cerebrum and cerebellum in intact rats showed higher mitochondrial oxygen consumption levels and ROS production rates than the liver, glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities were much lower in the cerebrum and cerebellum than in the liver. Especially, the cerebellum showed the highest oxygen consumption and ROS production rate and the lowest mitochondrial glutathione (GSH) levels among the tissues examined. In the MeHg-treated rats, decrease in the oxygen consumption and increase in the ROS generation were found only in the cerebellum mitochondria, despite a lower Hg accumulation in the mitochondrial fraction compared to the liver. Since MeHg treatment produced an enhancement of ROS generation in cerebellum mitochondria supplemented with succinate substrates, MeHg-induced oxidative stress might affect the complex II-III mediated pathway in the electron transfer chain in the cerebellum mitochondria. Our study suggested that inborn factors, high production system activity and low defense system activity of ROS in the brain, would relate to the high susceptibility of the central nervous system to MeHg toxicity. (orig.)

  10. Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Hauerberg, John; Jørgensen, Linda;

    2010-01-01

    The pathogenesis of cerebral edema in acute liver failure is suggested, in in vitro and animal studies, to involve a compromised oxidative metabolism with a decrease in cerebral ATP levels and an increase in purine concentrations. In this study we hypothesize that the cerebral concentrations...... of hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively)....

  11. [Acute damage to the myocardium and left lung is a complication of high-frequency percutaneous thermoablation of solitary metastasis of renal cancer into the liver (a clinical observation)].

    Science.gov (United States)

    Tipisev, D A; Gorobets, E S; Agapov, A A; Zotov, A V; Kosyrev, V Iu

    2005-01-01

    The paper describes a case of severe complication of radio-frequency percutaneous thermoablation of renal metastasis into the liver, which occurred in a young woman with the intact cardiovascular system and manifested itself in the development of alveolar edema of the lung and acute dilation of the stomach. Pulmonary edema resulted from left ventricular myocardial and pulmonary parenchymal lesions and acute mitral valvular insufficiency. The authors' considerations as to the possible cause and mechanisms of development of this life-threatening complication first described in the literature are also given.

  12. A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320

    Energy Technology Data Exchange (ETDEWEB)

    Sperduto, Paul W., E-mail: psperduto@mropa.com [Metro MN CCOP, Minneapolis, Minnesota (United States); Wang, Meihua [RTOG Statistical Center, Philadelphia, Pennsylvania (United States); Robins, H. Ian [University of Wisconsin Medical School Cancer Center, Madison, Wisconsin (United States); Schell, Michael C. [Wilmot Cancer Center, University of Rochester, Rochester, New York (United States); Werner-Wasik, Maria [Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Komaki, Ritsuko [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Souhami, Luis [McGill University, Montreal, Quebec (Canada); Buyyounouski, Mark K. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Khuntia, Deepak [University of Wisconsin Hospital, Madison, Wisconsin (United States); Demas, William [Akron City Hospital, Akron, Ohio (United States); Shah, Sunjay A. [Christiana Care Health Services, Inc, CCOP, Newark, Delaware (United States); Nedzi, Lucien A. [University of Texas Southwestern Medical School, Dallas, Texas (United States); Perry, Gad [The Ottawa Hospital Cancer Centre, Ottawa, Ontario (Canada); Suh, John H. [Cleveland Clinic Foundation, Cleveland, Ohio (United States); Mehta, Minesh P. [Northwestern Memorial Hospital, Chicago, Illinois (United States)

    2013-04-01

    Background: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. Methods and Materials: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m{sup 2}/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m{sup 2}/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. Results: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). Conclusion: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.

  13. Influence of liver X receptor-α activator T0901317 on expression of MPO and TNF-α in rat lung with acute lung injury%LXRα激活剂T0901317对急性肺损伤大鼠肺组织MPO、TNF-α表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐静; 李运成; 何春琳; 肖波; 王建春

    2011-01-01

    目的 观察LXRα(liver X receptor α)激活剂T0901317对急性肺损伤大鼠肺组织中髓过氧化物酶(MPO)、肿瘤坏死因子-α(TNF-α)表达的影响.方法 72只雄性Wistar大鼠,按随机数字表法分为对照组、脂多糖致伤组、T0901317干预组,在1h、2h、4h、8h时相点采集大鼠肺组织测定肺组织中MPO活性、TNF-α含量,并观察肺组织病理学变化.结果 与对照组比较,脂多糖致伤组各时间点MPO活性均显著升高(P<0.05),组织病理显示肺缉织受损;肺组织匀浆和动脉血清中TNF-α亦显著升高.T0901317干预组MPO活性及TNF-α表达下降,肺部炎症明显减轻.结论 T0901317能够显著降低急性肺损伤大鼠肺组织MPO活性、TNF-α水平,对急性肺损伤大鼠具有保护作用.%Objective To investigate inhibitory action of T0901317, a liver X receptor-α activator, on expression of MPO and TNF-α in rats with acute lung injury (ALI). Methods 72 male Wistar rats were randomly divided into three group: control group (C group), LPS group (L group), T0901317 group (LT group). The rats were killed at lb, 2h, 4h, 8h after treatment. The lung tissue was collected, myeloperoxidase activity, lung histopathologic changes and expression of TNF-α were observed. Results In rats with ALI, myeloperoxidase activity rised compared with control group (P < 0. 05 ), and lung injury is more severe than that in rats of control group. TNF-α increased markedly in lung homogenate and blood serum at the same period ( P < 0. 05 ). However, The expression of TNF-α and myeloperoxidase activity in rat lung tissues in LT group were significantly declined. Conclusion T0901317 has played an anti-inflammatory effect through suppressing the expression of TNF-α and myeloperoxidase activity in rat lung with acute lung injury .

  14. Interaction of four low dose toxic metals with essential metals in brain, liver and kidneys of mice on sub-chronic exposure.

    Science.gov (United States)

    Cobbina, Samuel Jerry; Chen, Yao; Zhou, Zhaoxiang; Wu, Xueshan; Feng, Weiwei; Wang, Wei; Li, Qian; Zhao, Ting; Mao, Guanghua; Wu, Xiangyang; Yang, Liuqing

    2015-01-01

    This study reports on interactions between low dose toxic and essential metals. Low dose Pb (0.01mg/L), Hg (0.001mg/L), Cd (0.005mg/L) and As (0.01mg/L) were administered singly to four groups of 3-week old mice for 120 days. Pb exposure increased brain Mg and Cu by 55.5% and 266%, respectively. Increased brain Mg resulted from metabolic activity of brain to combat insults, whiles Cu overload was due to alteration and dysfunction of CTR1 and ATP7A molecules. Reduction of liver Ca by 56.0% and 31.6% (on exposure to As and Cd, respectively) resulted from inhibition of Ca-dependent ATPase in nuclei and endoplasmic reticulum through binding with thiol groups. Decreased kidney Mg, Ca and Fe was due to uptake of complexes of As and Cd with thiol groups from proximal tubular lumen. At considerably low doses, the study establishes that, toxic metals disturb the homeostasis of essential metals.

  15. 根治性治疗后非小细胞肺癌的预防性脑照射%Prophylactic Cranial Irradiation for Preventing Brain Metastases in Patients Undergoing Radical Treatment for Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    李伟雄; 黄玉娟

    2008-01-01

    @@ 1 文献来源 Lester JF,Coles B,Macbeth FR.Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small cell lung cancer[DB/CD].The Cochrane Library 2007,Issue 3.

  16. Relationship between the expression of Toll-like receptor 2 and 4 in mononuclear cells and postoperative acute lung injury in orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    CHI Xin-jin; CAI Jun; LUO Chen-fang; CHENG Nan; HEI Zi-qing; LI Shang-rong; LUO Gang-jian

    2009-01-01

    Background The aim of this study was to investigate the potential relationship between the dynamic expression of Toll-like receptor 2 and 4 (TLR2/4) in peripheral blood mononuclear cells as well as changes in serum concentration of inflammatory factors and acute lung injury (ALl) in patients after orthotopic liver transplantation (OLT).Methods The peripheral blood samples of 27 patients (23 men and 4 women with ASA Ⅲ to Ⅳ) who received OLT were collected for measurement of TLR2/4 at T1 (after induction of anesthesia), T2 (25 minutes after anhepatic phase), T3 (3 hours after graft reperfusion) and T4 (24 hours after graft reperfusion). The expression of TLR2/4 in mononuclear cells was measured by flow cytometry. The serum concentrations of tumor necrosis factor (TNF)-a, intedeukin (IL)-113 and IL-8 were measured by enzyme-linked irnmunosorbent assay (ELISA). Twenty-seven patients were assigned to ALI group (n=9) and non-ALI group (n=18) according to the diagnostic criteria of ALI. The expression of TLR2/4 in the ALl group or non-ALI group was analyzed.Results Compared to the non-ALI group, the volumes of blood loss, ascites, total output and transfused red blood cells were higher in the ALI group, and the anhepallc phase lasted longer (P0.05). The expression of TLR2/4 in mononuclear cells increased significantly at T3 and 14 in the ALI group (P<0.05, P<0.01). A positive correlation was noted between the expression of TLR4 in mononuclear cells and the serum concentrations of TNF-α, IL-1β (P=0.041, P=0.046) in the ALl group. In the non-ALI group, statistical results showed that the expression level of TLR2/4 in mononuclear cells was not significantly different during the peri-operative period of OLT (besides TLR4 expression at T4). Compared to the non-ALI group, the increasing amplitude of TLR2/4 expression in mononuclear cells was more significant in the ALI group. The patients whose TLR2/4 expression in mononuclear cells exceeded that at T1 by one time were

  17. CNS, lung, and lymph node involvement in Gaucher disease type 3 after 11 years of therapy: clinical, histopathologic, and biochemical findings.

    Science.gov (United States)

    Burrow, Thomas A; Sun, Ying; Prada, Carlos E; Bailey, Laurie; Zhang, Wujuan; Brewer, Amanda; Wu, Steve W; Setchell, Kenneth D R; Witte, David; Cohen, Mitchell B; Grabowski, Gregory A

    2015-02-01

    A Caucasian male with Gaucher disease type 3, treated with continuous enzyme therapy (ET) for 11 years, experienced progressive mesenteric and retroperitoneal lymphadenopathy, lung disease, and neurological involvement leading to death at an age of 12.5 years. Autopsy showed significant pathology of the brain, lymph nodes, and lungs. Liver and spleen glucosylceramide (GluCer) and glucosylsphingosine (GluS) levels were nearly normal and storage cells were cleared. Clusters of macrophages and very elevated GluCer and GluS levels were in the lungs, and brain parenchymal and perivascular regions. Compared to normal brain GluCer (GC 18:0), GluCer species with long fatty acid acyl chains were increased in the patient's brain. This profile was similar to that in the patient's lungs, suggesting that these lipids were present in brain perivascular macrophages. In the patient's brain, generalized astrogliosis, and enhanced LC3, ubiquitin, and Tau signals were identified in the regions surrounding macrophage clusters, indicating proinflammation, altered autophagy, and neurodegeneration. These findings highlight the altered phenotypes resulting from increased longevity due to ET, as well as those in poorly accessible compartments of brain and lung, which manifested progressive disease involvement despite ET.

  18. Primary malignant melanoma of the liver: A case report

    Institute of Scientific and Technical Information of China (English)

    Li Gong; Yan-Hong Li; Jian-Ye Zhao; Xu-Xia Wang; Shao-Jun Zhu; Wei Zhang

    2008-01-01

    Primary malignant melanoma of the liver is an exceedingly rare tumor.Only 12 cases have been reported in the worldwide lirerature.We present a case of isolated malignant melanoma of the liver occurring in a 36-year-old Chinese male patient.Comprehensive dermatologic and ophthalmologic examinations revealed no evidence of a cutaneous or ocular primary lesion.Other lesions in brain,respiratory tract,lung,gastrointestinal tract and anus,were not demonstrated by serial position emission tomography(PET).Microscopic examination of the resected specimen revealed a malignant melanoma,which was confirmed by immunohistochemical staining for HMB-45,S-100 protein,melanoma-pan and vimentin.Moreover,electron microscopy demonstrated melanosomes in tumor cell cytoplasm.Our case shows that primary malignant melanoma may occur in the liver and should be considered when the histopathological appearance is not typical for other hepatic neoplasm.

  19. Paraneoplastic Syndromes of Hypercalcemia and Leukocytosis Associated with Colonic Metastases from Squamous Cell Carcinoma of the Lung: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Xiangtao Ma; Xu Wang; Liwei Yu; Jing Fu; Shan Wang; Ruyu Du; Zhirong Cui

    2006-01-01

    @@ Lung cancer is the most common cancer-related death in both men and women in the world. Approximately 25% of all cancer deaths are attributable to lung carcinoma. Moreover, about one-half of patients with lung cancer have metastases at the time of initial diagnosis, most frequently of lymph nodes, adrenals, liver, bone and brain.However metastasis to the colon is very rare. Over the past 25 years about 13 cases of symptomatic colonic metastases from lung malignancies of all types have been reported in the literature. Hypercalcemia and leukocytosis are two of the most common paraneoplastic syndromes associated with various malignancies. However, concomitant manifestation of hypercalcemia and leukocytosis are occasionally observed in the same cancer patients. Here, we present a rare case of colonic metastasis from a squamous cell carcinoma of the lung associated with paraneoplastic syndromes of hypercalcemia and leukocytosis.

  20. Brain in human nutrition and variant Creutzfeldt-Jakob disease risk (vCJD): detection of brain in retail liver sausages using cholesterol and neuron specific enolase (NSE) as markers.

    Science.gov (United States)

    Lücker, E; Horlacher, S; Eigenbrodt, E

    2001-08-01

    No information is available about the consumption of brain via meat products. With respect to the new variant of Creutzfeldt-Jakob disease (vCJD) and the presumed food-borne transmission of bovine spongiform encephalopathy (BSE) to humans, a preliminary survey for brain and/or spinal cord (tissues of the central nervous system, CNS) was conducted. We applied a previously developed integrated procedure using cholesterol and neuron specific enolase (NSE) as markers. Quantification of cholesterol had to be backed up by NSE immunochemistry in order to account for low specificity and relatively high variances. Out of 126 high-quality finely graded liver sausages, five samples (4 %) showed positive NSE immunoresponses. In four of these samples a transgression of the normal maximum cholesterol content was obtained. The identification of such a considerable number of CNS-positive sausages indicates that brain consumption is not as rare as previously assumed. Overall, the present integrated method could be successfully applied for the detection of CNS in heat-treated meat products. Its routine application in official food control would deter illegal practice and thus help to control transmissible spongiform encephalopathies.

  1. Chemotactic and inflammatory responses in the liver and brain are associated with pathogenesis of Rift Valley fever virus infection in the mouse.

    Directory of Open Access Journals (Sweden)

    Kimberly K Gray

    Full Text Available Rift Valley fever virus (RVFV is a major human and animal pathogen associated with severe disease including hemorrhagic fever or encephalitis. RVFV is endemic to parts of Africa and the Arabian Peninsula, but there is significant concern regarding its introduction into non-endemic regions and the potentially devastating effect to livestock populations with concurrent infections of humans. To date, there is little detailed data directly comparing the host response to infection with wild-type or vaccine strains of RVFV and correlation with viral pathogenesis. Here we characterized clinical and systemic immune responses to infection with wild-type strain ZH501 or IND vaccine strain MP-12 in the C57BL/6 mouse. Animals infected with live-attenuated MP-12 survived productive viral infection with little evidence of clinical disease and minimal cytokine response in evaluated tissues. In contrast, ZH501 infection was lethal, caused depletion of lymphocytes and platelets and elicited a strong, systemic cytokine response which correlated with high virus titers and significant tissue pathology. Lymphopenia and platelet depletion were indicators of disease onset with indications of lymphocyte recovery correlating with increases in G-CSF production. RVFV is hepatotropic and in these studies significant clinical and histological data supported these findings; however, significant evidence of a pro-inflammatory response in the liver was not apparent. Rather, viral infection resulted in a chemokine response indicating infiltration of immunoreactive cells, such as neutrophils, which was supported by histological data. In brains of ZH501 infected mice, a significant chemokine and pro-inflammatory cytokine response was evident, but with little pathology indicating meningoencephalitis. These data suggest that RVFV pathogenesis in mice is associated with a loss of liver function due to liver necrosis and hepatitis yet the long-term course of disease for those that

  2. Weekly gemcitabine as a radiosensitiser for the treatment of brain metastases in patients with non-small cell lung cancer:phase I trial

    Institute of Scientific and Technical Information of China (English)

    HUANG Yu-juan; WU Yi-long; XIE Song-xi; YANG Jing-ji; HUANG Yi-sheng; LIAO Ri-qiang

    2007-01-01

    Background Conventional treatment for non-small cell lung cancer (NSCLC) brain metastases (BM) is whole-brain radiotherapy (WBRT). The efficacy is limited. It might be increased by a Potent radiosensitizer such as gemcitabine,which is believed to cross the disrupted blood-brain barrier. The primary objective of this study was to determine the maximum tolerated dose (MTD) of weekly gemcitabine given concurrently with WBRT.Methods Patients with BM from NSCLC were included. The dose of WBRT was 3750 cGy (total 15 times, 3 weeks).Gemcitabine was given concurrently with WBRT on days 1, 8 and 15. The starting dose was 400 mg/m2, escalated by100 mg/m2 increments. At least three patients were included per level. Dose limiting toxicity (DLT) was defined as grade 4hematological or grade 2 neurological toxicity. When two or more patients experience DLT, the MTD was reached.Results A total of 16 patients were included; 69% had a performance status (PS) 1 (Eastern Cooperative Oncology Group, ECOG). A total of 69% had concurrent active extra cranial diseases. All had more than 3 BM. Up to 600 mg/m2(Ievel 3) no neurology toxicity was observed. At 600 mg/m2 two out of 9 patients developed grade 4 thrombocytopenia.One of the two patients' thrombocytopenia was confused with disseminated intravascular coagulation (DIC). At 700mg/m2 two out of 4 patients developed neurotoxicities. One developed grade 3 seizure and cognitive disorder. Another patient developed suspected grade 2 muscle weakness.Conclusions The MTD was reached at a dose of 700 mg/m2. The dose of 600 mg/m2 would be considered for further study.

  3. EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data

    Directory of Open Access Journals (Sweden)

    Fan Y

    2014-11-01

    Full Text Available Yun Fan,1,2 Xiaoling Xu,3 Conghua Xie4 1Zhongnan Hospital of Wuhan University, Department of Radiation Oncology, Wuhan, People's Republic of China; 2Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 3Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 4Zhongnan Hospital of Wuhan University, Department of Radiation Oncology, Wuhan, People’s Republic of China Introduction: Brain metastases are one of the leading causes of death from non-small-cell lung cancer (NSCLC. The use of epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs to treat brain metastases remains controversial. Thus, we performed a pooled analysis of published data to evaluate the efficacy of EGFR-TKIs in NSCLC patients with brain metastases, particularly for tumors with activating EGFR mutations. Methods: Several data sources were searched, including PubMed, Web of Science, and ASCO Annual Meetings databases. The end points were intracranial overall response rate (ORR, disease control rate (DCR, progression-free survival (PFS, overall survival (OS, and adverse events. The pooled ORR, DCR, PFS, and OS with 95% confidence intervals (CIs were calculated employing fixed- or random-effect models, depending on the heterogeneity of the included studies. Results: Sixteen published studies were included in this analysis, with a total of 464 enrolled patients. The EGFR mutational status was unknown for 362 (unselected group, and 102 had activating EGFR mutations. The pooled intracranial ORR and DCR were 51.8% (95% CI: 45.8%–57.8% and 75.7% (95% CI: 70.3%–80.5%, respectively. A higher ORR was observed in the EGFR mutation group than in the unselected group (85.0% vs 45.1%; a similar trend was observed for the DCR (94.6% vs 71.3%. The pooled median PFS and OS were 7.4 months (95% CI, 4.9–9.9 and 11.9 months (95% CI, 7.7–16.2, respectively, with longer PFS (12.3 months vs 5.9 months and OS (16.2 months vs

  4. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Directory of Open Access Journals (Sweden)

    Angeliki Lyssimachou

    Full Text Available Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT, which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR and peroxisome proliferator-activated receptor gamma (PPARγ. In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  5. Attenuation of lead-induced oxidative stress in rat brain, liver, kidney and blood of male Wistar rats by Moringa oleifera seed powder.

    Science.gov (United States)

    Velaga, Manoj Kumar; Daughtry, Lucius K; Jones, Angelica C; Yallapragada, Prabhakara Rao; Rajanna, Sharada; Rajanna, Bettaiya

    2014-01-01

    Moringa oleifera is a tree belonging to Moringaceae family and its leaves and seeds are reported to have ameliorative effects against metal toxicity. In the present investigation, M. oleifera seed powder was tested against lead-induced oxidative stress and compared against meso-2, 3-dimercaptosuccinic acid (DMSA) treatment. Male Wistar rats (100-120 g) were divided into four groups: control (2000 ppm of sodium acetate for 2 weeks), exposed (2000 ppm of lead acetate for 2 weeks), Moringa treated (500 mg/kg for 7 days after lead exposure), and DMSA treated (90 mg/kg for 7 days after lead exposure). After exposure and treatment periods, rats were sacrificed and the brain was separated into cerebellum, hippocampus, frontal cortex, and brain stem; liver, kidney, and blood were also collected. The data indicated a significant (poleifera restored all the parameters back to control, tissue-specifically, and also showed improvement in restoration better than DMSA treatment, indicating reduction of the negative effects of lead-induced oxidative stress.

  6. Brain metastasis of hepatocellular carcinoma detected after liver transplantation Metástase cerebral de carcinoma hepatocelular após transplante de fígado

    Directory of Open Access Journals (Sweden)

    Alex Vianey Callado França

    2004-09-01

    Full Text Available AIM: We report the case of a patient with hepatocellular carcinoma submitted to liver transplantation, who subsequently manifested tumor recurrence initially as brain metastasis. CASE DESCRIPTION: A 48-year-old male cirrhotic patient with hepatitis C infection, and two focal hepatic lesions, had a cytologic and histologic diagnosis of hepatocellular carcinoma. Before transplant, he was submitted to adjuvant treatment with a combination of arterial embolization and intratumoral ethanol injection. In the 3rd month post-liver transplantation, the patient developed headache, nausea and vomiting, without any neurological impairment. Brain computed tomography and magnetic resonance imaging identified an expansive hypervascular lesion with internal bleeding. Evaluation of the surgical explant revealed macroscopic invasion of portal vessels. CONCLUSION: Brain metastasis of a hepatocellular carcinoma after liver transplantation may occur. This metastasis may have occurred before or soon after the transplant. Patients with hepatocellular carcinoma, awaiting liver transplant, should be screened for cerebral metastasis. Vascular invasion may indicate hematogenic dissemination of the tumor.OBJETIVO: Relatar o caso de paciente com carcinoma hepatocelular submetido a transplante de fígado, que subseqüentemente manifestou recurrência tumoral em cérebro após o transplante. DESCRIÇÃO DO CASO: Homem de 48 anos de idade, com cirrose hepática secundária à infecção pelo vírus da hepatite C, com duas lesões focais hepáticas diagnosticadas como carcinoma hepatocelular pela citologia e histologia. Antes do transplante, foi submetido a tratamento coadjuvante com embolização da artéria hepática e injeção intra-tumoral de etanol. No terceiro mês pós-transplante, o paciente apresentou cefaléia, náuseas e vômitos, sem déficit neurológico focal. Tomografia computadorizada e ressonância magnética de crânio identificaram lesão expansiva

  7. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-10-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  8. In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice.

    Science.gov (United States)

    Piketty, C; Derouin, F; Rouveix, B; Pocidalo, J J

    1990-01-01

    The in vivo effects of antimicrobial agents against Toxoplasma gondii were evaluated in mice that were infected intraperitoneally with 10(4) tachyzoites of the RH strain by determination of survival rates and study of the kinetics of growth of T. gondii in infected mice. At various intervals after infection, subcultures of serial dilutions of blood, lung, and brain homogenates were performed in fibroblast tissue cultures for determination of parasitic loads. Pyrimethamine (18.5 mg/kg per day), sulfadiazine (375 mg/kg per day), and clindamycin (300 mg/kg per day) were administered for 10 days from day 1 or day 4 after infection. Untreated control mice died within 9 days and showed early and predominant lung involvement. All mice treated with sulfadiazine administered from day 1 survived and were apparently healthy; parasitic loads decreased early after treatment, but a relapse was observed 5 days after the cessation of therapy. When pyrimethamine was administered from day 1, 7 of 11 mice died within 25 days; by determination of parasitic loads, the effect of pyrimethamine was only demonstrable from day 6, and a relapse was constantly observed after the cessation of therapy. When pyrimethamine and sulfadiazine were administered in combination, 100% of mice survived; when therapy was started at day 1, parasites remained undetectable; in mice treated from day 4, parasites were eradicated by day 8 but infection relapsed 8 days after the cessation of therapy. All mice treated with clindamycin from day 1 or day 4 died within 10 days, but parasitemia was always undetectable. These results indicate that study of the kinetics of parasitic loads in blood and organs may provide additional information on the effect of antimicrobial agents against T. gondii in regard to the evolution of the infection and may represent a reliable basis for the determination of therapeutic regimens in humans. PMID:2221854

  9. The analysis of the whole body gamma knife treatment for lung metastasis after liver transplantation%肝癌移植术后肺内转移的体部伽玛刀应用分析

    Institute of Scientific and Technical Information of China (English)

    赵品婷; 卢少平; 梁昉; 邵秋菊; 梁军

    2011-01-01

    Objective : To evaluate the effects of radiation therapy for lung metastasis after liver transplantation. Methods : From November 2004 to October 2009 , 12 cases of lung metastasis after liver transplantation were treated with OUR -QCD whole body gamma knife. The target volumes were surrounded with 50% - 80% isodose curve, and the doses were 18 - 42Gy/3 -8f,3f/w. The max doses were 12 - 14Gy in the center of tumor,and the doses of the normal tissue were lower 2 Gy per time outside PTV. The volume of normal tissue exposed was controled with dose volume histogram ( DVH) . Results : After 3 months , the total local control rate was 91. 7% , which were evaluated by CT images. The median survival time was 10 months. No radiation pneumonitis above gradeⅢ occurred. Conclusion : Three - dimensional conformal radiation therapy for liver transplantation in patients with lung metastasis was effective. Three - dimensional conformal radiation therapy of more lesions and/or multiple times was still effective.%目的:探讨肝癌移植术后肺内转移的体部伽玛刀治疗方法及其效果.方法:2004年11月-2009年10月,应用体部伽玛刀治疗肝癌移植术后肺内转移患者12例.应用50%-80%等剂量曲线包绕靶区,剂量18-42Gy/3-8次,3次/周.肿瘤中心最大剂量12-14Gy、PTV外的正常组织在2 Gy/次以下;应用剂量体积直方图(DVH)减少正常组织受照体积.结果:治疗后3月复查CT,总局部控制率91.7%(11/12).中位生存时间10个月.无Ⅲ级以上放射性肺炎.结论: 三维适形放射治疗对于肝癌移植术后肺内转移患者有较好的疗效,多病灶、多次治疗仍具较好疗效.

  10. Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Tomohiko, E-mail: matsutomo_llp@yahoo.co.jp [Department of Radiation Oncology, Kumamoto University, Kumamoto (Japan); Kogo, Kasei [Kumamoto Radiosurgery Clinic, Kumamoto (Japan); Oya, Natsuo [Department of Radiation Oncology, Kumamoto University, Kumamoto (Japan)

    2013-03-15

    Purpose: To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy{sub 10}. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method. Results: Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions: This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.

  11. BRAIN METASTASES FROM CARCINOMA OF UTERINE CERVIX

    Institute of Scientific and Technical Information of China (English)

    张国楠; 徐世强; 石宇; 樊英; 吴艳丽; 殷红; 余健; 陈毅男

    2002-01-01

    Objective: To study the mechanism, clinical characteristics, therapy regimens, and survival of cervical carcinoma metastases to the brain. Methods: We retrospectively analyzed 11 patients with brain metastases from cervical carcinoma. Results: Two cases were at stage lb, two at IIa, and seven at IIIb, respectively. Histologically, they were squamous cell carcinoma (6 cases), adeno-squamous carcinoma (2 cases), small cell carcinoma (2 cases), or adenocarcinoma (1 cases), poorly differentiated. Eight were accompanied with lung, liver, and bone metastases disease and three had no any other systemic metastases at the time of the brain metastases diagnosis. Two had controlled, and other nine were uncontrolled or progressive primary disease. The median interval from the diagnosis of the primary carcinoma to the detection of brain lesion was 14.6 months. Headache was the most common symptom of brain metastases. Eight of 11 patients developed multiple lesions and other 3 cases had a solitary lesion in brain. The patients were treated by combination of surgery and whole brain radiation therapy (WBRT) (3 cases), stereotactic radiosurgery (SRS) (3 cases), or WBRT (5 cases). The patients had a median survival of 6.6 months. Conclusion: Brain metastases are not always a late complication of cervical carcinoma. The development of the metastases is related to pathological type, poorly differentiation, and advanced stage. Surgery and SRS arc the appropriate therapy regimen for these patients.

  12. Arsenic and nicotine co-exposure lead to some synergistic effects on oxidative stress and apoptotic markers in young rat blood, liver, kidneys and brain

    Directory of Open Access Journals (Sweden)

    Anshu Jain

    2015-01-01

    Full Text Available Arsenic and nicotine exposure has been a major health concern globally. Individually both these toxicants increase the risk to various diseases including cancers. However, limited information exists on the co-exposure. In this study, we evaluate the effects of their individual and combined exposure and if co-exposure to these toxicants might have a synergism or antagonism. Male rats were exposed to a very low dose of arsenic (25 ppm in drinking water or nicotine (0.25 mg/kg, sub-cutaneously for a period of 5 months and post exposure various biochemical variables indicative of oxidative stress and apoptosis evaluated. Almost all glutathione linked enzymes showed marked alteration in individual as well as co-exposure treated groups. While serum creatinine and apoptosis indicator, lactate dehydrogenase (LDH were significantly increased in both treatments, an additive effect was noted in co-exposure group. A similar trend was also seen in brain and liver but not in kidneys. Gene expression studies showed marked reduction in catalase, Cu-Zn SOD, GST, there was a significant up regulation in Bax, caspase 3 in various tissues along with urinary 8-OHdG levels, indicative of DNA damage and apoptosis. Interestingly, a decrease in liver arsenic concentration was noted in co-exposed group compared to arsenic alone exposed group. In conclusion, the present study suggests that arsenic and nicotine exhibited significant toxicity during individual exposure whereas co-exposure to these toxins showed variable conditions (indicative of both synergism and antagonism in male rats.

  13. Species- and tissue-specific relationships between mitochondrial permeability transition and generation of ROS in brain and liver mitochondria of rats and mice.

    Science.gov (United States)

    Panov, Alexander; Dikalov, Sergey; Shalbuyeva, Natalia; Hemendinger, Richelle; Greenamyre, John T; Rosenfeld, Jeffrey

    2007-02-01

    In animal models of neurodegenerative diseases pathological changes vary with the type of organ and species of the animals. We studied differences in the mitochondrial permeability transition (mPT) and reactive oxygen species (ROS) generation in the liver (LM) and brain (BM) of Sprague-Dawley rats and C57Bl mice. In the presence of ADP mouse LM and rat LM required three times less Ca(2+) to initiate mPT than the corresponding BM. Mouse LM and BM sequestered 70% and 50% more Ca(2+) phosphate than the rat LM and BM. MBM generated 50% more ROS with glutamate than the RBM, but not with succinate. With the NAD substrates, generation of ROS do not depend on the energy state of the BM. Organization of the respiratory complexes into the respirasome is a possible mechanism to prevent ROS generation in the BM. With BM oxidizing succinate, 80% of ROS generation was energy dependent. Induction of mPT does not affect ROS generation with NAD substrates and inhibit with succinate as a substrate. The relative insensitivity of the liver to systemic insults is associated with its high regenerative capacity. Neuronal cells with low regenerative capacity and a long life span protect themselves by minimizing ROS generation and by the ability to withstand very large Ca(2+) insults. We suggest that additional factors, such as oxidative stress, are required to initiate neurodegeneration. Thus the observed differences in the Ca(2+)-induced mPT and ROS generation may underlie both the organ-specific and species-specific variability in the animal models of neurodegenerative diseases.

  14. Comparison of mercury accumulation among the brain, liver, kidney, and the brain regions of rats administered methylmercury in various phases of postnatal development

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, M.; Nakano, A. [National Institute for Minamata Disease, Kumamoto (Japan)

    1995-10-01

    Several animal studies have indicated that a developing organism in its prenatal and early postnatal stage may be at higher risk in toxic metal exposure than in adult stage. Many infants were congenitally affected by methylmercury in the epidemics in Japan and Iraq. The infants reported from Minamata, Japan, had severe cerebral palsy, whereas their mothers had mild or no manifestations of poisoning. Some of the high susceptibility in infants may resulted from the specific features of the methylmercury metabolism in the developing organisms. Prenatal or postnatal development is characterized by functional immaturity of organs, which may affect the mercury (Hg) accumulation among organs. It seems possible that the Hg distribution might, in fact, reflect the toxic effects of methylmercury during a given developing phase. Thus, its distribution deserves closer examination. In our previous study, when a toxic level of methylmercury was administered, the Hg distribution and its effects on body weight gain and neurological disorders were found to be different among the rat postnatal developing phases. In the present study the Hg distribution among organs and brain regions was investigated during the several development phases with a nontoxic level of methylmercury treatment. 24 refs., 1 fig., 2 tabs.

  15. Zhang Huadong's Experiences in the Treatment of Sjogren Syndrome Based on the Theory of Liver and Lung Qi Activity%张华东从肝肺气机论治干燥综合征经验

    Institute of Scientific and Technical Information of China (English)

    桑永兵; 刘颖; 鲁构峰; 赵瑞英; 邓俊花; 张华东

    2016-01-01

    Sjogren syndrome( SS)results from the dysfunction of body fluids transformation and dis-tribution and is classified into the categories of“dryness syndrome”,“dryness toxin”and“dryness Bi syn-drome”in traditional Chinese medicine. Prof. Zhang Huadong accumulated rich clinical experiences in the treatment of SS and the treating theory of liver and lung qi activity is one of the characteristics. Prof. Zhang believed that the treatment of SS should focus on regulating liver and lung qi activity. Dysfunction of liver and lung qi in ascending and descending leads to deficiency of qi,blood and body fluids and distribution impair-ment,which is one of the key causative factors of the disease. Hence,the principles of treatment are regulating liver and lung qi ascending and descending and normalizing the distribution of qi,blood and body fluids. Based on the pattern/syndrome differentiation in clinic,the disease is differentiated as the mental hyperactivi-ty restricting the wood,the wood fire restricting the mental,the failure of metal to restrict the wood,the mental dryness burning up the wood,the wood dryness disturbing the mental,the steaming up of the mental and wood,etc. The treatment methods are modified in accordance with the symptoms. This therapy is widely used in clinical practice and has achieved the significant efficacy.%干燥综合征在中医看来,是津液化生与运行敷布失常,根据其临床表现当属“燥证”“燥毒”“燥痹”等范畴。张华东教授在治疗干燥综合征多年临床经验中,从肝肺气机论治是其特色之一,认为论治干燥综合征可从调理肝肺气机入手,肝肺气机升降失调引起气血津液盈亏、输布失常是本病发病的关键之一,治疗上应调理肝肺气机升降,平和气血津液输布。具体在临床辨证的分型中,有金亢制木、木火刑金、金不制木、金涸燎木、木枯扰金、金蒸木焖等等,实际中随证而治,广泛应用,疗效卓著。

  16. Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes.

    Science.gov (United States)

    Shen, Shuijie; Li, Lei; Ding, Xinxin; Zheng, Jiang

    2014-01-21

    Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e., styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. A dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes relative to that in the wild-type mouse lung microsomes; however, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knockout and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed a susceptibility to lung toxicity of styrene similar to that of the wild-type animals; however, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene.

  17. Impact of Prophylactic Cranial Irradiation Timing on Brain Relapse Rates in Patients With Stage IIIB Non-Small-Cell Lung Carcinoma Treated With Two Different Chemoradiotherapy Regimens

    Energy Technology Data Exchange (ETDEWEB)

    Topkan, Erkan, E-mail: docdretopkan@gmail.com [Baskent University Adana Medical Faculty, Department of Radiation Oncology, Kisla Saglik Yerleskesi, Adana (Turkey); Parlak, Cem; Kotek, Ayse; Yuksel, Oznur [Baskent University Adana Medical Faculty, Department of Radiation Oncology, Kisla Saglik Yerleskesi, Adana (Turkey); Cengiz, Mustafa [Hacettepe University Medical Faculty, Oncology Hospital, Department of Radiation Oncology, Sihhiye, Ankara (Turkey); Ozsahin, Mahmut [University of Lausanne, University Hospital, Department of Radiation Oncology, Lausanne (Switzerland); Pehlivan, Berrin [Akdeniz University Medical Faculty, Department of Radiation Oncology, Antalya (Turkey)

    2012-07-15

    Purpose: To retrospectively assess the influence of prophylactic cranial irradiation (PCI) timing on brain relapse rates in patients treated with two different chemoradiotherapy (CRT) regimens for Stage IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: A cohort of 134 patients, with Stage IIIB NSCLC in recursive partitioning analysis Group 1, was treated with PCI (30 Gy at 2 Gy/fr) following one of two CRT regimens. Regimen 1 (n = 58) consisted of three cycles of induction chemotherapy (ICT) followed by concurrent CRT (C-CRT). Regimen 2 (n = 76) consisted of immediate C-CRT during thoracic radiotherapy. Results: At a median follow-up of 27.6 months (range, 7.2-40.4), 65 patients were alive. Median, progression-free, and brain metastasis-free survival (BMFS) times for the whole study cohort were 23.4, 15.4, and 23.0 months, respectively. Median survival time and the 3-year survival rate for regimens 1 and 2 were 19.3 vs. 26.1 months (p = 0.001) and 14.4% vs. 34.4% (p < .001), respectively. Median time from the initiation of primary treatment to PCI was 123.2 (range, 97-161) and 63.4 (range, 55-74) days for regimens 1 and 2, respectively (p < 0.001). Overall, 11 (8.2%) patients developed brain metastasis (BM) during the follow-up period: 8 (13.8%) in regimen 1 and 3 (3.9%) in regimen 2 (p = 0.03). Only 3 (2.2%) patients developed BM at the site of first failure, and for 2 of them, it was also the sole site of recurrence. Median BMFS for regimens 1 and 2 were 17.4 (13.5-21.3) vs. 26.0 (22.9-29.1 months), respectively (p < 0.001). Conclusion: These results suggest that in Stage IIIB NSCLC patients treated with PCI, lower BM incidence and longer survival rates result from immediate C-CRT rather than ITC-first regimens. This indicates the benefit of earlier PCI use without delay because of induction protocols.

  18. Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

    Energy Technology Data Exchange (ETDEWEB)

    Parlak, Cem, E-mail: cemparlak@gmail.com [Department of Radiation Oncology, Baskent University, Adana Medical Faculty, Adana (Turkey); Mertsoylu, Hüseyin [Department of Medical Oncology, Baskent University, Adana Medical Faculty, Adana (Turkey); Güler, Ozan Cem; Onal, Cem; Topkan, Erkan [Department of Radiation Oncology, Baskent University, Adana Medical Faculty, Adana (Turkey)

    2014-03-15

    Purpose/Objectives: The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). Methods and Materials: A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. Results: Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. Conclusions: In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM.

  19. Liver Transplant

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  20. Prognostic factorsin inoperable adenocarcinoma of the lung: A multivariate regression analysis of 259 patiens

    DEFF Research Database (Denmark)

    Sørensen, Jens Benn; Badsberg, Jens Henrik; Olsen, Jens

    1989-01-01

    The prognostic factors for survival in advanced adenocarcinoma of the lung were investigated in a consecutive series of 259 patients treated with chemotherapy. Twenty-eight pretreatment variables were investigated by use of Cox's multivariate regression model, including histological subtypes...... and degree of differentiation, the new international staging system for lung cancer, and seven laboratory parameters. Staging of the patients included bone marrow examination but were otherwise nonextensive without routine bone, liver, and brain scans. Factors predicting poor survival were low performance...... status, stage IV disease, no prior nonradical resection, liver metastases, high values of white blood cell count, and lactate dehydrogenase, and low values of aspartate aminotransaminase. The nonradical resection may not be a prognostic factor because of the resection itself but may rather serve...

  1. Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.

    Science.gov (United States)

    Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S; Mohapatra, Subhra

    2014-10-01

    Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 h after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body.

  2. Influence of diabetes surgery on a gut-brain-liver axis regulating food intake and internal glucose production

    Directory of Open Access Journals (Sweden)

    G. Mithieux

    2013-01-01

    Full Text Available It has long been known that the brain, especially the hypothalamus, can modulate both insulin secretion and hepatic glucose fluxes, via the modulation of the sympathetic system (promoting glycogen breakdown and the parasympathetic system (stimulating glycogen deposition. Central insulin signalling or hypothalamic long-chain fatty acid oxidation can also control insulin's suppression of endogenous glucose production. Interestingly, intestinal gluconeogenesis can initiate a portal glucose signal, transmitted to the hypothalamus via the gastrointestinal nervous system. This signal may modulate the sensation of hunger and satiety and insulin sensitivity of hepatic glucose fluxes as well. The rapid improvements of glucose control taking place after gastric bypass surgery in obese diabetics has long been mysterious. Actually, the specificity of gastric bypass in obese diabetic mice relates to major changes in the sensations of hunger and to rapid improvement in insulin sensitivity of endogenous glucose production. We have shown that an induction of intestinal gluconeogenesis plays a major role in these phenomena. In addition, the restoration of the secretion of glucagon like peptide 1 and consequently of insulin plays a key additional role to improve postprandial glucose tolerance. Therefore, a synergy between incretin effects and intestinal gluconeogenesis might be a key feature explaining the rapid improvement of glucose control in obese diabetics after bypass surgery.

  3. Influence of diabetes surgery on a gut-brain-liver axis regulating food intake and internal glucose production.

    Science.gov (United States)

    Mithieux, G

    2013-03-01

    It has long been known that the brain, especially the hypothalamus, can modulate both insulin secretion and hepatic glucose fluxes, via the modulation of the sympathetic system (promoting glycogen breakdown) and the parasympathetic system (stimulating glycogen deposition). Central insulin signalling or hypothalamic long-chain fatty acid oxidation can also control insulin's suppression of endogenous glucose production. Interestingly, intestinal gluconeogenesis can initiate a portal glucose signal, transmitted to the hypothalamus via the gastrointestinal nervous system. This signal may modulate the sensation of hunger and satiety and insulin sensitivity of hepatic glucose fluxes as well. The rapid improvements of glucose control taking place after gastric bypass surgery in obese diabetics has long been mysterious. Actually, the specificity of gastric bypass in obese diabetic mice relates to major changes in the sensations of hunger and to rapid improvement in insulin sensitivity of endogenous glucose production. We have shown that an induction of intestinal gluconeogenesis plays a major role in these phenomena. In addition, the restoration of the secretion of glucagon like peptide 1 and consequently of insulin plays a key additional role to improve postprandial glucose tolerance. Therefore, a synergy between incretin effects and intestinal gluconeogenesis might be a key feature explaining the rapid improvement of glucose control in obese diabetics after bypass surgery.

  4. Brain size in birds is related to traffic accidents

    Science.gov (United States)

    Erritzøe, Johannes

    2017-01-01

    Estimates suggest that perhaps a quarter of a billion birds are killed by traffic annually across the world. This is surprising because birds have been shown to learn speed limits. Birds have also been shown to adapt to the direction of traffic and lane use, and this apparently results in reduced risks of fatal traffic accidents. Such behavioural differences suggest that individual birds that are not killed in traffic should have larger brains for their body size. We analysed the link between being killed by traffic and relative brain mass in 3521 birds belonging to 251 species brought to a taxidermist. Birds that were killed in traffic indeed had relatively smaller brains, while there was no similar difference for liver mass, heart mass or lung mass. These findings suggest that birds learn the behaviour of car drivers, and that they use their brains to adjust behaviour in an attempt to avoid mortality caused by rapidly and predictably moving objects.

  5. Whole brain radiation with supplementary boost for patients for unique brain metastasis from a primitive lung cancer; Experience de l'irradiation encephalique totale avec escalade de dose focalisee pour le traitement des metastases cerebrales uniques d'un carcinome bronchopulmonaire

    Energy Technology Data Exchange (ETDEWEB)

    Levy, A.; Lamproglou, I. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Chargari, C. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Service de radiotherapie, hopital d' instruction des armees Val-de-Grace, 75005 Paris (France); Mazeron, J.J. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Universite Pierre-et-Marie-Curie Paris 6, 4, place Jussieu, 75005 Paris (France); Krzisch, C. [Service de radiotherapie, CHU d' Amiens-Picardie, place Victor-Pauchet, 80054 Amiens cedex (France); Assouline, A. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Universite Pierre-et-Marie-Curie Paris 6, 4, place Jussieu, 75005 Paris (France); Service de radiotherapie, CHU d' Amiens-Picardie, place Victor-Pauchet, 80054 Amiens cedex (France)

    2011-08-15

    Purpose. - To assess the potential benefit of a boost in patients treated with whole brain irradiation by a conventional linear accelerator for lung cancer solitary brain metastasis. Patients and methods. - From 2002 to 2006, a retrospective analysis was carried out from 64 unselected consecutive patients with secondary brain metastasis from lung cancer, treated with whole brain irradiation without surgical resection. Thirty patients (47%) received a boost in their brain metastases. Three potential prognostic factors were studied: sex, RPA score and improvement of neurological symptoms after radiotherapy. An analysis was conducted to determine whether an additional dose may improve survival in the absence of surgical resection. Results. - The mean follow-up was 4.9 months. The median overall survival was 8.5 months (6.4 to 10.7 months). The total dose of radiotherapy was the only significant prognostic factor for overall survival. The median overall survival was 6.2 months for patients without additional radiation versus 11.2 months for patients receiving a boost dose (p = 0.011). Sex, RPA score and improvement of neurological symptoms after radiotherapy were not found as prognostic factors for overall survival. Conclusions. - Boost delivered after whole brain radiation therapy by a conventional particle accelerator may provide a benefit in selected patients, especially for centres that do not have radiotherapy techniques in stereotactic conditions. This warrants further prospective assessment. (authors)

  6. CT Perfusion Characteristics Identify Metastatic Sites in Liver.

    Science.gov (United States)

    Wang, Yuan; Hobbs, Brian P; Ng, Chaan S

    2015-01-01

    Tissue perfusion plays a critical role in oncology because growth and migration of cancerous cells require proliferation of new blood vessels through the process of tumor angiogenesis. Computed tomography (CT) perfusion is an emerging functional imaging modality that measures tissue perfusion through dynamic CT scanning following intravenous administration of contrast medium. This noninvasive technique provides a quantitative basis for assessing tumor angiogenesis. CT perfusion has been utilized on a variety of organs including lung, prostate, liver, and brain, with promising results in cancer diagnosis, disease prognostication, prediction, and treatment monitoring. In this paper, we focus on assessing the extent to which CT perfusion characteristics can be used to discriminate liver metastases from neuroendocrine tumors from normal liver tissues. The neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow (BF), blood volume (BV), mean transit time (MTT), permeability (PS), and hepatic arterial fraction (HAF), for tumor and normal liver. The result reveals the potential of CT perfusion as a tool for constructing biomarkers from features of the hepatic vasculature for guiding cancer detection, prognostication, and treatment selection.

  7. CT Perfusion Characteristics Identify Metastatic Sites in Liver

    Directory of Open Access Journals (Sweden)

    Yuan Wang

    2015-01-01

    Full Text Available Tissue perfusion plays a critical role in oncology because growth and migration of cancerous cells require proliferation of new blood vessels through the process of tumor angiogenesis. Computed tomography (CT perfusion is an emerging functional imaging modality that measures tissue perfusion through dynamic CT scanning following intravenous administration of contrast medium. This noninvasive technique provides a quantitative basis for assessing tumor angiogenesis. CT perfusion has been utilized on a variety of organs including lung, prostate, liver, and brain, with promising results in cancer diagnosis, disease prognostication, prediction, and treatment monitoring. In this paper, we focus on assessing the extent to which CT perfusion characteristics can be used to discriminate liver metastases from neuroendocrine tumors from normal liver tissues. The neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow (BF, blood volume (BV, mean transit time (MTT, permeability (PS, and hepatic arterial fraction (HAF, for tumor and normal liver. The result reveals the potential of CT perfusion as a tool for constructing biomarkers from features of the hepatic vasculature for guiding cancer detection, prognostication, and treatment selection.

  8. Characterization of cationic acid phosphatase isozyme from rat liver mitochondria.

    Science.gov (United States)

    Fujimoto, S; Murakami, K; Hosoda, T; Yamamoto, Y; Watanabe, K; Morinaka, Y; Ohara, A

    1992-05-01

    Acid phosphatase isozyme was highly purified from rat liver mitochondrial fraction. The enzyme showed an isoelectric point value of above 9.5 on isoelectric focusing, and the apparent molecular weight was estimated to be 32000 by Sephadex G-100 gel filtration or 16000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme catalyzed the hydrolysis of adenosine 5'-triphosphate, adenosine 5'-diphosphate, thiamine pyrophosphate, inorganic pyrophosphate, and phosphoprotein such as casein and phosvitin, but not of several phosphomonoesters, except for p-nitrophenyl phosphate and o-phosphotyrosine. The enzyme was not inhibited by L-(+)-tartrate, and was significantly activated by Fe2+ and reducing agents such as ascorbic acid, L-cysteine,and dithiothreitol. The enzyme was found to be distributed in various rat tissues including liver, spleen, kidney, small intestine, lung, stomach, brain and heart, but not in skeletal muscle.

  9. Comparison of molecular signatures in large scale protein interaction networks in normal and cancer conditions of brain, cervix, lung, ovary and prostate

    Directory of Open Access Journals (Sweden)

    Rajat Suvra Banik

    2016-04-01

    Full Text Available Background Cancer, the disease of intricateness, has remained beyond our complete perception so far. Network systems biology (termed NSB is one of the most recent approaches to understand the unsolved problems of cancer development. From this perspective, differential protein networks (PINs have been developed based on the expression and interaction data of brain, cervix, lung, ovary and prostate for normal and cancer conditions. Methods Differential expression database GeneHub-GEPIS and interaction database STRING were applied for primary data retrieval. Cytoscape platform and related plugins named network analyzer; MCODE and ModuLand were used for visualization of complex networks and subsequent analysis. Results Significant differences were observedamong different common network parameters between normal and cancer states. Moreover, molecular complex numbers and overlapping modularization found to be varying significantly between normal and cancerous tissues. The number of the ranked molecular complex and the nodes involved in the overlapping modules were meaningfully higher in cancer condition.We identified79 commonly up regulated and 6 down regulated proteins in all five tissues. Number of nodes, edges; multi edge node pair, and average number of neighbor are found with significant fluctuations in case of cervix and ovarian tissues.Cluster analysis showed that the association of Myc and Cdk4 proteins is very close with other proteins within the network.Cervix and ovarian tissue showed higher increment of the molecular complex number and overlapping module network during cancer in comparison to normal state. Conclusions The differential molecular signatures identified from the work can be studied further to understand the cancer signaling process, and potential therapeutic and detection approach. [Biomed Res Ther 2016; 3(4.000: 605-615

  10. Lung transplant

    Science.gov (United States)

    Solid organ transplant - lung ... the chance that the body will reject the transplant . Lungs can also be given by living donors. ... the person who is receiving it. During lung transplant surgery, you are asleep and pain-free (under ...

  11. Effects of "nourishing liver and kidney" acupuncture therapy on expression of brain derived neurotrophic factor and synaptophysin after cerebral ischemia reperfusion in rats.

    Science.gov (United States)

    Xia, Wen-Guang; Zheng, Chan-Juan; Zhang, Xuan; Wang, Juan

    2017-04-01

    The aim of the present study was to investigate the effect of "nourishing liver and kidney" acupuncture therapy on motor and cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via increasing the expression of brain derived neurotrophic factor (BDNF) and synaptophysin (SYN) in the hippocampus. Healthy adult male SD rats were randomly divided into sham operation group (n=51), model group (n=51), acupuncture group (n=51) and acupuncture control group (n=51). The middle cerebral I/R model was established. Acupunctures were performed in the acupuncture group and acupuncture control group at acupoints of Taixi (K103), Taichong (ST09) of both sides, for 30 min once daily every morning. The animals in the sham operation group and model group were conventionally fed in the cage, without any intervention therapy. The rats of each group were assessed with modified neurological severity scores (mNSS). The expression of BDNF and SYN in the hippocampus was detected by immunohistochemical SP method and the synaptic structure in hippocampus area was assessed morphologically and quantitatively at the 3rd, 7th and 14th day. The Morris water Maze (MWM) test was used to evaluate the rats' learning and memory abilities on the 15th day after acupuncture. The animals in the acupuncture control group and sham operation group presented no neurological deficit. In the acupuncture group, the nerve functional recovery was significantly better than that in the model group at the 7th and 14th day after modeling. The average MWM escape latency in the acupuncture group was shorter than that in the model group at the 3rd, 4th and 5th day. The number of crossings of the platform quadrant in the acupuncture group was significantly more than that in the model group. At the each time point, the expression levels of BDNF and SYN in the hippocampal regions increased significantly in the model group as compared with the sham operation group and the acupuncture

  12. Normalization of nano-sized TiO2-induced clastogenicity, genotoxicity and mutagenicity by chlorophyllin administration in mice brain, liver, and bone marrow cells.

    Science.gov (United States)

    El-Ghor, Akmal A; Noshy, Magda M; Galal, Ahmad; Mohamed, Hanan Ramadan H

    2014-11-01

    The intensive uses of titanium dioxide (TiO2) nanoparticles in sunscreens, toothpaste, sweats, medications, etc. making humans exposed to it daily by not little amounts and also increased its risks including genotoxicity. Thus, the present study was designed as one way to reduce nano-titanium-induced clastogenicity, genotoxicity, and mutagenicity in mice by co-administration of the free radical scavenger chlorophyllin (CHL). In addition, markers of oxidative stress were detected to shed more light on mechanism(s) underlying nano-sized TiO2 genotoxicity. Male mice were exposed to multiple injection into the abdominal cavity for five consecutive days with either CHL (40 mg/kg bw/day), or each of three dose levels of nano-sized TiO2 (500, 1000, or 2000 mg/kg bw/day) alone, or both simultaneously and sacrificed by cervical dislocation 24 h after the last treatment. After CHL co-administration, the observed dose-dependent genotoxicity of TiO2 nanoparticles indicated by the significant elevations in frequencies of both micronuclei and DNA damage induction was significantly decreased and returned to the negative control level. The observed induced mutations in p53 exons 5, 7, & 8 and 5 & 8 in the liver and brain, respectively, were declined in most cases. Moreover, CHL significantly decreased hepatic malondialdehyde level and significantly increased glutathione level and superoxide dismutase, catalase, and glutathione peroxidase activities that were significantly disrupted in animal groups treated with nano-TiO2 alone. In conclusion, the evidenced in vivo genotoxicity of nano-TiO2 in the present study was normalized after CHL co-administration which supports the previously suggested oxidative stress as the possible mechanism for titanium toxicity.

  13. A Case of Brain Metastases from Breast Cancer Treated with Whole-Brain Radiotherapy and Eribulin Mesylate

    Directory of Open Access Journals (Sweden)

    Carsten Nieder

    2012-01-01

    Full Text Available Patients with triple receptor-negative breast cancer often develop aggressive metastatic disease, which also might involve the brain. In many cases, systemic and local treatment is needed. It is important to consider the toxicity of chemo- and radiotherapy, especially when newly approved drugs become available. Randomised studies leading to drug approval often exclude patients with newly diagnosed brain metastases. Here we report our initial experience with eribulin mesylate and whole-brain radiotherapy (WBRT in a heavily pretreated patient with multiple brain, lung, and bone metastases from triple receptor-negative breast cancer. Eribulin mesylate was given after 4 previous lines for metastatic disease. Two weeks after the initial dose, that is, during the first cycle, the patient was diagnosed with 5 brain metastases with a maximum size of approximately 4.5 cm. She continued chemotherapy and received concomitant WBRT with 10 fractions of 3 Gy. After 3 cycles of eribulin mesylate, treatment was discontinued because of newly diagnosed liver metastases and progression in the lungs. No unexpected acute toxicity was observed. The only relevant adverse reactions were haematological events after the third cycle (haemoglobin 9.5 g/dL, leukocytes 3.1×109/L. The patient died from respiratory failure 18.5 months from diagnosis of metastatic disease, and 2.7 months from diagnosis of brain metastases. To the best of our knowledge, this is the first report on combined WBRT and eribulin mesylate.

  14. Expression of liver cancer associated gene HCCA3

    Institute of Scientific and Technical Information of China (English)

    Zheng-Xu Wang; Gui-Fang Hu; Hong-Yang Wang; Meng-Chao Wu

    2001-01-01

    AIM: To study and clone a novel liver cancer reisted gene,and to explore the molecular basis of liver cancer genesis. METHODS: Using mRNA differential display polymerasechain reaction (DDPCR), we investigated the difference of mRNA in human hepatocellular carcinoma (HCC) and paired surrounding liver tissues, and got a gene probe. By screening a human placenta cDNA library and genomic homologous extend, we obtained a full-length cDNA named HCCA3. We analyzed the expression of this novel gene in 42pairs of HCC and the surrounding liver tissues, and distribution in human normal tissues by means of Northern blot assay. RESULTS: A full-length cDNA of liver cancer associated gene HCCA3 has been submitted to the GeneBank nucleotide sequence databases ( Accession No. AF276707 ). The positive expression rate of this gene was 78.6% (33/42) in HCC tissues, and the clinical pathological data showed that the HCCA3 was closely associated with the invasion of tumor capsule ( P = 0.023) and adjacant small metastasis satellite nodules lesions ( P= 0.041). The HCCA3 was widely distributed in the human normal tissues, which was intensively expressed in lungs, brain and colon tissues,while lowly expressed in the liver tissues. CONCLUSION: A novel full-length cDNA was cloned and differentiated, which was highly expressed in liver cancer tissues. The high expression was closely related to the tumor invasiveness and metastasis, that may be the late heredited change in HCC genesis.

  15. A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats.

    Science.gov (United States)

    Tanvir, E M; Afroz, R; Chowdhury, Maz; Gan, S H; Karim, N; Islam, M N; Khalil, M I

    2016-09-01

    This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.

  16. Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells.

    Science.gov (United States)

    Basar, Norazah; Oridupa, Olayinka Ayotunde; Ritchie, Kenneth J; Nahar, Lutfun; Osman, Nashwa Mostafa M; Stafford, Angela; Kushiev, Habibjon; Kan, Asuman; Sarker, Satyajit D

    2015-06-01

    Glycyrrhiza glabra L. (Fabaceae), commonly known as 'liquorice', is a well-known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet-tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra.

  17. Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Berghoff, A.S. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Ilhan-Mutlu, A.; Preusser, M. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Woehrer, A.; Hainfellner, J.A. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Hackl, M. [Austrian National Cancer Registry, Statistics Austria, Vienna (Austria); Widhalm, G. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Dieckmann, K. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Radiotherapy, Vienna (Austria); Melchardt, T. [Paracelsus Medical University Hospital Salzburg, Third Medical Department, Salzburg (Austria); Dome, B. [Medical University of Vienna, Department of Surgery, Vienna (Austria); Heinzl, H. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Center for Medical Statistics, Informatics, and Intelligent Systems, Vienna (Austria); Birner, P. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Institute of Clinical Pathology, Vienna (Austria)

    2014-07-15

    Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0 %) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5 %) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies. (orig.) [German] Die Ueberlebensprognose von Patienten mit zerebralen Metastasen eines nicht-kleinzelligen Lungenkarzinoms (NSCLC) ist sehr variabel. Bisher werden gewebsbasierte Parameter nicht in die prognostische Beurteilung inkludiert. Neurochirurgische Resektate zerebraler NSCLC-Metastasen wurden in dieser Studie untersucht. Die Gefaessdichte (''microvascular density'', MVD), der Ki67-Proliferationsindex sowie der HIF-1α-Index wurden mittels

  18. Magnetic resonance imaging (MRI) of liver and brain in haematologic-organic patients with fever of unknown origin; Magnetresonanztomographie (MRT) der Leber und des Gehirns bei haematologisch-onkologischen Patienten mit Fieber unbekannter Ursache

    Energy Technology Data Exchange (ETDEWEB)

    Heussel, C.P.; Kauczor, H.U.; Poguntke, M.; Schadmand-Fischer, S.; Mildenberger, P.; Thelen, M. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Radiologie; Heussel, G. [Mainz Univ. (Germany). 3. Medizinische Klinik und Poliklinik

    1998-08-01

    To examine the advantage of liver and brain MRI in clinically anomalous haematological patients with fever of unknown origin. Material and Methods: Twenty liver MRI (T{sub 2}-TSE, T{sub 2}-HASTE, T{sub 1}-FLASH{+-}Gd dynamic) and 16 brain MRI (T{sub 2}-TSE, FLAIR, T{sub 1}-TSE{+-}Gd) were performed searching for a focus of fever with a suspected organ system. Comparison with clinical follow-up. Results: suspected organ system. Comparison with clinical follow-up. Results: A focus was detected in 11/20 liver MRI. Candidiasis (n=3), mycobacteriosis (n=2), relapse of haematological disease (n=3), graft versus host disease (n=1), non-clarified (n=2). The remaining 9 cases with normal MRI were not suspicious of infectious hepatic disease during follo-wup. In brain MRI, 3/16 showed a focus (toxoplasmosis, aspergillosis, mastoiditis). Clinical indication for an infectious involvement of the brain was found in 4/16 cases 2--5 months after initially normal brain MRI. No suspicion of an infectious involvement of brain was present in the remaining 9/16 cases. Conclusion: In case of fever of unknown origin and suspicion of liver involvement, MRI of the liver should be performed due to data given in literature and its sensitivity of 100%. Because of the delayed detectability of cerebral manifestations, in cases of persisting suspicion even a previously normal MRI of the brain should be repeated. (orig.) [Deutsch] Untersuchung des Nutzens der MRT der Leber und des Gehirns bei klinisch auffaelligen haematologischen Patienten mit Fieber unbekannter Ursache. Material und Methoden: Es wurden 20 MRT der Leber (T{sub 2}-TSE, T{sub 2}-HASTE, T{sub 1}-FLASH{+-}Gd dynamisch) und 16 MRT des Gehirns (T{sub 2}-TSE, FLAIR, T{sub 1}-TSE{+-}Gd) zur Fokussuche bei Infektionsverdacht und Organhinweisen durchgefuehrt. Es erfolgte der Abgleich mit dem weiteren klinischen Verlauf. Ergebnisse: 11/20 MRT-Untersuchungen der Leber zeigten einen Herdbefund: Candidiasis (n=3), Mykobakteriose (n=2

  19. Gene cloning and mRNA expression of glutamate dehydrogenase in the liver, brain and intestine of the swamp eel, Monopterus albus, exposed to freshwater, terrestrial conditions, environmental ammonia or salinity stress

    Directory of Open Access Journals (Sweden)

    C Y Toh

    2011-12-01

    Full Text Available The swamp eel, Monopterus albus, is an obligatory air-breathing teleost which can survive long period of emersion, has high environmental and tissue ammonia tolerance, and acclimate from fresh to brackish water. This study was undertaken to clone and sequence gdh expressed in the liver, intestine and brain of M. albus, to verify whether more than one form of gdh were expressed, and to examine the gdh mRNA expressions in these three organs in fish exposed to various adverse conditions using quantitative real-time PCR. Only one gdh gene sequence, consisted of a 133 bp 5’ UTR, a CDS region spanning 1629 bp and a 3’ UTR of approximately 717 bp, was obtained from the liver, intestine and brain of M. albus. The translated Gdh amino acid sequence from the liver of M. albus had 542 residues and was confirmed to be Gdh1a. It had sequence identity of >90% with Oncorhynchus mykiss Gdh1a, Salmo salar Gdh1a1, Bostrychus sinensis Gdh1a and Tribolodon hakonensis Gdh1a, and formed a monophyletic clade with B. sinensis Gdh1a, Tetraodon nigroviridis Gdh1a, Chaenocephalus aceratus Gdh1a, Salmo salar Gdh1a1 and Gdh1a2 and O. mykiss Gdh1a. An increase in mRNA expression of gdh1a could be essential for increased glutamate production in support of increases in glutamine synthesis under certain environmental condition. Indeed, exposure of M. albus to 1 day of terrestrial conditions or 75 mmol l-1 NH4Cl, but not brackish water, resulted in a significant increase in gdh1a mRNA expression in the liver. However, exposure to brackish water, but not terrestrial conditions or 75 mmol l-1 NH4Cl, lead to a significant increase in the intestinal mRNA expression of gdh1a. By contrast, all the three experimental conditions had no significant effects on the mRNA expression of gdh1a in the brain of M. albus. Our results indicate for the first time that gdh mRNA expression was differentially up-regulated in the liver and intestine of M. albus, in responses to ammonia toxicity and

  20. Gene Cloning and mRNA Expression of Glutamate Dehydrogenase in the Liver, Brain, and Intestine of the Swamp Eel, Monopterus albus (Zuiew), Exposed to Freshwater, Terrestrial Conditions, Environmental Ammonia, or Salinity Stress

    OpenAIRE

    Tok, Chia Y.; Shit F Chew; Yuen K Ip

    2011-01-01

    The swamp eel, Monopterus albus, is an obligatory air-breathing teleost which can undergo long period of emersion, has high environmental and tissue ammonia tolerance, and can survive in brackish water. We obtained a cDNA sequence of glutamate dehydrogenase (gdh), which consisted of a 133-bp 5′ UTR, a complete coding sequence region spanning 1629 bp and a 3′ UTR of approximately 717 bp, from the liver, intestine, and brain of M. albus. The translated Gdh amino acid sequence had 542 residues, ...

  1. Gene cloning and mRNA expression of glutamate dehydrogenase in the liver, brain and intestine of the swamp eel, Monopterus albus, exposed to freshwater, terrestrial conditions, environmental ammonia or salinity stress

    OpenAIRE

    C Y Toh; S F Chew; Ip, Alex Y.K.

    2011-01-01

    The swamp eel, Monopterus albus, is an obligatory air-breathing teleost which can survive long period of emersion, has high environmental and tissue ammonia tolerance, and acclimate from fresh to brackish water. This study was undertaken to clone and sequence gdh expressed in the liver, intestine and brain of M. albus, to verify whether more than one form of gdh were expressed, and to examine the gdh mRNA expressions in these three organs in fish exposed to various adverse conditions using qu...

  2. Different coexpressions of arthritis-relevant genes between different body organs and different brain regions in the normal mouse population.

    Science.gov (United States)

    Cao, Yanhong; Huang, Yue; Wang, Lishi; Zhu, Jiaqian; Gu, Weikuan

    2013-02-25

    Structural changes in different parts of the brain in rheumatoid arthritis (RA) patients have been reported. RA is not regarded as a brain disease. Body organs such as spleen and lung produce RA-relevant genes. We hypothesized that the structural changes in the brain are caused by changes of gene expression in body organs. Changes in different parts of the brain may be affected by altered gene expressions in different body organs. This study explored whether an association between gene expressions of an organ or a body part varies in different brain structures. By examining the association of the 10 most altered genes from a mouse model of spontaneous arthritis in a normal mouse population, we found two groups of gene expression patterns between five brain structures and spleen. The correlation patterns between the prefrontal cortex, nucleus accumbens, and spleen were similar, while the associations between the other three parts of the brain and spleen showed a different pattern. Among overall patterns of the associations between body organs and brain structures, spleen and lung had a similar pattern, and patterns for kidney and liver were similar. Analysis of the five additional known arthritis-relevant genes produced similar results. Analysis of 10 nonrelevant-arthritis genes did not result in a strong association of gene expression or clearly segregated patterns. Our data suggest that abnormal gene expressions in different diseased body organs may influence structural changes in different brain parts.

  3. [Wilson disease: liver form].

    Science.gov (United States)

    Guerra Montero, Luis; Ortega Álvarez, Félix; Sumire Umeres, Julia; Cok García, Jaime

    2015-01-01

    Wilson disease (WD) is a disorder of copper metabolism that is inherited as an autosomal recessive, which produces toxic copper accumulation mainly in the liver and brain, in general has two ways presentation, liver at early ages and neurological in later ages. We present the case of a female patient of 21 years diagnosed of WD in liver cirrhosis that started with an edematous ascites without any neurological symptoms despite the age. Their laboratory studies showed decrease in serum ceruloplasmin and high cupruria within 24 hours of the disease , characteristic data of WD. Although WD is not a common disease should be suspected in all chronic liver disease of unknown etiology with negative viral markers and autoimmunity with or without neurological manifestations as soon as posible and starting treatment with copper chelating mainly leads to a substantial improvement the prognosis of these patients.

  4. Liver regeneration.

    Science.gov (United States)

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  5. 非小细胞肺癌脑转移的靶向和免疫治疗%Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer with Brain Metastasis

    Institute of Scientific and Technical Information of China (English)

    宋琪; 焦顺昌; 李方

    2016-01-01

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, signiifcantly affects the patients’ quality of life. hTe prognosis of patients of NSCLC with brain metastasis is ex-tremely poor, the average median survival is only 1 m-2 m without treatment. hTe targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work.%脑转移是非小细胞肺癌(non-small cell lung cancer, NSCLC)常见并发症,发生率为30%-50%,大大影响了患者的生存质量。NSCLC一旦发生脑转移预后极差,未经治疗者的中位生存期仅为1个月-2个月。基于肺癌驱动基因的靶向治疗为肺癌脑转移提供了新的方法。目前免疫治疗已成为肿瘤治疗的新方向,它能通过刺激机体免疫系统提高抗肿瘤免疫效应。临床上靶向治疗和免疫治疗的结合运用可使患者获益。

  6. Early Palliative Care With Standard Care or Standard Care Alone in Improving Quality of Life of Patients With Incurable Lung or Non-colorectal Gastrointestinal Cancer and Their Family Caregivers

    Science.gov (United States)

    2017-01-24

    Liver Cancer; Anxiety Disorder; Depression; Small Cell Lung Cancer; Extrahepatic Bile Duct Cancer; Malignant Mesothelioma; Pancreatic Cancer; Esophageal Cancer; Gastric Cancer; Non-small Cell Lung Cancer

  7. Design and Construction of a Multi-Organ Microfluidic Chip Mimicking the in vivo Microenvironment of Lung Cancer Metastasis.

    Science.gov (United States)

    Xu, Zhiyun; Li, Encheng; Guo, Zhe; Yu, Ruofei; Hao, Hualong; Xu, Yitong; Sun, Zhao; Li, Xiancheng; Lyu, Jianxin; Wang, Qi

    2016-10-05

    Metastasis is a complex pathophysiological process. As the main cause of cancer mortality in humans it represents a serious challenge to both basic researchers and clinicians. Here we report the design and construction of a multi-organ microfluidic chip that closely mimics the in vivo microenvironment of lung cancer metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and two thin PDMS microporous membranes bonded to form three parallel microchannels. Bronchial epithelial, lung cancer, microvascular endothelial, mononuclear, and fibroblast cells were grown separated by the biomembrane in upstream "lung", while astrocytes, osteocytes, and hepatocytes were grown in distant chambers, to mimic lung cancer cell metastasis to the brain, bone, and liver. After culture in this system, lung cancer cells formed a "tumor mass", showed epithelial-mesenchymal transition (with altered expression of E-cadherin, N-cadherin, Snail1, and Snail2) and invasive capacity. A549 cells co-cultured with astrocytes overexpressed CXCR4 protein, indicating damage of astrocytes after cancer cell metastasis to the brain. Osteocytes overexpressed RANKL protein indicates damage of osteocytes after cancer cell metastasis to the bone, and hepatocytes overexpressed AFP protein indicates damage to hepatocytes after cancer cell metastasis to the liver. Finally, in vivo imaging of cancer growth and metastasis in a nude mice model validated the performance of metastasis in the organs-on-chip system. This system provides a useful tool to mimic the in vivo microenvironment of cancer metastasis and to investigate cell-cell interactions during metastasis.

  8. MR assessment of fetal lung development using lung volumes and signal intensities

    Energy Technology Data Exchange (ETDEWEB)

    Keller, Thomas M.; Michel, Sven C.A.; Marincek, Borut [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich (Switzerland); Rake, Annett; Wisser, Josef [Department of Obstetrics, University Hospital Zurich, Raemistrasse 100, 8091, Zurich (Switzerland); Seifert, Burkhardt [Department of Biostatistics, University of Zurich, Sumatrastrasse 30, 8006, Zurich (Switzerland); Kubik-Huch, Rahel A. [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich (Switzerland); Institute of Radiology, Kantonsspital Baden, 5404, Baden (Switzerland)

    2004-06-01

    The purpose of this study was to evaluate the monitoring and diagnostic potential of MRI in fetal lung development and disease using lung volume and signal intensity changes through gestation. Thirty-five healthy fetuses (22-42 weeks) were examined on a 1.5- T MR system using sagittal T2w single-shot fast spin-echo imaging (TR indefinite, TE 90 ms, slice thickness/gap 3-5/0 mm, FOV 26-40 cm, NEX 0.5). Fetal body and lung were segmented manually and volumes calculated. Signal intensities (SI) of fetal lung and three reference values were measured on the section best displaying the lung. Regions of interests were defined by including the maximal organ area possible. The following SI ratios were generated: lung/liver, lung/amniotic fluid, lung/muscle, liver/fluid and liver/muscle. Volumes and ratios were correlated with gestational age. Data from seven fetuses with pulmonary pathology were compared with these normative values. Absolute lung volume varied from 12.3 to 143.5 cm{sup 3} in correlation with gestational age (P<0.001); lung volume relative to total body volume ranged from 1.6 to 5.0%, decreasing with gestational age (P=0.001). (orig.)

  9. Deleted in malignant brain tumors 1 (DMBT1) elicits increased VEGF and decreased IL-6 production in type II lung epithelial cells

    DEFF Research Database (Denmark)

    Müller, Hanna; Nagel, Christian; Weiss, Christel

    2015-01-01

    between VEGF and IL-6 levels to DMBT1 expression in the lungs of preterm and term infants and in lung epithelial cells in vitro. METHODS: We examined by ELISA VEGF levels in 120 tracheal aspirates of 57 preterm and term infants and tested for correlation with different perinatal factors as well...... as with DMBT1 levels. To examine the effect of DMBT1 on VEGF and IL-6 expression we compared type II lung epithelial A549 cells stably transfected with a DMBT1 expression plasmid (DMBT1+ cells) to A549 cells stably transfected with an empty expression plasmid (DMBT1- cells). The concentrations of VEGF and IL-6...... that DMBT1 promotes VEGF and suppresses IL-6 production in alveolar tissues, which could point to DMBT1 having a possible role in the transition from inflammation to regeneration and being a potentially useful clinical marker....

  10. Activation of PPARγ in myeloid cells promotes lung cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Howard Li

    Full Text Available Activation of peroxisome proliferator-activated receptor-γ (PPARγ inhibits growth of cancer cells including non-small cell lung cancer (NSCLC. Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARγ in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγ(flox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Mac(neg, or control PPARγ(flox/flox mice. In both models, mice receiving PPARγ-Mac(neg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARγ may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells.

  11. Screening and Establishment of Human Lung Cancer Cell Lines 
with Organ-specific Metastasis Potential

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2014-03-01

    Full Text Available Background and objective Cancer metastasis is not only the malignant marker and characteristics, but also the main cause of failure to cure and lose their life in the patients with lung cancer. Lung cancer metastasis has organ-specific characteristics. The most common sites of lung cancer metastasis are mediastinal lymph node, brain, bone, liver and adrenal gland. The aim of this study is to screen and establish lung cancer cell model with organ-specific metastasis potential with human high-metastatic large cell lung cancer cell line L9981 established by our laboratory previously, and to provide cell models for studying the mechanisms and signal regulation of organ-specific metastasis of lung cancer. Materials and methods The parent lung cancer cell line, L9981-Luc, was inoculated in the armpit of nude mice. The live animal imaging system, IVIS-200, was used to detect the lung cancer organ-specific metastasis every week. When the organ-specific metastasis were established, the nude mices bearing the lung cancer were sacrificed when they became moribund. Under sterile conditions, the organs (mediastinal lymph nodes, lung, spinal column and brain with lung cancer organ-specific metastasis were removed and the metastasized nodules were dissected free of connective tissue and blood clots, and rinsed twice with medium. The metastasized nodules were finely minced using sterile scalpel blades in medium, and the cells were seeded in tissue culture dishes. Then, the cells with organ-specific metastasis potential were reinoculated into the armpit of nude mice, respectively. This processes were repeated to establish the organ-specific metastatic sublines of L9981-Luc cell line more than 10 times. Finally, the organ-specific metastasis sublines of L9981-Luc were screened and established, which the four cell lines have the characteristics only metastasized to brian, lung, bone and mediastinal lymph node. Results A group of organ-specific metastasis cell

  12. Lung function

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005200 The effect of body position changes on lung function, lung CT imaging and pathology in an oleic acid induced acute lung injury model. JI Xin-ping (戢新平), et al. Dept Emergency, 1st Affili Hosp, China Med Univ, Shenyang 110001. Chin J Tuberc Respir Dis, 2005;28(1) :33-36. Objective: To study the effect of body position changes on lung mechanics, oxygenation, CT images and pathology in an oleic acid-induced acute lung injury (ALl) model. Methods: The study groups con-

  13. Lung cancer with skin and breast metastasis: a case report and literature review.

    Science.gov (United States)

    Bhattarai, Bikash; Schmidt, Marie Frances; Ghosh, Meenakshi; Sinha Ray, Abhisekh; Manhas, Saveena; Oke, Vikram; Agu, Chidozie Charles; Basunia, Md Rawshan; Enriquez, Danilo; Quist, Joseph; Bianchi, Catherine; Hans, Ravi; Kandel, Saroj

    2015-01-01

    Lung cancer is one of the most common cancers in America. Frequent sites of metastasis include the Hilar lymph nodes, adrenal glands, liver, brain, and bone. The following case report is of a primary lung cancer with metastases to the breast and skin. Case. A 48-year-old African American male with a past medical history of poorly differentiated left breast cancer status after modified radical mastectomy (MRM), chronic obstructive pulmonary disease, and smoking (20 pack-years) presents to the ER with progressive shortness of breath on exertion, upper back pain, and weight loss for 2 months in duration. On physical examination he is found to have a MRM scar on his left breast and a left periumbilical cutaneous mass. Chest X-ray and chest CT reveal a right upper lobe mass and biopsies from the breast, lung, and the periumbilical mass indicate a poorly differentiated carcinoma of unclear etiology; all tumor markers are negative. The patient is male and a chronic smoker; therefore the diagnosis is made as lung carcinoma with metastases to the breast and skin. Conclusion. A high index of suspicion for cutaneous metastases should be cast when investigating cutaneous pathologies in patients at risk for primary lung malignancy.

  14. Liver Disease

    Science.gov (United States)

    ... stay still. Liver disease has many causes. Infection Parasites and viruses can infect the liver, causing inflammation ... beyond. National Institute of Diabetes and Digestive and Kidney Diseases. http://digestive.niddk.nih.gov/ddiseases/pubs/ ...

  15. Liver disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  16. Liver Diseases

    Science.gov (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

  17. Differences between in vitro and in vivo degradation of LHRH by rat brain and other organs

    Energy Technology Data Exchange (ETDEWEB)

    Carone, F.A.; Stetler-Stevenson, M.A.; May, V.; LaBarbera, A.; Flouret, G.

    1987-09-01

    Homogenates of brain, pituitary, liver, lung, ovary, and testes were incubated with (liver, lung, and brain of rats in vivo. There were no metabolites of (/sup 3/H)LHRH in venous blood liver and lung; however, metabolites 2-4 present in venous blood of the brain. Incubation of rat anterior pituitary cells with (/sup 3/H)LHRH yielded metabolites 1-4 but not metabolites 5 or 9 as in homogenates. Incubation of (/sup 3/H)LHRH with porcine follicular granulosa cells resulted in the generation of metabolites 2-7 and 9, similar to the profile in homogenates. Thus, since homogenates contain enzymes of disrupted cells, they do not always reflect mechanisms for in vivo hydrolysis of circulating LHRH. Brain degraded 12.1% of LHRH during a single vascular transit and may account for substantial degradation of the circulating hormone.

  18. Open lung biopsy

    Science.gov (United States)

    ... CT scan Disseminated tuberculosis Granulomatosis with polyangiitis Lung cancer - small cell Lung disease Lung needle biopsy Malignant mesothelioma Pulmonary tuberculosis Rheumatoid lung disease Sarcoidosis Simple pulmonary eosinophilia ...

  19. In vitro study of the biological activity of RNAs after incubation of hog liver, heart and brain tissue at room temperature

    DEFF Research Database (Denmark)

    Reichert, G H; Issinger, O G

    1985-01-01

    The biological activity of RNA, isolated from tissue which was incubated for 1, 3, or 6 hours at room temperature (simulation of post-mortem conditions), was preserved. However, the different organs used differ from each other. When liver is used, qualitative differences in the in vitro translati...

  20. Comparing Outcomes of Donation After Cardiac Death Versus Donation After Brain Death in Liver Transplant Recipients with Hepatitis C: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Malcolm Wells

    2014-01-01

    Full Text Available BACKGROUND: Liver transplantation (LT using organs donated after cardiac death (DCD is increasing due, in large part, to a shortage of organs. The outcome of using DCD organs in recipients with hepatits C virus (HCV infection remains unclear due to the limited experience and number of publications addressing this issue.

  1. Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

    Directory of Open Access Journals (Sweden)

    Watson CY

    2015-06-01

    Full Text Available Christa Y Watson, Ramon M Molina, Andressa Louzada, Kimberly M Murdaugh, Thomas C Donaghey, Joseph D BrainCenter for Nanotechnology and Nanotoxicology, Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USABackground: Zinc oxide engineered nanoparticles (ZnO ENPs have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV administration.Materials and methods: First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated 65ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa. Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively.Results: We found that the liver was the major site of initial uptake of 65ZnO ENPs. There was a time-dependent decrease in tissue levels of 65Zn in all organs examined, reflecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P. aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of

  2. 从“脑-肝-血管”轴初步探讨肝藏血、主疏泄的机制%preliminarily investigate the mechanism of liver storing blood, controlling conveyance and disPersion based on the“brain-liver-blood vessel”axis

    Institute of Scientific and Technical Information of China (English)

    寇冠军; 郑偕扣; 徐强; 王保和

    2015-01-01

    “The liver storing blood, controlling conveyance and dispersion” was an important content in tradition Chinese medicine doctrine of viscera state. This theory was widely used in many diseases which were treated by syndrome differentiation and treatment, especially in terms of hypertension treated from liver. While, the exact mechanism was not clear, including regulate blood pressure, regulate blood flow, and the way, the position. This paper collected related literature at home and abroad, based on the liver blood vessels and the physiological and innervation. Preliminary discussed the mechanism of “storing blood, controlling conveyance and dispersion”, and the relationship of them from the perspective of “brain-liver-blood vessel”axis. To provide for the related mechanism of the basis of deep research in the future.%“肝藏血,主疏泄”是中医藏象学说的重要内容,在中医辨证论治诸多疾病中应用广泛,尤其在高血压病的从肝论治方面。然其调节血压、调节肝血流的具体机制,调节血压血流的途径、部位等尚不甚明确。收集国内外相关文献,从“脑-肝-血管”轴的角度,基于肝血管和生理、神经支配等方面,初步探讨其“藏血、主疏泄”的机制,及两者之间的关系,为今后相关深入基础机制研究提供思路。

  3. A brief analysis of the experience of Professor LIU Jian_qiu using the methods of conditioning emotion and relieving the depressed liver on treating lung cancer%刘建秋教授运用调理情志、疏肝理气法治疗肺癌经验浅析

    Institute of Scientific and Technical Information of China (English)

    孙光; 吴超英; 丁蕾

    2015-01-01

    中医认为肺癌的发生、发展及转归与情志密切相关,刘建秋教授认为,疏肝理气、调理情志应该贯穿于肺癌治疗的始末,在具体临证应用上,则应以辨证为基础,根据不同病证灵活应用。%Traditional Chinese medicine holds that the occurrence, development and outcome of lung cancer is closely related to the emotion. Professor LIU Jian-qiu think relieving the depressed liver and conditioning emotion should run through the beginning and end of the treatment of lung cancer. On the specific clinical application, The methods should be based on the dialectical, flexible application ac-cording to different diseases.

  4. Metastatic Brain Tumors

    Directory of Open Access Journals (Sweden)

    Ersin Haciyakupoglu

    2014-04-01

    Full Text Available Metastatic tumor is secondary spread to the central nervous system of primer systemic cancers originating from tissues other than the central nervous system. In adults; there are metastases respectively from lungs, breasts, malign melanoma, renal cell carcinoma, colon and thyroid cancers. 30-60% of lung cancers metastasis to the brain. In children there are quite a few cerebral metastases. Most commonly leukemia, lymphoma, osteogenic sarcoma, rhabdomyosarcoma and germ cell tumors metastasis to the brain. %50 of malign melanoma, lung, breast and colon cancers intend to make multipl metastases but renal cell cancers intend to make solitary metastasis.While lung cancers metastasis to brain in 6-9 months after the definitive diagnosis, renal cancers in 1 year, colon cancers in 2 years, breast cancers and malign melanoma in 3 years metastasis to brain. In 6% of cases there are cerebral metastasis while there isn’t a symptom of a primary tumor. For treatment corticosteroids, surgery, Radiotherapy(RT, Chemotherapy(CT and Stereotactic Radiosurgery(SRS can be implemented. Small cell lung cancers, lymphoma, germ cell tumors are sensitive to RT and CT. Non small cell lung cancers, renal, colon cancers and malign melanoma are radioresistant. The purposes in the surgery of the metastatic brain tumors are; total resection of tumors without neurologic deficits, decreasing the intracranial pressure and decreasing the dose of postoperative radiotherapy. Key Words: Metastatic brain tumors, Stereotactic radiosurgery, Malign melanoma, Lung cancers, Renal cell carcinoma, Radiotherapy, Chemotherapy [Cukurova Med J 2014; 39(2.000: 191-202

  5. Prognostic factors in patients with stage Ⅳ non-small cell lung cancer%Ⅳ期非小细胞肺癌预后影响因素分析

    Institute of Scientific and Technical Information of China (English)

    马美丽; 沈洁; 姜丽岩

    2006-01-01

    Objective: To investigate the prognostic factors for stage Ⅳ non-small cell lung cancer (NSCLC) with distant metastasis and establish a reliable model of clinical prognostic index.Methods: From January 1990 to April 2005,313 primary NSCLC patients with metastasis,who had been treated in Shanghai Chest Hospital,were reviewed.Survival time was estimated according to the Kaplan-Meier method.Cox proportional hazard regression model was used for multivariate analysis.Results: Among the 313 cases of non-small cell lung cancer (NSCLC) at stage Ⅳ,there were 218 and 95 patients with metastasis to single and different organs,respectively.The overall median survival time for all 313 cases of NSCLC patients was 10.8 (9.00,12.30)months and the overall 1-,2-,3-,4- and 5-year survival rate was 45%,18%,12%,4% and 0%.There were 63,174,127,36,18,11 and 5 patients with metastasis to brain (20.13%),bone (55.59%),lung (40.58%),liver (11.50%),adrenal gland (5.75%),subcutaneous (3.51%) and others,respectively.The survival time was shortest in subcutaneous metastasis (4.6 months),and liver 7.0 months,brain 8.0 months,adrenal gland 8.6 months,bone 10.6 months,lung 11.8 months.Kaplan-Meier estimation showed that patients anatomic typing,KPS,numbers of organ with metastasis,appetite,liver,adrenal gland and subcutaneous metastasis,body weight loss,smoking,index of smoking,chemotherapy,cycles of chemotherapy were the predictors of survival.Multivariate analysis showed survival statistically significant correlation with anatomic typing,KPS,appetite,liver and subcutaneous metastasis,body weight loss,cycles of chemotherapy.The relative risk (RR) was 1.51,1.97,1.55,1.67,2.56,and 2.56 respectively.Conclusion: Survival time decreases distinctly in patients who had distant metastasis to more than two different organs (P<0.01).Bone is the commonest organ for distant metastasis in lung cancer.The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis

  6. Inhibition of membrane Na(+)-K+ Atpase of the brain, liver and RBC in rats administered di(2-ethyl hexyl) phthalate (DEHP) a plasticizer used in polyvinyl chloride (PVC) blood storage bags.

    Science.gov (United States)

    Dhanya, C R; Indu, A R; Deepadevi, K V; Kurup, P A

    2003-08-01

    Significant amounts of di(2-ethylhexyl) phthalate (DEHP) leach out into blood stored in DEHP plasticized polyvinyl chloride (PVC) bags resulting in the exposure of recipients of blood transfusion to this compound. The aim of this study was to find out whether DEHP at these low levels has any effect on the activity of membrane Na(+)-K+ ATPase, since a decrease in this enzyme activity has been reported to take place in a number of disorders like neurodegenerative and psychiatric disorders, coronary artery disease and stroke, syndrome-X, tumours etc. DEHP was administered (ip) at a low dose of 750 microg/100 g body weight to rats and the activity of membrane Na(+)-K+ ATPase in liver, brain and RBC was estimated. Histopathology of brain, activity of HMG CoA reductase (a major rate limiting enzyme in the isoprenoid pathway of which digoxin, the physiological inhibitor of Na(+)-K+ ATPase is a product), intracellular concentration of Ca2+ and Mg2+ in RBC (which is altered as a result of inhibition of Na(+)-K+ ATPase) were also studied. (In the light of the observation of increase of intracellular Ca2+ load and intracellular depletion of Mg2+ when Na(+)-K+ ATPase is inhibited). Histopathology of brain revealed areas of degeneration in the rats administered DEHP. There was significant inhibition of membrane Na(+)-K+ ATPase in brain, liver and RBC. Intracellular Ca2+ increased in the RBC while intracellular Mg2+ decreased. However activity of hepatic HMG CoA reductase decreased. Activity of Na(+)-K+ ATPase and HMG CoA reductase, however returned to normal levels within 7 days of stopping administration of DEHP. The inhibition of membrane Na(+)-K+ ATPase activity by DEHP may indicate the possibility of predisposing recipients of transfusion of blood or hemodialysis to the various disorders mentioned above. However since this effect is reversed when DEHP administration is stopped, it may not be a serious problem in the case of a few transfusion; but in patients receiving

  7. PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2017-01-23

    Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  8. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat.

    Science.gov (United States)

    Yousef, Mokhtar I; Omar, Sahar A M; El-Guendi, Marwa I; Abdelmegid, Laila A

    2010-11-01

    The present study was carried out to evaluate the potential protective role of quercetin and curcumin against paracetamol-induced oxidative injury, liver damage and impairment of kidney function, as well as haematotoxicity in rats. Also, N-acetylcysteine was used to evaluate the potency of quercetin and curcumin. Paracetamol caused an elevation in thiobarbituric acid-reactive substances (TBARS) paralleled with significant decline in glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase activities (in plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in lung, liver and kidney). The apparent oxidative injury was associated with evident hepatic necrosis confirmed in histological examination, elevated plasma transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol reduced plasma total protein, albumin and globulin, while increased bilirubin, urea and creatinine, and induced haematotoxicity. The presence of quercetin or curcumin with paracetamol successfully mitigated the rise in TBARS and restored the activities of antioxidant enzymes compared to the group treated with both paracetamol and N-acetylcysteine. They also protected liver histology, normalized liver and kidney functions, which was more pronounced with curcumin. Therefore, it can be concluded that concomitant administration of quercetin or curcumin with paracetamol may be useful in reversing the toxicity of the drug compared to N-acetylcysteine.

  9. What Is Liver Cancer?

    Science.gov (United States)

    ... Treatment? Liver Cancer About Liver Cancer What Is Liver Cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  10. Ventilatory strategy during liver transplantation

    DEFF Research Database (Denmark)

    Sørensen, Henrik; Grocott, Hilary P; Niemann, Mads;

    2014-01-01

    BACKGROUND: As measured by near infrared spectroscopy (NIRS), cerebral oxygenation (ScO2) may be reduced by hyperventilation in the anhepatic phase of liver transplantation surgery (LTx). Conversely, the brain may be subjected to hyperperfusion during reperfusion of the grafted liver. We...... liver, ScO2 increased by 5.5% (3.8-7.3%), EtCO2 by 0.7 kPa (0.5-0.8 kPa), and VE by 0.6 L/min (0.3-0.9 L/min; all P

  11. Induction of Lipocalin2 in a Rat Model of Lung Irradiation

    Directory of Open Access Journals (Sweden)

    Sadaf Sultan

    2016-04-01

    Full Text Available Previously, we showed that lipocalin2 (LCN2 serum levels increased after liver irradiation and during acute-phase conditions. Here, we evaluate LCN2 expression and serum levels after single-dose lung irradiation with 25 Gy, percutaneously administered to the lung of randomly-paired male Wistar rats. Due to the concave anatomy of the lung recesses, the irradiation field included the upper part of the liver. No rat died due to irradiation. In control tissue, lung immunohistochemistry showed a high constitutive expression of LCN2+ granulocytes. LCN2 mRNA levels in lung tissue increased up to 24 h (9 ± 2.3-fold after irradiation. However, serum LCN2 levels remained undetectable after lung irradiation. LCN2 expression in the upper part of the liver increased up to 4.2-fold after lung irradiation, but the lower liver showed an early decrease. Acute-phase cytokines (IL-1β and TNF-α showed a significant increase on transcript level in both lung and upper liver, whilst the lower liver did not show any considerable increase. In conclusion, constitutive expression of LCN2 in local immune cells demonstrates its local role during stress conditions in the lung. The absence of LCN2 in the serum strengthens our previous findings that the liver is the key player in secreting LCN2 during stress conditions with liver involvement.

  12. 热打击后小鼠肺和脑组织病理学的改变%Study on the pathological changes of the lung and brain in mice during heat stress

    Institute of Scientific and Technical Information of China (English)

    刘志锋; 唐柚青; 徐秋林; 童华生; 郭进强; 苏磊

    2011-01-01

    Objective To prepare mouse model with heat stress and determine its pathological changes of the lung and brain during heat stress. Methods BALB/c mouse were randomly (random number) divided into two groups, control group and heat stress group. The animals in the control group were sham- heated at a temperature of ( 25 ± 0.5) ℃ and humidity of (35 ± 5 ) %. The animals of heat stress group were placed in a prewarmed incubator maintained at (35.5 ± 0.5) ℃ and relative humidity of (60 ± 5) %. Rectal temperature (Tc) was monitored, and when Tc respectively reached 39 ℃, 40 ℃ , 41 ℃ and 42 ℃, those study animals were killed. The other animals were removed from the incubator and allowed to cool at an ambient temperature of (25 ±0. 5)℃ and humidity of (35 ±5)% , respectirvely for 12 and 24 hrs when Tc reached 41 ℃ , and for 6 hrs when Tc reached 42 ℃. The lung and brain of all the animals were isolated. Hematoxylin and eosin stain and light microscope were used to detect their pathological changes. Results All the animals displayed uniform response to the heat stress. Low degree of heat stress could induced obviously pathological changes of the lung, progressively greater damage to lung with further congestion of lung matrix, asystematic hemorrhage of alveolar space, abscission of alveolar epithelial cell and disappear of pulmonary alveolus tissue structure were detected with the rise of Tc to 42 ℃. However, absorption of congestion and hemorrhage and recovery of pulmonary alveolus tissue structure could also be seen with cooling at ambient temperature. With low degree of heat stress, the brain only showed moderate edema. Neuronal denaturation and necrosis were detected when Tc reached to 42 ℃. Interestingly, the lesions of brain further aggravated even through cooling treatment after Tc reached to 42 ℃ , but recovery could been observed after cooling treatment followed with Tc of 41 ℃. Conclusions The pathological changes of the lung and

  13. Oncocytic-type intraductal papillary mucinous neoplasm (IPMN-derived invasive oncocytic pancreatic carcinoma with brain metastasis - a case report

    Directory of Open Access Journals (Sweden)

    Chiang Kun-Chun

    2012-07-01

    Full Text Available Abstract Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.

  14. Oncocytic-type intraductal papillary mucinous neoplasm (IPMN)-derived invasive oncocytic pancreatic carcinoma with brain metastasis - a case report.

    Science.gov (United States)

    Chiang, Kun-Chun; Yu, Chi-Chang; Chen, Jim-Ray; Huang, Yu-Ting; Huang, Cheng-Cheng; Yeh, Chun-Nan; Tsai, Chien-Sheng; Chen, Li-Wei; Chen, Hsien-Cin; Hsu, Jun-Te; Wang, Cheng-Hsu; Chen, Huang-Yang

    2012-07-09

    Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC) and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.

  15. Lung density

    DEFF Research Database (Denmark)

    Garnett, E S; Webber, C E; Coates, G

    1977-01-01

    breathing in the sitting position ranged from 0.25 to 0.37 g.cm-3. Subnormal values were found in patients with emphsema. In patients with pulmonary congestion and edema, lung density values ranged from 0.33 to 0.93 g.cm-3. The lung density measurement correlated well with the findings in chest radiographs...

  16. Lung Cancer

    Science.gov (United States)

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  17. Lung transplantation

    Science.gov (United States)

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  18. Liver Transplant

    Science.gov (United States)

    ... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...

  19. Efifcacy of Gamma Knife Radiation Therapy in Lung Cancer Patients with Brain Metastasis Lesions and Whole Brain Radiation Therapy%肺癌脑转移病灶患者伽马刀放射治疗及全脑放射治疗的疗效

    Institute of Scientific and Technical Information of China (English)

    刘敬聘; 秦坤明; 王仁生; 阮林

    2015-01-01

    Objective: To investigate the efficacy analysis of lung lesions in patients with brain metastases Gamma Knife radiation therapy and whole brain radiation therapy.Methods:March 2002~ March 2013 in our hospital diagnosis and treatment of 500 cases of lung cancer patients with brain metastases as the research object. According to the specific circumstances of the patient decided to use the gamma knife radiation therapy or whole brain radiation therapy.Gamma Knife radiotherapy group and whole brain radiotherapy group in gender, age was not significantly different,P>0.05,comparable.Results:The Gamma Knife radiotherapy group and whole brain radiotherapy efficacy in the near future, with a median survival time and 1-year progression-free survival without brain lesions was no significant difference; 1-year survival rate was significantly higher than the gamma knife radiotherapy whole brain radiotherapy; adverse reaction rate of gamma knife radiotherapy group was significantly higher than the whole-brain radiotherapy.Conclusion:The adverse reaction rates using the gamma knife radiation is small, good effect, and thus overall due to the whole brain radiotherapy, but in clinical practice should also consider the specific circumstances of the patient treatment decisions for patients with larger tumors may be two were combined to achieve a more satisfactory outcome.%目的:探讨分析肺癌脑转移病灶患者伽马刀放射治疗(放疗)及全脑放射治疗的疗效。方法:选取2002年3月~2013年3月在我院接受诊断和治疗的500例肺癌脑转移患者作为研究对象。根据患者具体情况决定使用伽马刀放射治疗或全脑放射治疗。伽马刀放疗组和全脑放疗组患者在性别、年龄方面差异不明显,P>0.05,具有可比性。结果:伽马刀放疗组和全脑放疗组在近期疗效、中位生存期和1年无颅脑病灶进展生存率方面无明显差异;伽马刀放疗组的1年生存率明显高于全脑

  20. 吸入一氧化碳对大鼠脑死亡致肺损伤的影响%Effects of carbon monoxide inhalation on lung injury induced by brain death in rats

    Institute of Scientific and Technical Information of China (English)

    金笛; 周华成; 李文志; 潘鹏; 丁文刚

    2009-01-01

    Objective To investigate the effects of carbon monoxide (CO) inhalation on lung injury induced by brain death (BD) in rats. Methods Adult male Wistar rats weighing 250-300 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital sodium 60 mg/kg, tracheostomized and mechanically ventilated (VT 10 ml/kg, RR 50 bpm, PEEP 2 cm H2O). A balloon-tip catheter was placed in the cranium. Twenty-four rats in which Fogarty catheter was successfully placed in the cranium without complication were randomly divided into 3 groups ( n = 8 each) : group I sham operation (group S) ; group II BD and group Ⅲ BDCO. BD was induced by increase in intracranial pressure produced by inflating the balloon at the tip of the catheter. In group S the balloon of the catheter was not inflated. The animals inhaled 40% O2 for 150 min. In group BD, BD was induced and confirmed at 30 min after inflation of the balloon. Then 40% O2 was inhaled for 120 min. In group BDCO, 40% O2 and 0.025% CO were inhaled for 120 min after BD was confirmed at 30 min after balloon inflation. At the end of the experiment the animals were killed. Arterial blood samples were obtained for blood gas analysis before anesthesia (basline), immediately after confirmation of BD, and at 30, 60, 90 and 120 min of CO inhalation. Blood was collected for determination of plasma TNF-α, IL-6 and IL-10 concentrations at 120 min of CO inhalation. The lungs were obtained for determination of W/D lung weight ratio, and MPO activity in the lung tissue and microscopic examination. Lung injury scores were calculated. Results PaO2/FiO2 was stable during the 150 min in group S. Brain death significantly decreased PaO2/FiO2 at 30 min after balloon inflation. PaO2/FiO2 was gradually decreasing during the 120 min in group BD. CO inhalation prevented PaO2/FiO2 from decreasing further. W/D lung weight ratio and MPO activity were significantly higher in group BD than in group S and BDCO. The lung injury score (1

  1. Lung Cancer Screening

    Science.gov (United States)

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease in ...

  2. Lung Cancer Prevention

    Science.gov (United States)

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... to keep cancer from starting. General Information About Lung Cancer Key Points Lung cancer is a disease in ...

  3. What Is Lung Cancer?

    Science.gov (United States)

    ... Graphics Infographic Stay Informed Cancer Home What Is Lung Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet ... cancer starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may ...

  4. Anti-Apoptotic Effects of 3,3 ',5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats

    NARCIS (Netherlands)

    Rebolledo Acevedo, Rolando; Van Erp, Anne C.; Ottens, Petra J.; Wiersema-Buist, Jantje; Leuvenink, Henri G. D.; Romanque, Pamela

    2015-01-01

    Background Thyroid hormone treatment in brain-dead organ donors has been extensively studied and applied in the clinical setting. However, its clinical applicability remains controversial due to a varying degree of success and a lack of mechanistic understanding about the therapeutic effects of 3,3'

  5. The preventive effect of temozolomide on brain metastases from small-cell lung cancer%替莫唑胺对小细胞肺癌脑转移的预防作用

    Institute of Scientific and Technical Information of China (English)

    陈晨; 王浩渊

    2016-01-01

    Objective This study aimed to explore the preventive effect of temozolomide on brain metastases from small-cell lung cancer. Methods A total of 50 patients with small-cell lung cancer who achieved complete remission or partial response after radiation and chemotherapy were divided into treatment group and control group. 30 patients of the treatment group received maintain chemotherapy using temozolomide. 20 patients of the control group received prophylactic cranial irradiation (PCI). The brain metastases positive rate, overall survival rate and 1 year survival rate were analyzed. The adverse reactions of the two treatments were recorded. Results There were no significant differences between temozolomide chemotherapy group and PCI group in brain metastases positive rate (16.7%vs. 15.0%, P>0.05). There were no significant differences of the overall survival rate and 1 year survival rate between the two groups (31 months vs. 24 months, 86.3% vs. 79.1%, P>0.05). The adverse reactions of temozolomide chemotherapy group were mainly hematology and gastrointestinal reaction which was mild to moderate. The acute reactions of PCI group were mainly dizziness and nausea, and some patients had long-term nervous system adverse reaction. Conclusion The effect of temozolomide on maintaining chemotherapy to reduce brain metastasis from small-cell lung cancer is not worse than the traditional treatment of PCI and it is safe and feasible.%目的:探讨替莫唑胺维持化疗对小细胞肺癌脑转移的预防作用。方法采用前瞻、对照研究,将初治放化疗后达到完全缓解或部分缓解的小细胞肺癌患者50例分为治疗组(n=30)和对照组(n=20)。治疗组在放化疗结束后使用替莫唑胺维持化疗,对照组行预防性全脑照射(PCI)。统计分析两组患者脑转移阳性率,总生存期及1年生存率。分别记录两种治疗方案发生的不良反应。结果替莫唑胺化疗组与PCI组脑转移阳性

  6. Proliferation and cell death in an experimental model of brain tissue heterotopia in the lung Proliferação e morte celular na heterotopia encefálica experimental

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Veiga Quemelo

    2010-08-01

    Full Text Available PURPOSE: To investigate the proliferation and neuronal death in brain tissue heterotopia in the lung in an experimental model during both fetal and neonatal periods. METHODS: Twenty four pregnant female Swiss mice were used to induce brain tissue heterotopia on the 15th gestational day. Briefly, the brain of one fetus of each dam was extracted, disaggregated and injected into the right hemithorax of siblings. Six of these fetuses with pulmonary brain tissue implantation (PBI were collected on the 18th gestational day (group E18 and six other on the 8th postnatal day (group P8. Immunohistochemical staining for PCNA and Bcl2 were used to assess proliferation and cell death. RESULTS: PCNA Labelling Index (LI in heterotopic brain tissue was greater in fetal than postnatal period (E18 > P8 (pOBJETIVO: Investigar a proliferação e morte neuronal na heterotopia encefálica pulmonar em modelo experimental durante o período fetal e neonatal. MÉTODOS: Foram utilizados 24 camundongos Swiss fêmeas prenhes para induzir a heterotopia encefálica no pulmão. O tecido encefálico de um feto de cada fêmea prenha foi removido, picotado e injetado no pulmão dos irmãos. Seis fetos com Implantação Encefálica Pulmonar (IEP foram coletados no 18º dia gestacional (grupo E18 e seis outros fetos no 8º dia pós-natal (grupo P8. Foi realizada a reação Imuno-histoquímica para PCNA e Bcl2 para analisar a proliferação e morte celular. RESULTADOS: O índice de marcação (IM para PCNA era maior no período fetal quando comparado com o período pós-natal (E8 > P18 (p<0,05 e a imunomarcação para o anticorpo Bcl2 não apresentou diferença. CONCLUSÃO: A proliferação celular foi mantida no tecido heterotópico encefálico, embora a apoptose também foi observada.

  7. Liver spots

    Science.gov (United States)

    Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ultraviolet light, or causes that are not known. Liver spots are very common after age 40. They occur ...

  8. Distinct alterations in ATP-binding cassette transporter expression in liver, kidney, small intestine, and brain in adjuvant-induced arthritic rats.

    Science.gov (United States)

    Kawase, Atsushi; Norikane, Sari; Okada, Ayaka; Adachi, Mamiko; Kato, Yukio; Iwaki, Masahiro

    2014-08-01

    Pathophysiological changes of infection or inflammation are associated with alterations in the production of numerous absorption, distribution, metabolism and excretion-related proteins. However, little information is available on the effects of inflammation on the expression levels and activities of ATP-binding cassette (ABC) transporters. We examined the effect of acute (on day 7) and chronic (on day 21) inflammation on the expression of ABC transporters in some major tissues in rat. Adjuvant-induced arthritis (AA) in rats was used as an animal model for inflammation. The mRNA levels of mdr1a and mdr1b encoding P-glycoprotein (P-gp) decreased significantly in livers of AA rats on day 21. Hepatic protein levels of P-gp, Mrp2, and Bcrp decreased significantly in membranes but not homogenates of AA rats after 7 days and after 21 days of treatment with adjuvant. Contrary to liver, protein levels of P-gp and Mrp2, but not Bcrp in kidney, increased significantly in membranes. The biliary excretion of rhodamine 123 was decreased in rats with chronic inflammation owing to decreases in efflux activities of P-gp. Our results showed that the expression of transporters in response to inflammation was organ dependent. In particular, hepatic and renal P-gp and Mrp2 exhibited opposite changes in membrane protein levels.

  9. Ultradian feeding in mice not only affects the peripheral clock in the liver, but also the master clock in the brain.

    Science.gov (United States)

    Sen, Satish; Raingard, Hélène; Dumont, Stéphanie; Kalsbeek, Andries; Vuillez, Patrick; Challet, Etienne

    2017-01-01

    Restricted feeding during the resting period causes pronounced shifts in a number of peripheral clocks, but not the central clock in the suprachiasmatic nucleus (SCN). By contrast, daily caloric restriction impacts also the light-entrained SCN clock, as indicated by shifted oscillations of clock (PER1) and clock-controlled (vasopressin) proteins. To determine if these SCN changes are due to the metabolic or timing cues of the restricted feeding, mice were challenged with an ultradian 6-meals schedule (1 food access every 4 h) to abolish the daily periodicity of feeding. Mice fed with ultradian feeding that lost feeding. Mice fed with ultradian feeding that lost >10% body mass (i.e. hypocaloric) became more diurnal, hypothermic in late night, and displayed larger (3.5 h) advance of body temperature rhythm, more reduced PER1 expression in the SCN, and further modified gene expression in the liver (e.g. larger phase-advance of Per2 and up-regulated levels of Pgc-1α). While glucose rhythmicity was lost under ultradian feeding, the phase of daily rhythms in liver glycogen and plasma corticosterone (albeit increased in amplitude) remained unchanged. In conclusion, the additional impact of hypocaloric conditions on the SCN are mainly due to the metabolic and not the timing effects of restricted daytime feeding.

  10. High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases

    Institute of Scientific and Technical Information of China (English)

    Jian-Fei Zhu; Ling Cai; Xue-Wen Zhang; Yin-Sheng Wen; Xiao-Dong Su; Tie-Hua Rong; Lan-Jun Zhang

    2014-01-01

    High expression of fibrinogen and platelets are often observed in non-smal celllung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as wel as to determine the overal survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P < 0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months;P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months;P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698,P < 0.001 andR2 = 1.699,P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

  11. 肝移植术后新发肺癌、乳腺癌及胰腺癌风险性的meta分析%THE META-ANALYSIS OF THE RISK OF THE NEW ONSET OF LUNG CANCER、BREAST CANCER AND PANCREATIC CANCER AFTER THE LIVER TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    邢天宇; 夏强; 张建军

    2011-01-01

    目的 系统评价肝移植术后新发肺癌、乳腺癌以及胰腺癌的风险性.方法 计算机检索Cochrane图书馆、MEDLINE、EMbase数据库中肝移植术后患肺癌、乳腺癌及胰腺癌随机对照试验,检索时间为1980年1月至2011年9月.按照纳入与排除标准选择文献、评价文献质量和提取资料,而后采用RevMan 5.0软件进行Meta分析.结果 共纳入9个RCT,包括8162例肝移植术后患者,Meta分析结果显示:肝移植术后患肺癌的风险率相比于未移植组提高3.73倍(95%可信区间:2.73 ~5.10,P<0.001),而肝移植术后乳腺癌以及胰腺癌风险率相比1于未移植组未见明显提高发生比率分别为1.27倍(95%可信区间:0.97 - 1.65,P=0.08)以及1.32倍(95%可信区间:0.96 - 1.80,P=0.08),肝移植后诊断出新生肺癌的平均时间为4.2年.结论 肝移植后肺癌发生率明显上升,术后低剂量的CT检查有助于肝移植后新发肺癌的早期诊断及治疗从而提高远期生存率.%Objective To evaluate the risk of the new onset of lung cancer、breast cancer and pancreatic cancer after the Liver transplantation. Methods Databases such as The Cochrane Library, MEDLINE, Embase were searched from January of 1980 to September of 2011 to collect randomized controlled trials (RCTs) of the risk of lung cancer、breast cancer and pancreatic cancer after the Liver transplantation. The quality of RCTs was appraised and the data were extracted. Meta-analysis were conducted with Rev-Man5. 0 software for the standard RCTs. Results A total of nine RCTs were included. The meta-analysis was performed on data of 8162 patients and identified that standard incidence ratio of lung cancei\\breast cancer and pancreatic cancer of post liver transplantation is 3.73-fold higher (95% confidence interval 2.73 ~ 5. 10, P < 0. 001) ,1. 27-fold higher (95% confidence interval 0.97-1.65, P=0.08), 1. 32-fold higher (95% confidence interval 0. 96 ~ 1. 80, P =0. 08) than the non

  12. Chemotherapy or Liver Transplantation for Nonresectable Liver Metastases From Colorectal Cancer?

    DEFF Research Database (Denmark)

    Dueland, Svein; Guren, Tormod K; Hagness, Morten;

    2015-01-01

    OBJECTIVE:: The primary objective was to compare overall survival (OS) in patients with colorectal cancer (CRC) with nonresectable liver-only metastases treated by liver transplantation or chemotherapy. BACKGROUND:: CRC is the third most common cancer worldwide. About 50% of patients will develop...... metastatic disease primarily to the liver and the lung. The majority of patients with liver metastases receive palliative chemotherapy, with a median OS of trial patients of about 2 years, and less than 10% are alive at 5 years. METHODS:: Patients with nonresectable liver-only CRC metastases underwent liver...... transplantation in the SECA study (n = 21). Disease-free survival (DFS) and OS of patients included in the SECA study were compared with progression-free survival (PFS) and OS in a similar cohort of CRC patients with liver-only disease included in a first-line chemotherapy study, the NORDIC VII study (n = 47...

  13. [The cognitive disorders and raised free-radical activity of a brain of posterity of rats-females with experimental chronic alcoholic pathology of a liver].

    Science.gov (United States)

    Vakhnin, V A; Brukhin, G V

    2014-01-01

    It is established, that chronic alcoholic defeat of hepatobiliarity sistems leads to infringement of cognitive functions at posterity. At the given group of animals revealed distress of memory and ability to orientation in space in the conditions of Morris water maze is, the research behavior is oppressed. Besides, the animals, born from mothers with chronic alcoholic defeat of hepatobiliarity systems have raised free-radical activity, which plays an important role in maintenance of adaptive possibilities of a brain.

  14. 小细胞肺癌脑转移全脑放疗失败后挽救性分次立体定向放疗疗效分析%Fractionated stereotactic radiotherapy for recurrent small cell lung cancer brain metastases after whole brain radiotherapy

    Institute of Scientific and Technical Information of China (English)

    李祥攀; 李晔雄; 肖建平; 陈秀军; 姜雪松; 张烨; 徐英杰; 郇福奎; 方浩; 万宝

    2012-01-01

    Objective Evaluation the Fractionated Stereotactic Radiotherapy (FSRT) for the patients with small-cell lung cancer (SCLC) after the whole brain radiotherapy (WBRT) failure.Methods We retrospectively analyzed 35 patients with brain metastases from small-cell lung cancer treated with linear accelerator FSRT after the WBRT failure. Multivariate analysis was used to determine significant prognostic factor related to survival.Results The following-up rate was 100%.The median following-up time was 11 months.The median over-all survival (OS) time was 10.3( 1 -30) months after FSRT.Controlled extra cranial disease was the only identified significant predictor of increased median OS time (χ2 =4.02,P =0.045 ).The median OS time from the diagnosis of brain metastasis was 22 (6 - 134 )months.14 patients died from brain metastasis,14 from extra-cranial progression,1 from leptomeningeal metastases,and 3 from other causes. Local control at 6 months and 12 months was 91% and 76%,respectively.No significant late complications.New brain metastases outside of the treated area developed in 17% of patients at a median time of 4(2 -20) months; all patients had received previous WBRT.Conclusions Fractionated stereotactic radiotherapy was safe and effective treatment for recurrent small-cell lung carcinoma brain metastases.%目的 评价小细胞肺癌( SCLC)全脑放疗(WBRT)后颅内失败分次立体定向放疗(FSRT)挽救的价值.方法 回顾分析WBRT失败后使用FSRT挽救的35例SCLC脑转移患者的生存情况,多因素分析确定和生存相关的预后因素.结果 随访率为100%,中位随访时间11个月.全组总中位生存期为10.3个月,多因素分析显示颅外疾病控制状态和患者的生存相关(χ2=4.02,P=0.045).自诊断脑转移开始中位生存期为22.0个月,未发现严重晚期不良反应.6、12个月局部控制率分别为91%、76%.6例局部未控患者中3例行二程FSRT挽救,挽救治疗后生存时间分别为3、9

  15. Robo1蛋白在非小细胞肺癌和肺癌脑转移组织中的表达及意义%Robo1 expression in non-small cell lung cancer and its brain metastasis

    Institute of Scientific and Technical Information of China (English)

    李晓霞; 金玲; 孙增峰; 谷峰; 李文良; 马勇杰

    2013-01-01

    目的 探讨Robo1蛋白的表达与非小细胞肺癌(NSCLC)脑转移的关系.方法 采用免疫组化SP法检测80例NSCLC和52例癌旁组织中Robo1蛋白的表达情况,同时检测72例NSCLC脑转移患者(无其他脏器转移,脑转移灶为单发)脑转移瘤组织中Robo1蛋白的表达情况.另选取17例自身对照患者,检测肺癌和脑转移瘤组织中Robo1蛋白的表达情况.采用Kaplan-Meier法绘制生存曲线,并行Log rank检验.结果 Robo1蛋白在癌旁组织、肺癌组织和脑转移瘤组织中的阳性表达率分别为1.9%(1/52)、13.8%(11/80)和40.3%(29/72),差异有统计学意义(P<0.05).在17例自身对照患者中,Robo1蛋白在肺癌和脑转移瘤组织中的阳性表达率分别为17.6%和64.7%,差异有统计学意义(P<0.01).72例肺癌脑转移患者中,Robo1蛋白阳性表达患者的中位生存时间为10个月,明显短于阴性表达的患者(17个月,P <0.05).结论 Robo1蛋白在癌旁组织、肺癌组织和肺癌脑转移瘤组织中的表达依次增高,Robo1蛋白在肺癌脑转移瘤中的表达与脑转移患者的预后呈负相关.Robo1可能作为促癌基因促进了肺癌和脑转移瘤的发生和发展.%Objective To detect the expression of Robo1 in lung cancer tissues,adjacent noncancerous tissues as well as lung cancer brain metastasis,and explore the correlation of Robo1 expression to lung cancer brain metastasis.Methods SP (streptavidin-peroxidase) staining method was used to examine the Robo1 expression in specimens from 80 cases of NSCLC,52 cases of adjacent non-cancerous tissues and 72 cases of lung cancer with single brain metastasis (without metastasis in other organs).The Robo1 expression was further examined in 17 self control cases with lung cancer tissues and their brain metastasis tissues.The results were assessed by Kaplan-Meier analysis and log-rank test.Results The positive expression rate of Robo1 among adjacent non-cancerous tissues,lung cancers tissues and the

  16. Liver transplantation in Germany.

    Science.gov (United States)

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD.

  17. Lung Transplant

    Science.gov (United States)

    ... will recover in the hospital’s intensive care unit (ICU) before moving to a hospital room for one to three weeks. Your doctor may recommend pulmonary rehabilitation after your lung transplant surgery to help you ...

  18. Voriconazole and the liver

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Voriconazole is an azole useful for the prophylaxis andthe treatment of aspergillosis and other fungal infectionsin immunosuppressed subjects, as those found in aplasiaafter aggressive polychemotherapy treatments, afterhematopoietic stem cell, liver or lung transplantation.Its administration in therapeutic doses lead to extremelyvaried serum levels from patient to patient and even tothe same patient. The explanations are varied nonlinearpharmacokinetics, certain patient-related factors,including genetic polymorphisms in the cytochrome P4502C19 gene, the kidney and liver function, simultaneousadministration with other drugs metabolised by the samecytochrome. It is recommended to maintain the serumconcentrations of voriconazole between 1.5 and 4 μg/mL.At lower values its efficacy decreases and at highervalues the risk of neurological toxicity increases. Evenat these concentrations it is not excluded the possibleappearance of a variety of toxic effects, including onthe liver, manifested by cholestasis, hepatocytolisis, ortheir combination. It is recommended to monitor theclinical and laboratory evolution of all patients treatedwith voriconazole, and of the serum levels of the drugof those who belong to risk groups, even if there is stillno consensus on this issue, given the lack of correlationbetween the serum level and the occurrence of adverseeffects in many patients.

  19. Changes associated with Na,K-ATPase in brain, kidney, heart and liver of the spontaneously diabetic Goto-Kakizaki rat

    OpenAIRE

    2014-01-01

    Alterations in Na,K-ATPase activity, in isoenzyme expression and/or number of units of the pump present in the plasma membrane have been associated with diabetes. These changes were described in different organs and tissues such as brain, heart, kidney, among others, and may result from altered insulin levels. However, the vast majority of studies were conducted in animal models of chemically induced diabetes, which are not consensual models for type 2 diabetes (T2D). The major goal of this w...

  20. Repeated intratracheal instillation of PM10 induces lipid reshaping in lung parenchyma and in extra-pulmonary tissues.

    Directory of Open Access Journals (Sweden)

    Angela Maria Rizzo

    Full Text Available Adverse health effects of air pollution attributed mainly to airborne particulate matter have been well documented in the last couple of decades. Short term exposure, referring to a few hours exposure, to high ambient PM10 concentration is linked to increased hospitalization rates for cardiovascular events, typically 24 h after air pollution peaks. Particulate matter exposure is related to pulmonary and cardiovascular diseases, with increased oxidative stress and inflammatory status. Previously, we have demonstrated that repeated intratracheal instillation of PM10sum in BALB/c mice leads to respiratory tract inflammation, creating in lung a condition which could potentially evolve in a systemic toxic reaction. Additionally, plasma membrane and tissue lipids are easily affected by oxidative stress and directly correlated with inflammatory products. With this aim, in the present investigation using the same model, we analyzed the toxic potential of PM10sum exposure on lipid plasma membrane composition, lipid peroxidation and the mechanisms of cells protection in multiple organs such as lung, heart, liver and brain. Obtained results indicated that PM10 exposure led to lung lipid reshaping, in particular phospholipid and cholesterol content increases; concomitantly, the generation of oxidative stress caused lipid peroxidation. In liver we found significant changes in lipid content, mainly due to an increase of phosphatidylcholine, and in total fatty acid composition with a more pronounced level of docosahexaenoic acid; these changes were statistically correlated to lung molecular markers. Heart and brain were similarly affected; heart was significantly enriched in triglycerides in half of the PM10sum treated mice. These results demonstrated a direct involvement of PM10sum in affecting lipid metabolism and oxidative stress in peripheral tissues that might be related to the serious systemic air-pollution effects on human health.

  1. Liver metastases

    Science.gov (United States)

    ... no symptoms. When symptoms occur, they may include: Decreased appetite Confusion Fever , sweating Jaundice (yellowing of the skin ... can include: Blockage of the flow of bile Decreased appetite Fever Liver failure (usually only in the late ...

  2. Enlarged Liver

    Science.gov (United States)

    ... A blood sample is tested to determine liver enzyme levels. This can give clues about the health ... prescription medications. Limit contact with chemicals. Use aerosol cleaners, insecticides and other toxic chemicals only in well- ...

  3. Temozolomide combined with whole-brain radiotherapy in treatment of non-small cell lung cancer complicated with metastatic brain tumor%替莫唑胺联合全脑放疗治疗非小细胞肺癌脑转移瘤的近期临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    杨宏山; 瞿广桥

    2015-01-01

    Objective To observe the therapeutic effect and toxicity of temozolomide combined with whole-brain radiotherapy in the treatment of non-small cell lung cancer complicated with metastatic brain tumor.Methods 32 patients with non-small cell lung cancer who were diagnosed with brain metastases orally took temozolomide (75mg/m2·d) and received 40 Gy fractionated conventional external-beam radiotherapy (2 Gy per day,5 days per week) for 4 weeks.After radiotherapy,patients took temozolomide (200mg/m2·d) for 5 days every 4 weeks for 6 cycles.Progression-free survival curves and overall were estimated by Kaplan-Meier technique.Results All the 32 patients were evaluable for response with 5 cases of CR,19 PR,4 SD,and 4 PD.The overall response rate was 74.9% and the clinical benefit rate was 87.4%.The median progression-free survival time was 7.6 months.The main side effects were gastrointestinal reaction and myelosuppression,which were alleviated by symptomatic treatment.Conclusions Temozolomide combined with whole-brain radiotherapy is effective with mild toxicity for patients with non-small cell lung cancer who were diagnosed with brain metastases.%目的 观察替莫唑胺联合全脑放疗治疗非小细胞肺癌脑转移患者的临床疗效及安全性.方法 回顾分析了确诊非小细胞肺癌脑转移的患者32例,予以常规分割性全脑放疗,剂量DT 40 Gy (2Gy,1次/d,每周5d),放疗期间每日口服替莫唑胺75 mg,/(m2·d),放疗结束后每4周予以替莫唑胺200 mg/ (m2·d)口服5d方案化疗,共6周期.生存率使用Kaplan-Meier方法计算.结果 32例患者均可评价疗效,其中完全缓解5例(15.6%),部分缓解19例(59.3%),稳定4例(12.5%),进展4例(12.5%),近期治疗有效率74.9%,临床获益率87.4%,中位生存期7.6个月.治疗的不良反应主要表现为胃肠道症状、骨髓抑制,患者均可耐受.结论 替莫唑胺联合全脑放疗方案治疗非小细胞肺癌脑转移患者有较好的近期疗

  4. Liver function

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008308 Study on transplantation of induced bone marrow mesenchymal stem cells via a series of the treatment of chronic liver injury. SUN Yan(孙艳), et al. Dept Gastroenterol, 1st Hosp, Jilin Univ, Changchun 130021. Chin J Dig 2008;28(3):171-174.Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via a series of treatment of chronic liver injury.Methods MSCs were isolated and expanded by density

  5. Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients.

    Science.gov (United States)

    Qin, Fengxia; Zhang, Huikun; Ma, Li; Liu, Xiaoli; Dai, Kun; Li, Wenliang; Gu, Feng; Fu, Li; Ma, Yongjie

    2015-09-24

    Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast cancer brain metastasis for the first time. Our results demonstrated that (1) Invasive ductal carcinoma patients with low expression of Slit2 or Robo1 exhibited worse prognosis and brain-specific metastasis, but not liver, bone or lung. (2) Lower expression of Slit2 and Robo1 were observed in patients with brain metastasis, especially in their brain metastasis tumors, compared with patients without brain metastasis. (3) The interval from diagnosis of breast cancer to brain metastasis and brain metastasis to death were both much shorter in patients with low expression of Slit2 or Robo1 compared with the high expression group. Overall, our findings indicated that Slit2/Robo1 axis possibly be regarded as a significant clinical parameter for predicting brain metastasis in breast cancer patients.

  6. 65zinc uptake from blood into brain and other tissues in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Pullen, R.G.; Franklin, P.A.; Hall, G.H. (Sunderland Polytechnic, Tyne Wear (England))

    1990-10-01

    Zinc is essential for normal growth, development and brain function although little is known about brain zinc homeostasis. Therefore, in this investigation we have studied 65Zn uptake from blood into brain and other tissues and have measured the blood-brain barrier permeability to 65Zn in the anaesthetized rat in vivo. Adult male Wistar rats within the weight range 500-600 g were used. 65ZnCl2 and (125I)albumin, the latter serving as a vascular marker, were injected in a bolus of normal saline I.V. Sequential arterial blood samples were taken during experiments that lasted between 5 min and 5 hr. At termination, samples from the liver, spleen, pancreas, lung, heart, muscle, kidney, bone, testis, ileum, blood cells, csf, and whole brain were taken and analysed for radio-isotope activity. Data have been analysed by Graphical Analysis which suggests 65Zn uptake from blood by all tissues sampled was unidirectional during this experimental period except brain, where at circulation times less than 30 min, 65Zn fluxes were bidirectional. In addition to the blood space, the brain appears to contain a rapidly exchanging compartment(s) for 65Zn of about 4 ml/100g which is not csf.

  7. Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model

    Directory of Open Access Journals (Sweden)

    Israel L. Medeiros

    2012-09-01

    Full Text Available OBJECTIVE: Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. METHOD: Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex®was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. RESULTS: After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98. The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p =0.035. The mean pulmonary compliance was 46.8 cm H20 in Group 1 and 49.3 ml/cm H20 in Group 2 (p =0.816. The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p=0.87. The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0, and the apoptotic cell counts were 118.75/mm² and 137.50/mm², respectively (p=0.71. CONCLUSION: The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation.

  8. Extracorporeal membrane oxygenation after living-related liver transplant.

    Science.gov (United States)

    Gedik, Ender; Çelik, Muhammet Reha; Otan, Emrah; Dişli, Olcay Murat; Erdil, Nevzat; Bayındır, Yaşar; Kutlu, Ramazan; Yılmaz, Sezai

    2015-04-01

    Various types of extracorporeal membrane oxygenation methods have been used in liver transplant operations. The main indications are portopulmonary or hepatopulmonary syndromes and other cardiorespiratory failure syndromes that are refractory to conventional therapy. There is little literature available about extracorporeal membrane oxygenation, especially after liver transplant. We describe our experience with 2 patients who had living-related liver transplant. A 69-year-old woman had refractory aspergillosis pneumonia and underwent pumpless extracorporeal lung assist therapy 4 weeks after liver transplant. An 8-month-old boy with biliary atresia underwent urgent liver transplant; he received venoarterial extracorporeal membrane oxygenation therapy on postoperative day 1. Despite our unsuccessful experience with 2 patients, extracorporeal membrane oxygenation and pumpless extracorporeal lung assist therapy for liver transplant patients may improve prognosis in selected cases.

  9. Efficacy of gamma knife combined with gefitinib for non-small cell lung cancer patients with brain metastases%伽玛刀联合吉非替尼治疗非小细胞肺癌脑转移瘤的疗效分析

    Institute of Scientific and Technical Information of China (English)

    王建军; 陈绍华; 李国明; 杜熙

    2016-01-01

    目的:探讨伽玛刀联合吉非替尼治疗非小细胞肺癌脑转移瘤的疗效分析。方法将71例非小细胞肺癌脑转移瘤患者分为2组。观察组采用伽玛刀联合吉非替尼治疗,对照组采用全脑放射疗法联合吉非替尼治疗。对比2组患者的疗效、生存质量、生存率、不良反应。结果观察组和对照组总有效率(91.67% vs 82.86%)与控制率(97.22% vs 94.29%)比较差异均无统计学意义(χ2值分别为1.244、0.378,P 值均>0.05);观察组 Karofsky 得分有效率(72.22%)显著高于对照组(45.71%)(χ2=5.161,P0.05);观察组脱发、头痛、肝功能损害的发生率显著低于对照组(χ2值分别为27.070、17.154、6.693,P值均0.05). The effective rate in the observation group was significantly higher than that in the control group (72.22% vs 45.71%,χ2=5.161,P 0.05).The incidence of hair loss,headache,and liver function damage in the observation group was significantly lower than that in the control group (χ2 =27.070,17.154,6.693,respectively,all P <0.05).Conclusions Gamma knife combined with gefitinib has curative effect in the treatment of non-small cell lung cancer with brain metastasis,can better control the progression of the tumor,increase the survival rate,has small toxic and side effect,and effectively improve the quality of life of patients.

  10. Reye氏综合征引起肝、脑组织损伤机制的研究%Mechanisms of liver and brain damnification in Reye's syndrome

    Institute of Scientific and Technical Information of China (English)

    姚登福; 黄锋; 孟宪镛

    2005-01-01

    严重脑病伴急性脑水肿及肝脏出现大量的脂肪积聚,称为脑病脂肪肝综合征(encephalopalhy-liver falty metamorphosis syndmme),因Reye氏首先报道,通常称Reye氏综合征(Reye’s syndrome,RS)。临床主要特征为常发于前驱感染(主要为上呼吸道病毒感染)之后,出现频繁呕吐伴剧烈头痛并迅速发展为意识障碍,有肝功能障碍但可无肝脏肿大。患者肝线粒体变性、酶活性减低、脂肪酸β氧化功能低下、血氨升高、抗磷脂抗体阳性、颅内压增加、神经元和星形胶质细胞变性或肿胀,死亡率高。本文综述了近来RS发病机制等的研究进展。

  11. Interstitial Lung Diseases

    Science.gov (United States)

    Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and ... is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among coal ...

  12. Lung Carcinoid Tumor: Surgery

    Science.gov (United States)

    ... Disease Lung Carcinoid Tumor Treating Lung Carcinoid Tumors Surgery to Treat Lung Carcinoid Tumors Surgery is the ... be cured by surgery alone. Types of lung surgery Different operations can be used to treat (and ...

  13. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  14. Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and Vomiting due to Metastatic Brain Tumors of Rectal Cancer

    Directory of Open Access Journals (Sweden)

    M. Suzuki

    2014-01-01

    Full Text Available Brain lesions originating from metastasis of colorectal cancer represent 3-5% of all brain metastases and are relatively rare. Of all distant metastases of colorectal cancer, those to the liver are detected in 22-29% of cases, while those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for metastatic brain tumors include surgery, radiotherapy, chemotherapy and supportive care with steroids, etc. Untreated patients exhibit a median survival of only approximately 1 month. The choice of treatment for brain metastasis depends on the number of lesions, the patient's general condition, nerve findings and presence of other metastatic lesions. We herein report the case of a 78-year-old male who presented with brain metastases originating from rectal carcinoma. He suffered from nausea, vomiting, anorexia and vertigo during body movement. He received antiemetics, glycerol and whole brain radiation therapy; however, these treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25 mg every night. The persistent nausea disappeared the next day, and the frequency of vomiting subsequently decreased. The patient was able to consume solid food. Olanzapine is an antipsychotic that has recently been used as palliative therapy for refractory nausea and vomiting in patients receiving chemotherapy. We consider that olanzapine was helpful as a means of supportive care for the treatment of nausea and vomiting due to brain metastasis.

  15. Is brain uptake of leptin in vivo saturable and reduced by fasting?

    Energy Technology Data Exchange (ETDEWEB)

    Karonen, S.L.; Nikkinen, P. [Department of Clinical Chemistry, Helsinki University Central Hospital, FIN-00290 Helsinki (Finland); Koistinen, H.A.; Koivisto, V.A. [Department of Medicine, Helsinki University Central Hospital, FIN-00290 Helsinki (Finland)

    1998-06-01

    Leptin is a peptide hormone produced by adipocytes which provides a negative feedback signal to control the amount of body fat. The action of leptin on food intake and weight loss is thought to be mediated by interaction with its hypothalamic receptor. We examined the biodistribution and brain uptake of radioiodinated leptin ({sup 123}I-leptin) by dynamic gamma imaging in six anaesthetized New Zealand white rabbits. Leptin uptake was seen in the brain, lungs, liver and kidneys. In the brain, increase in radioactivity as a function of time was seen in the choroid plexus area. The choroid plexus to brain radioactivity ratio (CP/BR) was used as the target to background ratio. The CP/BR ratio increased up to approximately 40-60 min, after which a steady state in CP/BR was achieved. The steady state uptake ratio was higher in the rabbits that had fasted for only 6-8 h before the experiment (CP/BR approximately 2.5) than in those that had fasted for 25-27 h before the experiment (CP/BR approximately 1.8). Thus, leptin uptake in vivo occurs in the choroid plexus region of the brain and in the lungs, kidney and the liver. The uptake of leptin in the choroid plexus appears to be saturable, as indicated by the achieved steady state in the CP/BR radioactivity curve 40-60 min following {sup 123}I-leptin injection. The lower steady state CP/BR after prolonged fasting may be the result of the downregulation of leptin receptors in the choroid plexus. (orig.) With 4 figs., 36 refs.

  16. 肿瘤标志物与非小细胞肺癌脑转移的相关性%Relationship between serum tumor markers and brain metastasis in patients with ad-vanced non - small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    刘艳萍; 曾爱屏; 宋向群; 周韶璋; 于起涛

    2015-01-01

    Objective:To explore the relationship between serum tumor markers and brain metastasis in patients with advanced non - small cell lung cancer(NSCLC). Methods:The clinical data of 289 advanced NSCLC patients hospitalized from April 2009 to October 2013 were retrospectively analyzed. All the enrolled patients were newly diag-nosed NSCLC with stage Ⅳ and not received treatment previously. Of those patients,223 had no brain metastasis. The rest were diagnosed with brain metastasis. Results:The incidence of brain metastasis was 22. 8%(66 / 289),the medi-an survival time of patients with the brain metastasis was 9. 4 months. The 1 - year and 2 - year survival rates were 37% and 15% respectively. The serum level of carcinoembryonic antigen(CEA)was significantly different between no brain metastasis patients and those who had(P = 0. 001). The median value of CEA of patients with and without brain metastasis was 6. 8ng/ ml,16. 0ng/ ml respectively. Overall survival was significantly shorter among patients with elevated serum CEA(median survival 15 months vs. 8 months,P = 0. 027)or CA125(median survival 13 months vs. 7 months,P = 0. 008). In multivariate analysis,CA125,radiotherapy and sex were independent prognostic factors for brain metastasis(P < 0. 05). Conclusion:The high serum CEA level may be potentially used as an indicator to predict the probability of brain metastasis in patients with NSCLC. The high serum CA125 may be used as reference index of the prognosis of brain metastasis in patients with NSCLC.%目的:探讨血清 CEA、CA125、CA153、CA199、CA724和 CYFRA21-1水平与晚期非小细胞肺癌(NSCLC)脑转移发生和预后的相关性。方法:回顾性分析我院2009年4月至2013年10月289例(非脑转移223例,脑转移66例)未进行过任何治疗的Ⅳ期 NSCLC 患者临床资料。结果:全组病例脑转移发生率为22.8%(66/289),66例脑转移的中位生存期为9.4个月,1年、2年生存率分别为37%、15

  17. Protective effect of carboxymethyl chitosan(CMC)on the liver and brain in mice damaged by Dgalactose%羧甲基壳聚糖对D-半乳糖诱导氧化损伤模型小鼠肝、脑的保护作用

    Institute of Scientific and Technical Information of China (English)

    付青姐; 李明春; 李强

    2011-01-01

    目的:探索羧甲基壳聚糖(CMC)对D-半乳糖诱导氧化损伤模型小鼠肝、脑的作用.方法:实验分为4组:对照组、CMC组、D-半乳糖模型组、D-半乳糖+ CMC组.测定各组小鼠肝、脑超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性、丙二醛(MDA)的含量及蛋白质羰基化程度.结果:D-半乳糖可诱导小鼠蛋白质羰基化,诱导小鼠氧化损伤,CMC可使小鼠蛋白质羰基化含量降低,SOD,CAT活性增加,MDA含量降低.结论:CMC对D-半乳糖引起的氧化损伤有一定的保护作用.%OBJECTIVE To investigate the protective effect of CMC on the liver and brain in mice damaged by D-galactose. METHODS Animals were divided into four groups: control group; D-galactose treated animals; control + CMC group; D-galactose + CMC group. Protein carbonyl and SOD, CAT, MDA of the liver and brain were detected. RESULTS D-galactose induced protein carbonyl of brain and liver, CMC decreased it. CMC increased the activity of SOD and CAT and decreased the MDA content. CONCLUSION CMC might play a protective effect on the oxidative protein damage of brain and liver in mice.

  18. Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver

    DEFF Research Database (Denmark)

    Oertel, Michael; Menthena, Anuradha; Chen, Yuan-Qing

    2008-01-01

    BACKGROUND & AIMS: Previously, we showed high-level, long-term liver replacement after transplantation of unfractionated embryonic day (ED) 14 fetal liver stem/progenitor cells (FLSPC). However, for clinical applications, it will be essential to transplant highly enriched cells, while maintaining....... Rat ED14 FLSPC are alpha-fetoprotein(+)/cytokeratin-19(+) or alpha-fetoprotein(+)/cytokeratin-19(-) and contain all of the normal liver repopulation capacity found in fetal liver. Hematopoietic stem cells, a major component in crude fetal liver cell preparations that engraft in other organs......, such as bone marrow, spleen, and lung, are totally removed by Dlk-1 selection, and Dlk-1 purified FLSPC repopulate only the liver. CONCLUSIONS: This is the first study reporting purification of hepatic stem/progenitor cells from fetal liver that are fully capable of repopulating the normal adult liver...

  19. Lung surgery

    Science.gov (United States)

    ... are thoracotomy and video-assisted thoracoscopic surgery (VATS). Robotic surgery may also be used. Lung surgery using a ... clot from the pulmonary artery ( pulmonary embolism ) Treat complications of tuberculosis Video-assisted thoracoscopic surgery can be used to treat many of these ...

  20. [Humidifier lung].

    Science.gov (United States)

    Gerber, P; de Haller, R; Pyrozynski, W J; Sturzenegger, E R; Brändli, O

    1981-02-07

    Breathing air from a humidifier or an air conditioning unit contaminated by various microorganisms can cause an acute lung disease involving fever, cough and dyspnea, termed "humidifier fever". This type of hypersensitivity pneumonitis was first described in 1959 by PESTALOZZI in the Swiss literature and subsequently by BANASZAK et al. in the Anglo-American. Here a chronic form of this disease which led to pulmonary fibrosis is described: A 37-year-old woman who works in a cheese shop presented with dyspnea which had been progressive over two years, weight loss, a diffuse reticular pattern radiographically and a severe restrictive defect in lung function tests. Open lung biopsy revealed chronic interstitial and alveolar inflammation with non-caseating granulomas and fibrotic changes. Circulating immune complexes and precipitins against the contaminated humidifier water and cheese mites were found, but no antibodies suggesting legionnaires' disease. Two out of five otherwise healthy employees of this cheese shop, where a new humidifying system had been installed 7 years earlier, also had precipitins against the contaminated water from the humidifier and the cheese mites. Despite ending of exposure and longterm steroid and immunosuppressive therapy, the signs and symptoms of pulmonary fibrosis persisted. Contrary to the acute disease, this chronic form is termed "humidifier lung". The importance is stressed of investigating the possibility of exposure to contaminated humidifiers or air conditioning units in all cases of newly detected pulmonary fibrosis.

  1. Lung cancer

    DEFF Research Database (Denmark)

    Hansen, H H; Rørth, M

    1999-01-01

    The results of the many clinical trials published in 1997 had only modest impact on the treatment results using either cytostatic agents alone or combined with radiotherapy in lung cancer. In SCLC, combination chemotherapy including platin-compounds (cisplatin, carboplatin) and the podophyllotoxins...

  2. CXCR4/CXCL12 Axis in Non Small Cell Lung Cancer (NSCLC Pathologic Roles and Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Ori Wald, Oz M. Shapira, Uzi Izhar

    2013-01-01

    Full Text Available Lung cancer is the second most common malignancy and the leading cause of cancer-related death in the western world. Moreover, despite advances in surgery, chemotherapy and radiotherapy, the death rate from lung cancer remains high and the reported overall five-year survival rate is only 15%. Thus, novel treatments for this devastating disease are urgently needed. Chemokines, a family of 48 chemotactic cytokines interacts with their 7 transmembrane G-protein-coupled receptors, to guide immune cell trafficking in the body under both physiologic and pathologic conditions. Tumor cells, which express a relatively restricted repertoire of chemokine and chemokine receptors, utilize and manipulate the chemokine system in a manner that benefits both local tumor growth and distant dissemination. Among the 19 chemokine receptors, CXCR4 is the receptor most widely expressed by malignant tumors and whose role in tumor biology is most thoroughly studied. The chemokine CXCL12, which is the sole ligand of CXCR4, is highly expressed in primary lung cancer as well as in the bone marrow, liver, adrenal glands and brain, which are all sites for lung cancer metastasis. This review focuses on the pathologic role of the CXCR4/CXCL12 axis in NSCLC and on the potential therapeutic implication of targeting this axis for the treatment of NSCLC.

  3. Pyrosequencing reveals the complex polymicrobial nature of invasive pyogenic infections: microbial constituents of empyema, liver abscess, and intracerebral abscess.

    Science.gov (United States)

    Sibley, C D; Church, D L; Surette, M G; Dowd, S E; Parkins, M D

    2012-10-01

    The polymicrobial nature of invasive pyogenic infections may be underestimated by routine culture practices, due to the fastidious nature of many organisms and the loss of viability during transport or from prior antibacterials. Pyrosequencing was performed on brain and liver abscesses and pleural fluid and compared to routine culture data. Forty-seven invasive pyogenic infection samples from 44 patients [6 intracerebral abscess (ICA), 21 pyogenic liver abscess (PLA), and 18 pleural fluid (PF) samples] were assayed. Pyrosequencing identified an etiologic microorganism in 100 % of samples versus 45 % by culture, p <0.01. Pyrosequencing was also more likely than traditional cultures to classify infections as polymicrobial, 91 % versus 17 %, p <0.001. The median number of genera identified by pyrosequencing compared to culture was 1 [interquartile range (IQR) 1-3] versus 0 (IQR 0-1) for ICA, 7 (IQR 1-15) versus 1 (IQR 0-1) for PLA, and 15 (IQR 9-19) versus 0 (IQR 0-1) for PF. Where organisms were cultured, they typically represented the numerically dominant species identified by pyrosequencing. Complex microbial communities are involved in invasive pyogenic infection of the lung, liver, and brain. Defining the polymicrobial nature of invasive pyogenic infections is the first step towards appreciating the clinical and diagnostic implications of these complex communities.

  4. Liver Function Tests

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  5. Benign Liver Tumors

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  6. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  7. Liver Transplant: Nutrition

    Science.gov (United States)

    ... ZIP code here Enter ZIP code here Liver Transplant: Nutrition for Veterans and the Public Nutrition Liver ... apply to transplant and liver disease patients. Pre-Transplant Protein Malnutrition -- Many patients with end stage liver ...

  8. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  9. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008447 Identification of gene expression patterns in a rat model of nonalcoholic fatty liver disease. ZHANG Xuequn(张雪群), et al. Dept Gastroenterol, 1st Hosp, Med Coll, Zhejiang Univ, Hangzhou 310003. Chin J Dig 2008;28(5):323-327. Objective To compare and analyze gene expression patterns in a rat model of nonalcoholic fatty liver disease (NAFLD). Methods Twelve male Sprague-Dawley rats were randomly given either general diet (control group) or a high-fat diet (model group) for 4 weeks.

  10. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008310 Expression of αVβ3 integrin and platelet-endothelial cell adhesion molecule-1 in progressive liver fibrosis: experiment with rats. SONG Zhengji(宋正已), et al. Dept Gastroenterol, Zhongshan Hosp, Fudan Univ, Shanghai 200032. Natl Med J China 2008;88(16):1121-1125.Objective To investigate the expression ofαVβ3 integrin and platelet endothelial cell adhesion molecule-1(CD31)in progressive liver fibrosis of rats.Methods Sixty-four SD rats were randomly divided into 4 equal groups:TAA group,undergoing peritoneal injection of

  11. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008075 Effect of Jiangzhi granules on expression of leptin receptor mRNA, P-JAK2 and P-STAT3 in rats with non-alcoholic fatty liver disease. MA Zansong(马赞颂), et al. Dept Gastroenterol, Instit Spleen and Stomach Dis, Longhua Hosp. Shanghai TCM Univ, Shanghai 200032.World Chin J Digestol 2007;15(32):3360-3366. Objective To study the effect of Jiangzhi granules on non-alcoholic fatty liver disease in rats, and on the expression of

  12. Effect of Leukocytes Transfer on the Induction of Liver Damage after Renal Ischemia- Reperfusion in Inbred Mice

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    Hossein Khastar

    2012-07-01

    Full Text Available Introduction: Renal ischemia-reperfusion (IR induces organ damage in remote organs such as liver, brain and lung. The aim of this study was to assess the role of leukocytes in the induction of liver damage after renal IR injury.Methods: Inbred mice were subjected to either sham operation or bilateral renal IR injury (60 min ischemia followed by 3h reperfusion. Mice were then anesthetized for collection of leukocytes by heart puncture. Isolated leukocytes were transferred to two other groups: intact recipient mice that received leukocytes from IR mice and intact recipient mice that received leukocytes from sham-operated control mice. After 24h, recipient mice were anesthetized and blood and hepatic samples were collected.Results: Alanine aminotransferase (ALT, aspartate aminotransferase (AST and hepatic malondialdehyde (MDA increased significantly in intact recipient mice that received leukocytes from IR mice in comparison to intact recipient mice receiving leukocytes from sham-operated control mice. In addition, loss of normal liver architecture, cytoplasmic vacuolization and focal infiltration of leukocytes were observed.Conclusion: These results suggest that leukocytes are one of the possible factors that contribute to liver damage after renal IR injury and this damage is partly due to the induction of oxidative stress.

  13. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970345 An experimental and clinical study on α1-adrenergic receptor of liver plasma membranes in cir-rhosis with portal hypertension. ZHANG Youcheng(张有成), et al. Dept Surg, People’s Hosp, Beijing MedUniv, Beijing, 100044 Chin J Dig 1996; 16(6): 332-335.

  14. 脑死亡供体鼠吸入一氧化碳对受体鼠移植肺损伤的影响%Effects of carbon monoxide inhalation by brain death donor on the transplanted lung Injury in recipient of rats

    Institute of Scientific and Technical Information of China (English)

    周华成; 李文志; 潘鹏; 吕湘琪; 金笛; 丁文刚

    2009-01-01

    Objective To investigate the effects of carbon monoxide (CO) inhalation by brain death (BD) donor on transplanted lung injury in recipient of rats. Methods Twenty-four male Wistar rats weighing 250-300 g were randomly divided into 3 groups ( n = 8 each) : group Ⅰ donor without brain death (NBD) ; group Ⅱ brain death donor inhaling O2 (BDO2) and group Ⅲ brain death donor inhaling CO (BDCO). The donor rats were anesthetized with intraperitoneal pentobarbital sodium 60 mg/kg, trachoostomized and mechanically ventilated (VT 10 ml/kg, RR 50 bpm, PEEP 2 cm H2O). BD was induced by inserting a Fogarty catheter into the skull and brain was compressed by inflating the balloon according to Avlonitis VS. After BD was confirmed, 40% O2 was inhaled for 2 h in group Ⅱ and a mixture of 40% O2 + 0.025% CO was inhaled for 2 h in group Ⅲ . MAP was maintained at 80-100 mm Hg. Cuff technique was used for orthotopic left lung transplantation according to Mizobuchi T.Arterial blood samples were obtained every 30 min in recipient for blood gas analysis. The recipients were killed by exsangmnation at 2 h after lung transplantation and blood was collected for determination of SOD activity and MDA, IL-6, IL-10 and TNF-α concentrations. The transplant lung was removed for determination of W/D lung weight ratio, MPO activity in the lung tissue and microscopic examination. Lung injury scores were calculated. Results PaO2/FiO2, BE, pH, plasma SOD activity and IL-10 concentrations were significantly lower while W/D lung weight ratio, MPO activity in the lung tissue and lung injury scores of the transplant lung were significantly higher in group BDO2 and BDCO than in group (NBD). PaO2/FiO2, BE, pH, plasma SOD activity and IL-10 concentration were significantly higher and W/D ratio, MPO activity in the lung tissue, lung injury scores of the transplant lung and plasma concentrations of MDA, IL-6 and TNF-α were significantly lower in group BDCO than in group BDO2. Conclusion Inhalation of

  15. 同步加量放疗技术在非小细胞肺癌脑转移患者中的应用%Simultaneous integrated boost conformal radiotherapy in non -small cell lung cancer patients with brain metastases

    Institute of Scientific and Technical Information of China (English)

    王浩; 吴磊; 王天昶; 李涛; 王亚丽; 高艳梅; 刘秋芳

    2014-01-01

    目的:评估同步加量放疗技术在非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移应用中的临床疗效、不良反应、生存时间,探索该技术的可行性。方法:76例NSCLC脑转移患者以不同分割模式分为A组(42例)和B组(34例)。A组患者全脑放疗DT 40Gy/(20f·4周)后局部推量DT 20Gy/(10f·2周),B组患者全脑放疗DT 36Gy/(20f·4周)全程同步加量适形放疗DT 24Gy/(20f·4周)。比较两组放疗疗效、不良反应、半年、1年总生存率。结果:采用 RECIST 1.1标准,A组放疗有效率为95.2%(40/42),B组有效率为97.1%(33/34),两组疗效未见统计学差异。A、B两组患者在血液毒性、神经系统受损、消化道反应、脱发等方面均未见明显异常。A组中位生存时间为8.94个月,患者半年、1年生存率为71.4%、35.7%;B组患者中位生存时间为9.47个月,半年、1年生存率为82.4%、38.2%,两组无统计学差异。结论:两种分割模式在临床疗效、不良反应、生存时间方面疗效相当。全脑照射全程同步加量治疗脑转移近期疗效确切,患者耐受性很好,可缩短放疗时间。%Objective:To observe the local control rate,survival rate and side effects of the patients with brain me-tastases by whole brain radiotherapy (WBRT)with local simultaneous integrated boost conformal radiotherapy (SIB-CR).Methods:Seventy-six patients with brain metastasis of NSCLC were randomly divided into group A (n=42) and group B (n=34).Group A received 40Gy whole brain radiation in 20 fractions over four weeks followed by 20Gy focal radiation in 10 fractions over two weeks.Group B received 36Gy whole brain radiation in 20 fractions over four weeks with simultaneous integrated boost by 24Gy focal radiation in 20 fractions.Therapeutic effect,adverse reac-tions and survival time were evaluated.Results:Using RECIST 1 .1 treatment response

  16. Staging of Lung Cancer

    Science.gov (United States)

    ... is important for two reasons. First, staging your lung cancer helps decide which therapy (or therapies) should be used. Second, lung cancer ... 422-6237 http://www.cancer.gov/cancertopics/wyntk/lung/page8 http://www.cancer.gov/cancertopics/pdq/treatment/non- small-cell-lung/Patient/page2 National Lung ...

  17. [(Bio)artificial liver support: ready for the patient?].

    Science.gov (United States)

    Chamuleau, R A F M

    2016-05-01

    In 2016, an intensive-care physician has at his disposal a number of artificial organs for the support of patients with organ failure. Examples are the artificial kidney and the heart-lung machine. Artificial livers are being developed for patients with severe liver failure whose lives can only be saved at the present time by a transplant with a donor liver. These artificial livers are based either on a device that removes toxic materials from the patient's blood with, for example, albumin dialysis, or make use of bio-reactors filled with functioning liver cells, the so-called bio-artificial liver. In theory, the bio-artificial liver has the greatest potential to increase life expectancy. The results of clinical studies are also very promising. They are not yet sufficient, however, to permit general clinical use.

  18. Morte encefálica, cuidados ao doador de órgãos e transplante de pulmão Brain death, multiorgan donor and lung transplantation

    Directory of Open Access Journals (Sweden)

    Fernando D'Império

    2007-03-01

    patients. This position is a result of great advances in the field of immunology, critical care medicine and pharmacology. However, organ transplantation is now suffering from its own success as the number of patients in waiting lists is dramatically increasing the same is not happening with organ availability results in increasing number of mortalities while waiting for transplantation. Transplant community responses to this situation consist of reviewing the criteria for organ acceptability and developing new strategies to get organs as the called non-heart beating organ donors. CONTENTS: However the physiopathology of brain death and its consequences are now better understood helping in such patients' management. The purpose of this review is to help to identify the most important clinical and therapeutic aspects related to its physiopathology as depletion of vasoactives substances and its importance in the management of cardio and respiratory systems. We also discuss endocrine and hidroelectrolytes disturbances. Organ specific data are also focused in order to offer a whole view of donor management. CONCLUSIONS: It is important to observe that new technologies will be available in the near future to diminish the low rate between organ availability and organ waiting patients. In conclusion, with the raising numbers in transplant waiting lists and scarce resources of organs make us believe that we have to improve the management of multi organ donors and the preservation technology in order to reduce the mortality in such waiting lists.

  19. The Conceptual Oligometastatic Non-small Cell Lung Cancer and Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Xiaozheng KANG

    2012-04-01

    Full Text Available Non-small cell lung cancer (NSCLC ranks among the most prevalent malignancies and is the major cause of cancer-related deaths worldwide. Nearly 20%-50% will accompany by metastatic disease and the most common extrapulmonary sites of distant metastases are the brain, bone, liver and adrenal gland. The oligometastatic state is a biologically mild tumor stage and a intermediate state in which spread may be limited to specific organs and metastases might be present in limited numbers. Oligometastases are thought to arise from micrometastases, which have been dormant for a period of time. Local control may be an crucial component of a curative therapeutic strategy in the following four clinical schemes: to prohibit metastases; to cure occult metastatic disease; to remedy oligometastases; and to deracinate any residual lesion after systemic therapy. This review aims to outline the concept of the oligometastatic NSCLC and its strategies of treatment.

  20. Severe liver dysfunction in an infant with cystic fibrosis masquerading as metabolic liver disease

    Directory of Open Access Journals (Sweden)

    K P Srikanth

    2016-01-01

    Full Text Available We present a rare presentation of cystic fibrosis with neonatal cholestasis. Histological features of mucoviscidosis were present in liver involving the biliary tract, intestinal mucosa, pancreas, and lung. Besides, there was a rare association with autosomal dominant type of polycystic renal disease.

  1. Ultrasound for critical care physicians: 50 ways to line your liver

    Directory of Open Access Journals (Sweden)

    Skiles S

    2015-11-01

    Full Text Available No abstract available. Article truncated after first page. A 54 year-old man with a past medical history significant for traumatic brain injury and aspiration pneumonia presented with hypoxic respiratory failure secondary to foreign body aspiration. On presentation, the patient was found to be hypoxic and tachypneic, requiring endotracheal intubation and mechanical ventilation. Bronchoscopy was performed with removal of extensive food particles throughout both lungs. The patient subsequently developed sepsis secondary to aspiration pneumonia. He became hypotensive, requiring central venous catheter placement for vasopressor therapy. A right subclavian central line was attempted under ultrasound guidance. A beside ultrasound was subsequently performed (Video 1. What does the video obtained of a longitudinal view of the IVC at the level of the liver demonstrate? 1. Endocarditis; 2. Guidewire in the hepatic vein; 3. Hemopericardium; 4. Pneumothorax.

  2. Brain Basics

    Medline Plus

    Full Text Available ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  3. Brain Basics

    Science.gov (United States)

    ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  4. Cryptococcus gattii fungemia: report of a case with lung and brain lesions mimicking radiological features of malignancy Fungemia por Cryptococcus gattii: relato de um caso com lesões cerebrais e pulmonares nos achados radiológicos mimetizando câncer

    Directory of Open Access Journals (Sweden)

    Flávio de Mattos Oliveira

    2007-08-01

    Full Text Available A 64-year-old apparently immunocompetent white man developed lung and brain lesions of disseminated cryptococcosis. The radiologic features mimicked those of lung cancer metastatic to the central nervous system. C. gattii was recovered from cultures of bronchoalveolar lavage fluid, brain biopsy, and blood. The same fungus was recovered from pulmonary and brain specimens at autopsy. Serum and cerebrospinal fluid cryptococcal antigen tests were diagnostic in our case and should be included in the diagnostic evaluation of unexplained pulmonary and cerebral lesions. A literature search showed few reports of fungemia by this species of Cryptococcus, contrasting to C. neoformans.Homem branco de 64 anos, aparentemente imunocompetente, desenvolveu lesões pulmonares e cerebrais por criptococose disseminada. Os achados radiológicos foram similares àqueles encontrados em pacientes com câncer de pulmão e metástase no sistema nervoso central. C. gattii foi isolado de cultivos de lavado broncoalveolar, biópsia cerebral e sangue. O mesmo fungo foi encontrado em fragmentos pulmonares e cerebrais obtidos da autópsia. Testes de antígeno no soro e no líquido cefalorraquidiano foram diagnóstico no nosso caso e devem ser incluídos na avaliação diagnóstica de lesões pulmonares e cerebrais indefinidas. Pesquisa na literatura mostrou poucos relatos de fungemia por esta espécie de Cryptococcus, contrastando com C. neoformans.

  5. Impact of bronchopulmonary dysplasia on brain and retina.

    Science.gov (United States)

    Poon, Annie Wing Hoi; Ma, Emilie Xiao Hang; Vadivel, Arul; Jung, Suna; Khoja, Zehra; Stephens, Laurel; Thébaud, Bernard; Wintermark, Pia

    2016-04-15

    Many premature newborns develop bronchopulmonary dysplasia (BPD), a chronic lung disease resulting from prolonged mechanical ventilation and hyperoxia. BPD survivors typically suffer long-term injuries not only to the lungs, but also to the brain and retina. However, currently it is not clear whether the brain and retinal injuries in these newborns are related only to their prematurity, or also to BPD. We investigated whether the hyperoxia known to cause histologic changes in the lungs similar to BPD in an animal model also causes brain and retinal injuries. Sprague Dawley rat pups were exposed to hyperoxia (95% O2, 'BPD' group) or room air (21% O2, 'control' group) from postnatal day 4-14 (P4-14); the rat pups were housed in room air between P14 and P28. At P28, they were sacrificed, and their lungs, brain, and eyes were extracted. Hematoxylin and eosin staining was performed on lung and brain sections; retinas were stained with Toluidine Blue. Hyperoxia exposure resulted in an increased mean linear intercept in the lungs (P<0.0001). This increase was associated with a decrease in some brain structures [especially the whole-brain surface (P=0.02)], as well as a decrease in the thickness of the retinal layers [especially the total retina (P=0.0008)], compared to the room air control group. In addition, a significant negative relationship was observed between the lung structures and the brain (r=-0.49,P=0.02) and retina (r=-0.70,P=0.0008) structures. In conclusion, hyperoxia exposure impaired lung, brain, and retina structures. More severe lung injuries correlated with more severe brain and retinal injuries. This result suggests that the same animal model of chronic neonatal hyperoxia can be used to simultaneously study lung, brain and retinal injuries related to hyperoxia.

  6. Impact of bronchopulmonary dysplasia on brain and retina

    Directory of Open Access Journals (Sweden)

    Annie Wing Hoi Poon

    2016-04-01

    Full Text Available Many premature newborns develop bronchopulmonary dysplasia (BPD, a chronic lung disease resulting from prolonged mechanical ventilation and hyperoxia. BPD survivors typically suffer long-term injuries not only to the lungs, but also to the brain and retina. However, currently it is not clear whether the brain and retinal injuries in these newborns are related only to their prematurity, or also to BPD. We investigated whether the hyperoxia known to cause histologic changes in the lungs similar to BPD in an animal model also causes brain and retinal injuries. Sprague Dawley rat pups were exposed to hyperoxia (95% O2, ‘BPD’ group or room air (21% O2, ‘control’ group from postnatal day 4–14 (P4–14; the rat pups were housed in room air between P14 and P28. At P28, they were sacrificed, and their lungs, brain, and eyes were extracted. Hematoxylin and eosin staining was performed on lung and brain sections; retinas were stained with Toluidine Blue. Hyperoxia exposure resulted in an increased mean linear intercept in the lungs (P<0.0001. This increase was associated with a decrease in some brain structures [especially the whole-brain surface (P=0.02], as well as a decrease in the thickness of the retinal layers [especially the total retina (P=0.0008], compared to the room air control group. In addition, a significant negative relationship was observed between the lung structures and the brain (r=−0.49, P=0.02 and retina (r=−0.70, P=0.0008 structures. In conclusion, hyperoxia exposure impaired lung, brain, and retina structures. More severe lung injuries correlated with more severe brain and retinal injuries. This result suggests that the same animal model of chronic neonatal hyperoxia can be used to simultaneously study lung, brain and retinal injuries related to hyperoxia.

  7. [Changes in the intensity of ultrasound echograp