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Hydroxysafflor yellow A protects against thioacetamide-induced liver fibrosis in rats via suppressing proinflammatory/fibrogenic mediators and promoting hepatic stellate cell senescence and apoptosis
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作者 Sayed H.Seif el-Din Olfat A.Hammam +4 位作者 Shahira M.Ezzat Samira Saleh Marwa M.Safar Walaa H.El-Maadawy Naglaa M.El-Lakkany 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2023年第8期348-358,共11页
Objective:To evaluate the effect of hydroxysafflor yellow A(HSYA)on thioacetamide-induced liver fibrosis.Methods:Thioacetamide was administered to rats intraperitoneally in doses of 200 mg/kg twice a week for 12 weeks... Objective:To evaluate the effect of hydroxysafflor yellow A(HSYA)on thioacetamide-induced liver fibrosis.Methods:Thioacetamide was administered to rats intraperitoneally in doses of 200 mg/kg twice a week for 12 weeks.Thioacetamide-intoxicated rats were given silymarin(50 mg/kg)or HSYA(5 mg/kg)orally every day for 8 weeks.Liver enzymes,fibrosis markers,histological changes as well as immunohistochemistry of TNF-α,IL-6,p21,α-SMA,and caspase-3 were examined.The effect of HSYA on HSC-T6 activation/proliferation and apoptosis was also determined in vitro.Results:HSYA decreased liver enzymes,TNF-α,IL-6,and p21 expressions,hepatic PDGF-B,TIMP-1,TGF-β1,and hydroxyproline levels,as well as fibrosis score(S2 vs.S4)compared to the thioacetamide group.HSYA also downregulatedα-SMA while increasing caspase-3 expression.Surprisingly,at 500μg/mL,HSYA had only a slightly suppressive effect on HSC proliferation,with a 9.5%reduction.However,it significantly reduced TGF-β1,inhibitedα-SMA expression,induced caspase-3 expression,and promoted cell senescence.Conclusions:HSYA may be a potential therapeutic agent for delaying and reversing the progression of liver fibrosis.More research on HSYA at higher doses and for a longer period is warranted. 展开更多
关键词 Hydroxysafflor yellow A THIOACETAMIDE Hepatic stellate cells Inflammatory markers Liver fibrosis p21 α-SMA APOPTOSIS
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Codiaeum Variegatum Hydro Alcoholic Leaf Extracts and Their Fractions Inhibit Pro-Inflammatory Mediators in Vitro
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作者 Sylvain Pechangou Nsangou Charifa Ngbetkom Mandou +6 位作者 Carine Matsigang Fondjou Vigny Sayal Ngohoba Edie Brice Enang II Ibrahim Njingou Emmanuel Mfotie Njoya Frederic Nico Njayou Paul Moundipa Fewou 《Journal of Biosciences and Medicines》 CAS 2023年第5期40-54,共15页
Codiaeum variegatum has been widely investigated for its biological proprieties ranging from the antiamoebic potential to the phytochemical analysis. The aim of the present study was to evaluate the anti-inflammatory ... Codiaeum variegatum has been widely investigated for its biological proprieties ranging from the antiamoebic potential to the phytochemical analysis. The aim of the present study was to evaluate the anti-inflammatory potential of C. variegatum leaf extracts and fractions. A primary macrophage culture activated by Saccharomyces cereviseae (SC) was used to evaluate cell cytotoxicity and anti-inflammatory potential of the plant extracts and fractions. Macrophages were treated with different concentrations (0.1;1;10 and 100 μg/mL) of the extracts/fractions for the inhibition of 5-lipoxygenase activity, nitric oxide (NO) and Tumor Necrosis Factor Alpha (TNF-α) production. No significant difference was observed on cell viability in the presence of extracts and fractions at tested concentration during the incubation period. Extracts and fractions of C. variegatum inhibited the 5-lipoxygenase activity, NO and TNF-α production by viable primary mouse macrophages in a concentration-dependent manner. The fractionation process increased anti-inflammatory activity. Among fractions, HEF2, HEF3, HEF5, EEF1, EEF3 and EEF5 exhibited the best anti-inflammatory potential. C. variegatum extracts and fractions exhibited a greater anti-inflammatory potential throughout the inhibition of pro-inflammatory mediators such as NO, 5-Lox and TNF-α. 展开更多
关键词 C. variegatum ANTI-INFLAMMATORY 5-LIPOXYGENASE NO TNF-α
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Deciphering key genes involved in cisplatin resistance in kidney renal clear cell carcinoma through a combined in silico and in vitro approach
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作者 MUNEEBA MALIK MAMOONA MAQBOOL +8 位作者 TOOBA NISAR TAZEEM AKHTER JAVED AHMED UJAN ALANOOD SALGARNI FAKHRIA AAL JOUFI SULTAN SHAFI KALANAZI MOHAMMAD HADI ALMOTARED MOUNIR MSALEM BEKHIT MUHAMMAD JAMIL 《Oncology Research》 SCIE 2023年第6期899-916,共18页
The low survival rate of Kidney renal clear cell carcinoma(KIRC)patients is largely attributed to cisplatin resistance.Rather than focusing solely on individual proteins,exploring protein-protein interactions could of... The low survival rate of Kidney renal clear cell carcinoma(KIRC)patients is largely attributed to cisplatin resistance.Rather than focusing solely on individual proteins,exploring protein-protein interactions could offer greater insight into drug resistance.To this end,a series of in silico and in vitro experiments were conducted to identify hub genes in the intricate network of cisplatin resistance-related genes in KIRC chemotherapy.The genes involved in cisplatin resistance across KIRC were retrieved from the National Center for Biotechnology Information(NCBI)database using search terms as“Kidney renal clear cell carcinoma”and“Cisplatin resistance”.The genes retrieved were analyzed for hub gene identification using the STRING database and Cytoscape tool.Expression and promoter methylation profiling of the hub genes was done using UALCAN,GEPIA,OncoDB,and HPA databases.Mutational,survival,functional enrichment,immune cell infiltration,and drug prediction analyses of the hub genes were performed using the cBioPortal,GEPIA,GSEA,TIMER,and DrugBank databases.Lastly,expression and methylation levels of the hub genes were validated on two cisplatin-resistant RCC cell lines(786-O and A-498)and a normal renal tubular epithelial cell line(HK-2)using two high throughput techniques,including targeted bisulfite sequencing(bisulfite-seq)and RT-qPCR.A total of 124 genes were identified as being associated with cisplatin resistance in KIRC.Out of these genes,MCL1,IGF1R,CCND1,and PTEN were identified as hub genes and were found to have significant(p<0.05)variations in their mRNA and protein expressions and effects on the overall survival(OS)of the KIRC patients.Moreover,an aberrant promoter methylation pattern was found to be associated with the dysregulation of the hub genes.In addition to this,hub genes were also linked with different cisplatin resistance-causing pathways.Thus,hub genes can be targeted with Alvocidib,Estradiol,Tretinoin,Capsaicin,Dronabinol,Metribolone,Calcitriol,Acetaminophen,Acitretin,Cyclosporine,Azacitidine,Genistein,and Resveratrol drugs.As the pathogenesis of KIRC is complex,targeting hub genes and associated pathways involved in cisplatin resistance could bring a milestone change in the drug discovery and management of drug resistance,which might uplift overall survival among KIRC patients. 展开更多
关键词 KIRC Cisplatin resistance CHEMOTHERAPY Overall survival
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Hydro-Alcoholic Leaf Extract and Fractions of Codiaeum variegatum (var. Mollucanum) Exhibited an Improved Anti-Amoebic and Moderate Anti-Oxidant Potential
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作者 Sylvain Pechangou Nsangou Carine Matsingang Fondjou +5 位作者 Charifa Ngbetnkom Mandou Sunil Kumar Mfotie Njoya Emmanuel Frederic Nico Njayou Rakesh Sehgal Paul Fewou Moundipa 《American Journal of Plant Sciences》 CAS 2023年第3期339-356,共18页
Amoebiasis, classified as the third intestinal parasitic infection, represents a public health problem in low-income countries where hygiene and sanitation conditions are poor. With the resurgence of resistant pathoge... Amoebiasis, classified as the third intestinal parasitic infection, represents a public health problem in low-income countries where hygiene and sanitation conditions are poor. With the resurgence of resistant pathogenic strains as well as ancestral considerations in developing countries such as Cameroon, many people rely on medicinal plants to treat a plethora of diseases. This work aimed to highlight the anti-amoebic and anti-oxidant potential of Codiaeum variegatum extracts and fractions. The anti-amoebic potential of C. variegatum was assayed on the polyxenic culture of the clinical isolates of E. histolytica. Then, the anti-oxidant potential of the ethanolic/hydroethanolic extracts and fractions was evaluated through DPPH radical scavenging, iron reduction (FRAP), lipid peroxidation inhibitory potential and total antioxidant capacity tests followed by the determination of phenolic compound and flavonoid content. It was found that the fractionation process decreased the amoebicidal activities of C. variegatum leaf extracts. However hydroethanolic extract (CI<sub>50</sub>: 10.08 ± 0.42, 5.18 ± 0.09, 5.18 ± 0.09 μg/mL respectively after 24, 48 and 72 hours) was more active than ethanolic extract (CI<sub>50</sub>: 15.59 ± 6.17;9.61 ± 2.37;6.26 ± 3.22 μg/mL respectively after 24, 48 and 72 hours). Interestingly, the activities of hydroethanolic extract were significantly non-different compared to metronidazole CI<sub>50</sub>: 8.42 ± 0.44, 6.45 ± 0.22 and 3.42 ± 0.33 μg/mL, respectively after 24, 48 and 72 hours). Ethanolic extract and EF5 showed higher Phenolic compound contents and higher antioxidant activity than hydroethanolic extract and other fractions through DPPH radical scavenging power (EC50 = 311.50 ± 4.12 μg/mL) and total antioxidant capacity (44 ± 0.07 mgEAA/gF). However, these activities are significantly lower than those of ascorbic acid (EC50 = 31.20 ± 4.39 μg/mL, and 61.34 ± 4.42 μg/mL respectively). This low antioxidant activity was confirmed by poor phenolic and flavonoid compounds contents found in the extracts and fractions. The present result brings a new approach to the ethnopharmacological uses of C. variegatum against dysentery in cases associated with Amoebiasis in Cameroun. 展开更多
关键词 Codiaeum Variegatum AMOEBIASIS Antiamoebic Antioxidant
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Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump 被引量:20
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作者 Yvonne Meier Tina Zodan +5 位作者 Carmen Lang Roland Zimmermann Gerd A Kullak-Ublick Peter J Meier Bruno Stieger Christiane Pauli-Magnus 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第1期38-45,共8页
AIM: To study the association of three common ABCB11 and ABCC2 polymorphisms (ABCB11: 1331T>C V444A; ABCC2: 3563T>A V1188E and 4544G>A C1515Y) with intrahepatic cholestasis of pregnancy (ICP) and contraceptiv... AIM: To study the association of three common ABCB11 and ABCC2 polymorphisms (ABCB11: 1331T>C V444A; ABCC2: 3563T>A V1188E and 4544G>A C1515Y) with intrahepatic cholestasis of pregnancy (ICP) and contraceptive-induced cholestasis (CIC). METHODS: ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele.RESULTS: The ABCB11 1331T>C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls: C allele 76.2% (CI, 58.0-94.4) vs 51.3% (CI 35.8-66.7), respectively (P = 0.0007); and CC allele 57.1% (CI 36.0-78.3) vs 20% (CI 7.6-32.4), respectively (P = 0.0065). All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype.CONCLUSION: Our data support a role for the ABCB11 1331T>C polymorphism as a susceptibility factor for the ←←← development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and γ-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC. 展开更多
关键词 怀孕 避孕药 胆汁郁积 药物反应遗传学 胆汁盐
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Metabolic shift in liver: Correlation between perfusion temperature and hypoxia inducible factor-1α 被引量:5
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作者 Andrea Ferrigno Laura Giuseppina Di Pasqua +2 位作者 Alberto Bianchi Plinio Richelmi Mariapia VairettiAndrea Ferrigno 《World Journal of Gastroenterology》 SCIE CAS 2015年第4期1108-1116,共9页
AIM: To study at what temperature the oxygen carried by the perfusate meets liver requirements in a model of organ perfusion. METHODS: in this study, we correlated hypoxia induciblefactor(Hi F)-1α expression to the p... AIM: To study at what temperature the oxygen carried by the perfusate meets liver requirements in a model of organ perfusion. METHODS: in this study, we correlated hypoxia induciblefactor(Hi F)-1α expression to the perfusion temperature and the hepatic oxygen uptake in a model of isolated perfused rat liver. Livers from Wistar rats were perfused for 6 h with an oxygenated medium at 10, 20, 30 and 37 ℃. Oxygen uptake was measured by an oxygen probe; lactate dehydrogenase activity, lactate release and glycogen were measured spectrophotometrically; bile flow was gravitationally determined; p H of the perfusate was also evaluated; Hi F-1α m RNA and protein expression were analyzed by real time-polymerase chain reaction and ELi SA, respectively. RESULTS: Livers perfused at 10 and 20 ℃ showed no difference in lactate dehydrogenase release after 6 h of perfusion(0.96 ± 0.23 vs 0.93 ± 0.09 m U/min per g) and had lower hepatic damage as compared to 30 and 37 ℃(5.63 ± 0.76 vs 527.69 ± 45.27 m U/min per g, respectively, P s < 0.01). After 6 h, tissue ATP was significantly higher in livers perfused at 10 and 20 ℃than in livers perfused at 30 and 37 ℃(0.89 ± 0.06 and 1.16 ± 0.05 vs 0.57 ± 0.09 and 0.33 ± 0.08 nmol/mg, respectively, P s < 0.01). No sign of hypoxia was observed at 10 and 20 ℃, as highlighted by low lactate release respect to livers perfused at 30 and 37 ℃(121.4 ± 12.6 and 146.3 ± 7.3 vs 281.8 ± 45.3 and 1094.5 ± 71.7 nmol/m L, respectively, P s < 0.02), and low relative Hi F-1α m RNA(0.40 ± 0.08 and 0.20 ± 0.03 vs 0.60 ± 0.20 and 1.47 ± 0.30, respectively, P s < 0.05) and protein(3.72 ± 0.16 and 3.65 ± 0.06 vs 4.43 ± 0.41 and 6.44 ± 0.82, respectively, P s < 0.05) expression.CONCLUSION: Livers perfused at 10 and 20 ℃ show no sign of liver injury or anaerobiosis, in contrast to livers perfused at 30 and 37 ℃. 展开更多
关键词 ANAEROBIOSIS HYPOXIA INDUCIBLE factor-1 α ISCHEMIA
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Hepatocellular transport proteins and their role in liver disease 被引量:2
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作者 Carmen Stanca Diana Jung +1 位作者 Peter J.Meier Gerd A.Kullak-Ublick 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第2期157-169,共13页
MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte... MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte cultures and basolateral plasma membrane vesicles [2,4]. 展开更多
关键词 ABC transporters/genetics ABC transporters/physiology CARRIER proteins/physiology CARRIER proteins/genetics liver diseases/metabolisms1Division of Gastroenterology and HEPATOLOGY Department of Internal Medicine University Hospital CH-8091 Zurich/Sw
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Pyrrolidine dithiocarbamate and saxagliptin ameliorate ulcerative colitis in rats 被引量:1
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作者 Berween Mahmoud Elmahmoudy Mai A.Abd El Fattah +1 位作者 Mohamed F.Elyamany Laila A.Rashed 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2019年第9期373-380,共8页
Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were ora... Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine(500 mg/kg), pyrrolidine dithiocarbamate(100 mg/kg), and saxagliptin(10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase(MAPK), phosphorylated extracellular signal-regulated kinase(ERK), c AMP response element-binding protein(CREB), interleukin-12(IL-12), caspase-3, β-defensin, inducible nitric oxide synthase(i NOS) and glucagon like peptide-1(GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, i NOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and i NOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes. 展开更多
关键词 ULCERATIVE colitis Inflammatory MEDIATORS Oxidative stress PYRROLIDINE DITHIOCARBAMATE SAXAGLIPTIN THIOACETAMIDE
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Design, Synthesis of Analgesics and Anticancer of Some New Derivatives of Benzimidazole 被引量:2
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作者 Helmy M. Sakr Rezk R. Ayyad +2 位作者 Kazem Mahmoud Ahmed M. Mansour Ahmed. G Ahmed 《International Journal of Organic Chemistry》 CAS 2021年第3期144-169,共26页
T</span><span style="font-family:Verdana;">his work, contain</span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> some ... T</span><span style="font-family:Verdana;">his work, contain</span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> some new compounds from benzimidazole derivatives, which </span><span style="font-family:Verdana;">are </span><span style="font-family:Verdana;">synthesized by condensation of Orthophenylene diamine and Carbon disulfide resulting </span><span style="font-family:Verdana;">in </span><span style="font-family:Verdana;">2-Mercapto-benzimidazole which </span><span style="font-family:Verdana;">is </span><span style="font-family:Verdana;">treated by alcoholic potassium hydroxide forming potassium salt of 2-mercaptobenzimidazole which reacts with different substances (alkyl chlo</span><span style="font-family:Verdana;">roacetates, chloroacetic chloride, alkyl halides) also the ethoxy carbonyl methyl thiobenzimidazole reacts with different amines. In addition to chloromethyl benzimidazole which resulted from the reaction between orthophenylene diamine and chloroacetic acid, which reacted with different amines. The synthesized compound tested as analgesics and anticancer activity the new derivatives revealed moderate, strong and very strong analgesics and moderate and strong anticancer activity</span><span style="font-family:Verdana;">. 展开更多
关键词 BENZIMIDAZOLE Analgesics and Anticancer
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The Effect of MRP5-Expression on Human Erythroleukemia (HEL) Cell Growth and cGMP Levels
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作者 Xiaoyan Chen Roy A. Lysaa +2 位作者 Ragnhild Jaeger Emanuel Boadu Georg Sager 《Pharmacology & Pharmacy》 2016年第1期64-70,共7页
Background: Previous studies of patients with acute leukemia showed that plasma cGMP levels were markedly elevated before treatment, fell after successful therapy but increased after relapse. In many cells high concen... Background: Previous studies of patients with acute leukemia showed that plasma cGMP levels were markedly elevated before treatment, fell after successful therapy but increased after relapse. In many cells high concentrations of GMP have an antiproliferative effect. The cellular cGMP extrusion from cancer cells may represent an acquired resistance against an endogenous antiproliferative signal molecule. Multidrug resistance associated protein 5 (MRP5) has been identified as an important cGMP transporter. Methods: A human erythroleukemia cell line (HEL) was used to study the impact of cGMP and cGMP-elevating compounds like theophylline, sodium nitroprusside (SNP) and sodium nitrite (NaNO2). MRP5 was overexpressed in HEL cells by transfection. Concentrations of cGMP were determined with RIA or HPLC and cell densities were determined by cytometry. Results: The concentration ratio between extra- and intracellular cGMP concentrations was >1, meaning that HEL cells extruded cGMP against a concentration gradient and MRP5 was identified in these cells. In some cell types butyrate increases cellular cGMP levels by stimulating soluble guanylyl cyclase (sGC) and thereby the cellular efflux. This effect did not exist for HEL cells. MRP5 transfected HEL cells which were exposed to cGMP was clearly more sensitive to the antiproliferative effect than the wild type. On the other hand, exposing the transfected HEL cells to cGMP-elevating agents (theophylline, SNP and NaNO<sub>2</sub>) showed less sensitivity than the wildtype. Conclusion: This study supports the idea that some cancers acquire resistance against endogenous signal molecules with antiproliferative potency. 展开更多
关键词 Cyclic GMP MRP5 Resistance CANCER GROWTH REGULATION
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Assessment of Dietary Exposure and Health Risk to Multiple Heavy Metals amongst Some Workers in Yaounde, Cameroon
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作者 Angele N. Tchana Nina D. Kamnang +5 位作者 Arielle T. Maliedje Faustin T. Manfo Frederic N. Nj ayou Wilfred A. Abia Edouard A. Nantia Paul F. Moundipa 《Journal of Pharmacy and Pharmacology》 2018年第9期801-816,共16页
关键词 重金属分析 健康风险 喀麦隆 饮食 原子吸收分光光度计 FAO/WHO 评价 多重
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Misoprostol and the Sildenafil analog(PHAR-0099048)Modulate Cellular Efflux of cAMP and cGMP Differently
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作者 Elin Orvoll Roy A.Lysaa +1 位作者 Aina W.Ravna Georg Sager 《Pharmacology & Pharmacy》 2013年第1期104-109,共6页
In the present study we have characterized ATP-dependent transport of cAMP and cGMP in physiological, but also supraphysiological concentrations. The uptake into inside-out vesicles from human erythrocytes could be di... In the present study we have characterized ATP-dependent transport of cAMP and cGMP in physiological, but also supraphysiological concentrations. The uptake into inside-out vesicles from human erythrocytes could be dissected into two components with high and low affinity. The respective Km-values were 30.8 ± 5.2 and 352 ± 26 μM for cAMP and 2.6 ± 0.4 and 260 ± 15 μM for cGMP. The two cyclic nucleotides were unable to mutually inhibit cellular efflux for concentrations up to about 100 μM. At higher concentrations the inhibition curve showed a steep fall. The IC50-value for cAMP reduction of high affinity [3H]-cGMP transport was 695 ± 9 μM. The respective value for cGMP inhibition of [3H]-cAMP efflux was 284 ± 20 μM. These observations are compatible with two selective high affinity transport systems. Other endogenous substances such as prostaglandins did not discriminate between cyclic nucleotide transport. The IC50 values for inhibition of [3H]-cAMP and [3H]-cGMP were 4.1 and 4.2 μM for PGE1, 2.7 and 4.4 μM for PGE2, respectively. However, the prostaglandin analog misoprostol discriminated distinctly between cAMP and cGMP transport with respective IC50-values of 4.5 and 24 μM. The assumption that the specific PDE5-inhibitor sildenafil could distinguish between the two cyclic nucleotides was disproved with respective IC50 values of 3.8 and 2.9 μM for inhibition of [3H]-cAMP and [3H]-cGMP, respectively. However, at least one sildenafil analog (PHAR0099048) showed a clear difference with respective IC50 values of 2.0 and 0.52 μM. The other tested sildenafil analogs showed no or minor ability to discriminate with IC50 values of 0.16 and 0.17 μM for IS-39213, and 0.35 and 0.16 μM for IS-60049, respectively. In agreement with previous reports, the present study shows that proteins responsible for cyclic nucleotide transport are multiorganic anion pumps. However, the observation that drug analogs may discriminate between these two efflux systems makes them potential drug targets. 展开更多
关键词 ABC-Transporters CAMP CGMP MISOPROSTOL SILDENAFIL
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Smoothelin,a new marker to determine the origin of liver fibrogenic cells 被引量:2
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作者 Sébastien Lepreux Christelle Guyot +4 位作者 Fabrice Billet Chantal Combe Charles Balabaud Paulette Bioulac-Sage Alexis Desmoulière 《World Journal of Gastroenterology》 SCIE CAS 2013年第48期9343-9350,共8页
AIM:To explore this hypothesis that smooth muscle cells may be capable of acquiring a myofibroblastic phenotype,we have studied the expression of smoothelin in fibrotic conditions.METHODS:Normal liver tissue(n=3)was o... AIM:To explore this hypothesis that smooth muscle cells may be capable of acquiring a myofibroblastic phenotype,we have studied the expression of smoothelin in fibrotic conditions.METHODS:Normal liver tissue(n=3)was obtained from macroscopically normal parts of hepatectomy,taken at a distance from hemangiomas.Pathological specimens included post-burn cutaneous hypertrophic scars(n=3),fibrotic liver tissue(n=5),cirrhotic tissue(viral and alcoholic hepatitis)(n=5),and hepatocellular carcinomas(n=5).Tissue samples were fixed in 10%formalin and embedded in paraffin for immunohistochemistry or were immediately frozen in liquid nitrogen-cooled isopentane for confocal microscopy analysis.Sections were stained with antibodies against smoothelin,which is expressed exclusively by smooth muscle cells,andα-smooth muscle actin,which is expressed by both smooth muscle cells and myofibroblasts.RESULTS:In hypertrophic scars,α-smooth muscle actin was detected in vascular smooth muscle cells and in numerous myofibroblasts present in and around nodules,whereas smoothelin was exclusively expressed in vascular smooth muscle cells.In the normal liver,vascular smooth muscle cells were the only cells that expressα-smooth muscle actin and smoothelin.In fibrotic areas of the liver,myofibroblasts expressingα-smooth muscle actin were detected.Myofibroblasts co-expressingα-smooth muscle actin and smoothelin were observed,and their number was slightly increased in parallel with the degree of fibrosis(absent in liver with mild or moderate fibrosis;5%to 10%positive in liver showing severe fibrosis).In cirrhotic septa,numerous myofibroblasts co-expressedα-smooth muscle actin and smoothelin(more than 50%).In hepatocellular carcinomas,the same pattern of expression forα-smooth muscle actin and smoothelin was observed in the stroma reaction surrounding the tumor and around tumoral cell plates.In all pathological liver samples,α-smooth muscle actin and smoothelin were co-expressed in vascular smooth muscle cells.CONCLUSION:During development of advanced liver fibrosis,a subpopulation of myofibroblasts expressing smoothelin may be derived from vascular smooth muscle cells,illustrating the different cellular origins of myofibroblasts. 展开更多
关键词 Smooth MUSCLE CELLS MYOFIBROBLASTS α-smooth MUSCLE ACTIN SMOOTHELIN Fibrosis/cirrhosis Hepatocellular carcinoma
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Potent Anticonvulsant 1H-Imidazol-5(4H)-One Derivatives with Low Neurotoxicity 被引量:2
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作者 Mosaad Sayed Mohamed Rehab Kamel Mahmoud +1 位作者 Amira Ibrahim Sayed Moustafa E. El-Araby 《Open Journal of Medicinal Chemistry》 2012年第2期24-29,共6页
We report here the synthesis and in vivo anticonvulsant/neurotoxicity activities of a series of compounds belonging to 2-aryl-4-arylidene-1-phenyl-1H-imidazol-5(4H)-one. The scaffold is based on the commonality of 5-m... We report here the synthesis and in vivo anticonvulsant/neurotoxicity activities of a series of compounds belonging to 2-aryl-4-arylidene-1-phenyl-1H-imidazol-5(4H)-one. The scaffold is based on the commonality of 5-membered lactam ring structures as successful anticonvulsant agents. The present compounds exhibited a range of anticonvulsant activity in pentylenetetrazole (PTZ)-induced seizure test. In particular, the protection was excellent by compounds bearing furylmethylidene on C4, possibly due to good pharmacokinetic properties. It was found that high lipophilicity and/or electron deficient aryl ring substitution at C4 compromised the anticonvulsant activities. For example, chloro analogues were found much less active than unsubstituted phenyl or furyl derivatives. Regarding side effects, active compounds exerted no observable neurotoxic effect at their therapeutic doses in Chimney test. 展开更多
关键词 IMIDAZOLE IMIDAZOLONE ANTICONVULSANT ANTIEPILEPTIC Valproic Acid NEUROTOXICITY
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Biogenic Amines as Biomarkers for Neurotoxicity
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作者 SYED F.ALI LOUIS W.CHANG +1 位作者 WILLIAM SLIKKER JR 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 1991年第1期207-216,共10页
There has been a surge of interest over the past several years in the use of neurochemical endpoints to contribute to our understanding of the mechanism of action of neurotoxicants. In our present presentation, two bi... There has been a surge of interest over the past several years in the use of neurochemical endpoints to contribute to our understanding of the mechanism of action of neurotoxicants. In our present presentation, two biogenic amine systems were selected as examples of biomarkers for neurotoxicity. To investigate these neurochemical endpoints, two prototype neurotoxicants were evaluated in experimental animals. One agent, reserpine, was used to assess developmental neurotoxicity and administered prenatally, while the other, MDMA, was used in the adult animal. The neurochemical biomarkers measured were dopamine, serotonin, and their metabolite (DOPAC and 5-HIAA) concentrations by HPLC/EC and dopamine receptor binding by radioligand receptor techniques. A review of the background, experimental design, and results are presented in this article. Our findings indicate that components of the biogenic amine systems can be used as sensitive neurochemical biomarkers of neurotoxicity. These neurochemical biomarkers can be correlated with neuropathological and behavioral biomarkers to aid in the understanding of mechanisms of neurotoxicity. 展开更多
关键词 MDMA Biogenic Amines as Biomarkers for Neurotoxicity ORAL DOPAC
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Side Effects of Pfizer-BioNTech COVID-19 Vaccine among Libyan Young Adults: Observational Study
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作者 Taher I. Shailabi Elham O. Borwis +3 位作者 Nisreen Saed Majeed Nagat H. Bubtina Naeima Betamar Guma Abdeldaim 《Journal of Biosciences and Medicines》 2022年第1期33-45,共13页
<strong>Purpose:</strong> Since the mRNA technology used to manufacture Pfizer-BioNTech COVID-19 Vaccine is new, it is still difficult to predict its consequences. However, many young people, especially in... <strong>Purpose:</strong> Since the mRNA technology used to manufacture Pfizer-BioNTech COVID-19 Vaccine is new, it is still difficult to predict its consequences. However, many young people, especially in developing countries, think that they are less susceptible to severe infection with the Coronavirus 2 (SARS-CoV-2), Therefore, they do not prefer to take the COVID-19 vaccines. Accordingly, studies in this aspect are necessary to increase people’s awareness of the acceptance of vaccination, especially for the youth. <strong>Patients and Methods:</strong> This study was conducted on healthy young adults of both sexes. Participants (n = 81) were received two doses of the Pfizer-BioNTech COVID-19 Vaccine. A paper questionnaire was prepared, the survey asks about the side effects related to receiving the Vaccine. All participants completed the questionnaire twice, once after the first dose and again after the second dose. Data were collected and statistically analyzed. <strong>Results: </strong>The most common side effects were Muscle pain, Tiredness, Headache, and Fever. Less common side effects were Chills, Fainted, Breathlessness, and Coughing. Rare side effects include nausea and vomiting, Diarrhea, Anaphylactic Reaction, and Swollen Lymph Nodes. Side effects that are strongly associated with females are Headache, and Joint pain, for males, Anaphylactic reaction. The study revealed a significant difference between the number of females (96.5%) and males (85%) who suffered from the side effects of the Pfizer-BioNTech COVID-19 Vaccine (P = 0.033). <strong>Conclusion:</strong> Most of the side effects reported in our study were consistent with Pfizer’s fact sheet for recipients and caregivers. Through our follow-up to the participants in the study, we noticed that the reported side effects were not too bad, and they were able to carry out their daily activities, so we recommend taking the vaccine, especially for young people. 展开更多
关键词 Pfizer-BioNTech Side Effects COVID-19 Vaccine Young Adults
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Amiodaron in atrial fibrillation:post coronary artery bypass graft
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作者 Paria Habibollahi Shahrzad Hashemi Jam +2 位作者 Samad Shams Vahdati Hamidreza Morteza Baghi Hassan Amiri 《World Journal of Emergency Medicine》 CAS 2016年第4期250-254,共5页
BACKGROUND:Atrial fibrilation(AF) is the most common complication following heart surgeries;it often occurs in patients after coronary artery bypass graft(CABG).The purpose of this review is to categorize prophylaxes ... BACKGROUND:Atrial fibrilation(AF) is the most common complication following heart surgeries;it often occurs in patients after coronary artery bypass graft(CABG).The purpose of this review is to categorize prophylaxes or treatment by administration of Amiodaron in patients with CABG.DATA RESOURCES:We searched google scholar,pubmed,and Cochrane Library databases(the period 1970-2010) for articles on Amiodaron in CABG and cardiac surgery.A total of 1 561 articles were identified,and 30 articles met the criteria and were enrolled in this review.RESULTS:Most studies supported Amiodarone for prophylaxi purpose in patients who were performed with CABG;few papers supported Amiodaron as a drug for treating CABG.The prophylaxis can decrease the incidence rate of AF in CABG,but if it uses as a treatment,the side effect of Amiodaron will decrease because all of the patients will not get Amiodarone.In the other hand use of Amiodarone as a treatment does not influence the length of hospital stay significantly but these kinds of study are so few.CONCLUSION:No appropriate therapeutic method has been defined for AF.At present,the common way of treating AF following cardiac surgery is mainly based on prophylaxis in medical books and references. 展开更多
关键词 Pulmonary aspiration Lateral position Semi-lateral position
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Evaluation of a Pediatric Mock Code Educational Training Program at a Large, Tertiary Care Pediatric Hospital
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作者 Ayelet Rimon Amit Hess +3 位作者 Dennis Scolnik Oren Tavor Shirley Friedman Miguel Glatstein 《Open Journal of Pediatrics》 2015年第4期314-319,共6页
Background: Management of the acutely ill children represents one of the more complex clinical skills required of pediatric physicians. Our goal was to develop and evaluate a multidisciplinary pediatric mock code trai... Background: Management of the acutely ill children represents one of the more complex clinical skills required of pediatric physicians. Our goal was to develop and evaluate a multidisciplinary pediatric mock code training program for the pediatric residents in our institution. Methods: We performed a before and after evaluation of pediatric residents. The residents were educated by attending five mock code scenarios, followed by debriefing. Before and after the five sessions, the residents completed a self-assessment questionnaire. Results: Residents reported a significant improvement in their comfort in all aspects of managing pediatric resuscitations, with notable improvement seen in running a resuscitation requiring airway management, managing fluid resuscitation and performing endotracheal intubation. The most prominent change was demonstrated in the comfort level of the overall management of a pediatric resuscitation. Conclusion: The pediatric mock code educational training program improved residents’ self-reported knowledge and comfort level in managing pediatric emergency situations. 展开更多
关键词 Education MOCK CODE PEDIATRIC RESIDENTS EMERGENCY Medicine
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Are potassium levels in children with hemolytic uremic syndrome predictive of outcome?
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作者 Miguel M. Glatstein Vala Snehal +1 位作者 Syed Amir Ahmad Dennis Scolnik 《Open Journal of Pediatrics》 2012年第4期264-267,共4页
Objective: To ascertain the role of serum potassium levels in predicting clinical outcomes in diarrhea-associated hemolytic uremic syndrome (HUS D+). Methods: We reviewed clinical and laboratory data from HUS D+ patie... Objective: To ascertain the role of serum potassium levels in predicting clinical outcomes in diarrhea-associated hemolytic uremic syndrome (HUS D+). Methods: We reviewed clinical and laboratory data from HUS D+ patients at our tertiary care institution from 2001 to 2008. Serum potassium concentration at presentation and during the acute phase of acute renal failure were recorded and related to laboratory parameters and clinical outcomes. Results: 15 HUS D+ cases were identified. E. coli 0157:H7 was found in 9/15 cases (70%). Potassium levels were not predictive of clinical outcomes. Normal serum potassium levels were found in the majority of patients. Potassium levels <3.6 mmol/L were evident at presentation in 3/15 patients (23%), and no patient manifested hyperkalemia even when creatinine levels were concurrently increase. Conclusions: This study suggests the presence of vigorous compensatory mechanisms in the homoestasis of serum potassium levels during HUS D+ disease since neither the increase stool volumes associated with diarrhea nor the presence of renal failure resulted in clinically significant changes in serum potassium levels. 展开更多
关键词 DIARRHEA HEMOLYTIC UREMIC Syndrome HYPOKALEMIA POTASSIUM Metabolism Acute RENAL Failure
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Syrup versus Drops of Iron III Hydroxide Polymaltose in the Treatment of Iron Deficiency Anemia of Infancy
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作者 Ayala Yahav Chaim Kaplinsky +5 位作者 Miguel M. Glatstein Yaakov Shachter Aryeh Simmonds Yakov Shiff Dennis Scolnik Nechama Sharon 《Open Journal of Pediatrics》 2015年第1期34-38,共5页
Background: Iron deficiency anemia in infants is the most common micronutrient deficiency worldwide. The main cause is low iron intake in the presence of accelerated physiologic growth rate. Objective: The current stu... Background: Iron deficiency anemia in infants is the most common micronutrient deficiency worldwide. The main cause is low iron intake in the presence of accelerated physiologic growth rate. Objective: The current study aimed at prospectively comparing the efficacy of iron III hydroxide polymaltose syrup (IPS) versus iron III hydroxide polymaltose drops (IPD) in treating iron deficiency among infants attending the hematology outpatient clinic. Our hypothesis was that IPS would be less effective possibly related to the difficulty of giving the medication. Methods: Participants diagnosed with iron deficiency anemia between 11-24 months were randomly assigned to receive either IPS or IPD for 3 months. The main outcome parameter was hemoglobin blood level, while the secondary outcome parameters were: 1) iron;2) ferritin;3) transferrin (i.e.?total iron binding capacity);4) mean corpuscular volume;and 5) red blood cell distribution width. Results: Out of the 104 recruited infants, 55 (52%) completed the study: 29 in the IPS group and26 inthe IPD group. There was no significant difference in the main outcome parameter at either 1 or 3 months of treatment: mean hemoglobin was 10.5 versus 10.7 g/dL within a 1 month treatment, P = 0.4;mean hemoglobin was 11.0 versus 11.1 g/dL within a 3 months of treatment, P = 0.59. Likewise, no significant differences were found with respect to the occurrence of side effects. Conclusion: Oral IPD and IPS are equally effective in treating iron deficiency anemia in infants aged 11 - 24 months. 展开更多
关键词 IRON Deficiency Anemia (IDA) TREATMENT IRON III HYDROXIDE Polymaltose Formulation
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