96 research outputs found

    EFFECT OF AMLODIPINE ON ENTEROPATHY INDUCED BY INDOMETHACIN IN RATS

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    Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) have become well known for causing gastroduodenal mucosal damage. In addition, they are also known to affect the small intestine in humans. Amlodipine is a third-generation dihydropyridine-type calcium channel blocker; it can inhibit inflammatory cytokines and enhance antioxidant defenses. The aim of this study was to evaluate the effect of Amlodipine on indomethacin-induced enteropathy in rats. Methods: Enteropathy was induced by subcutaneous indomethacin (Indo) prepared in 5 % sodium bicarbonate administrated at a dose rate of 9 mg/kg for two days at 24h intervals. Amlodipine (10 mg/Kg body weight po) was administrated for seven consecutive days beginning 24 h after the first Indo injection. Rats were sacrificed under ether anesthesia on the 8th day. The small intestinal injury was assessed by body weight loss, small intestine weight/length ratio, macroscopic damage, histological study, as well as by biochemical measurement of reduced glutathione (GSH), lipid peroxides and superoxide dismutase (SOD) activity in the small intestine tissue. Results: The results showed that Amlodipine didn't decrease body weight loss, it decreased small intestine weight/length ratio, macroscopic and microscopic small intestinal damage scores caused by administration of Indo. It also increased SOD activity and decreased lipid peroxidation. The effect on the level of GSH wasn't observed. No statistical significance was observed when previous findings were compared to Indo induced enteropathy group (p>0.05). Conclusion: Amlodipine didn't produce an obvious enhancement in enteropathy induced by Indo in rats

    Serological Detection of Sarcocystiosis in Buffaloes

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    The study aimed to serologically detect the prevalence of Sarcocystis infection in buffaloes using the indirect enzyme-linked immunosorbent assay (ELISA) for the first time in Iraq. An overall 184 buffaloes of different ages and sexes were selected randomly from the regions of Wasit province (Iraq) from March to June (2022), and subjected to draining of venous blood under aseptic conditions. After centrifugation, the obtained sera were examined by indirect ELISA. Totally, 33.15% of study animals were positive for IgG antibodies. According to their concentrations, the ODs level showed a significant increase (P<0.0186) in mild infection (63.93%) when compared to moderate (27.87%) and strong (8.2%) infections. Subsequently, values of mild, moderate, and strong infections were 0.330 ± 0.01, 0.554 ± 0.019 and 0.912 ± 0.031 nm, respectively. Regarding age and sex factors, significantly higher positivity (P<0.0469) was shown in buffaloes aged >10 years old (57.89%); while the lowest was seen in those <1 year (13.64%). Subsequently, older buffaloes appeared significantly (P<0.0192) at higher risk (2.1685) when compared to other age groups. Females recorded an obvious increase (P<0.05) in positivity (35.95%) and risk (1.8569) in comparison with males; 19.35% and 0.5385, respectively. The results indicate that ELISA is of great value in the diagnosis of sarcocystosis

    Outer-sphere electron-transfer between horse heart cytochrome c and anionic Cu(II/I) complexes: Evidence for precursor formation and coordination sphere reorganization for electron transfer

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    The outer-sphere electron-transfer reaction between anionic bis(5,6-bis(4-sulfonatophenyl)-3- (2-pyridyl)-1,2,4-triazine)Cu(II) and cytochrome cII was investigated as a function of pH, ionic strength, concentration, temperature and pressure. The plot of the observed pseudo-first-order rate constant as a function of the Cu(II) complex concentration showed saturation at higher Cu(II) concentrations, from which the precursor formation constant and the electron transfer rate constant could be separated (K = (7.7 ′ 0.5) × 103 M 1 and kET= 6.2 ′ 0.4 s -1 at I = 0.2 M, pH 7.4 and 288 K). The pseudo-first-order electron-transfer rate constant was measured as a function of temperature and pressure at (low and) high Cu(II) concentrations (ΔH= (85 ′ 4) 89 ′ 4 kJ mol -1; ΔS= (-61 ′ 13) -79 ′ 15 J K-1 mol-1; ΔG (288 K) = (67.6) 66.1 kJ mol-1; ΔV= (+8.8 ′ 0.6)+8.0 ′ 0.7 cm3 mol-1). Within the volume change for the overall reaction, the volume profile for the electron transfer step is almost symmetrical. The redox process and the change in coordination of the copper centre are proposed to be clearly separated. The back reaction between the Cu(I) complex and cytochrome cIII was investigated as a function of Cu(I) concentration at pH 7.4 at l bar. The observed pseudo-first-order rate constant reaches a saturation at high Cu(I) concentrations from which the precursor formation constant and the electron-transfer rate constant were estimated (K' = (2.0 ′ 0.2) × 103 M-1 and k'ET = 0.014 ′ 0.001 s-1 at I = 0.2 M, pH 7.4 and 288 K). Simulations of the measured cyclovoltammogramms applying an EC mechanism with two redox systems and two homogeneous chemical reactions were performed. The results are discussed with reference to earlier studies involving Co, Ru and Cr complexes as redox partners for cytochrome c

    Aging enhances serum cytokine response but not task-induced grip strength declines in a rat model of work-related musculoskeletal disorders

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    <p>Abstract</p> <p>Background</p> <p>We previously reported early tissue injury, increased serum and tissue inflammatory cytokines and decreased grip in young rats performing a moderate demand repetitive task. The tissue cytokine response was transient, the serum response and decreased grip were still evident by 8 weeks. Thus, here, we examined their levels at 12 weeks in young rats. Since aging is known to enhance serum cytokine levels, we also examined aged rats.</p> <p>Methods</p> <p>Aged and young rats, 14 mo and 2.5 mo of age at onset, respectfully, were trained 15 min/day for 4 weeks, and then performed a high repetition, low force (HRLF) reaching and grasping task for 2 hours/day, for 12 weeks. Serum was assayed for 6 cytokines: IL-1alpha, IL-6, IFN-gamma, TNF-alpha, MIP2, IL-10. Grip strength was assayed, since we have previously shown an inverse correlation between grip strength and serum inflammatory cytokines. Results were compared to naïve (grip), and normal, food-restricted and trained-only controls.</p> <p>Results</p> <p>Serum cytokines were higher overall in aged than young rats, with increases in IL-1alpha, IFN-gamma and IL-6 in aged Trained and 12-week HRLF rats, compared to young Trained and HRLF rats (p < 0.05 and p < 0.001, respectively, each). IL-6 was also increased in aged 12-week HRLF versus aged normal controls (p < 0.05). Serum IFN-gamma and MIP2 levels were also increased in young 6-week HRLF rats, but no cytokines were above baseline levels in young 12-week HRLF rats. Grip strength declined in both young and aged 12-week HRLF rats, compared to naïve and normal controls (p < 0.05 each), but these declines correlated only with IL-6 levels in aged rats (r = -0.39).</p> <p>Conclusion</p> <p>Aging enhanced a serum cytokine response in general, a response that was even greater with repetitive task performance. Grip strength was adversely affected by task performance in both age groups, but was apparently influenced by factors other than serum cytokine levels in young rats.</p

    Abrogation of Cbl–PI3K Interaction Increases Bone Formation and Osteoblast Proliferation

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    Cbl is an adaptor protein and E3 ligase that plays both positive and negative roles in several signaling pathways that affect various cellular functions. Tyrosine 737 is unique to Cbl and phosphorylated by Src family kinases. Phosphorylated CblY737 creates a binding site for the p85 regulatory subunit of phosphatidylinositol 3 kinase (PI3K) that also plays an important role in the regulation of bone homeostasis. To investigate the role of Cbl–PI3K interaction in bone homeostasis, we examined knock-in mice in which the PI3K binding site on Cbl was ablated due to the substitution of tyrosine 737 to phenylalanine (CblYF/YF, YF mice). We previously reported that bone volume in these mice is increased due to decreased osteoclast function (Adapala et al., J Biol Chem 285:36745–36758, 19). Here, we report that YF mice also have increased bone formation and osteoblast numbers. In ex vivo cultures bone marrow-derived YF osteoblasts showed increased Col1A expression and their proliferation was also significantly augmented. Moreover, proliferation of MC3T3-E1 cells was increased after treatment with conditioned medium generated by culturing YF bone marrow stromal cells. Expression of stromal derived factor-1 (SDF-1) was increased in YF bone marrow stromal cells compared to wild type. Increased immunostaining of SDF-1 and CXCR4 was observed in YF bone marrow stromal cells compared to wild type. Treatment of YF condition medium with neutralizing anti-SDF-1 and anti-CXCR4 antibodies attenuated MC3T3-E1 cell proliferation. Cumulatively, these results show that abrogation of Cbl–PI3K interaction perturbs bone homeostasis, affecting both osteoclast function and osteoblast proliferation
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