Current Issue : January - March Volume : 2017 Issue Number : 1 Articles : 5 Articles
This study was aimed to evaluate the protective effects of fucoidan on lysosomal enzymes in isoproterenol induced\nmyocardial infarcted rats. Male albino Wistar rats were pretreated with fucoidan (150 mg/kg body weight) daily for a period of\n14 days. After the pretreatment period, isoproterenol (100 mg/kg body weight) was subcutaneously injected into rats twice at\nan interval of 24 h to induce myocardial infarction. The activities of lysosomal enzymes (�²-glucuronidase, �²-galactosidase,\ncathepsin-B and D) were increased significantly (P<0.05) in the serum and heart of isoproterenol induced myocardial infarcted\nrats. Isoproterenol also decreased the activities of �²-glucuronidase and cathepsin-D in lysosomal fractions and enhanced in\ncytosolic fractions. The activities of antioxidant enzymes were decreased significantly (P<0.05) in isoproterenol induced\nmyocardial infarcted rats. Pretreatment with fucoidan (150 mg/kg body weight) showed significant (P<0.05) protective effects\non lysosomal glycohydrolases and cathepsins in isoproterenol induced myocardial infarcted rats. Thus, the results of study\nreveal that fucoidan minimizes isoproterenol induced myocardial damage by reinstating the activities of lysosomal enzymes to\nnormal levels. The observed effects were due to the membrane stabilizing and antioxidant properties of fucoidan....
Background: Histamine assumes an important role as a major mediator in various\npathologic disorders associated with inflammation and immune reactions. However,\nthe involvement of histamine in the pathological conditions and symptoms of sepsis\nremains entirely unknown. In this study, we establish that histamine is identified as a\ncontributory mediator to promoting the development of organ injury in sepsis.\nMethods: Histidine decarboxylase (HDC) gene knockout (HDCâË?â??/âË?â??) mice, histamine H1-/\nH2-receptor gene-double knockout (H1RâË?â??/âË?â??/H2RâË?â??/âË?â??) mice, and their littermate wild-type\n(WT) C57BL/6J mice underwent cecal ligation and puncture (CLP) or sham operation.\nSome WT mice were injected intraperitoneally with d-chlorpheniramine and famotidine\n60 min before CLP to block H1- and H2-receptors, respectively.\nResults: In mice rendered septic by CLP, tissue histamine levels were elevated in\nassociation with increased HDC expression. Sepsis-induced abnormal cytokine\nproduction and multiple organ injury (lung, liver, and kidney) were significantly\nless pronounced in HDCâË?â??/âË?â?? mice as compared with WT controls, and HDC deficiency\nhad improved survival in sepsis. This benefit corresponded with a significant reduction\nin activation levels of the nuclear factor (NF)-Ã?ºB signaling pathway. H1RâË?â??/âË?â??/H2RâË?â??/âË?â?? mice\napparently behaved similar to HDC knockout mice in reducing sepsis-related pathological\nchanges. Pharmacological interventions with H1- and H2-receptor antagonists indicated\nthat both H1- and H2-receptors were involved in septic lung and liver injury, whereas only\nH2-receptors contributed to septic kidney injury.\nConclusions: In the setting of sepsis, histamine, through activation of H1- and H2-\nreceptors, serves as an aggravating mediator to contribute to the development of\nsepsis-driven major end-organ failure....
Background: The availability of GABAA receptor binding sites in the brain can be assessed by positron\nemission tomography (PET) using the radioligand, [18F]flumazenil. However, the brain uptake and binding\nof this PET radioligand are influenced by anesthetic drugs, which are typically needed in preclinical imaging\nstudies and clinical imaging studies involving patient populations that do not tolerate relatively longer scan\ntimes. The objective of this study was to examine the effects of anesthesia on the binding of [18F]flumazenil\nto GABAA receptors in mice.\nMethods: Brain and whole blood radioactivity concentrations were measured ex vivo by scintillation counting\nor in vivo by PET in four groups of mice following administration of [18F]flumazenil: awake mice and mice\nanesthetized with isoflurane, dexmedetomidine, or ketamine/dexmedetomidine. Dynamic PET recordings were\nobtained for 60 min in mice anesthetized by either isoflurane or ketamine/dexmedetomidine. Static PET\nrecordings were obtained at 25 or 55 min after [18F]flumazenil injection in awake or dexmedetomidine-treated\nmice acutely anesthetized with isoflurane. The apparent distribution volume (VT*) was calculated for the\nhippocampus and frontal cortex from either the full dynamic PET scans using an image-derived input\nfunction or from a series of ex vivo experiments using whole blood as the input function.\nResults: PET images showed persistence of high [18F]flumazenil uptake (up to 20 % ID/g) in the brains of\nmice scanned under isoflurane or ketamine/dexmedetomidine anesthesia, whereas uptake was almost indiscernible\nin late samples or static scans from awake or dexmedetomidine-treated animals. The steady-state VT* was twofold\nhigher in hippocampus of isoflurane-treated mice and dexmedetomidine-treated mice than in awake mice.\nConclusions: Anesthesia has pronounced effects on the binding and blood-brain distribution of [18F]flumazenil.\nConsequently, considerable caution must be exercised in the interpretation of preclinical and clinical PET studies\nof GABAA receptors involving the use of anesthesia....
Huntington�s disease is an inherited neurodegenerative disorder, where symptomatic treatments are available for\nHuntington�s disease. The present study investigates the beneficial effect of astaxanthin as a natural carotenoid against 3-\nnitropropionic acid (3-NP) induced Huntington�s disease in male wistar rats. Findings indicates daily intraperitoneal\nadministration of 3-NP for 14 days affect body weight, brain weight and neurobehavioral deficits by motor coordination,\ndepression and memory dysfunction as well as increased oxidative stress and raised brain LDH levels. The treatment with\nastaxanthin at doses of 12.5, 25 and 50 mg/kg significantly hasten the progression and improve the body weight and brain\nweight, motor co-ordination and cognition as well as alleviate depression. Further observed more improvement in the rats\nwhich were treated with astaxanthin 50 mg/kg and these improvements were also statistically significant as compared to\nastaxanthin 12.5 mg/kg. The increased oxidative stress in the brain was significantly attenuated with the astaxanthin 25 and 50\nmg/kg dose treatment. The high levels of striatum lactate dehydrogenase in HC rats was found to be significantly lowered in the\nrats treated with astaxanthin. Histopathological examination astaxanthin 50 mg/kg treated rats striatum revealed a marked\nimprovement with less neurodegenration and absence of pyknotic nuclei compared to Huntington control rat. In conclusion,\ntreatment of astaxanthin attenuates the symptoms of Huntington�s disease which might be because of its antioxidant and\nneuroprotective activity....
Two novel series of 3,4-dihydroisoquinolin with heterocycle derivatives (4aââ?¬â??t and 9aââ?¬â??e) were\nsynthesized and evaluated for their anticonvulsant activity using maximal electroshock (MES) test and\npentylenetetrazole (PTZ)-induced seizure test. All compounds were characterized by IR, 1H-NMR,\n13C-NMR, and mass spectral data. Among them, 9-(exyloxy)-5,6-dihydro-[1,2,4]triazolo[3,4-a]\nisoquinolin-3(2H)-one (9a) showed significant anticonvulsant activity in MES tests with an ED50 value\nof 63.31 mg/kg and it showed wide margins of safety with protective index (PI > 7.9). It showed much\nhigher anticonvulsant activity than that of valproate. It also demonstrated potent activity against\nPTZ-induced seizures. A docking study of compound 9a in the benzodiazepine (BZD)-binding site\nof Ã?³-aminobutyric acidA (GABAA) receptor confirmed possible binding of compound 9a with the\nBZD receptors....
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