This study was designed to test the pre-treatment doses of guggulipid (50 mg/kg), aspirin (100 mg/kg) per orally and co-administration of both drugs for 28 days followed by middle cerebral artery occlusion - a model of focal cerebral ischemia in rats. Middle cerebral artery was occluded for two hours, followed by reperfusion for 22 hours for the induction of focal cerebral ischemia in rats. Neurobehavioral tests like locomotor activity and grip strength tests were performed before sacrificing the animal. After neurobehavioral tests, the animals were sacrificed for the measurement of infarction areas and biochemical estimations in brain. Locomotor activity and grip strength were significantly improved in guggulipid and aspirin pre-treated rats. Guggulipid and aspirin pre-treatment reduced the infarction areas as compared with middle cerebral occluded (MCAO) rats. An elevation of nitrite, thiobarbituric acid reactive substance (TBARS), acetylcholine esterase activity (AchE) and reduction in antioxidant enzymes like superoxide dismutase (SOD), glutathione (GSH) and catalase were observed following MCAO. Pre-treatment with guggulipid and aspirin caused a reduction in TBARS and nitrite levels, AchE, but elevated GSH level, SOD and catalase activities as compared with MCAO rats. The protective effects observed in this study were due to antioxidant, anti-inflammatory and anti-hyperlipidemic properties of guggulipid. The protective effect of guggulipid in cerebral ischemia, that it may have a role in reversing the symptoms and may offer significant neuroprotection in stroke.
Schizophrenia (SCZ) is a debilitating disorder afflicting around 1% of the world population. Recent literature reveals oxidative injuries contribute enormously to the pathophysiology of SCZ alongside other psychopathological disturbances. Histamine H3R-antagonists have shown dual mechanism of action in experimental models of SCZ. Firstly it prevents oxidative stress and secondly alleviates schizophrenic symptoms, particularly the negative symptoms and cognitive deficits. In the present study, histamine H3R-antagonists used were ciproxifan (3.0 mg/kg, ip) and clobenpropit (15 mg/kg, ip) markedly controlled the elevated levels of various oxidative stress markers, for example, thiobarbituric acid reactive substance (TBARS), glutathione (GSH), superoxide dismutase, catalase, etc., as a result of augmented oxidative stress in the experimental models of SCZ such as amphetamine (0.5 mg/kg, sc) and dizocilpine (MK-801) (0.2 mg/kg, ip) induced locomotor hyperactivity, apomorphine (1.5 mg/kg, sc) induced climbing behavior and haloperidol (2.0 mg/kg, po) induced catalepsy. The results of the present study revealed that H3R-antagonists possess antioxidant activity and could serve with dual mechanism by supplementing antioxidant needs of SCZ and at the same time controlling symptoms of SCZ.
The current study aimed to develop alendronate (ALN)-loaded chitosan nanoparticles (CS-ALN-NPs) for brain delivery via intranasal route. These CS-ALN-NPs reduced the peripheral side effects and released ALN directly to brain. These NPs were formulated through ionic gelation technique by mixing sodium tripolyphosphate (1.5 mg/ml) in ALN-CS (1.75 mg/ml) solution. CS-ALN-NPs attained 135.75 ± 5.80 nm, 0.21 ± 0.013, 23.8 ± 3.69 mV, 72.46 ± 0.879% and 30.92 ± 0.375% mean particle size, PDI, zeta potential, entrapment efficiency and loading capacity, respectively. Furthermore, the TEM and SEM analysis of CS-ALN-NPs, respectively, revealed the particle size in 200 nm range and spherical shape. The in vitro and ex vivo release profile revealed a sustained drug release through CS-ALN-NPs as compared to pure drug solution. Also these NPs acquired a high concentration in mice brain and better pharmacokinetic profile than ALN solution (intranasal) CS-ALN-NPs were then evaluated against intracerebroventricular-streptozotocin (ICV-STZ) induced Alzheimer’s disease (AD)-like pathologies in mice. The intranasal CS-ALN-NP altered the ICV-STZ induced neurobehavioral, neurochemical and histopathological changes in mice. These effects were significant to those of ALN solution (intranasal). The neuroprotective potential of CS-ALN-NPs observed in ICV-STZ mice model of AD may be a promising brain-targeted delivery system for AD treatment along with further extensive exploration at both pre-clinical and clinical edge.HIGHLIGHTSCS-ALN-NPs were developed and optimised to overcome the poor pharmacokinetic profile and associated side effects of ALNCS-ALN-NPs showed particle size within 200 nm range as well as controlled and sustained release in in vitro release studyThese optimised NPs of ALN attained higher brain:blood ratio and better pharmacokinetic profile (Cmax, tmax, AUC)CS-ALN-NPs markedly altered ICV STZ induced impairment in cognitive functions of mice and changes in APP processing, neuroinflammatory cytokines and other biochemical parameters in mice hippocampus
The present study was carried out to evaluate whether the combined administration of sarcosine with risperidone possess any advantageous effects on dopaminergic and NMDA receptor-mediated glutamatergic neurotransmissions as compared to single drug administration in rats. The Wistar rats were divided into 7 groups each with different treatments. MK-801 (0.1 mg/kg, i.p.) was injected as single dose on 14th day for inducing learning and memory deficits in animals. Sarcosine (300 and 600 mg/kg, i.p.) and risperidone (0.2 mg/kg, i.p.) were administered daily for 14 days. Spatial habituation learning and hole board tests were performed on 14th day followed by measurement of GABA and 5-HT levels in brain tissues of rats. Pretreatment of sarcosine (600 mg/kg, i.p.) non-significantly improved learning and memory deficits induced by non-competitive NMDA receptor antagonist MK-801, significantly increased the GABA and decreased the 5-HT levels (p<0.05). Combined administration of sarcosine (300 mg/kg, i.p.) with risperidone (0.1 mg/kg, i.p.) synergistically improved cognitive deficits significantly, decreased % errors in hole board learning test, and increased centre time, corner time in spatial habituation learning test (p<0.05). The combined administration also potentiated the GABA and decreased 5-HT levels, indicating that the increased synaptic glycine concentrations may enhance NMDA receptor function which is directly linked with increased GABAergic transmission in striatum region and decreased 5-HT levels showed antagonistic action hence, enhancing the cognition. Our results suggest that combined administration of sarcosine with risperidone may strengthen glutamatergic tone in striatum. Thus, it may be a novel regime to improve psychotic symptoms and cognitive deficit in schizophrenia.
To investigate the hepatoprotective activity of L-ornithine-L-aspartate against thioacetamide (TAA)-induced hepataopathy in rats.The hepatoprotective activity of L-ornithine-L-aspartate (OA) at a dose of 2 g/kg, p.o. for 10 days was evaluated against TAA (250 mg/kg, i.p. for 2 days) induced hepatopathy in rats. Biochemical parameters such as serum aspartate transaminase, alanine transaminase, alkaline phosphatase, bilirubin and glutathione, thiobarbituric acid reactive substances, and protein in liver tissues were estimated to assess the liver function.TAA-induced pathogenic changes in the levels of the above indices were significantly (P < 0.01) reversed by the OA treatment. OA treatment also exhibited significant restoration of the hepatic architecture and lobular structure in histological evaluation of the rat liver sections.Ornithine aspartate exhibited significant hepatoprotective activity against TAA-induced hepatic damage in rats.
Background: Sacubitril (SAC), a neprilysin inhibitor prevent degradation of neprilysin and activate cGMP signaling pathways leading to rise in blood volume concurrent to blood pressure by means of vasoactive peptides, adrenomedullin, and bradykinin.Objective: The aim of this study was to evaluate the anti-ischemic effects of SAC through inhibiting neprilysin in isoproterenol (ISO) induced myocardial infarction (MI) in Wistar albino rats. ISO (85 mg/kg) was injected subcutaneously at the end of 14 days pre-treatment with SAC and valsartan (VAL).Result: Biochemical investigation revealed that SAC along with VAL significantly prevented the antioxidant enzymes (SOD, Catalase, GR, GPx, GST, and GSH) degradation and malondialdehyde (MDA) induced by ISO intoxication in Wistar rats. Along with this, cardiac biomarkers (LDH, CK-MB, ALT, AST, and ALP) were also significantly ameliorated by SACand VAL in ISO-treated rats. Concurrently, decreased infarction area (IA)and marked reduction in myofibril damage by SACand VAL further supported its protective benefits in MI.Conclusion: Taken together, the results suggest that inhibition of enzyme neprilysin alleviated the ISO induces myocardial damage mediated by its strong antioxidant potential.
Background: Urinary tract infection is a key public health issue causing morbidity, especially in women population. This problem is further aggravated in pregnant women. Aims:This study was designed to evaluate the drug prescribing behaviour and adverse drug reaction monitoring in urinary tract infection patients in a tertiary care hospital. Materials and Methods:The present study was prospective, observational and carried out for four months, and done to assess the drug utilization pattern, adverse drug reactions (ADRs) and to identify the bacterial pathogens associated with UTI and their susceptibility to antibiotics.Results:A total of 327 female patients were evaluated, out of which 248 (75.84%) cases were symptomatic. The study reflected maximum of 50.46% UTI in the age group 21-30 years. Pathogens isolated after a urine culture were of both Gram positive 131 (40.07%) and Gram negative 196 (59.93%) type. The maximum incidence (45.80 %) occurred in last trimester of pregnancy. The most frequently prescribed antibiotic to the pregnant patients in our study was Nitrofurantoin, whereas Amoxicillin with Clavulanic acid was most frequently used in non pregnant cases. Most common ADRs reported with almost all classes of antibiotics was nausea and vomiting followed by vaginal irritation, skin rash and photosensitivity.Conclusion:To ensure appropriate therapy, current knowledge of the pathogenic organism and their antibiotic susceptibility pattern is mandatory, especially in cases of UTI with pregnancy. Keywords: Drug utilization pattern,Adverse Drug Reactions, Urinary Tract Infection, Renal Pharmacology
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