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.
Cisplatin (CP) is a well-known anticancer drug used to effectively treat various kinds of solid tumors. CP causes acute kidney injury (AKI) and unfortunately, there is no therapeutic approach in hand to prevent AKI. Several signaling pathways are responsible for inducing AKI which leads to inflammation in proximal convoluted tubule cells in the kidney. Furthermore, the nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome is involved in the CP-induced AKI. In this study, we investigated therapeutic effects of rosmarinic acid (RA) against inflammation-induced AKI. RA was orally administered at the dose of 100 mg/kg for two consecutive days after 24 h of a single injection of CP at the dose of 20 mg/kg administered intraperitoneally in Swiss albino male mice. Treatment of RA inhibited the activation of NLRP3 signaling pathway by blocking the activated caspase-1 and downstream signal molecules such as IL-1β and IL18. CP activated HMGB1-TLR4/MyD88 axis was also found to be downregulated with the RA treatment. Activation of nuclear factor-κB and elevated protein expression of cyclooxygenase-2 (COX-2) were also found to be downregulated in RA-treated animals. Alteration of early tubular injury biomarker, kidney injury molecule-1 (KIM-1), was found to be subsided in RA-treated mice. RA has been earlier reported for antioxidant and anti-inflammatory properties. Our findings show that blocking a critical step of inflammasome signaling pathway by RA treatment can be a novel and beneficial approach to prevent the CP-induced AKI.
Rare gas halide lasers at 193 and 248/nm will require lower-loss optics if mirrors ad windows are not to be limiting factors in advanced DOE applications in laser fusion and photochemistry. This project addresses this problem in a number of ways, including materials investigations, test coatings, and fabrication of new uv laser coating designs, as described in more detail in the previous quarterly reports. Described in the final report are the process of making uv laser mirrors and the experimental strategy for attempting to improve them. Materials research is essential, and included selection and deposition of several condidate materials and an approximate ranking of their optical properties, so that new material combinations could be chosen, computer simulated, and deposited using improved vacuum techniques. Analysis of the electric fields within a laser mirror were employed to lower coating loss. A summary of test data is included, along with remarks on the survivability of uv laser optics, and possible future areas of inquiry, if truly low-loss uv laser mirrors are to ever be developed.
Boswellic acids are the main constituents of Boswellia serrata gum. These comprise of four pentacyclic triterpenes, 11-keto-β-boswellic acid (KBA) being one of them.Comparing the extraction efficiency of KBA through microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE) followed by optimizing the extraction process using response surface methodology (RSM) and validation of HPTLC.UAE and MAE of KBA were carried out employing methanol as an extracting solvent. To figure out the better mode of extraction, single factorial experiments were conducted for further optimization. Design expert software was used for optimization purposes where solvent to drug ratio, extraction temperature and extraction time were taken as input variables. Quantification of KBA in each extract was done through High-Performance Thin Layer Chromatography (HPTLC), and the method was validated as per International Council for Harmonization (ICH) guidelines.UAE stood out to be a better mode of extraction for KBA. Solvent to drug ratio of 20.42 mL/gram, extraction temperature of 44.01°C and extraction time of 11.54 minutes were established as optimum conditions, which yielded 8.44%w/w of KBA. Regarding HPTLC, the Rf value of KBA was measured, and the correlation coefficient was calculated from the standard curve. Accuracy, precision and recovery were found within limits.From this study, it was concluded that a non-thermal method is a better choice of extraction for KBA. All the input variables significantly affected KBA content, which was confirmed by model fitting. Moreover, the HPTLC method was developed for the quantification of KBA, which was found to be accurate, reliable and highly sensitive.
Background: Evidence from published studies raised doubt on microalbuminuria as a predictive marker for the development and progression of kidney disease in type 2 diabetes mellitus (T2DM) subjects. So, in this study, we are exploring the predictive potential of growth differentiation factor-15 (GDF-15) and galectin-3 biomarkers for the early detection of diabetic kidney disease (DKD). Methods and materials: This was an observational study conducted over a period of 1.2 years. The study protocol was approved by the Jamia Hamdard Institutional Ethics Committee. Patients were classified on the basis of estimated glomerular filtration rate (eGFR) and albuminuria. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potential of the marker, sensitivity and specificity were also calculated. All the analysis was performed using SAS v9.4. Results: A total of 90 patients completed the study. Patients were grouped as normoalbuminuria (30 patients), microalbuminuria (30 patients), and macroalbuminuria (30 patients). Mean age of the patients was 58.0 ± 11.08 years. Galectin-3 and PGDF-15 levels were significantly elevated in T2DM patients with macroalbuminuria as compared to T2DM patients with microalbuminuria and normoalbuminuria (p = <0.05). The patients with poor kidney function (Stage IV-V CKD) have higher levels of galectin-3 and GDF-15. Correlation analysis showed galectin-3 levels and GDF-15 levels were positively correlated with age, serum creatinine, and UACR. While, negative correlation was observed between galectin-3 (r = −0.472), GDF-15 (r = −0.917) biomarkers and eGFR (p = 0.000). The ROC analysis of galectin-3 and GDF-15 yielded an AUC of 0.776 (95% CI: 0.677 to 0.875; p = <0.0001) and 0.963 (95% CI: 0.929 to 0.997; p = <0.0001). The sensitivity and specificity of galectin-3 in the diagnosis of DKD were 0.53 and 0.97, while for GDF-15 it was 0.93 and 0.87. Conclusion: In DKD patient's galectin-3 and GDF-15 level increases as the eGFR decreases. ROC curve also confirms the diagnosis and prediction potential of galectin-3 and PGDF-15 in DKD.
Abstract There has been an escalation in the number, diversity, and complexity of medical devices. Regulation of these devices has also advanced due to the requirement of better regulatory perspective induced due to elevation in the number of adverse events associated with medical devices. All over the globe, various measures are undertaken to provide better safety to the patients along with attempts to improve the standard of medical devices. The initial and ultimate objective of the concept happens to be unfailingly to ensure patient safety as well as impart required guidance for both manufacturers and adept authorities enabling them to superintend cases coherently and appropriately. Materiovigilance programme of India (MvPI) was launched by the Drug Controller General of India at the Indian Pharmacopoeia commission (IPC) in Ghaziabad in 2015. The main purpose of this initiative is to monitor adverse events associated with medical devices in order to generate safety data, create awareness among the various stakeholders, and prescribe best practices for patient safety. Whilst the reforms in regulations have proposed policies and designs to elucidate, consolidate and accelerate the processes involved in manufacturing and importing medical devices to India, they consistently carry their challenges and limitations. To eliminate such complications the guidelines and regulations are anticipated to be implemented appropriately with the efficacious conclusion. India has been evident in matching with advancements in the World Medical Device regulation scenario, the current review at hand takes upon the question of ‘how successful has it been so far’?
Abstract The World Health Organization (WHO) has ranked depression the 4th leading cause of disability worldwide. Thymoquinone (TQ), is an active constituent of Nigella sativa having various medicinal properties but has poor solubility and bioavailability. This problem was overcome by developing nanoformulation of TQ. Previously TQ reported good antioxidant and anti-inflammatory effects. Recently TQ’s anti-depressant effect was demonstrated. However, the mechanisms underlying the antidepressant effect of TQ still needs evaluation. Activation of Indoleamine-2,3-dioxygenase (IDO), (an enzyme that participates in the tryptophan metabolism), leads to a decrease of serotonin (5-HT) levels. The expression of this enzyme is associated with immune system activation, which has been proposed as a common mechanism that links depression. The present study was performed in stressed animals where hippocampal levels of pro-inflammatory cytokines (IL-6 and TNF α levels), brain derived neurotropic factor (BDNF) and hippocampal kynurenine (KYN), tryptophan (TRP) and serotonin (5-HT) levels were estimated. Treatment with TQ solid lipid nanoparticles (TQSLN 20 mg/kg p.o) and TQ suspension (20 mg/kg p.o) demonstrated antidepressant-like activity in chronic forced-swim stress model. Further, it reduced the elevated hippocampal IL-6 & TNFα and reversed the increased activity of IDO as measured by ratio of hippocampal KYN/TRP and 5HT/TRP in stressed rats. The results of the present study confirm anti-inflammatory and neuroprotective effects of TQ which may be associated with 5-HT pathway. Thus, the present study offers a newer approach to reduce symptoms of depression using TQSLN. Our results are preliminary, further research is needed for more conclusive view.
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