MODULATORY ROLE OF NIMESULIDE, CAFFEIC ACID AND THEIR COMBINATION AGAINST IMMUNOLOGICALLY INDUCED MOUSE MODEL OF CHRONIC FATIGUE SYNDROME

Chronic Fatigue Syndrome (CFS) is a complex, debilitating illness characterized by persistent and relapsing fatigue that does not improve with rest. This study aimed to explore the neuroprotective effects of nimesulide, and caffeic acid and their combination as an antioxidant in the immunologically induced chronic fatigue-like condition. The CFS was assessed by water-immersion stress test and stress-induced hyperalgesia. Nimesulide (5 and 10 mg/kg), caffeic acid (5 and 10 mg/kg), and their low-dose combination (nimesulide 5mg/kg and caffeic acid 5mg/kg) were administered daily for 21 days. On the 22nd day, the brain of animals was isolated immediately after the behavioral assessments for estimation of oxidative stress markers (SOD, GSH, MDA, and nitrite). The mice challenged with lipopolysaccharide (LPS) used as immunogen (control group) followed by water immersion stress for 21 days showed a significant increase in immobility time and hyperalgesia. The rats also showed decreased levels of antioxidant defense enzymes (SOD, GSH, and MDA), and cortisol levels but markedly increased tumor necrosis factor-alpha (TNF-∝) levels. The daily drugs treated groups showed a significant (p<0.05) reduction in immobility time in stress-induced models and reversed various biochemical alterations as well as TNF-∝ and cortisol levels when compared to the control group. Furthermore, the lower dose combination of nimesulide and caffeic acid significantly (p<0.05) improved behavior performance and attenuated the chronic fatigue-like condition as compared to single drug-treated groups. The result of the present findings strongly demonstrates that the potential antioxidant effect of nimesulide and caffeic acid and its combination has protective effects against immunologic-induced fatigue and could be used in the management of chronic fatigue syndrome

Formulation of ayurvedic medicines and extracts of medicinal plants as an alternative therapeutic treatment option for nephrolithiasis

The incidence of nephrolithiasis, commonly known as kidney stone, is increasing worldwide with significant health and economic burden. Approximately 2 million people every year in India are affected by kidney stones. It affects all ages, genders, and races, but between the ages of 20 and 49 years, it affects most frequently in men than women. Different types of stones include calcium stones, cysteine stones, struvite or magnesium ammonium phosphate stones, uric acid stones, and drug-induced stones. This review article provides information about general pathophysiology, epidemiology, clinical presentation, and pharmacological treatment, which includes ayurvedic and herbal medicines for nephrolithiasis. Further understanding of the pathophysiological link between nephrolithiasis and systemic disorders is necessary for the development of new therapeutic options

Mechanisms of Antidiabetic Activity of Methanolic Extract of Punica granatum Leaves in Nicotinamide/Streptozotocin-Induced Type 2 Diabetes in Rats

The current study aimed to establish the mechanisms of antidiabetic activity of methanolic extract of Punica granatum leaves (MEPGL) in nicotinamide/streptozotocin-induced type 2 diabetes in rats. Phytochemical screening, HPLC analysis, and acute toxicity study of MEPGL were carried out. Various concentrations of MEPGL (100, 200, 400, and 600 mg/kg) were administered orally to diabetic rats for 45 days on a daily basis. The antidiabetic effect of MEPGL was examined by measuring blood glucose, plasma insulin, and glycated hemoglobin (HbA1c) levels, as well as with an oral glucose tolerance test. The antioxidant effect of MEPGL was determined by analyzing hepatic and renal antioxidant markers, namely superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation. The other biochemical markers alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea, and creatinine, as well as total cholesterol, triglycerides, and high-density lipoprotein (HDL) were also studied. Type 2 diabetes significantly altered these parameters, while oral administration of the MEPGL significantly ameliorated them. Moreover, the pancreatic histopathological changes were attenuated with MEPGL treatment. In a nutshell, oral MEPGL administration in diabetic rats showed antidiabetic activity due to its antioxidant activity, most probably due to the gallic acid, ellagic acid, and apigenin found in MEPGL

Efficacy of Lanthanum Carbonate and Sevelamer Carbonate as Phosphate Binders in Chronic Kidney Disease—A Comparative Clinical Study

(1) Background: Hyperphosphatemia is correlated with an increased rate of mortality and morbidity due to cardiovascular diseases in chronic kidney disease (CKD) patients. It can be improved by restricting dietary intake of phosphate and oral phosphate binders, such as lanthanum carbonate and sevelamer carbonate. (2) Objective: To evaluate the clinical efficacy of sevelamer carbonate in comparison to lanthanum carbonate as phosphate binders for the treatment of hyperphosphatemia in CKD patients. (3) Methods: A randomized control comparative clinical study was conducted for one year on 150 CKD patients associated with hyperphosphatemia, divided into two groups, i.e., Group 1 (n = 75) treated with sevelamer carbonate 800 mg thrice daily and Group 2 (n = 75) treated with lanthanum carbonate 500 mg thrice daily. The patients were assessed at the time of enrollment in the study, after three months and after six months from baseline for different parameters, i.e., complete blood count, liver function tests, renal function tests, electrolytes, and serum phosphate level. (4) Results: 150 CKD patients aged 51–60 participated in the study. The mean age of patients was 54 ± 4.6 years, and males (55.71%) were more common than females (44.29%). Hypertension was the common comorbidity in both groups with chronic kidney disease. After six months of treatment, the mean serum phosphate level was significantly decreased from 8.31 ± 0.09 mg/dL to 5.11 ± 0.18 (38%) in Group 1 and from 8.79 ± 0.28 mg/dl to 4.02 ± 0.12 (54%; p < 0.05) in Group 2, respectively. In both groups, no significant difference was found in other parameters such as parathyroid hormone, calcium, uric acid, LFT, RFT, CBC, etc. (5) Conclusion: Lanthanum carbonate is more efficacious in lowering serum phosphate concentrations and effectively managing hyperphosphatemia as compared to sevelamer carbonate

Efficacy of Lanthanum Carbonate and Sevelamer Carbonate as Phosphate Binders in Chronic Kidney Disease&mdash;A Comparative Clinical Study

(1) Background: Hyperphosphatemia is correlated with an increased rate of mortality and morbidity due to cardiovascular diseases in chronic kidney disease (CKD) patients. It can be improved by restricting dietary intake of phosphate and oral phosphate binders, such as lanthanum carbonate and sevelamer carbonate. (2) Objective: To evaluate the clinical efficacy of sevelamer carbonate in comparison to lanthanum carbonate as phosphate binders for the treatment of hyperphosphatemia in CKD patients. (3) Methods: A randomized control comparative clinical study was conducted for one year on 150 CKD patients associated with hyperphosphatemia, divided into two groups, i.e., Group 1 (n = 75) treated with sevelamer carbonate 800 mg thrice daily and Group 2 (n = 75) treated with lanthanum carbonate 500 mg thrice daily. The patients were assessed at the time of enrollment in the study, after three months and after six months from baseline for different parameters, i.e., complete blood count, liver function tests, renal function tests, electrolytes, and serum phosphate level. (4) Results: 150 CKD patients aged 51&ndash;60 participated in the study. The mean age of patients was 54 &plusmn; 4.6 years, and males (55.71%) were more common than females (44.29%). Hypertension was the common comorbidity in both groups with chronic kidney disease. After six months of treatment, the mean serum phosphate level was significantly decreased from 8.31 &plusmn; 0.09 mg/dL to 5.11 &plusmn; 0.18 (38%) in Group 1 and from 8.79 &plusmn; 0.28 mg/dl to 4.02 &plusmn; 0.12 (54%; p &lt; 0.05) in Group 2, respectively. In both groups, no significant difference was found in other parameters such as parathyroid hormone, calcium, uric acid, LFT, RFT, CBC, etc. (5) Conclusion: Lanthanum carbonate is more efficacious in lowering serum phosphate concentrations and effectively managing hyperphosphatemia as compared to sevelamer carbonate

Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients: a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial

International audienc

Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial

International audienceAbstract Background Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO 2 ) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO 2 with patients’ outcome. Methods Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO 2  300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO 2 -AUC), for hyperoxemia was significantly associated with mortality ( p = 0.003). Conclusions In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration : clinicaltrials.gov NCT02908308 , Registered September 20, 2016