Hepatoprotective Activity of Heptoplus on Isoniazid and Rifampicin Induced Liver Damage in Rats

The present study is designed to evaluate the efficacy of heptoplus a polyherbal formulation as an oral supplementary agent for isoniazid and rifampicin induced hepatotoxicity in rats. 50 and 100 mg/kg of heptoplus supplement were fed orally to the rats along with isoniazid and rifampicin and compared to rats treated with 100 mg/kg Liv 52 standard drug. Rats treated with isoniazid and rifampicin suffered from severe oxidative stress by the virtue of free radicals induced lipid per oxidation. As a result abnormal index of serum biochemical markers for liver function and increased liver lysosomal enzymes activity was observed. However rats nourished with 100 mg/kg of heptoplus and Liv 52 protected the liver from oxidative damage by maintaining normal antioxidant profile status and restored normal serum liver biochemical markers. Increased liver lysosomal enzymes activity is prevented in the rats supplemented with heptoplus and Liv 52. Histopathological analysis also revealed severe vascular changes and lobular necrosis in the treatment of isoniazid and rifampicin. Heptoplus (100 mg/kg) and Liv 52 supplemented rats liver apparently revealed normal architecture of liver. This study confirms that heptoplus has liver protective activity against Isoniazid and Rifampicin induced liver injury in rats, in par with Liv 52.     

Effect of ethanolic extracts of Justicia neesii Ramam. against experimental models of pain and pyrexia

Objective:The main objective of this study is to evaluate the analgesic and anti-pyretic activities of ethanolic extracts of Justicia neesii Ramam. by different experimental models.Results:In the hot plate model 400 mg/kg p.o. dose of J. neesii has shown its maximal effect at 3 h. The results are significant (P < 0.05) and comparable to the values of standard drug pentazocine (30 mg/kg i.p.). In acetic acid induced writhing model 400 mg/kg p.o. of plant extracts have shown highly significant activity (P < 0.001) and better than standard drug indomethacin (10 mg/kg p.o.). The 400 mg/kg p.o. dose of plant extract has given significant results against both yeast induced pyrexia and TAB vaccine induced pyrexia (P< 0.01 and 0.05 respectively). These values are comparable to that of paracetamol 100 mg/kg p.o. standard dose.Conclusion:This study shows that the ethanol extract of J. neesii has significant analgesic and antipyretic activity.KEY WORDS: Brewer''s yeast, hot plate, pyrexia, TAB vaccine, writhing     

Platelet Indices and Their Kinetics Predict Mortality in Patients of Sepsis

Platelet indices are inexpensive, easily accessible parameters and potentially useful prognostic indicators in sepsis. In this study we explore the differences in platelet indices and their kinetics between sepsis survivors and non-survivors. A retrospective cohort-study of 97 cases of culture-positive sepsis at a tertiary-care center in North India. Demographics, clinical and laboratory parameters at admission were assessed. Platelet count (PLT), mean-platelet-volume (MPV), platelet-distribution-width (PDW) and plateletcrit (PCT) on admission, and third, fifth and last days of hospitalization were analyzed. Fractional change in platelet indices (ΔMPV_72h, ΔPDW_72h, ΔPCT_72h, and ΔPLT_72h) by day-3 were calculated. Unpaired and paired t-tests were used to compare survivors with non-survivors, and to study the change in platelet indices with time. Logistic regression was used for multivariate analysis. ROC-curves and optimum cut-offs to predict mortality were obtained. There were 64 survivors. Non-survivors had significantly higher ΔMPV_72h, ΔPDW_72h, day-1 MPV and PDW, and lower ΔPLT_72h. MPV and PDW increased, and PLT decreased with time among non-survivors. Trends were reversed in survivors. Only MPV and PDW showed significant change by day-3. Both were independent predictors of mortality on multivariate analysis, alongside ΔMPV_72h and ΔPLT_72h. On ROC analysis, MPV, PDW, ΔMPV_72h, ΔPDW_72h and ΔPLT_72h effectively predicted mortality. Cut-off for MPV was 10.25 fL (sensitivity = 93.9%, specificity = 60.9%), and PDW, 12.6% (sensitivity = 84.8%, specificity = 51.6%). A rise in MPV and a fall in PLT was associated with mortality in this study. MPV and PDW values at admission are effective predictors of mortality and may be used in conjunction with traditional parameters.     

Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases: A prospective cohort study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.     

Relationships between inflammation,hemodynamic function and RAAS in longstanding type 1 diabetes and diabetic kidney disease

The renin angiotensin aldosterone system (RAAS) is associated with renal disease and inflammation in a diabetes setting, however, little is known about the implicated mechanisms in individuals with long standing diabetes. Accordingly, our aim was to perform an observational study to quantify urinary excretion of inflammatory biomarkers in participants with long standing type 1 diabetes (T1D) (with and without diabetic kidney disease [DKD]) and controls, at baseline and in response to RAAS activation. GFR_INULIN, ERPF_PAH, and 42 urine inflammatory biomarkers were measured in 74 participants with T1D for ≥50 years (21 with DKD and 44 without DKD [DKD resistors]) and 73 healthy controls. Additionally, inflammatory biomarkers were measured before and after an angiotensin II infusion (ANGII, 1 ng?kg^?1?min^?1). Significantly lower urinary excretion of cytokines (IL-18, IL-1RA, IL-8), chemokines (MCP1, RANTES) and growth factors (TGF-α, PDGFAA, PDGFBB, VEGF-A) was observed in participants with T1D at baseline compared to controls. Urinary IL-6 was higher in DKD than in DKD resistors in an exploratory analysis unadjusted for multiple comparisons. In T1D only, lower GFR_INULIN correlated with greater excretion of proinflammatory biomarkers (IL-18, IP-10, & RANTES), growth factors (PDGF-AA & VEGFAA), and chemokines (eotaxin & MCP-1). ANGII increased 31 of 42 inflammatory biomarkers in T1D vs controls (p < 0.05), regardless of DKD resistor status. In conclusion, lower GFR and intra-renal RAAS activation were associated with increased inflammation even after longstanding T1D. The increased urinary IL-6 in patients with DKD requires further investigation to determine whether IL-6 is a candidate protective biomarker for prognostication or targeted therapy in DKD.     

Association of TNF level with production of circulating cellular microparticles during clinical manifestation of human cerebral malaria

Microparticles (MPs) resulting from vesiculation of different cell types in Plasmodium falciparum infection correlate with the level of proinflammatory cytokine TNF that may thereby determine the disease severity. Using TruCount tube based flow cytometric method for the exact quantification of MP and enzyme linked immunosorbent assay for the measurement of TNF, we conducted a hospital based case control study on P. falciparum malaria patients to scrutinize and infer the link between the two. In 52 cerebral malaria (CM), 21 multi-organ-dysfunction (MOD), 12 non cerebral severe malaria (NCSM) and 43 uncomplicated malaria patients, the MP level was found to be significantly elevated in febrile malaria patients compared to healthy controls and a striking decrease in MP level was observed with the clearance of the P. falciparum infection in the patients upon follow-up. The lowering of the parasite density with the level of plasma TNF and the positive correlation of the cytokine with the cell derived MPs and negative correlation with the respective cell count in human malaria patients suggests that TNF may be a key stimulant to the cells resulting in the release of MPs in malaria infection.