Renal Adverse Effects of Tenofovir Containing Regimens in HIV-Infected Children and Adolescents in North India.

OBJECTIVE: To study the prevalence of abnormal renal functions among children living with HIV (CLHIV) receiving tenofovir disoproxil fumarate (TDF) containing antiretroviral therapy (ART). METHODS: A prospective, observational study was conducted among CLHIV aged 10 years to 21 years attending the pediatric HIV clinic. We included CLHIV weighing ≥ 30 kg who had been receiving TDF-containing regimens for at least 6 months, with estimated glomerular filtration rate (eGFR) > 60 ml/min/m2 at enrolment and for whom baseline laboratory parameters were available before starting ART. Clinical and laboratory parameters like serum creatinine, serum phosphate, urinary protein and glucose estimation, CD4 count and viral load were noted from records. The mean change in serum creatinine, estimated glomerular filtration rate (eGFR), creatinine clearance, serum phosphate, and presence of urinary glucose and protein by dipstick were assessed at 3- and 12-months follow-up. RESULTS: We enrolled 70 patients with mean (SD) age 14.99 (2.45) years who had been receiving TDF-based ART for a mean (SD) duration of 14.60 (12.80) months. At 3-months and 12-months follow-up, 32.85% and 41.42% patients, respectively, had eGFR below 90 mL/min/1.73m2, while 4.2% and 2.8% patients, respectively, had eGFR between 50-60 mL/min/1.73m2. One patient had creatinine clearance below 50 mL/min/1.73m2. Four patients had hypophosphatemia at the first and last follow-up respectively, and five patients had proteinuria. There was no statistically significant change in CD4 counts, serum potassium, or serum uric acid during study duration. CONCLUSION: TDF-containing ART regimen is associated with decreased eGFR, creatinine clearance and proteinuria.

Effect of the timing of antiretroviral treatment initiation on CD4 count in children and youths living with HIV in North India.

BACKGROUND: Immediate start of antiretroviral treatment (ART) among non-hospitalized outpatient children living with HIV may improve or worsen clinical outcomes due to immune reconstitution. OBJECTIVE: Role of immediate versus post-stabilization start of antiretroviral treatment in children and youths living with HIV on CD4 count and viral load suppression. METHODS: This was a single blinded, randomized controlled trial conducted on outpatients attending a tertiary care hospital associated HIV clinic in North India. We enrolled ART-naive children and youths living with HIV aged 18 months to 21 years in a 1:1 ratio. Block randomization was done using computerized software. Children and youths living with HIV were either started with ART on diagnosis immediately within 24 h (Group A) or post stabilization at 2 weeks (Group B) as per National AIDS Control Organization (NACO) India guidelines. Both groups were comparable for baseline characteristics. RESULTS: There was no significant difference seen in CD4 counts between two groups at 6 months follow up. CD4 count increased significantly in immediate group but not in post-stabilization group at 6 months. No significant changes/differences was seen in WHO clinical staging or anthropometry; one patient developed tuberculosis in both groups. Viral load at 6 months in both the groups did not differ significantly. CONCLUSION: Immediate ART in children and youths living with HIV results in significant increase in CD4 count at 6 months follow up exemplifying immunological response to ART.

Aphrodisiac properties of hydro-alcoholic extract of Cassia auriculata flower in male rats.

Cassia auriculata is a commonly found plant in Asia, widely used in Ayurveda and Siddha medicines as a tonic, astringent and in general for diabetes. Herbal tea made from this plant has been marketed as a product for restoring sexual vitality, to increase sperm count and counteract ejaculatory disorders. However, the scientific evidences are scarce to prove this concept. Here, we examined the effect of hydro-alcoholic extract obtained from C. auriculata flower upon the expression of male Wistar albino rat's sexual behaviour. Sildenafil was used as a positive control. Penile erection index (PEI), mount latency (ML), intromission latency (IL), ejaculation latency (EL), mounting frequency (MF), intromission frequency (IF), ejaculation frequency (EF) and post-ejaculatory interval (PEjI) were recorded for days 0, 7, 14 and 28 and also after the withdrawal of the treatment on days 7 and 15. Significant reduction in ML, IL and PEjI, and increment in EL, PEI, MF, IF and EF were observed (p < 0.05, <0.01). However, neither extract nor sildenafil sustains the effect after withdrawal of the treatment. The present finding demonstrates the aphrodisiac potential of hydro-alcoholic extract of C. auriculata flower in vivo and lends support to the traditional utilisation as a sexual stimulating agent.

Effect of Cinnamomum zeylanicum extract on scopolamine-induced cognitive impairment and oxidative stress in rats.

OBJECTIVE: Cinnamomum zeylanicum (CZ) is commonly known as cinnamon in traditional system of medicine having antibacterial, antioxidant, antidiabetic, hypolipidemic, and other activities. The present study was designed to assess the effect of extract of CZ bark on cognitive performance of scopolamine (SCOP)-treated rats and on associated altered oxidative stress markers in the brain of rats. METHODS: The extract was administered orally in three doses (100, 200, and 400 mg/kg) for a period of 21 days. SCOP was administered in the dose of 1.0 mg/kg intraperitoneally. The Morris water maze and passive avoidance step-down tasks were performed to assess cognitive functions. At the end of the study, oxidative stress parameters namely, malondialdehyde (MDA) and reduced glutathione (GSH) were also analyzed in the brain tissue of rats. RESULTS: SCOP-treated group showed significantly impaired acquisition and retention of memory as compared to the saline- and vehicle-treated groups. Pretreatment with CZ extract (200 and 400 mg/kg) for 21 days significantly reversed SCOP-induced amnesia as evidenced by increased step-down latency in passive avoidance and decreased latency in Morris water maze test compared to the SCOP-treated group. SCOP administration also caused the increase of MDA and reduction of GSH levels. Pretreatment with CZ extract (200 and 400 mg/kg) resulted in a significant decrease in MDA levels and increase in GSH levels as compared to the SCOP-treated animals. DISCUSSION: The results suggest that CZ can induce cognitive improvement in SCOP-treated rats and this effect can be attributed to a certain extent to decreased oxidative stress.

Eugenia jambolana pretreatment prevents isoproterenol-induced myocardial damage in rats: evidence from biochemical, molecular, and histopathological studies.

Preventive effects of hydroalcoholic extract of fruit pulp of Eugenia jambolana (HEEJ) on isoproterenol (ISP)-induced myocardial damage in rats were evaluated. Rats were pre-treated with HEEJ (100, 200, and 400 mg/kg) daily for 30 days. ISP (85 mg/kg bw) was administered on the 28th and 29th days at an interval of 24 h. Ischemic control group exhibited significant increases in oxidative stress parameters, markers of inflammation, cardiac damage markers, and apoptotic markers. Oral pre-treatment with HEEJ (100, 200, and 400 mg/kg bw) provided cardioprotective activity by decreasing levels of malondialdehyde, cardiac markers (serum glutamate oxaloacetate transaminase, creatine kinase-myocardial band, cardiac troponin I), and markers of inflammation (interleukin-6, C-reactive protein, and tumor necrosis factor alpha); and increased levels of superoxide dismutase and reduced glutathione. HEEJ (400 mg/kg bw) was found to exert significantly greater effects in comparison to HEEJ (100 and 200 mg/kg bw). Apoptotic marker Bcl-2 was increased, while Bax was decreased in pre-treated rats, which was further confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The present study provides evidence that pre-treatment with HEEJ attenuates oxidative stress, apoptosis and improves cardiac architecture in ISP-induced rats and, hence, is cardioprotective.

Protective effect of Morus rubra L. leaf extract on diet-induced atherosclerosis in diabetic rats.

The antiatherosclerotic effect of aqueous leaves extract of Morus rubra was studied in streptozotocin-induced diabetic rats fed with atherosclerotic (Ath) diet [1.5 ml olive oil containing 8 mg (3, 20,000 IU) vitamin D2 and 40 mg cholesterol] for 5 consecutive days. A short-term toxicity assessment was also conducted in healthy rats to examine toxic effects of the extract. Oral administration of extract to diabetic rats (100, 200 and 400 mg/kg body weight per day for a period of 30 days) produced significant (p<0.001) fall in fasting blood glucose (FBG) in a dose-dependent manner. Treatment with the extract (400 mg/kg) showed significant (p<0.001) improvement in body weight and serum lipid profile i.e., total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol, when compared with diabetic control. Endothelial dysfunction parameters (sVCAM-1, Fibrinogen, total NO levels and oxidized LDL), apolipoprotein A and apolipoprotein B were significantly (p<0.001) reversed to near normal, following treatment with the extract. Thus, our study shows that aqueous leaf extract of Morus rubra (400 mg/kg) significantly improves the homeostasis of glucose and fat and possesses significant anti-atherosclerotic activity.

Antidiabetogenic action of Morus rubra L. leaf extract in streptozotocin-induced diabetic rats.

OBJECTIVES: Researchers all over the world are exploring herbal supplements to control diabetes and its complications. This study evaluated the antidiabetic action of Morus rubra L. aqueous leaf extract through its effect on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-induced diabetic rats. METHODS: The extract was orally administered to diabetic rats (100, 200 and 400 mg/kg body weight) daily for 21 days. Fasting blood glucose was measured on days 0, 7, 14 and 21. At the end of the experiment, blood samples were drawn to measure glucose tolerance, glycosylated haemoglobin, insulin, C-peptide and lipid parameters. Antioxidant enzymes (superoxide dismutase and catalase), reduced glutathione and lipid peroxides were determined in blood and liver tissue. Histopathological examination of pancreatic tissue was also performed. KEY FINDINGS: The extract showed a dose-dependent fall in fasting blood glucose. Treatment with 400 mg/kg extract produced a significant reduction in glycosylated haemoglobin with a concomitant elevation in plasma insulin and C-peptide levels. The altered serum lipids in diabetic rats were significantly restored following treatment with the extract. In erythrocytes, as well as liver, the activity of antioxidant enzymes and content of reduced glutathione were found to be significantly enhanced, while levels of serum and hepatic lipid peroxides were suppressed in extract-fed diabetic rats. Histopathological examination of pancreatic tissue revealed an increased number of islets and beta-cells in extract-treated diabetic rats. CONCLUSIONS: M. rubra aqueous leaf extract leads to control over hyperglycaemia and dyslipidaemia. The study also demonstrates its antioxidant nature, and hence it may be protective against diabetic complications.