Therapeutic Potentials of Syzygium fruticosum Fruit (Seed) Reflected into an Array of Pharmacological Assays and Prospective Receptors-Mediated Pathways.

Syzygium fruticosum (SF), a valuable Bangladeshi fruit, is considered an alternative therapeutic agent. Mainly, seeds are used as nutritional phytotherapy to ease physical and mental status by preventing chronic diseases. Here, we scrutinized the S. fruticosum seed's fundamental importance in traditional medicine by following an integrated approach combining in vivo, in vitro, and in silico studies. The SF was fractionated with different solvents, and the ethyl acetate fraction of SF (EaF-SF) was further studied. Mice treated with EaF-SF (200 and 400 mg/kg) manifested anxiolysis evidenced by higher exploration in elevated plus maze and hole board tests. Similarly, a dose-dependent drop of immobility time in a forced swimming test ensured significant anti-depressant activity. Moreover, higher dose treatment exposed reduced exploratory behaviour resembling decreased movement and prolonged sleeping latency with a quick onset of sleep during the open field and thiopental-induced sleeping tests, respectively. In parallel, EaF-SF significantly (p < 0.001) and dose-dependently suppressed acetic acid and formalin-induced pain in mice. Also, a noteworthy anti-inflammatory activity and a substantial (p < 0.01) clot lysis activity (thrombolytic) was observed. Gas chromatography-mass spectrometry (GC-MS) analysis resulted in 49 bioactive compounds. Among them, 12 bioactive compounds with Lipinski's rule and safety confirmation showed strong binding affinity (molecular docking) against the receptors of each model used. To conclude, the S. fruticosum seed is a prospective source of health-promoting effects that can be an excellent candidate for preventing degenerative diseases.

Weekly regimen of vitamin D supplementation is more efficacious than stoss regimen for treatment of vitamin D deficiency in children with chronic liver diseases.

There are no evidence-based recommendations on the ideal dose and regimen for supplementation of vitamin D in children with chronic liver disease (CLD). This study aimed to compare the safety and efficacy of weekly and stoss regimens for treatment of vitamin D deficiency in these children. Children between the ages of 1 to 18 years with CLD and hypovitaminosis D defined by 25-OH vitamin D (25(OH)D) < 30µg/l were included. They were randomized to receive either stoss regimen (600,000 IU on day 1) or weekly (60,000 IU weekly) regimen of vitamin D. The 25(OH)D levels at 3 and 6 months were compared in the two groups. A total of 210 suspected cases of CLD were assessed for eligibility. Of a total of 67 children satisfying the inclusion criteria, 33 and 34 were randomized to receive stoss and weekly regimen, respectively. Final analysis included 28 children in each group. Clinical rickets was seen in 25.4% of children with hypovitaminosis D. The rise in levels of 25(OH)D at 3 months was higher with weekly regimen (34.3 ± 30.7 µg/l) as compared to stoss regimen (17.2 ± 11.5 µg/l) (p = 0.009). Rise at 6 months as compared to baseline was significantly higher with weekly regimen (30.7 ± 24µg/l) as compared to stoss regimen (11 ± 8.4 µg/l) (p < 0.001). Normal levels of 25(OH)D at 6 months were achieved in 24/28 (85.7%) of those receiving weekly regimen and 9/28 (32.1%) of those receiving stoss regimen (p < 0.001). With stoss therapy, 25(OH)D increased at 3 months as compared to baseline but thereafter dropped significantly at 6 months (p = 0.008). CONCLUSION: Weekly regimen of vitamin D supplementation is more effective than stoss regimen for treatment of hypovitaminosis D in children with CLD. Once normal levels are achieved, child should be shifted to 60,000 IU per month as maintenance dose. What is Known: • Vitamin D deficiency is more common and severe in children with chronic liver diseases. • Currently used doses fail to achieve normal vitamin D levels in these children. What is New? • Weekly regimen of 60,000 IU of vitamin D3 is the most effective regimen for treating vitamin D deficiency in children with CLD. • Children with CLD should further receive maintenance dose of 60,000 IU every month.

Clinical Spectrum and Outcome of Pediatric Drug Induced Liver Injury.

Limited literature is available in pediatric population regarding drug-induced liver injury (DILI) making it a diagnostic challenge. This study was thus planned to determine the clinical spectrum and the outcome of DILI in children. All patients with DILI under 18 y of age were retrospectively reviewed and details regarding clinical presentation, Roussel Uclaf Causality Assessment Method (RUCAM) scale, drugs implicated, biochemical abnormalities and outcome were noted. DILI constituted 3.7% of all children with liver disease. Cases were divided into the hepatocellular (18, 50%), cholestatic (10, 27.8%), and mixed pattern (8, 22.2%). Complementary and alternative medicines (CAM) and antitubercular (ATT) drugs accounted for three-fourth cases of total DILI (39% and 33% cases respectively). Overall, 4 (11%) patients died and 5 (14%) patients progressed to chronic DILI. Presence of ascites, non-hepatocellular injury pattern and high serum total IgG levels were significantly associated with unfavourable outcome (death or chronicity).

Effect of short term zinc supplementation on iron status of children with acute diarrhea.

OBJECTIVE: To study the effect of short term (2 wk) zinc supplementation on hemoglobin and iron status of children with acute diarrhea. METHODS: This study was a prospective, open label, single arm interventional trial conducted from June 2008 through October 2009 in a teaching hospital of North India. Three to sixty months old children presenting with acute diarrhea participated in the study. Subjects were supplemented with recommended doses of oral zinc gluconate for 2 wk. Changes in levels of hemoglobin, serum iron, total iron binding capacity, and serum ferritin were the main outcome measures. RESULTS: Sixty-two patients completed the study successfully. The prevalence of anemia before and after 2 wk of zinc supplementation remained unchanged. However, a small decline (p > 0.05) was observed in mean hemoglobin (from 8.95 ± 1.4 to 8.73 ± 1.43 g/dL), serum iron (79.56 ± 45.81 to 78.61 ± 44.41 µg/dL) and ferritin (84.77 ± 45.35 to 83.55 ± 44.10 ng/mL) levels. Total iron binding capacity increased from 331.60 ± 109.72 to 341.30 ± 119.90 µg/dL post supplementation (p > 0.05). CONCLUSIONS: Even though statistically insignificant, the small change observed in the levels of hemoglobin, and indicators of iron status following short term zinc supplementation might assume significance in some settings in developing countries where children receive short courses of zinc repeatedly for frequent diarrheal episodes.

Clinical and prothrombotic profile of hepatic vein outflow tract obstruction.

OBJECTIVE: To study the clinical as well as prothrombotic profile and outcome of hepatic venous outflow tract obstruction in children. METHODS: This is a prospective study of a cohort of hepatic venous outflow tract obstruction (HVOTO) pediatric cases. All children and adolescents presenting with acute or chronic liver disease were screened for HVOTO with ultrasound and Doppler imaging and confirmed by multidetector computerised tomography (MDCT) with contrast enhancement. RESULTS: Of the 162 cases of chronic liver disease, 13 (7.4 %) were diagnosed to have HVOTO. Ascites and edema over the feet were the most prominent features. Anabolic steroids and herbal drugs were being taken by one case each. Six cases were diagnosed on Doppler and for rest 7 cases conclusive diagnosis was made on multidetector computerised tomography. Five out of 13 cases were heterogenous (CT) for mutation of the gene encoding methylene tetrahydrofolate reductase (MTHFR) and one case of these was also heterogenous for Factor Leiden V. One case was known celiac and developed HVOTO and was also found to be having hepatocellular carcinoma. Other causes were drug induced, pressure on inferior vena cava (IVC) and inferior vena cava (IVC) web. Thus the authors could find a prothrombotic cause for 10 out of 13 (76.9 %) cases. Three cases did not need any intervention. In one patient with infective thrombus of the IVC intervention was not planned. Six underwent angioplasty and 3 underwent transjugular intrahepatic portosystemic shunt. All were asymptomatic with improving growth parameters at follow up. CONCLUSIONS: Ascites, pedal edema, prominent abdominal veins and hepatomegaly should raise the suspicion of HVOTO in childhood liver disease. Majority of the cases would be harbouring a prothrombotic cause. MTHFR mutation was the commonest cause of HVOTO in the present study. Angioplasty and/or transjugular intrahepatic portosystemic shunt (TIPSS) can successfully treat HVOTO.

The efficacy of zinc supplementation in young children with acute lower respiratory infections: a randomized double-blind controlled trial.

BACKGROUND & AIM: Acute lower respiratory infections are the most frequent illnesses globally in children less than 5 years old. The aim of this randomized double blind controlled trial is to assess the effectiveness of zinc gluconate supplementation for 2 months period compared to placebo in reducing respiratory morbidity in acute lower respiratory infected children up to 5 years of age living in zinc poor population. METHODS: Children were randomly assigned to receive either 10 mg zinc gluconate or placebo for 60 days. Demographic and clinical data were collected at baseline and every two weeks for 180 days. RESULTS: The final analysis included 96 children allocated equally to the two groups. The number of episodes of acute lower respiratory infections and severe acute lower respiratory infections were significantly lower in zinc group compared to placebo group (20.8% vs. 45.8% (P = 0.009) and 21.7% vs. 58.3% (P < 0.001), respectively). The acute lower respiratory infections free days were higher in the zinc supplemented group (P < 0.001). The median recovery time of morbidity was significantly shorter in zinc group (P < 0.001). CONCLUSIONS: Zinc supplement may result in significant reduction in respiratory morbidity among children with acute lower respiratory infections in zinc poor population. This study was registered under ClinicalTrials.gov Identifier no. NCT00536133.