Narciclasine improves outcome in sepsis among neonatal rats via inhibition of calprotectin and alleviating inflammatory responses.

Sepsis is associated with exacerbated inflammatory response which subsequently results in multiple organ dysfunction. Sepsis accounts for high mortality and morbidity among newborns worldwide. Narciclasine is a plant alkaloid which has shown to possess anti-inflammatory properties. In this study we investigated the effect and mechanism of action of narciclasine in neonatal sepsis rat models. The excessive release of S100A8/A9 or calprotectin in neonatal sepsis could be detrimental as it could exacerbate the inflammatory responses. We found that narciclasine significantly reduced the plasma levels of S100A8/A9 and also suppressed its expression in the liver and lung. The systemic and local bacterial load was also reduced in the narciclasine treated rats. The systemic and local production of pro-inflammatory cytokines in plasma and organs (liver and lungs) was significantly reduced in the narciclasine treated rats. The histopathological studies showed that narciclasine prevents the organ damage associated with sepsis and improved the survival of neonatal rats. Sepsis increased the phosphorylated NF-κß p65 protein expression in the liver. Narciclasine suppressed the phosphorylation of NF-κß p65 and the degradation of NF-κß inhibitory protein alpha. It could also suppress the expression of adaptor proteins of the toll like receptor signaling pathway viz., myeloid differentiation factor 88 (MyD88), Interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor associated factor 6 (TRAF6). These results suggest that narciclasine protects against sepsis in neonatal rats through the inhibition of calprotectin, pro-inflammatory cytokines and suppression of NF-κß signaling pathway.

Effect of Zinc Supplementation on Early Outcome of Neonatal Sepsis--A Randomized Controlled Trial.

OBJECTIVE: To find the effect of zinc supplementation on the outcome of neonatal sepsis at one month of age. METHODS: This randomized controlled trial was conducted in a tertiary care neonatal unit, enrolling neonates with clinical features of sepsis and positive blood culture or positive sepsis screening tests. The treatment group received 3 mg/kg/twice a day of zinc sulfate monohydrate orally for 10 d along with standard antibiotic therapy. The control group received standard antibiotic treatment without zinc. Samples were collected from both the groups before and after the treatment. Babies were monitored till discharge and followed up as out-patients till one month of age. RESULTS: Demographic characteristics were similar between the cases and controls. After 10 d of treatment, the mean serum zinc level between the two groups was 737.09 ± 219.97 vs. 801.26 ± 405.56, (p = 0.20). Outcome measures like days of hospital stay (15 vs. 15; p = 0.69) and mortality rate (4.5% vs. 13.6%; p = 0.27) were not found to be significantly different between the groups. At one month of age, more number of control neonates had abnormal neurological findings as compared to the zinc supplemented group [(P = 0.02); RR (95%CI) = 0.28 (0.11-0.73)]. CONCLUSIONS: Zinc supplementation in neonates with sepsis improves the neurological status at one month of age although the mortality reduction was not statistically significant.

Global DNA methylation in neonatal sepsis.

OBJECTIVE: To find out whether gDNA methylation can be used as a diagnostic/prognostic method for neonatal sepsis. METHODS: The study was conducted in the neonatal division of a tertiary care referral hospital. Fifty one newborns as cases and thirty seven newborns as controls were enrolled in the study. Using 5-mC DNA ELISA method, the percentage of genomic DNA methylated in these newborns was established. RESULTS: Highly significant difference in percentage of gDNA methylated was found between the cases and controls (Cases: 2.4 ± 0.39; CONTROLS: 2.07 ± 0.35; P < 0.0001). Culture proven and possible cases were also significantly distinguishable (P < 0.05). No significant differences in methylation were observed in terms of gestational age, birth weight and outcomes such shock, thrombocytopenia, except for renal failure. CONCLUSIONS: The index results showed that genomic DNA methylation varies significantly among newborns with sepsis (clinical, probable and culture positive) and without sepsis. Although the global DNA methylation was not a highly sensitive diagnostic method, this study reveals that DNA methylation might play a vital role in neonatal sepsis susceptibility. Identification of the specific differentially methylated genes might serve as a promising future diagnostic/prognostic marker for neonatal sepsis.