Synthesis, molecular docking and kinetic studies of novel quinolinyl based acyl thioureas as mushroom tyrosinase inhibitors and free radical scavengers.

The enzyme tyrosinase plays a vital role in melanin biosynthesis and enzymatic browning of vegetables and fruits. A series of novel quinolinyl thiourea analogues (11a-j) were synthesized by reaction of 3-aminoquinoline and corresponding isothiocyanates, in moderate to excellent yields with different substitutions and their inhibitory effect on mushroom tyrosinase and free radical scavenging activity were evaluated. The compound N-(quinolin-3-ylcarbamothioyl)hexanamide (11c) exhibited the maximum tyrosinase inhibitory effect (IC50 = 0.0070 ±â€¯0.0098 µM) compared to other derivatives and the reference Kojic acid (IC50 = 16.8320 ±â€¯0.0621 µM). The docking studies were carried out and the compound (11c) showed most negative estimated free energy of -7.2 kcal/mol in mushroom tyrosinase active site. The kinetic analysis revealed that the compound (11c) inhibits the enzyme tyrosinase non-competitively to form the complex of enzyme and inhibitor. The results revealed that 11c could be identified as putative lead compound for the design of efficient tyrosinase inhibitors.

Sialic acid levels in breast milk from HIV-positive Tanzanian women and impact of maternal diet.

OBJECTIVE: To quantify total sialic acid in milk from HIV-positive Tanzanian mothers and to determine the impact of maternal diet on milk sialic acid levels. DESIGN: Milk samples were analyzed from 74 HIV-positive, Tanzanian women enrolled in a randomized, controlled clinical study of a dietary macronutrient supplement. Women were provided with a daily protein-calorie supplement and a micronutrient supplement or micronutrient supplement only during the last trimester of pregnancy and up to the first 6 months of breastfeeding. METHODS: Milk samples were collected at approximately 2 weeks and at least 3 months postpartum and assayed for total sialic acid. Milk sialic acid was assessed relative to maternal macronutrient intake, age, BMI, CD4+ cell count and infant birth weight. RESULTS: The mean concentration of milk sialic acid was highest in the first 2 weeks postpartum (6.89 ±â€Š2.79 mmol/l) and declined rapidly by 3 months (2.49 ±â€Š0.60 mmol/l). Sialic acid content in milk was similar between both treatment arms of the study, and did not correlate with maternal macronutrient intake. No correlation was found between maternal age, BMI, CD4+ cell count or infant birth weight and total milk sialic acid concentration. CONCLUSION: Milk sialic acid levels in HIV-positive, Tanzanian women without malnutrition are comparable with reported values for women of European descent and show a similar temporal decline during early lactation. These findings suggest that total milk sialic acid is maintained despite macronutrient deficiencies in maternal diet and support a conserved role for milk sialic acid in neonatal development.

The premature infant gut microbiome during the first 6 weeks of life differs based on gestational maturity at birth.

BACKGROUND: The impact of degree of prematurity at birth on premature infant gut microbiota has not been extensively studied in comparison to term infants in large cohorts. METHODS: To determine the effect of gestational age at birth and postnatal exposures on gut bacterial colonization in infants, we analyzed 65 stool samples from 17 premature infants in the neonatal intensive care unit, as well as 13 samples from 13 mostly moderate-to-late premature infants and 189 samples from 176 term infants in the New Hampshire Birth Cohort Study. Gut colonization patterns were determined with 16S rDNA microbiome profiling. RESULTS: Gut bacterial alpha-diversity differed between premature and term infants at 6 weeks of age, after adjusting for exposures (p = 0.027). Alpha-diversity varied between extremely premature (<28 weeks gestation) and very premature infants (≥28 but <32 weeks, p = 0.011), as well as between extremely and moderate-to-late premature infants (≥32 and <37 weeks, p = 0.004). Newborn antibiotic use among premature infants was associated with lower Bifidobacterium and Bacteroides abundance (p = 0.015 and p = 0.041). CONCLUSION: Gestational age at birth and early antibiotic exposure have significant effects on the premature infant gut microbiota.

Fetal exposures and perinatal influences on the stool microbiota of premature infants.

OBJECTIVE: To test the hypothesis that maternal complications significantly affect gut colonization patterns in very low birth weight infants. METHODS: Forty-nine serial stool samples were obtained weekly from nine extremely premature infants enrolled in a prospective longitudinal study. Sequencing of the bacterial 16S rRNA gene from stool samples was performed to approximate the intestinal microbiome. Linear mixed effects models were used to evaluate relationships between perinatal complications and intestinal microbiome development. RESULTS: Subjects with prenatal exposure to a non-sterile intrauterine environment, i.e. prolonged preterm premature rupture of membranes (PPPROM) and chorioamnionitis exposure, were found to have a relatively higher abundance of potentially pathogenic bacteria in the stool across all time points compared to subjects without those exposures, irrespective of exposure to postnatal antibiotics. Compared with those delivered by Caesarean section, vaginally delivered subjects were found to have significantly lower diversity of stool microbiota across all time points, with lower abundance of many genera, most in the family Enterobacteriaceae. CONCLUSIONS: We identified persistently increased potential pathogen abundance in the developing stool microbiota of subjects exposed to a non-sterile uterine environment. Maternal complications appear to significantly influence the diversity and bacterial composition of the stool microbiota of premature infants, with findings persisting over time.

Breast milk from Tanzanian women has divergent effects on cell-free and cell-associated HIV-1 infection in vitro.

Transmission of HIV-1 during breastfeeding is a significant source of new pediatric infections in sub-Saharan Africa. Breast milk from HIV-positive mothers contains both cell-free and cell-associated virus; however, the impact of breast milk on HIV-1 infectivity remains poorly understood. In the present study, breast milk was collected from HIV-positive and HIV-negative Tanzanian women attending antenatal clinics in Dar es Salaam. Milk was analyzed for activity in vitro against both cell-free and cell-associated HIV-1. Potent inhibition of cell-free R5 and X4 HIV-1 occurred in the presence of milk from all donors regardless of HIV-1 serostatus. Inhibition of cell-free HIV-1 infection positively correlated with milk levels of sialyl-Lewis(X) from HIV-positive donors. In contrast, milk from 8 of 16 subjects enhanced infection with cell-associated HIV-1 regardless of donor serostatus. Milk from two of these subjects contained high levels of multiple pro-inflammatory cytokines including TNFα, IL-1ß, IL-6, IL-8, MIP-1α, MIP-1ß, MCP-1 and IP-10, and enhanced cell-associated HIV-1 infection at dilutions as high as 1∶500. These findings indicate that breast milk contains innate factors with divergent activity against cell-free and cell-associated HIV-1 in vitro. Enhancement of cell-associated HIV-1 infection by breast milk may be associated with inflammatory conditions in the mother and may contribute to infant infection during breastfeeding.

Optimizing successful breastfeeding in the newborn.

PURPOSE OF REVIEW: The purpose of this article is to present an overview of the state of breastfeeding in the United States and to examine recent evidence for strategies aimed at optimizing successful breastfeeding in the neonatal period. RECENT FINDINGS: Although rates of any and exclusive breastfeeding are rising, American mothers and infants are still unable to meet the Healthy People 2010 objectives. A review of the current literature demonstrates that the 'Ten Steps to Successful Breastfeeding' and the Baby Friendly Hospital Initiative are effective measures to increase breastfeeding initiation, duration, and exclusivity. A recent national survey reveals a significant proportion of pediatricians are not providing evidence-based recommendations for breastfeeding guidance and support. SUMMARY: The Baby Friendly Hospital Initiative, based upon the 'Ten Steps to Successful Breastfeeding', is an effective evidence-based model of perinatal care that protects, promotes, and supports breastfeeding. Pediatricians should aim to provide anticipatory guidance and management consistent with the 'Ten Steps' to optimize breastfeeding outcomes for mothers and their newborns.