Outcome of children born to human immunodeficiency virus positive mothers - A retrospective study

Background: Mother-to-child transmission of human immunodeficiency virus (HIV) is a major route of new infections in children.The use of anti-retroviral therapy and nevirapine to mother-baby pairs has shown to be quite effective in preventing the transmissionof virus from mother-to-child. Objectives: To analyze the incidence of HIV transmission in children born to HIV-infected pregnantwomen and to analyze the outcome of these children. Methods: This retrospective study was conducted in a tertiary care referralhospital of central India for a period of 3 years. Data analysis of the mothers with HIV-positive serology up to their delivery andfollow-up of their babies for 18 months was performed. Perinatal mortality rate (PMR) and neonatal mortality rates (NMRs),mother-to-child transmission rate, and the outcome of their children on the basis of various factors - such as maternal CD4 count,treatment taken, and feeding practices - were analyzed. Results: 161 HIV-positive mothers gave birth to 164 babies (including1 triplet and 1 twin) during the study period. An incidence of mother-to-child transmission was 8.06% and it was influenced bymaternal CD4 count, maternal comorbidities, mode of delivery, and feeding practices. In our study, PMR was 48.78/1000 live births;NMR was 54.87/1000 live births as compared to 25/1000 live births in children born to seronegative mothers. Conclusion: The riskof vertical transmission of HIV from mother-to-baby was 8%. Maternal HIV transmission is the primary means by which infantsbecome infected. Hence, the prevention of maternal HIV transmission is of paramount importance

To study the short-term outcome of kangaroo mother care in newborn with birth weight less than 1.5 kg

Introduction: Kangaroo mother care (KMC) is an effective way to meet babies need for warmth, breastfeeding, and protection from infection, stimulation, safety, and love in resource-limited settings. Objective: To assess the effect of KMC on newborns weighing <1.5 kg on weight gain, duration of stay in hospital, and breastfeeding. Methods: A prospective case-control study was conducted in a tertiary care hospital of central India over 11-month period. A total of 70 newborns weighing <1.5 kg were included (35 each cases and controls) and were evaluated for short-term outcome of KMC on weight gain, breastfeeding, and duration of stay in hospital. Results: Mean daily weight gain was more in KMC group (16.94±3.84 vs. 4.29±6.94 g) (p<0.05). Mean weight at the time of discharge was more in KMC group (1.46±0.64 vs. 1.34±0.11 kg) (p>0.05). Breastfeeding was established 68.5% of babies in KMC group and in 34.2% in control group on discharge (p<0.05). The study showed that babies in KMC group were discharged earlier than controls (11.4±4.3 vs. 17.68±8.64 days) (p<0.05). Conclusion: Our study showed that babies in KMC group demonstrated more weight gain, both daily and on discharge. Duration of stay was shorter in them and more babies were shifted to breastfeeding earlier in KMC group. We conclude KMC as significant method of caring very low birth weight baby in resource-limited settings

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Albumin–Quercetin Combination Offers a Therapeutic Advantage in the Prevention of Reduced Survival of Erythrocytes in Visceral Leishmaniasis

Visceral leishmaniasis is associated with the reduced survival of erythrocytes, the cause of which remains to be fully explored. Here, we described the mechanism underlying the shortened lifespan of erythrocytes in visceral leishmaniasis and proposed a combination therapy with quercetin and hamster serum albumin towards its rectification. Decreased redox potential in erythrocytes followed by oxidative denaturation of hemoglobin and pathologic association of iron with the cell membrane facilitated premature hemolysis during leishmanial infection. Recently, we have reported the therapeutic efficacy of quercetin in arresting the enhanced destruction of erythrocytes in visceral leishmaniasis. Since serum albumin, the principal carrier protein for quercetin gets depleted in visceral leishmaniasis, the situation may compromise the efficacy of quercetin in this disease. We now report the use of quercetin–hamster serum albumin combination to increase the bioavailability of quercetin. The combination targeted hemoglobin oxidation and produced an effective attenuation of heme degradation. This led to decreased iron decompartmentalization, thereby increasing the life span of erythrocytes during leishmanial infection. Thus, we speculate that suppression of iron decompartmentalization, with the combination of quercetin and serum albumin might be a new approach in the prevention of reduced survival of erythrocytes in visceral leishmaniasis

Quercetin Interferes With iron Metabolism in Leishmania donovani and Targets Ribonucleotide Reductase to Exert Leishmanicidal Activity

The possibility of developing antileishmanial drugs was evaluated by intervention in the parasite’s iron metabolism, utilizing quercetin (Qr) under in vivo conditions, and identifying the target of this lipophilic metal chelator against Leishmania donovani. Methods: Interaction between Qr and serum albumin (SA) was studied by using the intrinsic fluorescence of Qr as a probe. The effect of treatment with Qr and SA on the proliferation of amastigotes was determined by evaluating splenic parasite load. Disintegration of parasites in response to combination treatment was assessed from ultrastructural analysis using a transmission electron microscope. Quenching of the tyrosyl radical of ribonucleotide reductase (RR) in treated amastigotes was detected by an electron paramagnetic resonance study. Results: Treatment with a combination of Qr and SA increased bioavailability of the flavonoid and proved to be of major advantage in promoting the effectiveness of Qr towards the repression of splenic parasite load from 75%, P < 0.01 to 95%, P < 0.002. Qr-mediated down-regulation of RR (P < 0.05), catalysing the rate-limiting step of DNA synthesis in the pathogens, could be related to the deprivation of the enzyme of iron which in turn destabilized the critical tyrosyl radical required for its catalysing activity. Conclusions: Results have implications for improved leishmanicidal action of Qr in combination with SA targeting RR and suggest future drug design based on interference with the parasite’s iron metabolism under in vivo conditions

Protective effect of creatine against inhibition by methylglyoxal of mitochondrial respiration of cardiac cells.

Previous publications from our laboratory have shown that methylglyoxal inhibits mitochondrial respiration of malignant and cardiac cells, but it has no effect on mitochondrial respiration of other normal cells [Biswas, Ray, Misra, Dutta and Ray (1997) Biochem. J. 323, 343-348; Ray, Biswas and Ray (1997) Mol. Cell. Biochem. 171, 95-103]. However, this inhibitory effect of methylglyoxal is not significant in cardiac tissue slices. Moreover, post-mitochondrial supernatant (PMS) of cardiac cells could almost completely protect the mitochondrial respiration against the inhibitory effect of methylglyoxal. A systematic search indicated that creatine present in cardiac cells is responsible for this protective effect. Glutathione has also some protective effect. However, creatine phosphate, creatinine, urea, glutathione disulphide and beta-mercaptoethanol have no protective effect. The inhibitory and protective effects of methylglyoxal and creatine respectively on cardiac mitochondrial respiration were studied with various concentrations of both methylglyoxal and creatine. Interestingly, neither creatine nor glutathione have any protective effect on the inhibition by methylglyoxal on the mitochondrial respiration of Ehrlich ascites carcinoma cells. The creatine and glutathione contents of several PMS, which were tested for the possible protective effect, were measured. The activities of two important enzymes, namely glyoxalase I and creatine kinase, which act upon glutathione plus methylglyoxal and creatine respectively, were also measured in different PMS. Whether mitochondrial creatine kinase had any role in the protective effect of creatine had also been investigated using 1-fluoro-2,4-dinitrobenzene, an inhibitor of creatine kinase. The differential effect of creatine on mitochondria of cardiac and malignant cells has been discussed with reference to the therapeutic potential of methylglyoxal