Deepak Sharma

Lactoferrin and Neonatology- Role in neonatal sepsis and necrotizing enterocolitis: Present, past and future

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, Jan 10, 2015

Neonatal sepsis and necrotizing enterocolitis (NEC) are two most important neonatal problem in nu... more Neonatal sepsis and necrotizing enterocolitis (NEC) are two most important neonatal problem in nursery which constitute the bulk of neonatal mortality and morbidity. Inflammatory mediators secondary to sepsis and NEC increases morbidity, by effecting various system of body like lung, brain and eye, thus causing long term implications. Lactoferrin (LF) is a component of breast milk and multiple actions that includes antimicrobial, antiviral, anti-fungal, and anti-cancer and various other actions. Few studies has been completed and number of them are in progress for evaluation of efficacy and safety of LF in the prevention of neonatal sepsis and NEC in field of neonatology. In the coming future LF prophylaxis and therapy may have a significant impact in improving clinical outcomes of vulnerable preterm neonates. This review analyse the role of lactoferrin in prevention of neonatal sepsis and NEC, with emphasis on mechanism of action, recent studies and current studies going on around the globe.

Differential activation of NF-κB and nitric oxide in lymphocytes regulates in vitro and in vivo radiosensitivity

Mutation research, Jan 21, 2010

Lymphocytes are more sensitive to radiation in vivo than in vitro. However, the mechanism of this... more Lymphocytes are more sensitive to radiation in vivo than in vitro. However, the mechanism of this differential response is poorly understood. In the present study, it was found that the lipid peroxidation and cell death were significantly higher in lymphocytes following whole body irradiation (WBI) as compared to lymphocytes exposed to radiation in vitro. EL-4 cells transplanted in mice were also more sensitive to radiation than EL-4 cells irradiated in vitro. DNA repair, as assessed by comet assay, was significantly faster in lymphocytes exposed to 4 Gy radiation in vitro as compared to that in lymphocytes obtained from whole body irradiated mice exposed to the same dose of radiation. This was associated with increased NF-κB activation in response to genotoxic stress and lesser activation of caspase in lymphocytes in vitro compared to in vivo. To explain the differential radiosensitivity, we postulated a role of nitric oxide, an extrinsic diffusible mediator of radiosensitivity that has also been implicated in DNA repair inhibition. Nitric oxide levels were significantly elevated in the plasma of whole body irradiated mice but not in the supernatant of cells irradiated in vitro. Addition of sodium nitroprusside (SNP), a nitric oxide donor to cells irradiated in vitro inhibited the repair of DNA damage and enhanced apoptosis (increased Bax to Bcl-2 ratio). Administration of L-NAME, a nitric oxide synthase inhibitor, to mice significantly protected lymphocytes against WBI-induced DNA damage and inhibited in vivo radiation-induced production of nitric oxide. These results confirm that the observed differential radiosensitivity of lymphocytes was due to slow repair of DNA due to nitric oxide production in vivo.

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Use of transcranial Doppler ultrasonography and jugular oximetry to optimize hemodynamics during pediatric posterior fossa craniotomy

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2010

We describe a 13-year-old child who developed inadvertent intraoperative cerebral oxygen desatura... more We describe a 13-year-old child who developed inadvertent intraoperative cerebral oxygen desaturation attributed to empiric hyperventilation during posterior fossa craniotomy, diagnosed by jugular venous oximetry. Although restoration of normocapnia at age-appropriate mean arterial blood pressure improved jugular venous saturation (SjvO), it remained below acceptable values. Transcranial-Doppler (TCD) ultrasonography-guided stepwise increase in mean arterial pressure led to a linear increase in the mean flow velocity of the middle cerebral artery and SjvO₂ to desirable values. Intraoperative SjvO₂ monitoring and TCD ultrasonography may be utilized together to individualize hemodynamic targets and ventilation parameters and maintain adequate cerebral oxygenation during paediatric craniotomies.

Reference material development for calibration and verification of image-based particle analyzers

International journal of pharmaceutics, Jan 15, 2011

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Perioperative management of adult traumatic brain injury

Anesthesiology clinics, 2012

This article presents an overview of the management of traumatic brain injury (TBI) as relevant t... more

Thermophilic anaerobic co-digestion of poultry litter and thin stillage

Bioresource technology, 2013

The purpose of this study was to test whether the performance of a thermophilic CSTR digester tha... more The purpose of this study was to test whether the performance of a thermophilic CSTR digester that has been stabilized on poultry litter will be enhanced or diminished by the addition of thin stillage as co-substrate. Replicate laboratory digesters, derived from a stable pilot-scale digester, were operated with increasing ratios (w/w) of thin stillage/poultry litter feedstock. After a period of adaptation to 20% and 40% thin stillage, digester performance showed increases in biogas, percent methane and COD removal, as well as a decrease in volatile acids. Peak performance occurred with 60% thin stillage. However, 80% thin stillage caused significant reduction of performance, including declines of methanogenic activity and COD removal. In conclusion, supplementing the thermophilic digestion of poultry litter with thin stillage improved the bioenergy (methane) output, but thin stillage became inhibitory at high concentrations.

Congenital epulis

Archives of disease in childhood. Fetal and neonatal edition, 2014

Mitigation of radiation-induced hematopoietic injury via regulation of cellular MAPK/phosphatase levels and increasing hematopoietic stem cells

Free radical biology & medicine, 2014

Here we describe a novel strategy for mitigation of ionizing radiation-induced hematopoietic synd... more Here we describe a novel strategy for mitigation of ionizing radiation-induced hematopoietic syndrome by suppressing the activity of MKP3, resulting in ERK activation and enhanced abundance of hematopoietic stem cells, using the antioxidant flavonoid baicalein (5,6,7-trihydroxyflavone). It offered complete protection to mouse splenic lymphocytes against radiation-induced cell death. Inhibitors of ERK and Nrf-2 could significantly abrogate baicalein-mediated radioprotection in lymphocytes. Baicalein inhibited phosphatase MKP3 and thereby enhanced phosphorylation of ERK and its downstream proteins such as Elk and Nrf-2. It also increased the nuclear levels of Nrf-2 and the mRNA levels of its dependent genes. Importantly, baicalein administration to mice before radiation exposure led to significant recovery of loss of bone marrow cellularity and also inhibited cell death. Administration of baicalein increased the hematopoietic stem cell frequency as measured by side-population assay and also by antibody staining. Further, baicalein offered significant protection against whole-body irradiation (WBI; 7.5 Gy)-induced mortality in mice. Interestingly, we found that baicalein works by activating the same target molecules ERK and Nrf-2 both in vitro and in vivo. Finally, administration of all-trans-retinoic acid (inhibitor of Nrf-2) significantly abrogated baicalein-mediated protection against WBI-induced mortality in mice. Thus, in contrast to the generalized conception of antioxidants acting as radioprotectors, we provide a rationale that antioxidants exhibit pleiotropic effects through the activation of multiple cellular signaling pathways.

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Cyclopia syndrome

BMJ case reports, 2014

Application of Anaerobic Digestion Model No. 1 to describe the syntrophic acetate oxidation of poultry litter in thermophilic anaerobic digestion

Bioresource technology, 2014

A molecular analysis found that poultry litter anaerobic digestion was dominated by hydrogenotrop... more A molecular analysis found that poultry litter anaerobic digestion was dominated by hydrogenotrophic methanogens which suggests that bacterial acetate oxidation is the primary pathway in the thermophilic digestion of poultry litter. IWA Anaerobic Digestion Model No. 1 (ADM1) was modified to include the bacterial acetate oxidation process in the thermophilic anaerobic digestion (TAD). Two methods for ADM1 parameter estimation were applied: manual calibration with non-linear least squares (MC-NLLS) and an automatic calibration using differential evolution algorithms (DEA). In terms of kinetic parameters for acetate oxidizing bacteria, estimation by MC-NLLS and DEA were, respectively, km 1.12 and 3.25 ± 0.56 kg COD kg COD(-1)d(-1), KS 0.20 and 0.29 ± 0.018 kg COD m(-3) and Yac-st 0.14 and 0.10 ± 0.016 kg COD kg COD(-1). Experimental and predicted volatile fatty acids and biogas composition were in good agreement. Values of BIAS, MSE or INDEX demonstrate that both methods (MC-NLLS and DEA) increased ADM1 accuracy.

The Ded1/DDX3 subfamily of DEAD-box RNA helicases

Critical reviews in biochemistry and molecular biology

In eukaryotic organisms, the orthologs of the DEAD-box RNA helicase Ded1p from yeast and DDX3 fro... more In eukaryotic organisms, the orthologs of the DEAD-box RNA helicase Ded1p from yeast and DDX3 from human form a well-defined subfamily that is characterized by high sequence conservation in their helicase core and their N- and C- termini. Individual members of this Ded1/DDX3 subfamily perform multiple functions in RNA metabolism in both nucleus and cytoplasm. Ded1/DDX3 subfamily members have also been implicated in cellular signaling pathways and are targeted by diverse viruses. In this review, we discuss the considerable body of work on the biochemistry and biology of these proteins, including the recently discovered link of human DDX3 to tumorigenesis.

Use of lactoferrin in the newborn: where do we stand?

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, Jan 9, 2014

Abstract Sepsis and necrotizing enterocolitis (NEC) cause significant morbidity and mortality in ... more Abstract Sepsis and necrotizing enterocolitis (NEC) cause significant morbidity and mortality in the newborn. Their ill effects persist in spite of appropriate and effective antibiotic therapy. Lactoferrin as an adjunct to antibiotics in the treatment of sepsis or NEC in the newborn may improve the clinical outcomes by enhancing the host defense and modulating the inflammatory response. This review focuses on the various aspects of lactoferrin use in the newborn.

Chlorhexidine - a novel intervention to decrease the nursery stay and antibiotic exposure duration - randomized trial

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, Jan 23, 2014

Abstract Objective: To study the effect of chlorhexidine (CHD) application on umbilical cord and ... more Abstract Objective: To study the effect of chlorhexidine (CHD) application on umbilical cord and evaluate its impact on duration of NICU stay and antibiotic exposure days. Method: We enrolled 140 newborns in our study (70 in intervention group and 70 in control group), and their data were collected. Newborns in control group were given routine umbilical cord care, and intervention group received CHD spray on umbilical cord three times a day and for the next three days of cord fall. In this study, swabs were sent from umbilical cord at the age of three and seven days of life for culture. Data regarding culture-proven sepsis, duration of NICU stay and antibiotic days were recorded in the proforma for data collection. Results: This is a secondary analysis of the data of the randomized control trial. A significant reduction in duration of nursery stay was seen in CHD group in comparison with control group (12.4 ± 5.38 d versus 14.7 ± 6.62 d, p = 0.04, significant). Significant reduction was also seen in days of antibiotic exposure in the intervention group (9.74 ± 6.88 d versus 12.1 ± 7.78 d, p = 0.04, significant). Conclusion: Application of CHD to umbilical cord shortens duration of nursery stay and antibiotic days during nursery admission. This simple intervention may be used as mode in places where nursery facilities are limited, as aid in early discharge and shortening the exposure to antibiotic, which may help in reducing the prevalence of multidrug-resistance microbes. This cheap intervention may also be effective in reducing the economical burden on the health infrastructure of the country and parents.

Evolutionary constraints acting on DDX3X protein potentially interferes with Rev-mediated nuclear export of HIV-1 RNA

PloS one, 2010

Differential host-pathogen interactions direct viral replication in infected cells. In HIV-1 infe... more Differential host-pathogen interactions direct viral replication in infected cells. In HIV-1 infected cells, nuclear export of viral RNA transcripts into cellular cytoplasm is governed by interaction of HIV-1 Rev, Exportin-1 (CRM-1) and DDX3X. Knock down of DDX3X has been shown to drastically impair HIV replication. Here we show that evolutionary forces are responsible for demarking previously unidentified critical functionally important residues on the surface of DDX3X. Using computational approaches, we show that these functional residues, depending on their location, are capable of regulating ATPase and RNA helicase functions of DDX3X. The potential of these residues in designing better blockers against HIV-1 replication was also assessed. Also, using stepwise docking simulations, we could identify DDX3X-CRM-1 interface and its critical functional residues. Our data would help explain the role of DDX3X in HIV-1 Rev function with potential to design new intervention strategies against HIV-1 replication.

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Evaluation of the Vapor and Chemical Sensing Mechanism for Pentacene Field Effect Transistors

MRS Online Proceeding Library

ABSTRACT Properties such as semicondutor film grain size, morphology, and channel length are know... more ABSTRACT Properties such as semicondutor film grain size, morphology, and channel length are known to effect the sensing response in pentacene based organic thin film transistors (OTFTs). The sensing behavior for low and high mobility pentacene devices are reported here exhibiting different temperature dependent behaviors. The lower mobility OTFT exhibits an expected thermally activated response during alcohol testing with an increasing mobility with temperature along with a decreasing mobility at each temperature for increasing concentration. The higher mobility device exhibits a decrease in mobility with increasing temperature along with a decrease in mobility with increasing concentration at each temperature. In both sets of devices, the polar analyte produced reductions in drain current and shifts in threshold voltage.

P.1.g.002 Results of adapted sex offenders therapy (SOTSEC-ID) in learning disabled sex offenders in a forensic hospital in UK

European Neuropsychopharmacology, 2010

Role of Cellular Redox Homeostasis in Modulation of Immune Responses

T HELPER CELL DIFFERENTIATION (TH1/TH2) DURING RECOVERY FROM RADIATION-INDUCED LYMPHOPENIA AND ITS MODULATION BY CHLOROPHYLLIN

... CHLOROPHYLLIN D. Sharma, SK Sandur, R. Raghu and KB Sainis Radiation Biology & Health Sci... more

ROLE OF SPECIFIC SIGNALLING MOLECULES DURING PROLIFERATION OF CD4+ T CELLS IN RESPONSE TO DIFFERENT STIMULI

... 22. R. Rashmi, D. Sharma, R. Ramakrishnan, S. Khanam, GJ Chintalwar, KB Sainis, Immunol Lett.... more

Health Benefits of Chlorophyllin and its Mechanism of Action: Redox Modulation, Radioprotection and Immunomodulation

[摘要]: 正Chlorophyllin (CHL), a water-soluble analogue of green pigment chlorophyll, is being exten... more

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