akhil maheshwari - Academia.edu (original) (raw)

Papers by akhil maheshwari

Advances in pediatrics, 2002

Immune-mediated neonatal neutropenias include alloimmune neonatal neutropenia, neonatal autoimmun... more Immune-mediated neonatal neutropenias include alloimmune neonatal neutropenia, neonatal autoimmune neutropenia, and autoimmune neutropenia of infancy. These disorders have remained somewhat nebulous entities with difficulties persisting in both clinical identification and laboratory confirmation. A review of these disorders is presented, with basic information on the neutrophil antigen systems, pathophysiologic mechanisms, laboratory diagnosis, and therapeutic options.

Cytokine, 2002

The human fetal/neonatal gastrointestinal tract is exposed to biologically significant concentrat... more The human fetal/neonatal gastrointestinal tract is exposed to biologically significant concentrations of interleukin (IL)-8 swallowed with amniotic fluid and human milk. We hypothesized that IL-8 has a physiologic function in the developing human intestine. IL-8 was measured in preterm and term human milk, tested for stability under conditions simulating neonatal gastric and proximal small intestinal digestion, and its receptors were sought in human fetal bowel. The effect of IL-8 was then measured on intestinal cells in vitro. We observed that IL-8 is present in significant concentrations in human milk and that it is stable under conditions simulating digestion. Both IL-8 receptors, CXCR1 and CXCR2, are expressed extensively in the fetal intestine. When human fetal and adult intestinal cells are treated with rhIL-8 in vitro, there is a consistent increase in cell migration, proliferation, and differentiation. IL-8 also protects intestinal cells against chemical injury. These results suggest that besides its better-known role as a neutrophil chemoattractant, IL-8 has a trophic function in the developing human intestine.

Indian journal of pediatrics, 2001

Abstract. A severely growth retarded baby was born at 38 weeks gestation. He had multiple craniof... more Abstract. A severely growth retarded baby was born at 38 weeks gestation. He had multiple craniofacial anomalies, microbrachycephaly, phocomelia in the upper limbs and renal cysts visible on ultrasound. He died of recurrent apneas. The autopsy showed left sided multicystic ...

Indian journal of pediatrics, 2001

Early Onset Mixed Morganella and Klebsiella Sepsis ... Akhil Maheshwari, Sourabh Dutta, Praveen K... more Early Onset Mixed Morganella and Klebsiella Sepsis ... Akhil Maheshwari, Sourabh Dutta, Praveen Kumar and Anil Narang ... Neonatology Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh-160012, India

Neonatal Network: The Journal of Neonatal …, 2005

Necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of preterm infants, is the most c... more Necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of preterm infants, is the most common gastrointestinal emergency and a major cause of morbidity and mortality in these infants. In this article, the authors review the pathophysiology and clinical presentation of NEC and provide a critical appraisal of the evidence supporting various prophylactic and therapeutic strategies. A literature search was performed using the databases PubMed, EMBASE, and Scopus. Current pathophysiological models of NEC suggest that the disease occurs when mucosal injury in the preterm intestine results in translocation of luminal bacteria across the epithelial barrier, triggering an exaggerated and damaging local inflammatory response. Medical management of NEC is largely supportive and likely does not modify the etiopathogenesis of this disease. Antenatal steroids, human milk feedings, adoption of standardized feeding regimens, and probiotics hold promise for prevention of NEC. Future research should focus on early recognition that occurs well before the onset of intestinal necrosis, and prevention of this disease.

The Annals of Pharmacotherapy, 2002

Journal of …, 2006

The lamina propria of the gastrointestinal mucosa contains the largest population of mononuclear ... more The lamina propria of the gastrointestinal mucosa contains the largest population of mononuclear phagocytes in the body, yet little is known about the cellular mechanisms that regulate mononuclear cell recruitment to noninflamed and inflamed intestinal mucosa. Here, we show that intestinal macrophages do not proliferate. We also show that a substantial proportion of intestinal macrophages express chemokine receptors for interleukin (IL)-8 and transforming growth factor-␤ (TGF-␤), and a smaller proportion expresses receptors for N-formylmethionyl-leucyl-phenylalanine and C5a, but, surprisingly, they do not migrate to the corresponding ligands. In contrast, autologous blood monocytes, which express the same receptors, do migrate to the ligands. Blood monocytes also migrate to conditioned medium (CM) derived from lamina propria extracellular matrix, which we show contains IL-8 and TGF-␤ that are produced by epithelial cells and lamina propria mast cells. This migration is specific to IL-8 and TGF-␤, as preincubation of the stroma-CM with antibodies to IL-8 and TGF-␤ significantly blocked monocyte chemotaxis to the stromal products. Together, these findings indicate that blood monocytes are the exclusive source of macrophages in the intestinal mucosa and underscore the central role of newly recruited blood monocytes in maintaining the macrophage population in noninflamed mucosa and in serving as the exclusive source of macrophages in inflamed mucosa.

Stem cells and …, 2004

Autoimmune diseases afflict more than 3% of the U.S. population. Current therapy for mild to mode... more Autoimmune diseases afflict more than 3% of the U.S. population. Current therapy for mild to moderate cases is symptomatic, however advanced cases suffer high morbidity and mortality. Advanced patients have benefited from stem cell therapy in the form of bone marrow transplantation in conjunction with high-dose cytotoxic therapy. Broader application of stem cell therapy requires better understanding of how adult stem cells affect development and foster treatment of autoimmune pathologies, and of better ways to manipulate the host immune responses. While extensive research documents the role of hematopoietic stem cells (HSCs) in autoimmune disease, few studies have addressed if and how mesenchymal stem cells (MSCs) contribute to their etiopathology. Recent characterization of MSCs and their role in hematopoiesis and immune modulation suggest that their potential for cell therapy extends beyond their traditional accessory function in HSC engraftment. MSCs contribute significantly to tissue restructuring and immune functioning, in addition to facilitating durable, long-lasting stem cell engraftment. MSCs are relatively easy to obtain and expand in in vitro cultures, rendering them a prime candidate for genetic manipulations for stem cell therapy. They have the potential to differentiate into multiple lineages such as osteoblasts, adipose tissue, cartilage, tendon, and stromal cells. The role of MSCs for autoimmune disease therapy could thus be based both on immune function modulation and contribution to hematopoiesis. In this review, we examine the biology of MSCs, and their potential for cell therapy of autoimmune disease.

Journal of …, 2006

Intestinal macrophages, unlike macrophages from other tissues, do not support HIV-1 infection or ... more Intestinal macrophages, unlike macrophages from other tissues, do not support HIV-1 infection or produce proinflammatory cytokines. In vitro studies suggest this unique, functional phenotype is a result of the exposure of newly recruited blood monocytes to intestinal stromal products. However, in AIDS-related CMV colitis, mucosal macrophages express HIV-1 and proinflammatory cytokines. Therefore, we investigated the mechanism by which CMV confers permissiveness to HIV-1 and cytokine production on intestinal macrophages. We show that intestinal stroma-conditioned media (S-CM) down-regulated monocyte-derived macrophage infection by HIV-1 (pseudotyped with YU2 envelope or vesicular stomatitis virus glycoprotein) and production of TNF-alpha, but preinfection of the cells with CMV reversed this down-regulation, enhancing HIV-1 infection, p24 production, and TNF-alpha release. The ability of CMV to reverse S-CM down-regulation of macrophage HIV-1 infection was blocked by anti-TNF-alpha antibodies and over-ridden by exogenous TNF-alpha. Immunohistochemical analysis of monocyte-derived macrophages exposed to CMV and HIV-1 (YU2 pseudotype) revealed that the cells infrequently contained CMV and HIV-1 viral proteins. In addition, analysis of colon tissue sections from HIV-1-infected patients with CMV colitis showed that some macrophage-like cells contained CMV and TNF-alpha proteins, others contained HIV-1 and TNF-alpha proteins, but cells infrequently contained CMV and HIV-1 proteins. These results indicate that CMV blocks stromal product inhibition of HIV-1 infection in macrophages, and this inhibition is mediated, at least in part, by CMV-induced TNF-alpha acting in trans to enhance HIV-1 infection.

Cytokine, 2002

The human fetal/neonatal gastrointestinal tract is exposed to biologically significant concentrat... more The human fetal/neonatal gastrointestinal tract is exposed to biologically significant concentrations of interleukin (IL)-8 swallowed with amniotic fluid and human milk. We hypothesized that IL-8 has a physiologic function in the developing human intestine. IL-8 was measured in preterm and term human milk, tested for stability under conditions simulating neonatal gastric and proximal small intestinal digestion, and its receptors were sought in human fetal bowel. The effect of IL-8 was then measured on intestinal cells in vitro. We observed that IL-8 is present in significant concentrations in human milk and that it is stable under conditions simulating digestion. Both IL-8 receptors, CXCR1 and CXCR2, are expressed extensively in the fetal intestine. When human fetal and adult intestinal cells are treated with rhIL-8 in vitro, there is a consistent increase in cell migration, proliferation, and differentiation. IL-8 also protects intestinal cells against chemical injury. These results suggest that besides its better-known role as a neutrophil chemoattractant, IL-8 has a trophic function in the developing human intestine.

Indian Journal of Community Medicine, 2009

The growing menace created by the HIV/AIDS (human immunodeficiency virus/acquired immunodeficienc... more The growing menace created by the HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) has alarmed not only the public health officials but also the general community. The Voluntary Counseling and Testing Centre (VCTC) services have begun as a cost-effective intervention in reversing this epidemic. 1. To study the sociodemographic characteristics of HIV-positive clients and their risk behaviors. 2. To elucidate the reasons for their visit to the VCTC and know the problems anticipated by the clients after revealing their HIV-positive status. A cross-sectional record-based study. The study was conducted in August 2007 among clients who tested positive for HIV in the VCTC of a district hospital in Karnataka from January to July 2007. Study included 249 individuals, of whom 64.7% were males, 88.7% (age, 15-49 years), married (72.7% males and 84.0% females) and literate (females 71.5% and males 85.7%). A high percentage of nonresponse regarding the pattern of risk b...

Background: The clinical effi cacy of highly active antiretroviral therapy (HAART) in children ha... more Background: The clinical effi cacy of highly active antiretroviral therapy (HAART) in children has been well documented in the developed countries, although most of the regimens are Protease Inhibitor (PI) based which are too expensive. To circumvent this problem World Health Organization (WHO) has recommended Non-Nucleotide Reverse Transcriptase Inhibitor (NNRTI) based regimen for resource-limited countries. Aim: To assess the long-term effi cacy of fi rst line World Health Organization (WHO)-recommended generic highly active antiretroviral therapy (HAART) regimens in treatment-naïve children. Materials and methods: Observational retrospective analysis was done. Thirty patients on HAART for > 6 months were included (27 on Stavudine; three on Zidovudine with Lamivudine/ Nevirapine). No protease inhibitors were used. Results: median age was seven years (Interquartile [IQR]: 5.62-8.50) and median duration on HAART was 18 months (IQR: 6-24). No new staging events were observed after six months of initiation of HAART. The median CD4% increased from 6.0 % at baseline to 15.5% at six months, 21.7% at 12 months, 25.4% at 18 months, 24.6 % at 24 months 25.3% at 30 months and 23.7% at 36 months. There was only one case of immunological failure. Stratifi ed analysis based on baseline CD4 % show that even patients with a baseline CD4 % of <5% achieved percentage of >25% at 18-24 months and maintained it subsequently. Signifi cant increase in the weight and body mass index Z scores was observed but signifi cant fall in the height Z scores were observed. This sub group of patients with poor linear height velocity would require detailed endocrine evaluation after testing for viral loads. Conclusions: Non-Nucleotide Reverse Transcriptase Inhibitor based HAART regi mens are feasible and effective in long term in resource-limited setting despite initiation of treatment in advanced stages. These can be continued in NACO/WHO scale up programmes at present for children.

Journal of Biological Chemistry, 2008

CXC chemokines with a glutamate-leucine-arginine (ELR) tripeptide motif (ELR ؉ CXC chemokines) pl... more CXC chemokines with a glutamate-leucine-arginine (ELR) tripeptide motif (ELR ؉ CXC chemokines) play an important role in leukocyte trafficking into the tissues. For reasons that are not well elucidated, circulating leukocytes are recruited into the tissues mainly in small vessels such as capillaries and venules. Because ELR ؉ CXC chemokines are important mediators of endothelial-leukocyte interaction, we compared chemokine expression by microvascular and aortic endothelium to investigate whether differences in chemokine expression by various endothelial types could, at least partially, explain the microvascular localization of endothelial-leukocyte interaction. Both in vitro and in vivo models indicate that ELR ؉ CXC chemokine expression is higher in microvascular endothelium than in aortic endothelial cells. These differences can be explained on the basis of the preferential activation of endothelial chemokine production by low intensity shear stress. Low shear activated endothelial ELR ؉ CXC chemokine production via cell surface heparan sulfates, ␤ 3-integrins, focal adhesion kinase, the mitogen-activated protein kinase p38␤, mitogen-and stress-associated protein kinase-1, and the transcription factor.

…, 2007

Twenty-five elderly patients with oligoblastic acute myeloid leukemia (AML) received subcutaneous... more Twenty-five elderly patients with oligoblastic acute myeloid leukemia (AML) received subcutaneous granulocyte colony-stimulating factor (filgrastim) in addition to supportive care. Ninety-two percent of the patients had multilineage dysplasia, 17% hypoplasia, and 48% a high-risk ...

American Journal of Respiratory Cell and Molecular Biology, 2011

AJP: Gastrointestinal and Liver Physiology, 2014

Fetal swallowing of amniotic fluid, which contains numerous cytokines and growth factors, plays a... more Fetal swallowing of amniotic fluid, which contains numerous cytokines and growth factors, plays a key role in gut mucosal development. Preterm birth interrupts this exposure to amniotic fluid-borne growth factors, possibly contributing to the increased risk of necrotizing enterocolitis (NEC) in premature infants. We hypothesized that supplementation of formula feeds with amniotic fluid can provide amniotic fluid-borne growth factors and prevent experimental NEC in rat pups. We compared NEC-like injury in rat pups fed with infant formula vs. formula supplemented either with 30% amniotic fluid or recombinant hepatocyte growth factor (HGF). Cytokines/growth factors in amniotic fluid were measured by immunoassays. Amniotic fluid and HGF effects on enterocyte migration, proliferation, and survival were measured in cultured IEC6 intestinal epithelial cells. Finally, we used an antibody array to investigate receptor tyrosine kinase (RTK) activation and immunoblots to measure phosphoinositi...

AJP: Gastrointestinal and Liver Physiology, 2013

Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the i... more Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β. Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-κB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzy...

Advances in pediatrics, 2002

Immune-mediated neonatal neutropenias include alloimmune neonatal neutropenia, neonatal autoimmun... more Immune-mediated neonatal neutropenias include alloimmune neonatal neutropenia, neonatal autoimmune neutropenia, and autoimmune neutropenia of infancy. These disorders have remained somewhat nebulous entities with difficulties persisting in both clinical identification and laboratory confirmation. A review of these disorders is presented, with basic information on the neutrophil antigen systems, pathophysiologic mechanisms, laboratory diagnosis, and therapeutic options.

Cytokine, 2002

The human fetal/neonatal gastrointestinal tract is exposed to biologically significant concentrat... more The human fetal/neonatal gastrointestinal tract is exposed to biologically significant concentrations of interleukin (IL)-8 swallowed with amniotic fluid and human milk. We hypothesized that IL-8 has a physiologic function in the developing human intestine. IL-8 was measured in preterm and term human milk, tested for stability under conditions simulating neonatal gastric and proximal small intestinal digestion, and its receptors were sought in human fetal bowel. The effect of IL-8 was then measured on intestinal cells in vitro. We observed that IL-8 is present in significant concentrations in human milk and that it is stable under conditions simulating digestion. Both IL-8 receptors, CXCR1 and CXCR2, are expressed extensively in the fetal intestine. When human fetal and adult intestinal cells are treated with rhIL-8 in vitro, there is a consistent increase in cell migration, proliferation, and differentiation. IL-8 also protects intestinal cells against chemical injury. These results suggest that besides its better-known role as a neutrophil chemoattractant, IL-8 has a trophic function in the developing human intestine.

Indian journal of pediatrics, 2001

Abstract. A severely growth retarded baby was born at 38 weeks gestation. He had multiple craniof... more Abstract. A severely growth retarded baby was born at 38 weeks gestation. He had multiple craniofacial anomalies, microbrachycephaly, phocomelia in the upper limbs and renal cysts visible on ultrasound. He died of recurrent apneas. The autopsy showed left sided multicystic ...

Indian journal of pediatrics, 2001

Early Onset Mixed Morganella and Klebsiella Sepsis ... Akhil Maheshwari, Sourabh Dutta, Praveen K... more Early Onset Mixed Morganella and Klebsiella Sepsis ... Akhil Maheshwari, Sourabh Dutta, Praveen Kumar and Anil Narang ... Neonatology Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh-160012, India

Neonatal Network: The Journal of Neonatal …, 2005

Necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of preterm infants, is the most c... more Necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of preterm infants, is the most common gastrointestinal emergency and a major cause of morbidity and mortality in these infants. In this article, the authors review the pathophysiology and clinical presentation of NEC and provide a critical appraisal of the evidence supporting various prophylactic and therapeutic strategies. A literature search was performed using the databases PubMed, EMBASE, and Scopus. Current pathophysiological models of NEC suggest that the disease occurs when mucosal injury in the preterm intestine results in translocation of luminal bacteria across the epithelial barrier, triggering an exaggerated and damaging local inflammatory response. Medical management of NEC is largely supportive and likely does not modify the etiopathogenesis of this disease. Antenatal steroids, human milk feedings, adoption of standardized feeding regimens, and probiotics hold promise for prevention of NEC. Future research should focus on early recognition that occurs well before the onset of intestinal necrosis, and prevention of this disease.

The Annals of Pharmacotherapy, 2002

Journal of …, 2006

The lamina propria of the gastrointestinal mucosa contains the largest population of mononuclear ... more The lamina propria of the gastrointestinal mucosa contains the largest population of mononuclear phagocytes in the body, yet little is known about the cellular mechanisms that regulate mononuclear cell recruitment to noninflamed and inflamed intestinal mucosa. Here, we show that intestinal macrophages do not proliferate. We also show that a substantial proportion of intestinal macrophages express chemokine receptors for interleukin (IL)-8 and transforming growth factor-␤ (TGF-␤), and a smaller proportion expresses receptors for N-formylmethionyl-leucyl-phenylalanine and C5a, but, surprisingly, they do not migrate to the corresponding ligands. In contrast, autologous blood monocytes, which express the same receptors, do migrate to the ligands. Blood monocytes also migrate to conditioned medium (CM) derived from lamina propria extracellular matrix, which we show contains IL-8 and TGF-␤ that are produced by epithelial cells and lamina propria mast cells. This migration is specific to IL-8 and TGF-␤, as preincubation of the stroma-CM with antibodies to IL-8 and TGF-␤ significantly blocked monocyte chemotaxis to the stromal products. Together, these findings indicate that blood monocytes are the exclusive source of macrophages in the intestinal mucosa and underscore the central role of newly recruited blood monocytes in maintaining the macrophage population in noninflamed mucosa and in serving as the exclusive source of macrophages in inflamed mucosa.

Stem cells and …, 2004

Autoimmune diseases afflict more than 3% of the U.S. population. Current therapy for mild to mode... more Autoimmune diseases afflict more than 3% of the U.S. population. Current therapy for mild to moderate cases is symptomatic, however advanced cases suffer high morbidity and mortality. Advanced patients have benefited from stem cell therapy in the form of bone marrow transplantation in conjunction with high-dose cytotoxic therapy. Broader application of stem cell therapy requires better understanding of how adult stem cells affect development and foster treatment of autoimmune pathologies, and of better ways to manipulate the host immune responses. While extensive research documents the role of hematopoietic stem cells (HSCs) in autoimmune disease, few studies have addressed if and how mesenchymal stem cells (MSCs) contribute to their etiopathology. Recent characterization of MSCs and their role in hematopoiesis and immune modulation suggest that their potential for cell therapy extends beyond their traditional accessory function in HSC engraftment. MSCs contribute significantly to tissue restructuring and immune functioning, in addition to facilitating durable, long-lasting stem cell engraftment. MSCs are relatively easy to obtain and expand in in vitro cultures, rendering them a prime candidate for genetic manipulations for stem cell therapy. They have the potential to differentiate into multiple lineages such as osteoblasts, adipose tissue, cartilage, tendon, and stromal cells. The role of MSCs for autoimmune disease therapy could thus be based both on immune function modulation and contribution to hematopoiesis. In this review, we examine the biology of MSCs, and their potential for cell therapy of autoimmune disease.

Journal of …, 2006

Intestinal macrophages, unlike macrophages from other tissues, do not support HIV-1 infection or ... more Intestinal macrophages, unlike macrophages from other tissues, do not support HIV-1 infection or produce proinflammatory cytokines. In vitro studies suggest this unique, functional phenotype is a result of the exposure of newly recruited blood monocytes to intestinal stromal products. However, in AIDS-related CMV colitis, mucosal macrophages express HIV-1 and proinflammatory cytokines. Therefore, we investigated the mechanism by which CMV confers permissiveness to HIV-1 and cytokine production on intestinal macrophages. We show that intestinal stroma-conditioned media (S-CM) down-regulated monocyte-derived macrophage infection by HIV-1 (pseudotyped with YU2 envelope or vesicular stomatitis virus glycoprotein) and production of TNF-alpha, but preinfection of the cells with CMV reversed this down-regulation, enhancing HIV-1 infection, p24 production, and TNF-alpha release. The ability of CMV to reverse S-CM down-regulation of macrophage HIV-1 infection was blocked by anti-TNF-alpha antibodies and over-ridden by exogenous TNF-alpha. Immunohistochemical analysis of monocyte-derived macrophages exposed to CMV and HIV-1 (YU2 pseudotype) revealed that the cells infrequently contained CMV and HIV-1 viral proteins. In addition, analysis of colon tissue sections from HIV-1-infected patients with CMV colitis showed that some macrophage-like cells contained CMV and TNF-alpha proteins, others contained HIV-1 and TNF-alpha proteins, but cells infrequently contained CMV and HIV-1 proteins. These results indicate that CMV blocks stromal product inhibition of HIV-1 infection in macrophages, and this inhibition is mediated, at least in part, by CMV-induced TNF-alpha acting in trans to enhance HIV-1 infection.

Cytokine, 2002

The human fetal/neonatal gastrointestinal tract is exposed to biologically significant concentrat... more The human fetal/neonatal gastrointestinal tract is exposed to biologically significant concentrations of interleukin (IL)-8 swallowed with amniotic fluid and human milk. We hypothesized that IL-8 has a physiologic function in the developing human intestine. IL-8 was measured in preterm and term human milk, tested for stability under conditions simulating neonatal gastric and proximal small intestinal digestion, and its receptors were sought in human fetal bowel. The effect of IL-8 was then measured on intestinal cells in vitro. We observed that IL-8 is present in significant concentrations in human milk and that it is stable under conditions simulating digestion. Both IL-8 receptors, CXCR1 and CXCR2, are expressed extensively in the fetal intestine. When human fetal and adult intestinal cells are treated with rhIL-8 in vitro, there is a consistent increase in cell migration, proliferation, and differentiation. IL-8 also protects intestinal cells against chemical injury. These results suggest that besides its better-known role as a neutrophil chemoattractant, IL-8 has a trophic function in the developing human intestine.

Indian Journal of Community Medicine, 2009

The growing menace created by the HIV/AIDS (human immunodeficiency virus/acquired immunodeficienc... more The growing menace created by the HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) has alarmed not only the public health officials but also the general community. The Voluntary Counseling and Testing Centre (VCTC) services have begun as a cost-effective intervention in reversing this epidemic. 1. To study the sociodemographic characteristics of HIV-positive clients and their risk behaviors. 2. To elucidate the reasons for their visit to the VCTC and know the problems anticipated by the clients after revealing their HIV-positive status. A cross-sectional record-based study. The study was conducted in August 2007 among clients who tested positive for HIV in the VCTC of a district hospital in Karnataka from January to July 2007. Study included 249 individuals, of whom 64.7% were males, 88.7% (age, 15-49 years), married (72.7% males and 84.0% females) and literate (females 71.5% and males 85.7%). A high percentage of nonresponse regarding the pattern of risk b...

Background: The clinical effi cacy of highly active antiretroviral therapy (HAART) in children ha... more Background: The clinical effi cacy of highly active antiretroviral therapy (HAART) in children has been well documented in the developed countries, although most of the regimens are Protease Inhibitor (PI) based which are too expensive. To circumvent this problem World Health Organization (WHO) has recommended Non-Nucleotide Reverse Transcriptase Inhibitor (NNRTI) based regimen for resource-limited countries. Aim: To assess the long-term effi cacy of fi rst line World Health Organization (WHO)-recommended generic highly active antiretroviral therapy (HAART) regimens in treatment-naïve children. Materials and methods: Observational retrospective analysis was done. Thirty patients on HAART for > 6 months were included (27 on Stavudine; three on Zidovudine with Lamivudine/ Nevirapine). No protease inhibitors were used. Results: median age was seven years (Interquartile [IQR]: 5.62-8.50) and median duration on HAART was 18 months (IQR: 6-24). No new staging events were observed after six months of initiation of HAART. The median CD4% increased from 6.0 % at baseline to 15.5% at six months, 21.7% at 12 months, 25.4% at 18 months, 24.6 % at 24 months 25.3% at 30 months and 23.7% at 36 months. There was only one case of immunological failure. Stratifi ed analysis based on baseline CD4 % show that even patients with a baseline CD4 % of <5% achieved percentage of >25% at 18-24 months and maintained it subsequently. Signifi cant increase in the weight and body mass index Z scores was observed but signifi cant fall in the height Z scores were observed. This sub group of patients with poor linear height velocity would require detailed endocrine evaluation after testing for viral loads. Conclusions: Non-Nucleotide Reverse Transcriptase Inhibitor based HAART regi mens are feasible and effective in long term in resource-limited setting despite initiation of treatment in advanced stages. These can be continued in NACO/WHO scale up programmes at present for children.

Journal of Biological Chemistry, 2008

CXC chemokines with a glutamate-leucine-arginine (ELR) tripeptide motif (ELR ؉ CXC chemokines) pl... more CXC chemokines with a glutamate-leucine-arginine (ELR) tripeptide motif (ELR ؉ CXC chemokines) play an important role in leukocyte trafficking into the tissues. For reasons that are not well elucidated, circulating leukocytes are recruited into the tissues mainly in small vessels such as capillaries and venules. Because ELR ؉ CXC chemokines are important mediators of endothelial-leukocyte interaction, we compared chemokine expression by microvascular and aortic endothelium to investigate whether differences in chemokine expression by various endothelial types could, at least partially, explain the microvascular localization of endothelial-leukocyte interaction. Both in vitro and in vivo models indicate that ELR ؉ CXC chemokine expression is higher in microvascular endothelium than in aortic endothelial cells. These differences can be explained on the basis of the preferential activation of endothelial chemokine production by low intensity shear stress. Low shear activated endothelial ELR ؉ CXC chemokine production via cell surface heparan sulfates, ␤ 3-integrins, focal adhesion kinase, the mitogen-activated protein kinase p38␤, mitogen-and stress-associated protein kinase-1, and the transcription factor.

…, 2007

Twenty-five elderly patients with oligoblastic acute myeloid leukemia (AML) received subcutaneous... more Twenty-five elderly patients with oligoblastic acute myeloid leukemia (AML) received subcutaneous granulocyte colony-stimulating factor (filgrastim) in addition to supportive care. Ninety-two percent of the patients had multilineage dysplasia, 17% hypoplasia, and 48% a high-risk ...

American Journal of Respiratory Cell and Molecular Biology, 2011

AJP: Gastrointestinal and Liver Physiology, 2014

Fetal swallowing of amniotic fluid, which contains numerous cytokines and growth factors, plays a... more Fetal swallowing of amniotic fluid, which contains numerous cytokines and growth factors, plays a key role in gut mucosal development. Preterm birth interrupts this exposure to amniotic fluid-borne growth factors, possibly contributing to the increased risk of necrotizing enterocolitis (NEC) in premature infants. We hypothesized that supplementation of formula feeds with amniotic fluid can provide amniotic fluid-borne growth factors and prevent experimental NEC in rat pups. We compared NEC-like injury in rat pups fed with infant formula vs. formula supplemented either with 30% amniotic fluid or recombinant hepatocyte growth factor (HGF). Cytokines/growth factors in amniotic fluid were measured by immunoassays. Amniotic fluid and HGF effects on enterocyte migration, proliferation, and survival were measured in cultured IEC6 intestinal epithelial cells. Finally, we used an antibody array to investigate receptor tyrosine kinase (RTK) activation and immunoblots to measure phosphoinositi...

AJP: Gastrointestinal and Liver Physiology, 2013

Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the i... more Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β. Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-κB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzy...