Varsha Singh - Academia.edu (original) (raw)
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Papers by Varsha Singh
Clinical Gastroenterology and Hepatology, 2014
Diarrheal diseases remain a leading cause of morbidity and mortality for children in developing c... more Diarrheal diseases remain a leading cause of morbidity and mortality for children in developing countries while representing an important cause of morbidity worldwide. The WHO recommended low osmolarity oral rehydration solutions plus zinc save lives in patients with acute diarrhea 1 , but there are no approved, safe drugs which have been shown to be effective against most causes of acute diarrhea. Identification of abnormalities in electrolyte handling by the intestine in diarrhea, including increased intestinal anion secretion and reduced Na + absorption, suggest a number of potential drug targets. This is based on the view that successful drug therapy for diarrhea will result from correcting the abnormalities in electrolyte transport that are pathophysiologic for diarrhea. We review the molecular mechanisms of physiologic regulation of intestinal ion transport and changes that occur in diarrhea and the status of drugs being developed to correct the transport abnormalities in Na + absorption which occur in diarrhea. Mechanisms of Cl − secretion and approaches to anti-Cl − secretory therapies of diarrhea are discussed in a companion review.
AJP: Gastrointestinal and Liver Physiology, 2011
P-glycoprotein (P-gp) mediates efflux of xenobiotics and bacterial toxins from the intestinal muc... more P-glycoprotein (P-gp) mediates efflux of xenobiotics and bacterial toxins from the intestinal mucosa into the lumen. Dysregulation of P-gp has been implicated in inflammatory bowel disease. Certain probiotics have been shown to be effective in treating inflammatory bowel disease. However, direct effects of probiotics on P-gp are not known. Current studies examined the effects of Lactobacilli on P-gp function and expression in intestinal epithelial cells. Caco-2 monolayers and a mouse model of dextran sulfate sodium-induced colitis were utilized. P-gp activity was measured as verapamil-sensitive [3H]digoxin transepithelial flux. Multidrug resistant 1 (MDR1)/P-gp expression was measured by real-time quantitative PCR and immunoblotting. Culture supernatant (CS; 1:10 or 1:50, 24 h) of Lactobacillus acidophilus or Lactobacillus rhamnosus treatment of differentiated Caco-2 monolayers (21 days postplating) increased (∼3-fold) MDR1/P-gp mRNA and protein levels. L. acidophilus or L. rhamnosu...
Clinical Gastroenterology and Hepatology, 2014
Diarrheal diseases remain a leading cause of morbidity and mortality for children in developing c... more Diarrheal diseases remain a leading cause of morbidity and mortality for children in developing countries while representing an important cause of morbidity worldwide. The WHO recommended low osmolarity oral rehydration solutions plus zinc save lives in patients with acute diarrhea 1 , but there are no approved, safe drugs which have been shown to be effective against most causes of acute diarrhea. Identification of abnormalities in electrolyte handling by the intestine in diarrhea, including increased intestinal anion secretion and reduced Na + absorption, suggest a number of potential drug targets. This is based on the view that successful drug therapy for diarrhea will result from correcting the abnormalities in electrolyte transport that are pathophysiologic for diarrhea. We review the molecular mechanisms of physiologic regulation of intestinal ion transport and changes that occur in diarrhea and the status of drugs being developed to correct the transport abnormalities in Na + absorption which occur in diarrhea. Mechanisms of Cl − secretion and approaches to anti-Cl − secretory therapies of diarrhea are discussed in a companion review.
AJP: Gastrointestinal and Liver Physiology, 2011
P-glycoprotein (P-gp) mediates efflux of xenobiotics and bacterial toxins from the intestinal muc... more P-glycoprotein (P-gp) mediates efflux of xenobiotics and bacterial toxins from the intestinal mucosa into the lumen. Dysregulation of P-gp has been implicated in inflammatory bowel disease. Certain probiotics have been shown to be effective in treating inflammatory bowel disease. However, direct effects of probiotics on P-gp are not known. Current studies examined the effects of Lactobacilli on P-gp function and expression in intestinal epithelial cells. Caco-2 monolayers and a mouse model of dextran sulfate sodium-induced colitis were utilized. P-gp activity was measured as verapamil-sensitive [3H]digoxin transepithelial flux. Multidrug resistant 1 (MDR1)/P-gp expression was measured by real-time quantitative PCR and immunoblotting. Culture supernatant (CS; 1:10 or 1:50, 24 h) of Lactobacillus acidophilus or Lactobacillus rhamnosus treatment of differentiated Caco-2 monolayers (21 days postplating) increased (∼3-fold) MDR1/P-gp mRNA and protein levels. L. acidophilus or L. rhamnosu...