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Full-Text Articles in Medicine and Health Sciences
Pharmacological Modulation Of Cgmp Levels By Phosphodiesterase 5 Inhibitors As A Therapeutic Strategy For Treatment Of Respiratory Pathology In Cystic Fibrosis., Hongwei Yu, Jens Poschet, Graham Timmons, Jennifer Taylor-Cousar, Wojciech Ornatowski, Joseph Fazio, Elizabeth Perkett, Kari Wilson, Hugo De Jonge, Vojo Deretic
Pharmacological Modulation Of Cgmp Levels By Phosphodiesterase 5 Inhibitors As A Therapeutic Strategy For Treatment Of Respiratory Pathology In Cystic Fibrosis., Hongwei Yu, Jens Poschet, Graham Timmons, Jennifer Taylor-Cousar, Wojciech Ornatowski, Joseph Fazio, Elizabeth Perkett, Kari Wilson, Hugo De Jonge, Vojo Deretic
Hongwei Yu
The CFTR gene encodes a chloride channel with pleiotropic effects on cell physiology and metabolism. Here, we show that increasing cGMP levels to inhibit epithelial Na(+) channel in cystic fibrosis (CF) respiratory epithelial cells corrects several aspects of the downstream pathology in CF. Cell culture models, using a range of CF cell lines and primary cells, showed that complementary pharmacological approaches to increasing intracellular cGMP, by elevating guanyl cyclase activity though reduced nitric oxide, addition of cell-permeable cGMP analogs, or inhibition of phosphodiesterase 5 corrected multiple aspects of the CF pathological cascade. These included correction of defective protein glycosylation, bacterial …
The Pseudomonas Aeruginosa Sensor Kinase Kinb Negatively Controls Alginate Production Through Algw-Dependent Muca Proteolysis, Hongwei Yu, F. Damron, Dongru Qiu
The Pseudomonas Aeruginosa Sensor Kinase Kinb Negatively Controls Alginate Production Through Algw-Dependent Muca Proteolysis, Hongwei Yu, F. Damron, Dongru Qiu
Hongwei Yu
Mucoidy, or overproduction of the exopolysaccharide known as alginate, in Pseudomonas aeruginosa is a poor prognosticator for lung infections in cystic fibrosis. Mutation of the anti-sigma factor MucA is a well-accepted mechanism for mucoid conversion. However, certain clinical mucoid strains of P. aeruginosa have a wild-type (wt) mucA. Here, we describe a loss-of-function mutation in kinB that causes overproduction of alginate in the wt mucA strain PAO1. KinB is the cognate histidine kinase for the transcriptional activator AlgB. Increased alginate production due to inactivation of kinB was correlated with high expression at the alginate-related promoters P(algU) and P(algD). Deletion of …
Apolipoprotein C3 Polymorphisms, Cognitive Function And Diabetes In Caribbean Origin Hispanics, Caren E. Smith, Katherine L. Tucker, Tammy M. Scott, Maria Van Rompay, Josiemer Mattei, Chao-Qiang Lai, Laurence D. Parnell, Mireia Junyent, Yu-Chi Lee, Bibiana Garcia-Bailo, Jose M. Ordovas
Apolipoprotein C3 Polymorphisms, Cognitive Function And Diabetes In Caribbean Origin Hispanics, Caren E. Smith, Katherine L. Tucker, Tammy M. Scott, Maria Van Rompay, Josiemer Mattei, Chao-Qiang Lai, Laurence D. Parnell, Mireia Junyent, Yu-Chi Lee, Bibiana Garcia-Bailo, Jose M. Ordovas
Katherine L. Tucker
Background Apolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3) gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention. Methods We examined whether APOC3 single nucleotide polymorphisms (SNPs) m482 (rs2854117) and 3u386 (rs5128) were related to cognitive measures, whether …
Bladder Inflammatory Transcriptome In Response To Tachykinins: Neurokinin 1 Receptor-Dependent Genes And Transcription Regulatory Elements, Ricardo Saban, Cindy Simpson, Rajanikanth Vadigepalli, Sylvie Memet, Igor Dozmorov, Marcia R. Saban
Bladder Inflammatory Transcriptome In Response To Tachykinins: Neurokinin 1 Receptor-Dependent Genes And Transcription Regulatory Elements, Ricardo Saban, Cindy Simpson, Rajanikanth Vadigepalli, Sylvie Memet, Igor Dozmorov, Marcia R. Saban
Rajanikanth Vadigepalli
Background Tachykinins (TK), such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could …
A Potential Role For Adjunctive Vitamin D Therapy In The Management Of Weight Gain And Metabolic Side Effects Of Second-Generation Antipsychotics, Benjamin U. Nwosu, Bruce Meltzer, Louise Maranda, Carol A. Ciccarelli, Daniel Reynolds, Laura A. Curtis, Jean A. King, Jean A. Frazier, Mary M. Lee
A Potential Role For Adjunctive Vitamin D Therapy In The Management Of Weight Gain And Metabolic Side Effects Of Second-Generation Antipsychotics, Benjamin U. Nwosu, Bruce Meltzer, Louise Maranda, Carol A. Ciccarelli, Daniel Reynolds, Laura A. Curtis, Jean A. King, Jean A. Frazier, Mary M. Lee
Benjamin U. Nwosu
Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best …