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Full-Text Articles in Medicine and Health Sciences

Antioxidants Condition Pleiotropic Vascular Responses To Exogenous H2o2: Role Of Modulation Of Vascular Tp Receptors And The Heme Oxygenase System, Nitin Puri, Fan Zhang, Sumit R. Monu, Komal R. Sodhi, Lars Bellner, Brian D. Lamon, Yilun Zhang, Nader G. Abraham, Alberto Nasjletti Nov 2013

Antioxidants Condition Pleiotropic Vascular Responses To Exogenous H2o2: Role Of Modulation Of Vascular Tp Receptors And The Heme Oxygenase System, Nitin Puri, Fan Zhang, Sumit R. Monu, Komal R. Sodhi, Lars Bellner, Brian D. Lamon, Yilun Zhang, Nader G. Abraham, Alberto Nasjletti

Biochemistry and Microbiology

Aims: Hydrogen peroxide (H(2)O(2)), a nonradical oxidant, is employed to ascertain the role of redox mechanisms in regulation of vascular tone. Where both dilation and constriction have been reported, we examined the hypothesis that the ability of H(2)O(2) to effect vasoconstriction or dilation is conditioned by redox mechanisms and may be modulated by antioxidants.

Results: Exogenous H(2)O(2) (0.1-10.0 μM), dose-dependently reduced the internal diameter of rat renal interlobular and 3rd-order mesenteric arteries (p<0.05). This response was obliterated in arteries pretreated with antioxidants, including tempol, pegylated superoxide dismutase (PEG-SOD), butylated hydroxytoluene (BHT), and biliverdin (BV). However, as opposed to tempol or PEG-SOD, BHT & BV, antioxidants targeting radicals downstream of H(2)O(2), also uncovered vasodilation.

Innovations: Redox-dependent vasoconstriction to H(2)O(2) was blocked by inhibitors of cyclooxygenase (COX) (indomethacin-10 μM), thromboxane (TP) synthase (CGS13080-10 μM), and TP receptor antagonist (SQ29548-1 μM). However, H(2)O(2) …


Expression Of Mucoid Induction Factor Muce Is Dependent Upon The Alternate Sigma Factor Algu In Pseudomonas Aeruginosa, Yeshi Yin, F. Heath Damron, T. Ryan Withers, Christopher L. Prichett, Xin Wang, Michael J. Schurr, Hongwei Yu Oct 2013

Expression Of Mucoid Induction Factor Muce Is Dependent Upon The Alternate Sigma Factor Algu In Pseudomonas Aeruginosa, Yeshi Yin, F. Heath Damron, T. Ryan Withers, Christopher L. Prichett, Xin Wang, Michael J. Schurr, Hongwei Yu

Biochemistry and Microbiology

Background

Alginate overproduction in P. aeruginosa, also referred to as mucoidy, is a poor prognostic marker for patients with cystic fibrosis (CF). We previously reported the construction of a unique mucoid strain which overexpresses a small envelope protein MucE leading to activation of the protease AlgW. AlgW then degrades the anti-sigma factor MucA thus releasing the alternative sigma factor AlgU/T (σ22) to initiate transcription of the alginate biosynthetic operon.

Results

In the current study, we mapped the mucE transcriptional start site, and determined that PmucE activity was dependent on AlgU. Additionally, the presence of triclosan and …


Involvement Of Reactive Oxygen Species In A Feed-Forward Mechanism Of Na/K-Atpase Mediated Signaling, Yanling Yan, Anna P. Shapiro, Steven Haller, Vinal Katragadda, Lijun Liu, Jiang Tian, Venkatesha Basrur, Deepak Malhotra, Zi-Jian Xie, Nader G. Abraham, Joseph I. Shapiro Md, Jiang Liu Oct 2013

Involvement Of Reactive Oxygen Species In A Feed-Forward Mechanism Of Na/K-Atpase Mediated Signaling, Yanling Yan, Anna P. Shapiro, Steven Haller, Vinal Katragadda, Lijun Liu, Jiang Tian, Venkatesha Basrur, Deepak Malhotra, Zi-Jian Xie, Nader G. Abraham, Joseph I. Shapiro Md, Jiang Liu

Biochemistry and Microbiology

Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial 22Na+ transport. Disruption of the Na/K-ATPase·c-Src signaling complex attenuated ouabain-stimulated protein carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal of ouabain, and this reversibility is largely independent of de novo protein synthesis and degradation by either the lysosome or the proteasome pathways. Furthermore, …


Lactobacillus Acidophilus Alleviates Platelet-Activating Factor-Induced Inflammatory Responses In Human Intestinal Epithelial Cells, Alip Borthakur, Sumit Bhattacharyya, Anoop Kumar, Arivarasu Natarajan Anbazhagan, Joanne K. Tobacman, Pradeep K. Dudeja Oct 2013

Lactobacillus Acidophilus Alleviates Platelet-Activating Factor-Induced Inflammatory Responses In Human Intestinal Epithelial Cells, Alip Borthakur, Sumit Bhattacharyya, Anoop Kumar, Arivarasu Natarajan Anbazhagan, Joanne K. Tobacman, Pradeep K. Dudeja

Clinical & Translational Sciences

Probiotics have been used as alternative prevention and therapy modalities in intestinal inflammatory disorders including inflammatory bowel diseases (IBD) and necrotizing enterocolitis (NEC). Pathophysiology of IBD and NEC includes the production of diverse lipid mediators, including platelet-activating factor (PAF) that mediate inflammatory responses in the disease. PAF is known to activate NF-kB, however, the mechanisms of PAF-induced inflammation are not fully defined. We have recently described a novel PAF-triggered pathway of NF-κB activation and IL-8 production in intestinal epithelial cells (IECs), requiring the pivotal role of the adaptor protein Bcl10 and its interactions with CARMA3 and MALT1. The current studies …


Effects Of Acute Or Chronic Ethanol Exposure During Adolescence On Behavioral Inhibition And Efficiency In A Modified Water Maze Task, Shawn K. Acheson, Craig Bearison, Mary-Louise Risher, Sabri H. Abdelwahab, Wilkie A. Wilson, H. Scott Swartzwelder Oct 2013

Effects Of Acute Or Chronic Ethanol Exposure During Adolescence On Behavioral Inhibition And Efficiency In A Modified Water Maze Task, Shawn K. Acheson, Craig Bearison, Mary-Louise Risher, Sabri H. Abdelwahab, Wilkie A. Wilson, H. Scott Swartzwelder

Biomedical Sciences

Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape) and a new hidden platform was added …


A Standardized Patient Counseling Rubric For A Pharmaceutical Care And Communications Course, Niambi Horton Pharmd, Kenna D. Payne Pharmd, Michelle Jernigan Pharmd, Jill Frost Pharmd, Stephen Wise Pharmd, Mary Klein Pharmd, Joel Epps Mba, H. Glenn Anderson Pharmd Sep 2013

A Standardized Patient Counseling Rubric For A Pharmaceutical Care And Communications Course, Niambi Horton Pharmd, Kenna D. Payne Pharmd, Michelle Jernigan Pharmd, Jill Frost Pharmd, Stephen Wise Pharmd, Mary Klein Pharmd, Joel Epps Mba, H. Glenn Anderson Pharmd

Pharmaceutical Science and Research

Objective. To restructure a required pharmaceutical care and communications course to place greater emphasis on communication skills and include a high-stakes assessment.

Design. A standardized counseling rubric was developed for use throughout the pharmacy curriculum and the counseling laboratory practicals were changed to high-stakes assessments.

Assessment. An annual mid-semester and end-of-semester high-stakes patient-counseling objective structured clinical examination (OSCE) conducted prior to and after revision of the course and counseling rubric documented improvements in students’ scores. Performance on the post-course annual assessment patient counseling OSCE improved compared to that on the pre-course (p,0.001).

Conclusion. The 2010 course revision improved …


Pparδ Binding To Heme Oxygenase 1 Promoter Prevents Angiotensin Ii-Induced Adipocyte Dysfunction In Goldblatt Hypertensive Rats, Komal Sodhi, Nitin Puri, Dong Hyun Kim, Terry D. Hinds Jr., Lance A. Stechschulte, Gaia Favero, Luigi Rodella, Joseph I. Shapiro M.D., David C. Jude, Nader X. Abraham Jun 2013

Pparδ Binding To Heme Oxygenase 1 Promoter Prevents Angiotensin Ii-Induced Adipocyte Dysfunction In Goldblatt Hypertensive Rats, Komal Sodhi, Nitin Puri, Dong Hyun Kim, Terry D. Hinds Jr., Lance A. Stechschulte, Gaia Favero, Luigi Rodella, Joseph I. Shapiro M.D., David C. Jude, Nader X. Abraham

Biochemistry and Microbiology

Abstract:

OBJECTIVE: Renin–angiotensin system (RAS) regulates adipogenic response with adipocyte hypertrophy by increasing oxidative stress. Recent studies have shown the role of peroxisome proliferator-activated receptor-d (PPARδ) agonist in attenuation of angiotensin II-induced oxidative stress. The aim of this study was to explore a potential mechanistic link between PPARδ and the cytoprotective enzyme heme oxygenase-1 (HO-1) and to elucidate the contribution of HO-1 to the adipocyte regulatory effects of PPARδ agonism in an animal model of enhanced RAS, the Goldblatt 2 kidney 1 clip (2K1C) model.

METHOD: We first established a direct stimulatory effect of the PPARδ agonist (GW 501516) on …


Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu Jun 2013

Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ22). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP …


Long-Term Effects Of Chronic Intermittent Ethanol Exposure In Adolescent And Adult Rats: Radial-Arm Maze Performance And Operant Food Reinforced Responding, Mary-Louise Risher, Rebekah L. Fleming, Nathalie Boutros, Svetlana Semenova, Wilkie A. Wilson, Edward D. Levin, Athina Markou, H. Scott Swartzwelder, Shawn K. Acheson May 2013

Long-Term Effects Of Chronic Intermittent Ethanol Exposure In Adolescent And Adult Rats: Radial-Arm Maze Performance And Operant Food Reinforced Responding, Mary-Louise Risher, Rebekah L. Fleming, Nathalie Boutros, Svetlana Semenova, Wilkie A. Wilson, Edward D. Levin, Athina Markou, H. Scott Swartzwelder, Shawn K. Acheson

Biomedical Sciences

Background: Adolescence is not only a critical period of late-stage neurological development in humans, but is also a period in which ethanol consumption is often at its highest. Given the prevalence of ethanol use during this vulnerable developmental period we assessed the long-term effects of chronic intermittent ethanol (CIE) exposure during adolescence, compared to adulthood, on performance in the radial-arm maze (RAM) and operant food-reinforced responding in male rats.

Methodology/Principal Findings: Male Sprague Dawley rats were exposed to CIE (or saline) and then allowed to recover. Animals were then trained in either the RAM task or an operant task using …


A Case Of Congenital Unilateral Absence Of The Vas Deferens, Bi Mo, Vishnu Garla, Lawrence M. Wyner M.D. Apr 2013

A Case Of Congenital Unilateral Absence Of The Vas Deferens, Bi Mo, Vishnu Garla, Lawrence M. Wyner M.D.

Surgery

Background

Congenital unilateral absence of the vas deferens occurs in 0.5%–1.0% of males. It has been associated with various genitourinary abnormalities, including renal agenesis. We report a case of congenital unilateral absence of the vas deferens found incidentally during vasectomy in a patient with known unilateral renal agenesis.

Case presentation

A 24-year-old male presented to our urology clinic requesting vasectomy. His past history was significant for left renal agenesis. Following successful right vasectomy, several attempts to locate the left vas deferens were unsuccessful. We diagnosed congenital unilateral absence of the vas deferens. Follow-up semen analysis showed azoospermia.

Conclusion

As vasectomies …


Principles Of Quantitative Fluid And Cation Replacement In Extreme Hyperglycemia, Antonios H. Tzamaloukas, Yijuan Sun, Nikifor K. Konstantinov, Richard I. Dorin, Todd S. Ing, Deepak Malhorta, Glenn H. Murata, Joseph I. Shapiro M.D. Mar 2013

Principles Of Quantitative Fluid And Cation Replacement In Extreme Hyperglycemia, Antonios H. Tzamaloukas, Yijuan Sun, Nikifor K. Konstantinov, Richard I. Dorin, Todd S. Ing, Deepak Malhorta, Glenn H. Murata, Joseph I. Shapiro M.D.

Biochemistry and Microbiology

Hyperglycemia may cause profound deficits of water, sodium and potassium through osmotic diuresis, which continues during treatment as long as there is glucosuria. Replacement fluids should cover both the deficits at presentation and the ongoing losses during treatment. At presentation with hyperglycemia, quantitative estimates of the deficits in water, sodium and potassium are based on rapid body weight changes, which indicate changes in body water, and on the serum sodium concentration corrected to a normal serum glucose level. The corrected serum sodium concentration provides a measure of the water deficit relative to the cation deficit (sodium, plus potassium) that is …


Increased Heme-Oxygenase 1 Expression In Mesenchymal Stem Cell-Derived Adipocytes Decreases Differentiation And Lipid Accumulation Via Upregulation Of The Canonical Wnt Signaling Cascade, Luca Vanella, Komal Sodhi, Dong Hyun Kim, Nitin Puri, Mani Maheshwari, Terry D . Hinds, Lars Bellner, Dov Goldstein, Stephen J . Peterson, Joseph I. Shapiro M.D., Nader G. Abraham Mar 2013

Increased Heme-Oxygenase 1 Expression In Mesenchymal Stem Cell-Derived Adipocytes Decreases Differentiation And Lipid Accumulation Via Upregulation Of The Canonical Wnt Signaling Cascade, Luca Vanella, Komal Sodhi, Dong Hyun Kim, Nitin Puri, Mani Maheshwari, Terry D . Hinds, Lars Bellner, Dov Goldstein, Stephen J . Peterson, Joseph I. Shapiro M.D., Nader G. Abraham

Biochemistry and Microbiology

Introduction:

Heme oxygenase (HO), a major cytoprotective enzyme, attenuates oxidative stress and obesity. The canonical Wnt signaling cascade plays a pivotal role in the regulation of adipogenesis. The present study examined the interplay between HO-1and the Wnt canonical pathway in the modulation of adipogenesis in mesenchymal stem cell (MSC)-derived adipocytes.

Methods:

To verify the role of HO-1 in generating small healthy adipocytes, cobalt protoporphyrin (CoPP), inducer of HO-1, was used during adipocyte differentiation. Lipid accumulation was measured by Oil red O staining and lipid droplet size was measured by BODIPY staining.

Results:

During adipogenesis in vitro, differentiating pre-adipocytes display transient …


Inhibition Of Cholinergic Signaling Causes Apoptosis In Human Bronchioalveolar Carcinoma, Jamie K. Lau, Kathleen C. Brown, Brent A. Thornhill, Clayton M. Crabtree, Aaron M. Dom, Theodore R. Witte, W. Elaine Hardman, Christopher A. Mcnees, Cody A. Stover, A. Betts Carpenter, Haitao Luo, Yi C. Chen, Brandon S. Shiflett, Piyali Dasgupta Feb 2013

Inhibition Of Cholinergic Signaling Causes Apoptosis In Human Bronchioalveolar Carcinoma, Jamie K. Lau, Kathleen C. Brown, Brent A. Thornhill, Clayton M. Crabtree, Aaron M. Dom, Theodore R. Witte, W. Elaine Hardman, Christopher A. Mcnees, Cody A. Stover, A. Betts Carpenter, Haitao Luo, Yi C. Chen, Brandon S. Shiflett, Piyali Dasgupta

Biochemistry and Microbiology

Recent case-controlled clinical studies show that bronchioalveolar carcinomas (BAC) are correlated with smoking. Nicotine, the addictive component of cigarettes, accelerates cell proliferation through nicotinic acetylcholine receptors (nAChR). In this study, we show that human BACs produce acetylcholine (ACh) and contain several cholinergic factors including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1, SLC5A7), vesicular acetylcholine transporter (VAChT, SLC18A3), and nACh receptors (AChRs, CHRNAs). Nicotine increased the production of ACh in human BACs, and ACh acts as a growth factor for these cells. Nicotine-induced ACh production was mediated by α7-, α3β2-, and β3-nAChRs, ChAT and VAChT pathways. We observed that …


Cyclooxygenase-2 Dependent Metabolism Of 20-Hete Increases Adiposity And Adipocyte Enlargement In Mesenchymal Stem Cell-Derived Adipocytes, Dong Hyun Kim, Nitin Puri, Komal Sodhi, John R. Falck, Nader G. Abraham, Joseph I. Shapiro M.D., Michal L. Schwartzman Jan 2013

Cyclooxygenase-2 Dependent Metabolism Of 20-Hete Increases Adiposity And Adipocyte Enlargement In Mesenchymal Stem Cell-Derived Adipocytes, Dong Hyun Kim, Nitin Puri, Komal Sodhi, John R. Falck, Nader G. Abraham, Joseph I. Shapiro M.D., Michal L. Schwartzman

Biochemistry and Microbiology

Abstract 20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome P450 (CYP)-catalyzed [1] -hydroxylation of arachidonic acid, induces oxidative stress and, in clinical studies, is associated with increased body mass index (BMI) and the metabolic syndrome. This study was designed to examine the effects of exogenous 20- HETE on mesenchymal stem cell (MSC)-derived adipocytes.

The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases in humans) in MSCs decreased during adipocyte differentiation; however, exogenous administration of 20-HETE (0.1–1 M) increased adipogenesis in a dose dependent manner in these cells ( P < 0.05). The inability of a 20-HETE analog to reproduce these effects suggested the involvement of a metabolic product of 20-HETE in mediating its pro-adipogenic effects. A cyclooxygenase (COX)-1 selective inhibitor enhanced, whereas a COX-2 selective or a dual COX-1/2 inhibitor attenuated adipogenesis induced by 20-HETE. The COX-derived metabolite of 20-HETE, 20-OH-PGE 2 , enhanced adipogenesis and lipid accumulation in MSCs. The pro-adipogenic effects of 20-HETE and 20-OH-PGE 2 resulted in the increased expression of the adipogenic regulators PPAR and -catenin in MSC-derived adipocytes. Taken together we show for the fi rst time that 20-HETE-derived COX-2-dependent 20-OH-PGE 2 enhances mature infl amed adipocyte hypertrophy in MSC undergoing adipogenic differentiation. — Kim, D. H., N. Puri, K. Sodhi, J. R. Falck, N. G. Abraham, J. Shapiro, and M. L. Schwartzman. Cyclooxygenase-2 dependent metabolism of 20-HETE increasesadiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes.


Principles Of Management Of Severe Hyponatremia, Antonios H. Tzamaloukas Md, Deepak Malhorta Md, Phd, Bradley H. Rosen Do, Dominic S. C. Raj S. C. Raj Md, Glen H. Murata Md, Joseph I. Shapiro Md Jan 2013

Principles Of Management Of Severe Hyponatremia, Antonios H. Tzamaloukas Md, Deepak Malhorta Md, Phd, Bradley H. Rosen Do, Dominic S. C. Raj S. C. Raj Md, Glen H. Murata Md, Joseph I. Shapiro Md

Pharmaceutical Science and Research

Hyponatremia represents a serious health hazard.1 Hospitalized patients,2 nursing home residents,3 women,4,5 and children6 exhibit high frequency and/or severity of hyponatremia. Hyponatremia developing during the course of other morbid conditions increases their severity.7–10 Estimates of direct costs for treating hyponatremia in the United States ranged between $1.61 and $3.6 billion.11

Clinical manifestations of hyponatremia are universal12,13 and range from subtle (disturbances of balance, problems in cognition detected only during specific testing) to life-threatening manifestations of increased intracranial pressure with life-threatening hypoxia14–16 and noncardiac pulmonary edema.17 Although the treating physicians must …


Gender Differences In The Development Of Uremic Cardiomyopathy Following Partial Nephrectomy: Role Of Progesterone, Christopher A. Drummond, George Buddny, Steven T. Haller, Jiang Liu, Yanling Yan, Zijian Xie, Deepak Malhotra, Joseph I. Shapiro Md, Jiang Tian Jan 2013

Gender Differences In The Development Of Uremic Cardiomyopathy Following Partial Nephrectomy: Role Of Progesterone, Christopher A. Drummond, George Buddny, Steven T. Haller, Jiang Liu, Yanling Yan, Zijian Xie, Deepak Malhotra, Joseph I. Shapiro Md, Jiang Tian

Biochemistry and Microbiology

Gender difference has been suggested as a risk factor for developing cardiovascular and renal diseases in humans and experimental animals. As a major sex hormone, progesterone was reported to compete with cardiotonic steroid binding to Na/K-ATPase. Our previous publication demonstrated that cardiotonic steroids (e.g., marinobufagenin) play an important role in the development of experimental uremic cardiomyopathy. We also observed that the putative mineralocorticoid antagonists, spironolactone and its major metabolite canrenone, antagonize binding of cardiotonic steroids to Na/K-ATPase in a competitive manner and also ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy. In the following studies, we noted that progesterone displayed …


Antibiotic-Like Actions Of Vitamin D, Franklin D. Shuler Md, Phd, Josh Hendrix, Adam Short, Sammy Hodroge Jan 2013

Antibiotic-Like Actions Of Vitamin D, Franklin D. Shuler Md, Phd, Josh Hendrix, Adam Short, Sammy Hodroge

Orthopaedics

Vitamin D is a secosteroid hormone that has expanding importance for a healthy lifestyle and disease prevention. A multitude of studies have highlighted that vitamin D acts not only in bone and calcium homeostasis but is critically important for human immunity. The discovery that the storage form of vitamin D (25-hydroxyvitamin D3) can be locally converted to the active form (1,25-hydroxyvitamin D3) in immune cells, epithelial cells and numerous other non-renal tissues highlights the importance of maintaining sufficient stores. When responding to a specific external stimulus, like bacterial invasion, intracrine synthesis of active vitamin D has the ability to regulate …