PubMed Health⌕ Search

Biomedical subjects

K M Desai

Publications and source records attributed to K M Desai.

At least 19 recordsLinked to original sources
PubMed2006

The regulation of adiponectin receptors in human prostate cancer cell lines.

Obesity is a risk factor for prostate cancer, and plasma levels of the adipokine, adiponectin, are low in the former but high in the latter. Adiponectin has been shown to modulate cell proliferation and apoptosis, suggesting that adiponectin and its receptors (Adipo-R1, Adipo-R2) may provide a molecular association between obesity and prostate carcinogenesis. We show for the first time, the protein distribution of Adipo-R1 and Adipo-R2 in LNCaP and PC3 cells, and in human prostate tissue. Using real-time RT-PCR we provide novel data demonstrating the differential regulation of Adipo-R1 and Adipo-R2 mRNA expression by testosterone, 5-alpha dihydrotestosterone, beta-estradiol, tumour necrosis factor-alpha, leptin, and adiponectin in LNCaP and PC3 cells. Our findings suggest that adiponectin and its receptors may contribute to the molecular association between obesity and prostate cancer through a complex interaction with other hormones and cytokines that also play important roles in the pathophysiology of obesity and prostate cancer.

Adiponectin↗
PubMed2006

Histologic results 1 year after bioprosthetic repair of paraesophageal hernia in a canine model.

BACKGROUND: The use of prosthetic materials for the repair of paraesophageal hiatal hernia (PEH) may lead to esophageal stricture and perforation. High recurrence rates after primary repair have led surgeons to explore other options, including various bioprostheses. However, the long-term effects of these newer materials when placed at the esophageal hiatus are unknown. This study assessed the anatomic and histologic characteristics 1 year after PEH repair using a U-shaped configuration of commercially available small intestinal submucosa (SIS) mesh in a canine model. METHODS: Six dogs underwent laparoscopic PEH repair with SIS mesh 4 weeks after thoracoscopic creation of PEH. When the six dogs were sacrificed 12 months later, endoscopy and barium x-ray were performed, and biopsies of the esophagus and crura were obtained. RESULTS: The mean weight of the dogs 1 year after surgery was identical to their entry weight. No dog had gross dysphagia, evidence of esophageal stricture, or reherniation. At sacrifice, the biomaterial was not identifiable grossly. Biopsies of the hiatal region showed fibrosis as well as muscle fiber proliferation and regeneration. No dog had erosion of the mesh into the esophagus. CONCLUSIONS: This reproducible canine model of PEH formation and repair did not result in erosion of SIS mesh into the esophagus or in stricture formation. Native muscle ingrowth was noted 1 year after placement of the biomaterial. According to the findings, SIS may provide a scaffold for ingrowth of crural muscle and a durable repair of PEH over the long term.

Animals↗
PubMed2004

Results of laparoscopic Heller-Toupet operation for achalasia.

BACKGROUND: Laparoscopic myotomy has become the preferred treatment for achalasia. Controversy persists on the need for fundoplication and/or its type; when used, most series have utilized the Dor fundoplication. We report a large series of laparoscopic Heller-Toupet procedures. METHODS: All patients operated for achalasia were entered into a prospective database. Pre and postoperative esophageal symptoms, satisfaction scores, and SF-36 variables were compared. Surgical failures were defined as recurrent or persistent dysphagia leading to secondary treatment. Data are expressed as mean +/- S.D. RESULTS: One hundred consecutive cases were analyzed (61 men, 39 women, age 47 +/- 17 yr). Heller-Toupet was performed in 94, whereas six patients had a Dor fundoplication because of mucosal perforation (three) or technical difficulties performing a posterior wrap (three). Operative time was 148 +/- 21 min. There were 13 intraoperative adverse events managed laparoscopically, and no conversions. Minor postoperative complications were noted in two cases, whereas there were no major complications or deaths. Mean hospital stay was 1.2 +/- 0.5 days, (range 1-4). Follow-up was complete in 92% at 26 +/- 17 months. Failures leading to further treatment occurred in 4%. All symptom scores were significantly improved (p < 0.0001). Solid dysphagia score went from 6.4 to 1.0 postoperatively; regurgitation score went from 4.5 to 0.2 (combined frequency and severity, range 0-8). Postoperative global esophageal symptoms scale revealed improvement in 97%, and all domains of the SF-36 were improved. CONCLUSIONS: Although the best surgical approach to achalasia is yet to be determined, laparoscopic Heller-Toupet operation in experienced hands is a safe and effective procedure with low rates of morbidity and failure and high patient satisfaction.

Adolescent↗
PubMed2003

Influence of spastic motor disorders of the esophageal body on outcomes from laparoscopic antireflux surgery.

BACKGROUND: The clinical outcomes of laparoscopic antireflux surgery (LARS) in patients with the spectrum of nonspecific spastic esophageal motor disorders (NSSDs) are not known. METHODS: From a prospective database of patients undergoing LARS between 1997 and 2000, those with preoperative manometry at our institution and follow-up at ?6 months were identified. RESULTS: Of the 121 patients, 35 had NSSDs. There were no differences in symptoms between groups preoperatively, but in the immediate postoperative period NSSD patients had more symptoms than nonspastic patients. At 18-month mean follow-up, NSSD patients reported significantly more heartburn (22% vs 7%), waterbrash (14% vs 4%), and medication usage (17% vs 5%) than nonspastic patients (p <0.05 for each). Despite this difference, nearly all patients reported subjective improvement postoperatively, and the degree of improvement was similar between groups. CONCLUSIONS: Patients with NSSDs are more likely to have esophageal symptoms following LARS than subjects without these abnormalities. However, these patients still experience significant improvement in preoperative symptoms.

Anti-Ulcer Agents↗
PubMed2002

Symptomatic outcomes of laparoscopic antireflux surgery in patients eligible for endoluminal therapies.

BACKGROUND: This study compared clinical outcomes after laparoscopic antireflux surgery (LARS) in patients with gastroesophageal reflux disease (GERD) who would be eligible for endoluminal therapies (ET) with those in patients who would be excluded from ET. METHODS: From 1995 to the present, 459 patients who underwent LARS were analyzed prospectively. Of these, 117 patients (25%) without preoperative dysphagia, stricture, esophagitis worse than grade 2 or hiatal hernia larger than 2 cm were considered potential candidates for ET (group 1). By these criteria, 342 patients (75%) were not eligible for ET (group 2). Medication use and GERD symptoms were evaluated and compared between the two groups. RESULTS: Perioperative outcomes including duration of operation, morbidity, length of hospital stay and return to work were similar in the two groups. Although LARS significantly reduced medication use and GERD symptoms in both groups during a mean follow-up period longer than 2 years, there were no outcome differences between groups 1 and 2. The reported improvement in esophageal symptoms and overall satisfaction was 90% or more in both groups. CONCLUSIONS: The findings show that LARS is an effective treatment option in patients with GERD whether they are candidates for ET or not. In patients with uncomplicated GERD who currently meet inclusion criteria for ET, LARS provides excellent symptom relief and marked reduction in medication use during a mean follow-up period longer than 2 years.

Adult↗
PubMed2000

Endothelial dysfunction accompanies a pro-oxidant, pro-diabetic challenge in the insulin resistant, obese Zucker rat in vivo.

We have recently made the novel observation that a pro-oxidant challenge with hydroquinone in combination with buthionine sulfoximine (each at 50 mg/kg i.p. daily for 7 days) provokes the onset of type II diabetes mellitus in a model of insulin resistance, the obese Zucker rat. Since endothelial dysfunction in oxidant stress may aggravate in vivo insulin resistance, we have now investigated endothelium-dependent and nitric oxide (NO)-mediated vascular responses in the obese Zucker rat in vivo following this pro-oxidant insult. Pro-oxidant-treated animals exhibited defective vasodepression to the endothelium-dependent agent acetylcholine and to a lesser extent, the NO donor glyceryl trinitrate, together with a reduction in circulating levels of cGMP. Our data therefore suggest that the progression to type II diabetes mellitus in the obese Zucker rat mediated by a pro-oxidant insult is associated with impairments in agonist-stimulated, endothelium-dependent vasodilation and vascular NO signalling.

Acetylcholine↗
PubMed1999

F2-isoprostane evidence of oxidant stress in the insulin resistant, obese Zucker rat: effects of vitamin E.

We have concurrently investigated oxidant stress, glucose tolerance and glucose-stimulated insulin responses in the obese Zucker rat, a widely used model of insulin resistance. The plasma level of the lipid peroxidation product 8-epi-prostaglandin F2alpha, a sensitive in vivo marker of oxidant stress, was elevated approximately 5-fold in 13-week old obese relative to age-matched, insulin-sensitive lean Zucker rats. Supplementation of the diet with vitamin E (as (+)-alpha-tocopherol acetate, 0.5% w/w) for 4 weeks, reduced plasma 8-epi-prostaglandin F2alpha and concomitantly reversed glucose-stimulated hyperinsulinaemia in the obese Zucker rat without worsening glucose tolerance. We therefore provide evidence of oxidant stress, measured as elevated plasma 8-epi-prostaglandin F2alpha, for the first time in the obese Zucker rat which now provides a rationale for the beneficial effects of antioxidants on insulin action previously reported in this model of insulin resistance.

Animals↗
PubMed1999

Pro-oxidant challenge in vivo provokes the onset of NIDDM in the insulin resistant obese Zucker rat.

We investigated the ability of an acute pro-oxidant challenge in vivo to deteriorate glycaemic control and insulin action in the obese Zucker rat, a model of insulin resistance associated with oxidant stress. In obese animals, the daily administration for 1 week of hydroquinone (HQ) in combination with L-buthionine sulphoximine (BSO), elevated fasting plasma glycaemia and insulinaemia and markedly aggravated i.v. glucose-stimulated hyperinsulinaemia without significantly affecting i.v. glucose tolerance, suggesting exacerbated insulin resistance. Intermediate effects on hyperinsulinaemia in obese animals were determined with HQ treatment alone while BSO treatment alone had no effect. In contrast, none of the pro-oxidant treatments affected age-matched, insulin sensitive, lean Zucker rats. Our data therefore demonstrate for the first time, a vulnerability to deterioration in insulin action in an established insulin resistant state following an environmental pro-oxidative insult. This may have relevance in the conversion of insulin resistance syndrome (IRS) to non-insulin dependent diabetes mellitus (NIDDM).

Animals↗
PubMed1999

Is the measurement of serum testosterone routinely indicated in men with erectile dysfunction?

OBJECTIVE: To investigate the usefulness of serum testosterone levels as a relevant or useful indicator of sexual potency in men attending an erectile dysfunction clinic. PATIENTS AND METHODS: Ninety consecutive men attending the erectile dysfunction clinic completed a sexual-activity questionnaire, and underwent a focused physical examination and questioning about their medical history. The serum testosterone level was measured in all patients and the results analysed in relation to the patient's age. Patients with low serum testosterone levels commenced replacement therapy comprising three intramuscular injections of testosterone (Sustanontrade mark, Organon, The Netherlands) 250 mg every third week. Potency status and serum testosterone were reassessed after 3 months' treatment. RESULTS: Of the 90 men, 28 (31%) were aged < 50 years whilst 62 (69%) were >/=50 years old. Nineteen (21%) patients overall had low testosterone levels; four of these were < 50 and 15 were >/=50 years old. Five of 90 patients had a decreased libido; two of these also had low testosterone levels and all were < 50 years old. Testosterone levels returned to normal in all patients who received replacement therapy but potency returned in only two (10%); both were in the older group. CONCLUSION: Measuring testosterone was not helpful in assessing potency or libido and low serum levels were not related to age. Correcting low testosterone did not improve either impotence or libido.

Adult↗
PubMed1999

A new automated system for urine analysis: a simple, cost-effective and reliable method for distinguishing between glomerular and nonglomerular sources of haematuria.

OBJECTIVE: To determine the ability, reliability and accuracy of a new automated system of urine analysis in differentiating glomerular from nonglomerular bleeding in the initial investigation of haematuria, and compare its efficacy with conventional phase-contrast microscopy (PCM). PATIENTS AND METHODS: One hundred and six urine samples from patients in whom the final diagnosis was available were analysed using electrical flow impedance to detect, enumerate and size red blood cells in a conductive fluid (the cellfacts analyser, Microbial Systems Ltd, Coventry, UK). All the samples were also tested using a dipstick method and PCM was carried out for comparison on 45 of the 106 urine specimens. The results of cellfacts analysis were correlated with the final diagnoses to assess sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of this method; the costs were also analysed. RESULTS: Sixty-nine urine samples tested positive for blood on dipstick urine analysis and all these were confirmed to have red blood cells on cellfacts analysis. The remaining 37 samples were negative for blood on dipstick testing and cellfacts analysis, although seven patients had been referred with previously detected microscopic haematuria, none of whom were found to have any detectable pathology in the urinary tract on clinical examination and investigations. The remaining 30 patients were diagnosed to have urological or nephrological conditions with no haematuria. In the positive group, 20 (29%) patients were from the glomerular group, with a mean (range) red blood cell size of 4.25 (4-5.1) micrometer, and 49 (71%) from the nonglomerular group, with red blood cells of 5.47 (4.67-5.70) micrometer. These ranges overlapped at 4.67-5.1 micrometer at the decision threshold of 4.75 micrometer, the distribution of dysmorphic and eumorphic red blood cells for the glomerular group was 18 (90%) and two (10%), respectively, and for the nonglomerular group was 2 (4%) and 47 (96%), respectively. The sensitivity, specificity, PPV and NPV were 90%, 96%, 90% and 96%, respectively. Consumable and labour costs were very low. CONCLUSIONS: Cellfacts analysis is a simple, rapid, objective and cost-effective method for differentiating glomerular from nonglomerular urinary red blood cells, especially when few such cells are present.

Adult↗
PubMed1997

Nitric oxide synthase inhibitors attenuate transforming-growth-factor-beta 1-stimulated capillary organization in vitro.

Angiogenesis is a complex process involving endothelial cell (EC) proliferation, migration, differentiation, and organization into patent capillary networks. Nitric oxide (NO), an EC mediator, has been reported to be antigenic as well as proangiogenic in different models of in vivo angiogenesis. Our aim was to investigate the role of NO in capillary organization using rat microvascular ECs (RFCs) grown in three-dimensional (3D) collagen gels. RFCs placed in 3D cultures exhibited extensive tube formation in the presence of transforming growth factor-beta 1. Addition of the NO synthase (NOS) inhibitors L-nitro-arginine methylester (L-NAME, 1 mmol/L) or L-monomethyl-nitro-l-arginine (1 mmol/L) inhibited tube formation and the accumulation of nitrite in the media by approximately 50%. Incubation of the 3D cultures with excess L-arginine reversed the inhibitory effect of L-NAME on tube formation. In contrast to the results obtained in 3D cultures, inhibition of NO synthesis by L-NAME did not influence RFC proliferation in two-dimensional (2D) cultures or antagonize the ability of transforming growth factor-beta 1 to suppress EC proliferation in 2D cultures. Reverse transcriptase-polymerase chain reaction revealed the constitutive expression of all three NOS isoforms, neuronal, inducible, and endothelial NOSs, in 2D and 3D cultures. Moreover, Western blot analysis demonstrated the presence of immunoreactive protein for all NOS isoforms in 3D cultures of RFCs. In addition, in the face of NOS blockade, co-treatment with the NO donor sodium nitroprusside or the stable analog of cGMP, 8-bromo-cGMP, restored capillary tube formation. Thus, the autocrine production of NO and the activation of soluble guanylate cyclase are necessary events in the process of differentiation and in vitro capillary tube organization of RFCs.

Adipose Tissue↗
PubMed1996

Elevated blood pressures in mice lacking endothelial nitric oxide synthase.

Nitric oxide produced in endothelial cells affects vascular tone. To investigate the role of endothelial nitric oxide synthase (eNOS) in blood pressure regulation, we have generated mice heterozygous (+/-) or homozygous (-/-) for disruption of the eNOS gene. Immunohistochemical staining with anti-eNOS antibodies showed reduced amounts of eNOS protein in +/- mice and absence of eNOS protein in -/- mutant mice. Male or female mice of all three eNOS genotypes were indistinguishable in general appearance and histology, except that -/- mice had lower body weights than +/+ or +/- mice. Blood pressures tended to be increased (by approximately 4 mmHg) in +/- mice compared with +/+, while -/- mice had a significant increase in pressure compared with +/+ mice (approximately 18 mmHg) or +/- mice (approximately 14 mmHg). Plasma renin concentration in the -/- mice was nearly twice that of +/+ mice, although kidney renin mRNA was modestly decreased in the -/- mice. Heart rates in the -/- mice were significantly lower than in +/- or +/+ mice. Appropriate genetic controls show that these phenotypes in F2 mice are due to the eNOS mutation and are not due to sequences that might differ between the two parental strains (129 and C57BL/6J) and are linked either to the eNOS locus or to an unlinked chromosomal region containing the renin locus. Thus eNOS is essential for maintenance of normal blood pressures and heart rates. Comparisons between the current eNOS mutant mice and previously generated inducible nitric oxide synthase mutants showed that homozygous mutants for the latter differ in having unaltered blood pressures and heart rates; both are susceptible to lipopolysaccharide-induced death.

Analysis of Variance↗
PubMed1995

The Golgi association of endothelial nitric oxide synthase is necessary for the efficient synthesis of nitric oxide.

The particulate enzyme, endothelial nitric oxide synthase (eNOS), produces nitric oxide to maintain normal vasodilator tone in blood vessels. In this study, we demonstrate that eNOS is a Golgi-associated protein in cultured endothelial cells and intact blood vessels. Using a heterologous expression system in HEK 293 cells, we show that wild-type myristoylated and palmitoylated eNOS, but not mutant, non-acylated eNOS targets to the Golgi. More importantly, HEK 293 cells expressing wild-type eNOS release substantially more NO than cells expressing the mutant, non-acylated enzyme. Thus, eNOS is a novel Golgi-associated protein, and Golgi compartmentalization is necessary for the enzyme to respond to intracellular signals and produce NO.

Amino Acid Oxidoreductases↗
PubMed1994

5-HT3 receptors do not mediate vagally-induced relaxation or contraction of the isolated stomach of the guinea-pig.

1. We have tested whether 5-HT3 receptors mediate vagally-induced relaxation or contraction of the isolated stomach of the guinea-pig. 2. The antagonists of 5-HT3 receptors, ondansetron (1-10 microM) or metoclopramide (1-30 microM) did not inhibit vagally-induced relaxations at low concentrations but partially inhibited them at 30 microM or 60 microM, respectively. These higher concentrations of ondansetron and metoclopramide also inhibited relaxations induced by 1,1-dimethyl-4-phenylpiperazinium iodide (30 microM) but did not affect those induced by glyceryl trinitrate (0.7-1.1 microM). 3. Desensitization to 5-HT (100 microM) or 2-Me-5-HT (100 microM) did not affect relaxations or contractions induced by vagal stimulation. 4. Ondansetron (30 microM) or metoclopramide (60 microM) did not inhibit vagally-induced gastric contraction. 5. Thus, 5-HT3 receptors do not mediate vagally-induced relaxation or contraction in the guinea-pig stomach.

Animals↗
PubMed1994

Nitric oxide, and not vasoactive intestinal peptide, as the main neurotransmitter of vagally induced relaxation of the guinea pig stomach.

1. Nitric oxide synthase (NOS) was localized in the guinea pig stomach by immunocytochemistry. In vitro experiments were carried out on the isolated stomach of the guinea pig to study any possible links between nitric oxide (NO) and vasoactive intestinal peptide (VIP) in mediating relaxations induced by vagal stimulation. 2. NOS was localized to nerve cell bodies and nerve fibre varicosities of the myenteric plexus in wholemounts of the longitudinal muscle-myenteric plexus of the stomach fundus. The NOS-positive cells had a Dogiel type I morphology characteristic of motor neurones. 3. The cross-sections of the stomach wall showed NOS-positive neurones mainly in the myenteric plexus ganglia and NOS-positive nerve fibre varicosities in the circular muscle layer. 4. Relaxations induced by vagal stimulation were almost completely prevented by L-NAME with an IC50 value of 5.5 x 10(-6) M. This inhibition was reversed by L-arginine (2 mM). 5. VIP (100 nM) induced reproducible relaxations of the stomach. These were unaffected by tetrodotoxin (2 microM) or N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM). 6. Desensitization to the relaxant effect of VIP partially reduced relaxations induced by vagal stimulation, glyceryl trinitrate or sodium nitroprusside but not noradrenaline. 7. These results show that NO has a neuronal origin in the guinea pig stomach, and support NO, and not VIP, as the major neurotransmitter of vagally induced gastric relaxation in the guinea pig.

Amino Acid Oxidoreductases↗
PubMed1991

Nitroxergic nerves mediate vagally induced relaxation in the isolated stomach of the guinea pig.

Here we show that the relaxation induced by stimulation of the vagus nerve in the presence of cholinergic (muscarinic) and adrenergic blockade in the isolated stomach of the guinea pig is mediated by nitric oxide (NO). This is substantiated by inhibition of vagal relaxation by NG-monomethyl-L-arginine, an inhibitor of NO synthesis. The effect of NG-monomethyl-L-arginine was partially reversed by coincubation with L-arginine but not with D-arginine. NO activates soluble guanylate cyclase, and relaxation of the stomach induced by vagal stimulation was prevented by an inhibitor of soluble guanylate cyclase, methylene blue, further supporting our conclusions. The relaxant effect of vagal stimulation was also ablated by hexamethonium, an inhibitor of ganglionic nicotinic receptors, thereby showing that ganglionic transmission did not rely on NO, through its release from preganglionic neurons. However, hexamethonium did not inhibit the gastric relaxation brought about by increasing the intragastric pressure, which is also mediated by NO as previously described by us. The selective inhibition by hexamethonium of only the vagally mediated relaxation but not of the pressure-induced relaxation of the stomach indicates the existence of at least two separate neuronal pathways able to generate NO and bring about gastric accommodation of food or fluid.

Animals↗
PubMed1991

Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food or fluid.

The fundus of the guinea-pig stomach actively dilates in response to low increases in intragastric pressure. This physiological response, now called adaptive relaxation, accommodates the intake of liquid or food. It is independent of external innervation, resistant to ganglion blockade, but reflex in origin. The nerves involved are neither adrenergic nor cholinergic in nature. Non-adrenergic, non-cholinergic (NANC) nerves have now been recognized in many parts of the gastrointestinal tract and have recently been linked with release of nitric oxide (NO) on electrical stimulation. Here we show that adaptive relaxation in isolated stomach of the guinea pig is mediated by a NANC neurotransmitter substance indistinguishable from NO derived from L-arginine. This is substantiated by inhibition of adaptive relaxation by NG-monomethyl-L-arginine or N omega-nitro-L-arginine methyl ester, both inhibitors of NO synthesis, and by methylene blue, an inhibitor of soluble guanylate cyclase. There are two distinct neuronal pathways signalling NO-dependent adaptive relaxation, as evidenced by tetrodotoxin sensitivity. The first is a local reflex arc, the afferent fibres of which sense changes in intragastric pressure. The second is stimulated by an agonist for ganglionic nicotinic receptors. Thus, the functional significance of NO release from NANC nerves in the stomach is to bring about adaptive relaxation through a reflex response to increases in intragastric pressure.

Animals↗