bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin sensitivity during oral glucose tolerance test and its relations to parameters of glucose metabolism and endothelial function in type 2 diabetic subjects under metformin and thiazolidinedione
Authors: Kautzky‐Willer A. , Tura A. , Winzer C. , Wagner O. F. , Ludvik B. , Hanusch‐Enserer U. , Prager R. , Pacini G. 
Published: September 2006

Aim:  This study was designed to assess the usefulness of a model‐based index of insulin sensitivity during an oral glucose tolerance test (OGTT) in the identification of possible changes in this metabolic parameter produced by pharmacological agents known to be potent insulin sensitizers, that is metformin (M) and thiazolidinedione (T). The association of these agents with several other factors related to glucose metabolism was also investigated, as well as the relation of insulin sensitivity and secretion with markers of endothelial function such as different adhesion molecules (cAMs), that is vascular cell adhesion molecule‐1, intercellular adhesion molecule‐1 and E‐Selectin.Methods:  Twenty type 2 diabetic patients treated with diet only underwent a 3‐h OGTT for measurement of plasma glucose, insulin, proinsulin, C‐peptide and cAMs before and after administration of randomly given M (n = 9; 1700 mg/day) or T (n = 11; 600 mg/day). After 16 weeks of treatment, a second OGTT was performed. Insulin sensitivity was calculated with homeostasis model assessment and with oral glucose insulin sensitivity (OGIS), which quantifies dynamic glucose clearance per unit change of insulin. Insulin secretion was assessed by modelling technique. Differences in these parameters before and after treatment, as well as possible relationships with cAMs, were assessed.Results:  Basal and stimulated plasma glucose decreased after therapy in both the groups by approximately 20%. Basal insulin resistance also decreased. Insulin sensitivity in dynamic conditions (OGIS: ml/min/m2) increased with M (289.3 ± 18.8 vs. 234.7 ± 18.1, p < 0.02) and tended to improve with T (323.5 ± 18.1 vs. 286.8 ± 22.1, p = 0.09). Total insulin secretion over the OGTT [TIS: nmol/l(3 h)] tended to decrease with M (17.1 ± 2.5 vs. 27.3 ± 0.3, p = 0.08) but not with T (23.6 ± 3.5 vs. 22.5 ± 2.7). Plasma concentrations of E‐Selectin decreased in T (38.0 ± 2.3 vs. 51.2 ± 6.1 ng/ml, p < 0.05). No correlation was found between insulin sensitivity and cAMs.Conclusions:  Model‐based indices of insulin sensitivity and secretion during an OGTT can be able to detect changes observed in patients under treatment with pharmacological agents such as M or T. Both the drugs improved glucose control similarly. Decreased plasma E‐Selectin concentrations were seen in patients on T therapy only.
Blockade of noradrenaline transport abolishes 4‐methylthioamphetamine‐induced contraction of the rat aortain vitro
Authors: Quinn S. T. , Guiry P. J. , Schwab T. , Keenan A. K. , McBean G. J. 
Published: September 2006

Summary1 The aim of this study was to characterize the effects of 4‐methylthioamphetamine (4‐MTA) on contractility and noradrenaline (NA) transport and release in the isolated rat aorta.2 Descending thoracic aortic rings were isolated from male Wistar rats (220–240 g) and the effect of 4‐MTA on contractility was measured by isometric force displacement. 4‐MTA (0.1 μm–1 mm) induced a concentration‐dependent contraction of aortic rings, with a pD2of 4.40 ± 0.38, and anEmaxof 0.80 ± 0.05 g tension.3 Theα1‐adrenoceptor antagonist, prazosin (1 μm) andα2antagonist, yohimbine (1 μm) inhibited maximal contraction to 100 μm4‐MTA by 45.0 ± 6.7% and 53.5 ± 7.1% of control values respectively, whereas the 5‐hydroxytryptamine (5‐HT) antagonist, ketanserin (100 nm) had no effect on the 4‐MTA‐mediated contraction. The specific NA transport inhibitor, nisoxetine (1 μm) abolished contraction of the aorta by 4‐MTA.4 Nisoxetine‐sensitive [3H]‐NA transport in aortic rings was measured over a concentration range of 0–5 μm[3H]‐NA, and had a maximal rate of transport (Vmax) of 0.77 ± 0.07 pmol [3H]‐NA min−1 mg−1protein and a Michaelis affinity constant (KM) of 2.3 ± 0.5 μm. 4‐MTA inhibited nisoxetine‐sensitive [3H]‐NA transport with a pIC50of 6.16 ± 0.18 and the pIC50for inhibition of nisoxetine‐sensitive [3H]‐NA transport by 3,4‐methylenedioxymethamphetamine (MDMA) was 6.83 ± 0.13. 4‐MTA (1–100 μm) significantly stimulated release of pre‐loaded [3H]‐NA from aortic rings and 4‐MTA‐induced [3H]‐NA release was inhibited by 1 μmnisoxetine.5 These data suggest that 4‐MTA causes contraction of the rat aortain vitroby a mechanism that is consistent with an ability to cause release of NA at the level of the NA transporter. It is concluded that 4‐MTA has the potential to increase the extracellular concentration of NA peripherally as well as centrally, and that this may cause adverse cardiovascular effects in its users.
Alpha1A/L‐adrenoceptors mediate contraction of the circular smooth muscle of the pig urethra
Authors: Bagot K. , Chess‐Williams R. 
Published: September 2006

Summary 1 Sympathetically mediated urethral tone is essential for the maintenance of continence and involves the activation of postjunctional α1‐adrenoceptors. This study characterizes the α1‐adrenoceptor subtypes responsible for mediating contraction of the urethral circular smooth muscle of the pig. 2 The potency order of a number of agonists and the affinities of several receptor selective antagonists were determined on pig‐isolated circular smooth muscle strips in the presence of cocaine (1 μm) and corticosterone (10 μm) to inhibit amine uptake and propranolol (1 μm) to antagonize β‐adrenoceptors. 3 The potency order for agonists was N‐[5‐(4,5‐dihydro‐1H‐imidazol‐2yl)‐2‐hydroxy‐5,6,7,8‐tetrahydronaphthalen‐1‐yl]methanesulphonamide (A61603) > noradrenaline = phenylephrine = M6434 > methoxamine with pEC50 values of 7.3, 5.8, 5.7, 5.6 and 5.0 respectively. 4 The α1D‐adrenoceptor‐selective antagonist 8‐[2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]ethyl]‐8‐azaspiro[4,5]decane‐7,9‐dione (BMY7378) caused rightward shifts of the concentration–response curves to noradrenaline, yielding a low affinity estimate (6.6) for the urethral receptor. The α1A‐adrenoceptor‐selective antagonists, RS100329 and 5‐methylurapidil, gave relatively high affinity estimates (9.6 and 8.8 respectively) for this receptor. All three antagonists produced Schild plots with slopes close to unity but did reduce maximum responses at higher concentrations. Prazosin antagonized responses of the urethra to noradrenaline, yielding a mean affinity estimate of 9.0. Although the Schild plot for prazosin again had a slope of unity, this drug also reduced maximum responses to noradrenaline at all concentrations examined (10–100 nm). N‐[2‐(2‐cyclopropylmethoxyphenoxy)ethyl]‐5‐chloro‐α,α‐dimethyl‐1H‐indole‐3‐ethanamide (RS17053), which discriminates between responses mediated via α1A (high affinity) and α1L‐adrenoceptors (low affinity) at concentrations up to 3 μm, failed to antagonize responses of the urethra. 5 These results suggest that contraction of urethral circular smooth muscle in the pig is mediated via a single population of adrenoceptors with the pharmacological characteristics of the α1A/L‐adrenoceptor, most probably the α1L‐adrenoceptor.
Dopamine receptor subtypes in the human pulmonary arterial tree
Authors: Ricci A. , Mignini F. , Tomassoni D. , Amenta F. 
Published: September 2006

Summary 1 Dopamine induces vasorelaxation of pulmonary artery primarily through an endothelium‐dependent mechanism, but dopamine receptor subtypes involved in these mechanisms have not been identified yet. The expression and localization of dopamine D1‐like (D1 and D5) and D2‐like (D2, D3 and D4) receptors were investigated in hilar, lobar and intrapulmonary branches of human pulmonary artery by immunoblotting and immunohistochemistry. 2 Pulmonary artery expresses dopamine D1, D2, D4 and D5 receptor subtypes, but not the D3 receptor subtype. Dopamine D1 and to a lesser extent D5 receptors were accumulated primarily in the endothelium of extrapulmonary branches of pulmonary artery. A faint dopamine D1 and D5 receptor immunoreactivity was found in the inner media of extrapulmonary and of large sized intrapulmonary branches of pulmonary artery, but not in medium‐ or small‐sized intrapulmonary artery branches. 3 Dopamine D2 and to a lesser extent D4 receptor immunoreactivity co‐localized with the tyrosine hydroxylase‐immunoreactive sympathetic plexus supplying pulmonary artery was found in the adventitia and in the adventitia‐media of both extra‐ and different‐sized intrapulmonary branches of pulmonary artery. 4 These findings suggest the possible role of dopamine receptors in the pulmonary endothelium‐dependent vasorelaxing activity. The D1 receptor subtype seems to be the most involved in this mechanism. Dopamine D2‐like receptors are prejunctional and are located at the level of sympathetic neuroeffector plexus. The heterogeneous distribution and density of dopamine receptor subtypes along the human pulmonary arterial tree may be related to the different functional roles of dopamine at various levels of the pulmonary circulation.
Editorials: The Cardiovascular Effects of Arteriovenous Fistulas in Chronic Kidney Disease: A Cause for Concern?
Authors: MacRae Jennifer M. , Levin Adeera , Belenkie Israel 
Published: September 2006

AbstractArteriovenous fistulas (AVFs) are the preferred type of vascular access, but relatively little is known regarding their effects on cardiovascular remodeling and cardiac function. The following is a review regarding the immediate and long‐term complications associated with AVF creation, including the development of left ventricular hypertrophy, high‐output cardiac failure, exacerbation of coronary ischemia, and the possible contribution to the development of central vein stenosis.
Pulmonary Hypertension in Hemodialysis Patients: An Unrecognized Threat
Authors: Yigla Mordechai , Abassi Zaid , Reisner Shimon A. , Nakhoul Farid 
Published: September 2006

AbstractPulmonary hypertension (PH) is a progressive, fatal pulmonary circulatory disease that accompanies many conditions (including left to right side shunt) with compensatory elevated cardiac output. PH also complicates chronic hemodialysis (HD) therapy immediately after the creation of an arteriovenous (AV) access, even before starting HD therapy. It tends to regress after temporary AV access closure and after successful kidney transplantation. Affected patients have significantly higher cardiac output. This syndrome is associated with a statistically significant survival disadvantage. The laboratory hallmark of this syndrome is reduced basal and stimulatory nitric oxide (NO) levels. It appears that patients with end‐stage renal disease (ESRD) acquire endothelial dysfunction that reduces the ability of their pulmonary vessels to accommodate the AV access‐mediated elevated cardiac output, exacerbating the PH. Doppler echocardiographic screening of ESRD patients scheduled for HD therapy for the occurrence of PH is indicated. Early diagnosis enables timely intervention, currently limited to changing dialysis modality or referring for kidney transplantation.
Three Controversial Issues in Extracorporeal Toxin Removal
Authors: Feinfeld Donald A. , Rosenberg Jeffrey W. , Winchester James F. 
Published: September 2006

AbstractThe optimal method of extracorporeal removal of many toxic compounds is often a matter of debate. Due to the lack of well‐designed studies, we are often left with circumstantial evidence, and we must exercise our best clinical judgment as to whether extracorporeal drug removal is beneficial and if so, by what method. It is clear, however, that rapidity in toxin removal is beneficial. We present three issues dealing with extracorporeal removal of toxins for which there is no definitive answer but which may arise in clinical practice. The first is whether continuous renal replacement therapy (CRRT) is better at removing dialyzable toxins than classic hemodialysis. The second is whether charcoal hemoperfusion is at all useful in treating paraquat poisoning. Finally, is any modality of extracorporeal treatment useful in the treatment of amatoxin poisoning? After a thorough literature review, it is evident that definitive answers are not strikingly apparent. However, extracorporeal treatment in the latter two instances may have potential benefit and may be the only hope for patient survival. Due to the urgent nature of treatment for poisoning, as well as the somewhat obscure nature of these issues, there may never be well‐designed evidence‐based studies to help guide us. In the meantime, we must continue to use less than ideal evidence and our own experience in dealing with these controversial issues to guide our decision‐making process.
Use of Antiepileptic Drugs in Patients with Kidney Disease
Authors: Israni Rubeen K. , Kasbekar Nishaminy , Haynes Kevin , Berns Jeffrey S. 
Published: September 2006

AbstractThe number of medications used to treat different types of seizures has increased over the last 10–15 years. Most of the newer antiepileptic drugs (AEDs) are likely to be unfamiliar to many nephrologists. For both the older and newer AEDs, basic pharmacokinetic information, recommendations for drug dosing in patients with reduced kidney function or who are on dialysis, and adverse renal and fluid‐electrolyte effects are reviewed. Newer AEDs are less likely to have significant drug–drug interactions than older agents, but are more likely to need dosage adjustment in patients with reduced kidney function. The most common renal toxicities of these drugs include metabolic acidosis, hyponatremia, and nephrolithiasis; interstitial nephritis and other adverse effects are less common. Little is known about the clearance of most of the newer AEDs with high‐efficiency hemodialyzers or with peritoneal dialysis. Monitoring of drug levels when available, careful clinical assessment of patients taking AEDs, and close collaboration with neurologists is essential to the management of patients taking AEDs.
ASDIN Original Investigation: Successful Treatment of the Chronically Thrombosed Dialysis Access Graft: Resuscitation of Dead Grafts
Authors: Beathard Gerald A. 
Published: September 2006

AbstractThe most common contributing cause of thrombosis of an arteriovenous graft (AVG) in the hemodialysis patient is the presence of venous stenosis. In the face of a recovery of renal function either spontaneously or as a result of renal transplantation, an AVG commonly thromboses. In cases in which the AVG was recently placed, it is unlikely to have had a significant anatomic lesion at the time function was lost. Even though the access that has been left untreated has become a “dead” AVG, it offers an opportunity for “resuscitation.” Thirteen cases that met the specific criteria of being placed only a short period of time prior to thrombosis (3 weeks to 6 months), thrombosing after a return of renal function and having been left untreated (3 months to 8 years) were attempted over a 12 year period. The technique applied was modified from the one routinely used based on the presumption that very little or no thrombus was present. The effort was met with success in 8 of the 13 patients. After being opened, the AVG appeared to follow the same patency pattern as other AVGs. It appears that attempting restoration of function of an AVG meeting these criteria may be indicated. Limited experience using this approach in AVGs that do not meet these specific criteria has uniformly met with failure.
Fellows' Forum in Dialysis: Interdialytic Weight Gain: Implications in Hemodialysis Patients
Authors: Sarkar Shubho R. , Kotanko Peter , Levin Nathan W. 
Published: September 2006

ABSTRACTInterdialytic weight gain (IDWG) is an easily measurable parameter in the dialysis unit, routinely assessed at the beginning of the dialysis session. It is used along with clinical symptoms and signs and predialysis blood pressure readings to make decisions regarding the amount of fluid removal during a dialysis session. IDWG is also used as a basis for fluid and salt intake recommendations. However, advising fluid and salt restriction based solely on IDWG may not be appropriate because of its status as a nutritional indicator, as well. Very few studies have been designed to determine the direct effect of IDWG on morbidity and mortality. Any such effect is confounded by residual renal function and various comorbidities, the effects of which might be difficult to separate from those of IDWG. Most attempts to control IDWG have concentrated on requiring patients to reduce fluid and dietary salt intake. Although there does not seem to be a consensus at this point, it is likely that within the lower values of IDWG (less than 5.7% of dry weight), tighter control of fluid and salt intake might not be warranted since these values may reflect higher protein and calorie intake, indicating better nutritional status.
A Dialysis Case Presentation and Discussion: A Case of Fatal Cardiac Tamponade During Hemodialysis
Authors: Schmiege Lorenz M. , Wolf Dwayne A. 
Published: September 2006

ABSTRACTA 27‐year‐old Hispanic man with a history of hypertension and end‐stage renal disease for 4 years became unresponsive, apneic, and pulseless during hemodialysis. During his 4 year period on dialysis, vascular access had become increasingly difficult and ultimately a transhepatic catheter had been placed 9 months prior to this event. Resuscitation was unsuccessful. At autopsy, death was determined to be due to cardiac tamponade secondary to perforation of the right atrium by the transhepatic catheter. Cardiac tamponade is a rare cause of sudden death during hemodialysis with a long‐standing catheter.
Monoamine Metabolism and Behavioral Responses to Ethanol in Mitochondrial Aldehyde Dehydrogenase Knockout Mice
Authors: Fernandez Elizabeth , Koek Wouter , Ran Qitao , Gerhardt Greg A. , France Charles P. , Strong Randy 
Published: September 2006

Background: It is widely accepted that, in addition to removing acetaldehyde produced during the metabolism of ethanol, mitochondrial aldehyde dehydrogenase (ALDH2) functions in the pathway by which aldehyde metabolites of the monoamines dopamine (DA) and serotonin (5‐HT) are converted to their acidic metabolites. Moreover, studies of ALDH2 inhibitors used for treating alcoholism suggest that their antidipsotropic effects may be related to inhibition of monoamine metabolism. Therefore, we examined the hypothesis that altered brain monoamine metabolism is related to the influence of ALDH2 on behavioral responses to ethanol.Methods: Mice were generated with a gene‐trap mutation of the ALDH2 gene. ALDH2 mRNA was absent in ALDH2−/− mice. Western blot analysis of liver mitochondria confirmed the absence of ALDH2 protein in the ALDH2−/− mice. Wild‐type and ALDH2‐deficient mice were tested for the effects of different doses of ethanol on locomotor activity, ataxia, and a 2‐bottle ethanol–water preference test.Results: Wild‐type and ALDH2+/− mice preferred ethanol to water. However, ALDH2−/− mice drank significantly less ethanol than wild‐type or ALDH2+/− mice. Locomotor activity and ataxia were significantly more affected by ethanol in ALDH2−/− mice than in wild‐type or ALDH2+/− mice. There was no effect of genotype on levels of 5‐HT, DA, or their precursors or metabolites in several brain regions, as measured by HPLCec.Conclusions: The results indicate that: (1) the effect of the mutant genotype on behavioral responses to ethanol is unrelated to altered brain monoamine metabolism and (2) ALDH2 is not required for the metabolism of brain monoamines in vivo.
Gene Array Profiles of Alcohol and Aldehyde Metabolizing Enzymes in Brains of C57BL/6 and DBA/2 Mice
Authors: Bhave Sanjiv V. , Hoffman Paula L. , Lassen Natalie , Vasiliou Vasilis , Saba Laura , Deitrich Richard A. , Tabakoff Boris 
Published: September 2006

Background: Differences in ethanol metabolizing enzymes expressed in brain have been suggested to contribute to the significant differences in ethanol (alcohol) preference between inbred C57BL/6 and DBA/2 mouse strains.Methods: We have utilized 2 different platforms of oligonucleotide microarray technology (CodeLink UniSet I BioArray from G.E. Healthcare and MG U74A v2.0 from Affymetrix) to simultaneously assess expression of alcohol and acetaldehyde metabolizing enzymes in the whole brain of naïve (no exposure to alcohol) C57BL/6 and DBA/2 mice.Results: There were no significant differences between the 2 strains of mice in gene expression intensity for alcohol dehydrogenases (ADH), catalase, and a number of the cytochrome P450 family of genes, which can be involved in ethanol catabolism. However, significantly higher expression of mRNA for aldehyde dehydrogenase 2 (ALDH2), an isoform mainly responsible for the catabolism of acetaldehyde, was observed in whole brains of DBA/2 mice with both platforms. Aldehyde dehydrogenase 2 protein was also higher in DBA/2 brain. Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) mRNA was found to be higher in brains of DBA/2 mice, when measured with the CodeLink platform, but not when measured with Affymetrix arrays or quantitative reverse transcriptase–real‐time polymerase chain reaction (qRT‐PCR). The ALDH1A1 protein, however, reflected the results obtained with the CodeLink arrays and was higher in DBA/2 brain, compared with brains of C57BL/6 mice. In contrast, the expression intensity for the aldehyde dehydrogenase 7A1 (ALDH7A1) mRNA and protein was significantly higher in C57BL/6 mice than DBA/2 mice. These expression differences are consistent with more rapid metabolism of acetaldehyde in brains of DBA/2 mice.Conclusions: The use of 2 different microarray platforms provides important cross‐validation of many results, and some discrepancies can be resolved with qRT‐PCR and immunoblotting. The expression differences that were validated may affect alcohol/aldehyde metabolism in brain and/or alcohol preference in the 2 strains of mice.