Chlorpropamide treatment restores the reduced carrageenan-induced paw edema and pleural exudate volume in diabetic rats

Objective and design: Knowing that hyperglycemia is a hallmark of vascular dysfunction in diabetes and that neonatal streptozotocin-induced diabetic rats (n-STZ) present reduced inflammatory response, we decided to evaluate the effect of chlorpropamide-lowered blood glucose levels on carrageenan-induced rat paw edema and pleural exudate in n-STZ. Materials: Diabetes was induced by STZ injection (160 mg/kg, ip) in neonates (2-day-old) Wistar rats. Treatment: n-STZ diabetic rats were treated with chlorpropamide (200 mg/kg, 15 d, by gavage) 8 weeks after STZ injection. Methods: Carrageenan-induced paw edema and pleural exudate volumes were assessed concomitantly with peripheral and exudate leukocyte count. We also evaluated the expression of inducible nitric oxide synthase (iNOS) in lungs of all experimental groups. Results: Chlorpropamide treatment improved glucose tolerance, beta-cell function (assessed by HOMA-beta), corrected paw edema, and pleural exudate volume in n-STZ. Neither leukocyte count nor iNOS expression were affected by diabetes or by chlorpropamide treatment. Conclusion: Chlorpropamide treatment by restoring beta-cell function, reducing blood sugar levels, and improving glucose tolerance might be contributing to the correction of the reduced inflammatory response tested as paw edema and pleural exudate in n-STZ diabetic rats.

Enalapril treatment corrects the reduced response to bradykinin in diabetes increasing the B2 protein expression

Considering the growing importance of the interaction between components of kallikreinkinin and renin-angiotensin systems in physiological and pathological processes, particularly in diabetes mellitus, the aim of the present study was to investigate the effect of enalapril on the reduced response of bradykinin and on the interaction between angiotensin-(1-7) (Ang-(1-7)) and bradykinin (BK), important components of these systems, in an insulin-resistance model of diabetes. For the above purpose, the response of mesenteric arterioles of anesthetized neonatal streptozotocin-induced (n-STZ) diabetic and control rats was evaluated using intravital microscopy. In n-STZ diabetic rats, enalapril treatment restored the reduced response to BK but not the potentiation of BK by Ang-(1-7) present in non-diabetic rats. The restorative effect of enalapril was observed at a dose that did not correct the altered parameters induced by diabetes such as hyperglycernia, glicosuria, insulin resistance but did reduce the high blood pressure levels of n-SZT diabetic rats. There was no difference in mRNA and protein expressions of B1 and B2 kinin receptor subtypes between n-STZ diabetic and control rats. Enalapril treatment increased the B2 kinin receptor expression. From our data, we conclude that in diabetes enalapril corrects the impaired BK response probably by increasing the expression of B2 receptors. The lack of potentiation of BK by Ang-(1-7) is not corrected by this agent. (c) 2008 Elsevier Inc. All rights reserved.

Reduced allergic lung inflammation in rats following formaldehyde exposure: Long-term effects on multiple effector systems

Clinical and experimental evidences show that formaldehyde (FA) exposure has an irritant effect on the upper airways. As being an indoor and outdoor pollutant, FA is known to be a causal factor of occupational asthma. This study aimed to investigate the repercussion of FA exposure on the course of a lung allergic process triggered by an antigen unrelated to FA. For this purpose, male Wistar rats were subjected to FA inhalation for 3 consecutive days (1%, 90-min daily), subsequently sensitized with ovalbumin (OVA)-alum via the intraperitoneal route, and 2 weeks later challenged with aerosolized OVA. The OVA challenge in rats after FA inhalation (FA/OVA group) evoked a low-intensity lung inflammation as indicated by the reduced enumerated number of inflammatory cells in bronchoalveolar lavage as compared to FA-untreated allergic rats (OVA/OVA group). Treatment with FA also reduced the number of bone marrow cells and blood leukocytes in sensitized animals challenged with OVA, which suggests that the effects of FA had not been only localized to the airways. As indicated by passive cutaneous anaphylactic reaction, FA treatment did not impair the anti-OVA IgE synthesis, but reduced the magnitude of OVA challenge-induced mast cell degranulation. Moreover, FA treatment was associated to a diminished lung expression of PECAM-1 (platelet-endothelial cell adhesion molecule 1) in lung endothelial cells after OVA challenge and an exacerbated release of nitrites by BAL-cultured cells. Keeping in mind that rats subjected solely to either FA or OVA challenge were able to significantly increase the cell influx into lung, our study shows that FA inhalation triggers long-lasting effects that affect multiple mediator systems associated to OVA-induced allergic lung such as the reduction of mast cells activation, PECAM-1 expression and exacerbation of NO generation, thereby contributing to the decrease of cell recruitment after the OVA challenge. In conclusion, repeated expositions to air-borne FA may impair the lung cell recruitment after an allergic stimulus, thereby leading to a non-responsive condition against inflammatory stimuli likely those where mast cells are involved. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Exercise training enhances rat pancreatic islets anaplerotic enzymes content despite reduced insulin secretion

Endurance exercise has been shown to reduce pancreatic islets glucose-stimulated insulin secretion (GSIS). Anaplerotic/cataplerotic pathways are directly related to GSIS signaling. However, the effect of endurance training upon pancreatic islets anaplerotic enzymes is still unknown. In this sense, we tested the hypothesis that endurance exercise decreases GSIS by reducing anaplerotic/cataplerotic enzymes content. Male Wistar rats were randomly assigned to one of the four experimental groups as follows: control sedentary group (CTL), trained 1 day per week (TRE1x), trained 3 days per week (TRE3x) and trained 5 days per week (TRE5x) and submitted to an 8 weeks endurance-training protocol. After the training protocol, pancreatic islets were isolated and incubated with basal (2.8 mM) and stimulating (16.7 mM) glucose concentrations for GSIS measurement by radioimmunoassay. In addition, pyruvate carboxylase (PYC), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), ATP-citrate lyase (ACL) and glutamate dehydrogenase (GDH) content were quantified by western blotting. Our data showed that 8 weeks of chronic endurance exercise reduced GSIS by 50% in a dose-response manner according to weekly exercise frequency. PYC showed significant twofold increase in TRE3x. PYC enhancement was even higher in TRE5x (p < 0.0001). PDH and PDK4 reached significant 25 and 50% enhancement, respectively compared with CTL. ACL and GDH also reported significant 50 and 75% increase, respectively. The absence of exercise-induced correlations among GSIS and anaplerotic/cataplerotic enzymes suggests that exercise may control insulin release by activating other signaling pathways. The observed anaplerotic and cataplerotic enzymes enhancement might be related to beta-cell surviving rather than insulin secretion.

Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3 expression in patients with Common Variable Immunodeficiency: A link to autoimmunity?

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease characterized by defective immunoglobulin production and often associated with autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T regulatory (Treg) cells and ask whether perturbations in their frequency in peripheral blood could underlie the high incidence of autoimmune disorders in CVID patients. In this study, we report for the first time that CVID patients with autoimmune disease have a significantly reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a decreased intensity of FOXP3 expression. Notably, although CVID patients in whom autoimmunity was not diagnosed had a reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those in healthy controls. In conclusion, these data suggest compromised homeostasis of CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity, and may implicate Treg cells in pathological mechanisms of CVID. (C) 2009 Elsevier Inc. All rights reserved.

Reduced gradient method combined with augmented Lagrangian and barrier for the optimal power flow problem

A new approach for solving the optimal power flow (OPF) problem is established by combining the reduced gradient method and the augmented Lagrangian method with barriers and exploring specific characteristics of the relations between the variables of the OPF problem. Computer simulations on IEEE 14-bus and IEEE 30-bus test systems illustrate the method. (c) 2007 Elsevier Inc. All rights reserved.

Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome

Purpose Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients and Methods We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS). Results Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and >= 65 years had 2-year survival rates as follows: 44% (95% Cl, 37% to 52%), 50% (95% Cl, 41% to 59%), 34% (95% Cl, 25% to 43%), and 36% (95% Cl, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% Cl, 35% to 49%), 35% (95% Cl, 27% to 43%), 45% (95% Cl, 36% to 54%), and 38% (95% Cl, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P>.3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. Conclusion With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.

WHICH TOPOLOGIES HAVE IMMEDIATE PREDECESSORS IN THE POSET OF HAUSDORFF TOPOLOGIES?

We study which topology have an immediate predecessor in the poset of Sigma(2) of Hausdorff topologies on set X. We show that certain classes of H-closed topologies, do have predecessors. and we give examples of second countable H-closed topologies which are not upper Sigma(2.)

REALIZING PROFINITE REDUCED SPECIAL GROUPS

Special groups are an axiomatization of the algebraic theory of quadratic forms over fields. It is known that any finite reduced special group is the special group of some field. We show that any special group that is the projective limit of a projective system of finite reduced special groups is also the special group of some field.

NATURAL TOPOLOGIES ON COLOMBEAU ALGEBRAS

We define intrinsic, natural and metrizable topologies T(Omega), T, T(s,Omega) and T(s) in G(Omega), (K) over bar, G(s)(Omega) and (K) over bar (s) respectively. The topology T(Omega) induces T, T(s,Omega) and T(s). The topologies T(s,Omega) and T(s) coincide with the Scarpalezos sharp topologies.

Determination of catechins in green tea infusions by reduced flow micellar electrokinetic chromatography

A sulfated-beta-cyclodextrin (s-beta-CD) modified reduced flow micellar electrokinetic chromatography (RF-MEKC) method was developed and validated for the determination of catechins in green tea. The optimal electrolyte consisted of 0.2% triethylamine, 50 mmol/L SDS and 0.8% s-beta-CD (pH = 2.9), allowing baseline separation of five catechins in 4 min. The samples and standards were injected at 0.6 psi for 5 s under constant voltage of -30 kV. Sample preparation simply involved extraction of 2 g of tea with 200 mL water at 95 C under constant stirring for 5 min. The method demonstrated excellent performance, with limits of detection (LOD) and quantification (LOQ) of 0.02-0.1 and 0.1-0.5 mu g/mL, respectively, and recovery percentages of 94-101%. The method was applied to six samples of Brazilian green tea infusions. Epigallocatechin gallate (23.4-112.4 mu g/mL) was the major component, followed by epigallocatechin (18.4-78.9 mu g/mL), epicatechin gallate (5.6-29.6 mu g/mL), epicatechin (4.6-14.5 mu g/mL) and catechin (3.2-8.2 mu g/mL). (C) 2011 Elsevier Ltd. All rights reserved.

Carbohydrate metabolism during exercise in females : effect of reduced fat availability

This study examined the effect of reduced plasma free fatty acid (FFA) availability on carbohydrate metabolism during exercise. Six untrained women cycled for 60 minutes at approximately 58% of maximum oxygen uptake after ingestion of a placebo (CON) or nicotinic acid (NA), 30 minutes before exercise (7.4 ± 0.5 mg·kg⁻¹ body weight), and at 0 minutes (3.7 ± 0.3 mg·kg⁻¹) and 30 minutes (3.7 ± 0.3 mg·kg⁻¹) of exercise. Glucose kinetics were measured using a primed, continuous infusion of [6,6-²H] glucose. Plasma FFA (CON, 0.86 ± 0.12; NA, 0.21 ± 0.11 mmol·L⁻¹ at 60 minutes, P < .05) and glycerol (CON, 0.34 ± 0.05; NA, 0.10 ± 0.04 mmol·L⁻¹ at 60 minutes, P < .05) were suppressed throughout exercise. Mean respiratory exchange ratio (RER) during exercise was higher (P < .05) in NA (0.89 ± 0.02) than CON (0.83 ± 0.02). Plasma glucose and glucose production were similar between trials. Total glucose uptake during exercise was greater (P < .05) in NA (1,876 ± 161 μmol·kg⁻¹) than in CON (1,525 ± 107 μmol·kg⁻¹). Total fat oxidation was reduced (P < .05) by approximately 32% during exercise in NA. Total carbohydrate oxidized was approximately 42% greater (P < .05) in NA (412 ± 40 mmol) than CON (290 ± 37 mmol), of which, approximately 16% (20 ± 10 mmol) could be attributed to glucose. Plasma insulin and glucagon were similar between trials. Catecholamines were higher (P < .05) during exercise in NA. In summary, during prolonged moderate exercise in untrained women, reduced FFA availability results in a compensatory increase in carbohydrate oxidation, which appears to be due predominantly to an increase in glycogen utilization, although there was a small, but significant, increase in whole body glucose uptake.

Reduced-order output feedback controllers for discrete-time systems

This article considers the stabilization by output feedback controllers for discrete-time systems. The controller can place all of the closed-loop poles within a specified disk D(-α, 1/β), centred at (-α,0) with radius 1/β, where | - α|  + 1/β < 1. The design method involves the decomposition of the system into two portions. The first portion comprises of all of the poles that are lying outside of the specified disk. A reduced-order model is constructed for this portion. The second portion comprises of all of the remaining poles of the system and is characterized by an H_∞-norm bound. The controller design is then accomplished by using H_∞-control theory. It is shown that, subject to the solvability of an algebraic Riccati equation, output feedback controllers can be systematically derived. The order of the controller is low, and can be as low as the number of the open-loop poles that are lying outside of the specified disk. A step-by-step design algorithm is provided. Numerical examples are given to illustrate the attractiveness of the design method.

Analysis of zinc transporter, hZnT4(Slc30A4), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk

Zinc deficiency, causing impaired growth and development, may have a nutritional or genetic basis. We investigated two cases of inherited zinc deficiency found in breast-fed neonates, caused by low levels of zinc in the maternal milk. This condition is different from acrodermatitis enteropathica but has similarities to the "lethal milk" mouse, where low levels of zinc in the milk of lactating dams leads to zinc deficiency in pups. The mouse disorder has been attributed to a defect in the ZnT4 gene. Little is known about the expression of the human orthologue, hZnT4 (Slc30A4). Sequence analysis of cDNA, real-time PCR and Western blot analysis of hZnT4, carried out on control cells and cells from unrelated mothers of two infants with zinc deficiency, showed no differences. The hZnT4 gene was highly expressed in mouthwash buccal cells compared with lymphoblasts and fibroblasts. The hZnT4 protein did not co-localise with intracellular free zinc pools, suggesting that hZnT4 is not involved in transport of zinc into vesicles destined for secretion into milk. This observation, combined with phenotypic differences between the "lethal milk" mouse and the human disorder, suggests that the "lethal milk" mouse is not the corresponding model for the human zinc deficiency condition.