We tested if ex vivo delivery of carbon monoxide (CO) to the kidney would ameliorate the renal injury of cold storage that can complicate renal transplantation. Orthotopic syngeneic kidney transplantation was performed in Lewis rats following 24 h

of cold preservation in University of Wisconsin Selleck OTX015 solution equilibrated without or with CO (soluble CO levels about 40 mu M). Ischemia/reperfusion injury in control grafts resulted in an early upregulation of inflammatory mediator mRNAs and progressive deterioration of graft function. In contrast, the grafts preserved with CO had significantly less oxidative injury and this was associated with improved recipient survival compared to the control group. Renal injury in the control group showed considerable degradation of cytochrome P450 heme proteins, active heme metabolism and increased detrimental intracellular free heme levels. Kidney grafts preserved in CO-equilibrated solution maintained their cytochrome P450 protein levels, had normal intracellular heme levels and had less lipid peroxidation. Our results show that CO-mediated suppression of click here injurious heme-derived redox reactions offers protection of kidney grafts from cold ischemia/reperfusion injury.”
“Using drugs acting on nicotinic acetylcholine receptors (nAChRs), we examined temporal-parietal and frontal cortex, hippocampus, and cerebellum to identify sites of cognition enhancement in 4- and 27-month rabbits.

First, we compared radioligand receptor binding for neuronal alpha beta heteromeric nAChRs ([(3)H] epibatidine) and alpha(7) homomeric nAChRs ([(3)H] methyllycaconitine) in rabbits and rats. In cerebellum, nAChR levels of both species are low, about at the detection limit of the radioligand binding assays. Next, we compared nAChRs in 4- and Cell press 27-month vehicle-treated rabbits trained in delay eyeblink conditioning. Older rabbits conditioned more poorly and had lower alpha beta heteromeric nAChR binding in hippocampus than young rabbits. For cognition enhancement, galantamine ( mild cholinesterase inhibitor and allosteric modulator of nAChRs) or MEM-3389 (alpha 7nAChR agonist formerly identified as AR-R 17779) was injected before

conditioning. Drugs improved learning in both age groups. In 27-month rabbits, drugs increased expression of frontal and temporal-parietal alpha beta heteromeric nAChRs and hippocampal alpha beta and alpha 7nAChRs. In 4-month rabbits, drugs increased expression of alpha 7 homomeric nAChRs in frontal and temporal-parietal cortex and hippocampus, but increased expression of alpha beta heteromeric nAChRs only occurred in temporal- parietal cortex. Increased expression of alpha beta nAChRs was more extensive in older drug-treated rabbits, whereas increased expression of alpha 7nAChRs was more prevalent in younger drug-treated rabbits, suggesting different substrates for amelioration (27-month rabbits) vs facilitation (4-month rabbits) of learning.

05) in vitro, and the expression of Endo G mRNA in the hypoxic groups was significantly higher than that in the control groups both in vitro and in vivo (P<0.05). VM and LPPCN cell numbers in the ischemic group were higher than those in the control group in the early stage of tumor AG-120 mw growth. Finally, the survival time for patients whose samples showed LPPCN and VM was significantly shorter

than that of patients with one or neither of those factors. We speculated that under hypoxic conditions, some melanoma cells might undergo LPPCN, thus providing a spatial foundation for VM channel formation.”
“Ependymal cells form the walls of the ventricles, and take part in the production of cerebrospinal fluid (CSF). Aquaporin-4 (AQP4), a predominant water channel of the brain, is restricted to basolateral plasma membranes of ependymal cells. The highly polarized expression

of AQP4 suggests it may be SC75741 involved in maintaining the structural and functional integrity of the ependyma. This hypothesis was validated by using adult AQP4 knockout mice generated by our laboratory [Fan Y, Zhang J, Sun XL, Gao L, Zeng XN, Ding JH, Cao C, Niu L, Hu G (2005) Sex- and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout mice. J Neurosci Res 82:458-464]. Histological analysis showed disorganized ependymal layer of the learn more lateral ventricle and aqueduct in AQP4-deficiency mice. A majority (92.7%) of null mice displayed reduced lateral ventricular volume, while a small fraction (7.3%) had enlarged or normal ventricular size with a narrow aqueduct.

Immunohistochemistry demonstrated that AQP4 deletion resulted in decreased expression of gap junction protein connexin43 in the ependymal cells. Electron microscopy confirmed junctional complex absence at basolateral membranes of ependynnocytes. Moreover, AQP4 knockout mice showed decreased CSF production and increased brain water content compared with wild-type mice. These results highlight a key role of AQP4 in maintaining the structure and function of the ependyma. In addition, variable profiles of ventricle system in adult AQP4 null mice indicate functional AQP4 polymorphisms. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Solid tumors contain regions of poor oxygenation that relate to the abnormal vascular network. Clinical investigations in cervical carcinoma have shown that positive lymph node status in patients with cervical carcinoma correlates with hypoxia. Earlier, in an orthotopic cervical cancer model, we had shown that exposure to acute hypoxia enhances lymph node metastasis. This study describes a technique for sorting hypoxic cells directly from the cervical xenograft model and reports the expression of ‘metastasis-related’ genes in hypoxic cells from xenografted cervix and lymph node tumors.

Each participant received 160 perturbations, 25% of which were combined

with a SAS. We varied the direction and magnitude of the perturbations, as well as the prior knowledge of perturbation direction. Perturbation trials were interspersed with SAS-only trials. The SAS accelerated and strengthened postural responses with clear functional benefits (better balance control), but this was only true for responses that protected against falling backwards (i.e. in tibialis anterior and rectus femoris). These muscles also demonstrated RAD001 clinical trial the most common SAS-triggered responses without perturbation. Increasing the perturbation magnitude accelerated postural responses, but again with a larger acceleration for backward perturbations. We conclude that postural responses selleck products to backward and forward perturbations may be processed by different neural circuits, with influence of startle pathways on postural responses to

backward perturbations. These findings give directions for future studies investigating whether deficits in startle pathways may explain the prominent backward instability seen in patients with Parkinson’s disease and progressive supranuclear palsy. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Patients affected by panic disorder with agoraphobia (PDA) often suffer from visuo-spatial disturbances. In the present study, we tested the place-learning abilities in a sample of 31 PDA patients compared to 31 healthy controls (CTR) using the computer-generated AZD3965 chemical structure arena (C-G Arena), a desktop-based computer program developed at the University of Arizona (Jacobs et al 1997, for further detail about the program, see http://web.arizona.edu/similar to arg/data.html). Subjects were asked to search the computer-generated space, over several

trials, for the location of a hidden target. Results showed that control subjects rapidly learned to locate the invisible target and consistently returned to it, while PDA patients were divided in two subgroups: some of them (PDA-A) were as good as controls in place learning, while some others (PDA-B) were unable to learn the correct strategies to find the target. Further analyses revealed that PDA-A patients were significantly younger and affected by panic disorder from less time than PDA-B, indicating that age and duration of illness can be critical factors that influence the place-learning abilities.

Our results show that VHSV infection induced caspases 3, 8 and 9 in

cell culture.”
“Lipotoxicity occurs as a consequence of chronic exposure of non-adipose tissue and cells to elevated concentrations of fatty acids, triglycerides and/or cholesterol. The contribution of mitochondria to lipotoxic cell dysfunction, damage and death is associated with elevated production of reactive oxygen species and initiation of apoptosis. Although there is a broad consensus on the involvement of these phenomena with lipotoxicity, the molecular mechanisms that initiate, mediate and trigger mitochondrial dysfunction in response to substrate overload remain unclear. Here, we focus on protein phosphorylation as an important phenomenon in lipotoxicity that harms mitochondria-related signal transduction and integration in cellular metabolism. Moreover, the degradation of mitochondria by mitophagy is discussed as an important landmark that leads to cellular apoptosis Selinexor datasheet in lipotoxicity.”
“The rat vas deferens has scattered sensory afferens plus a dense network of sympathetic motor efferens; these fibers are not known to interact functionally. We ascertained whether sensory fibers modulate the release of sympathetic transmitters through the release of calcitonin generelated peptide (CGRP) and reciprocally

assessed whether sympathetic transmitters modulate the overflow of ir-CGRP from sensory fibers. The tissue overflow of electrically evoked sympathetic co-transmitters (ATP/metabolites, BMS-777607 noradrenaline (NA), and immunoreactive neuropeptide tyrosine (ir-NPY)) PF299804 mouse and the motor responses elicited were quantified following either exogenous CGRP or capsaicin

application to elicit peptide release. Conversely, the outflow of ir-CGRP was examined in the presence of sympathetic transmitters. Exogenous CGRP reduced in a concentration-dependent manner the electrically evoked outflow of ATP/metabolites, NA, and ir-NPY with EC50 values of 1.3, 0.18, and 1.9 nM, respectively. CGRP also reduced the basal NA overflow. The CGRP-evoked modulation was blocked by CGRP8-37 or H-89. Release of endogenous CGRP by capsaicin significantly reduced the basal overflow of NA, ir-NPY, and the electrically evoked sympathetic transmitter release. ADP, 2-methylthioadenosine-5′-O-diphosphate (2-MeSADP), or UTP decreased the electrically evoked ir-CGRP overflow, whereas clonidine, a,beta-methyleneadenosine 5′-triphosphate (alpha,beta-mATP), or adenosine (ADO) were inactive. CGRP acting postjunctionally also reduced the motor responses elicited by exogenous NA, ATP, or electrically evoked contractions. We conclude that CGRP exerts a presynaptic modulator role on sympathetic nerve endings and reciprocally ATP or related nucleotides influence the release of ir-CGRP from sensory fibers, highlighting a dynamic sympatho-sensory control between sensory fibers and sympathetic nerve ending.

Potential Sonidegib mw sources of p-cresol excess in ASD, such as gut infection, chronic constipation, antibiotics, abnormal intestinal permeability, and environmental exposure, are being investigated. P-cresol may contribute to worsen autism severity and gut dysfunction, often present in autistic children. It may also contribute to

a multibiomarker diagnostic panel useful in small autistic children. (C) 2012 Elsevier Inc. All rights reserved.”
“Human papillomavirus genotyping is being considered in cervical screening programs and for monitoring the effectiveness of HPV vaccination. Both approaches require access to fast, easy and high-throughput technology. The aim of this study was to compare a new commercial assay (f-HPV typing (TM)) with the Hybrid Capture II (R) (HC2) to detect HPV infection. The F-HPV typing is a multiplex fluorescent PCR method recognizing E6 and E7 regions of 13 high-risk (HR) HPV types, the same set of HR-types targeted HC2 test. A subset of 157 cervical samples was tested with both assays. The percentage of positive HR-HPV DNA samples was 24% (37/155) by HC2 and 33% (49/155) by f-HPV typing. Concordant results were found in 133/155 (overall agreement, 85.8%; Cohen’s kappa = 0.65). The analytical sensitivity and specificity of f-HPV were 97.6 and 93, respectively.

Repotrectinib price In conclusion, this study shows that the f-HPV assay provides a good alternative to HC2 to detect HPV infection, allowing simple and rapid HPV genotyping and detecting

multiple infections. (C) 2012 Elsevier B.V. All rights reserved.”
“Progression to metastasis is the critical point in colorectal cancer (CRC) survival. However, the proteome associated to CRC metastasis is very poorly understood at the moment. In this study, we used stable isotope labeling by amino acids in cell culture to compare two CRC cell lines: KM12C and KM12SM, representing poorly versus highly metastatic potential, to find and quantify the differences in protein expression, mostly at the cell surface level. After biotinylation followed by affinity purification, membrane proteins were separated by SDS-PAGE and analyzed using nanoflow LC-ESI-LTQ. A total of 291 membrane and membrane-associated proteins were identified with a p value<0.01, selleck inhibitor from which 60 proteins were found to be differentially expressed by more than 1.5-fold. We identified a number of cell signaling, CDs, integrins and other cell adhesion molecules (cadherin 17, junction plakoglobin (JUP)) among the most deregulated proteins. They were validated by Western blot, confocal microscopy and flow cytometry analysis. Immunohistochemical analysis of paired tumoral samples confirmed that these differentially expressed proteins were also altered in human tumoral tissues. A good correlation with a major abundance in late tumor stages was observed for JUP and 17-beta-hydroxysteroid dehydrogenase type 8 (HSD17B8).

We then show that a similar pattern of deficits is observable in his PS-341 mouse ability to negotiate between non-targets: that is, M.H. selectively fails to take account of obstacles in his right visual field, but only

while reaching with his right hand. Finally we demonstrate that this obstacle avoidance deficit disappears following a 5 s delay in response: under these conditions M.H. now takes account of both non-target objects with either hand. The results are interpreted within the ‘two visual streams’ model of cortical visual processing. (C) 2008 Elsevier Ltd. All rights reserved.”
“w Background/Aims: The serum- and glucocorticoid-inducible kinase SGK1 was originally cloned as a glucocorticoid-regulated gene and later as a transcriptional target for mineralocorticoids. SGK1 regulates

channels and transporters including the renal Na(+) channel ENaC. It contributes to mineralocorticoid regulation of renal Na(+) excretion and salt appetite. The present study explored the contribution Evofosfamide mouse of SGK1 to effects of glucocorticoids on mineral and electrolyte metabolism. Methods: SGK1-knockout mice (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)) were analyzed in metabolic cages with or without treatment for 14 days with dexamethasone (3 mg/kg b.w., i.p.). Blood pressure was determined by the tail-cuff method. Results: Prior to treatment fluid intake, urinary flow rate, urinary Na(+), K(+), phosphate and Cl(-) excretion, plasma electrolyte and glucose concentrations as well as blood pressure were similar in sgk1(-/-) and sgk1(+/+) mice. selleck compound Dexamethasone did not significantly alter renal Na(+), K(+), Cl and Ca(2+) excretion but decreased plasma Ca(2+) and phosphate concentration in sgk1(+/+) mice. The effect

on Ca(2+) was significantly augmented and the effect on phosphate significantly blunted in sgk1(-/-) mice. Dexamethasone significantly increased fasting blood glucose concentrations in both genotypes. Dexamethasone increased blood pressure in sgk1(+/+) mice, an effect significantly blunted in sgk1(-/-) mice. Conclusions: The present observations disclose SGK1-sensitive glucocorticoid effects on calcium-phosphate metabolism and blood pressure. Copyright (C) 2008 S. Karger AG, Basel.”
“In an early description of the mu rhythm, Gastaut and Bert [Gastaut, H. J., & Bert, J. (1954). EEG changes during cinematographic presentation. Clinical Neurophysiology, 6, 433-444] noted that it was blocked when an individual identified himself with an active person on the screen, suggesting that it may be modulated by the degree to which the individual can relate to the observed action. Additionally, multiple recent studies suggest that the mirror neurons system (MNS) is impaired in individuals with autism spectrum disorders (ASD), which may affect their ability to relate to others. The current study aimed to investigate MNS sensitivity by examining mu suppression to familiarity, i.e.

Our recent study

shows that endogenous nitric oxide (NO) contributes to chronic mild stress (CMS)-induced depression by suppressing hippocampal neurogenesis.

Objectives The aim of this study was to investigate the effects of exogenous NO in CMS-induced depression in young adult mice.

Results In normal mice, administration of a pure NO donor (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) aminio] diazen-1-ium-1,2-diolate (DETA/NONOate; 0.4 mg/kg, i.p., for 7 days) produced an antidepressant-like effect and significantly increased hippocampal neurogenesis. Ralimetinib in vitro The mice exposed to CMS exhibited behavioral changes typical of depression and impaired neurogenesis in the hippocampus. Treatment with DETA/NONOate (0.4 mg/kg, i.p., for 7 days) reversed CMS-induced behavioral despair and hippocampal neurogenesis impairment. We treated mice with a telomerase inhibitor 3′-azido-deoxythymidine (AZT; 100 mg/kg, i.p., for 14 days) to disrupt Blasticidin S cell line neurogenesis. From day

4 to day 11 of AZT treatment, mice were injected with DETA/NONOate (0.4 mg/kg, i.p., for 7 days). Disrupting hippocampal neurogenesis blocked the antidepressant effect of DETA/NONOate.

Conclusions Our findings suggest that exogenous NO benefits chronic stress-induced depression by stimulating hippocampal neurogenesis and may represent a novel approach for the treatment of depressive disorders.”
“Much has been published on the application of genetically modified (GM) crops in Africa, but agricultural performance has hardly been addressed. This paper discusses the main consequences of GM crops on agricultural performance in Ethiopia. Three main

criteria of performance productivity, equitability and sustainability are evaluated in the context of the Ethiopian agricultural sector. We conclude that the application of GM crops can improve the agricultural productivity and sustainability, whereas equitability cannot be stimulated and might even exacerbate the gap between socioeconomic classes. Before introducing GM crops to Ethiopian agriculture, regulatory issues should be addressed, public research should be fostered, and more ex ante values Selleckchem KU55933 and socioeconomic studies should be included.”
“Rationale Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats.

Objectives As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT(-/-)), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT(+/+)) and heterozygous (SERT(+/-)) rats.

32-3.3) and 1.32 (1.07-1.65) at Lag1 PM2.5 and PM10, respectively. The interactions between current smoking and acute exposures (Lag0; Lag1; Lag2) were significant in relationship to VE. Acute exposures were not significantly associated with supraventricular SN-38 mouse ectopy (SVE), or with VE among nonsmokers. Subacute (Lag1-30) exposures were not

significantly associated with arrhythmia. Acute PM2.5 and PM10 exposure is directly associated with the odds of VE among smokers, suggesting that they are more vulnerable to the arrhythmogenic effects of PM.”
“We have recently characterized a form of ex vivo depotentiation (depotentiation(ex vivo)), which correlates tightly with fear extinction, at thalamic input synapses onto the lateral amygdala. Here, we examined the effects of learning-attenuating drugs, reported to impair fear extinction when microinjected into the learn more basolateral amygdala, on depotentiatione(ex vivo). U0126, a mitogen-activated protein kinase inhibitor, and cycloheximide,

a protein synthesis inhibitor, blocked depotentiation(ex vivo). However, ifenprodil, an NIR2B-containing NMDA receptor inhibitor, did not alter depotentiation(ex vivo), although it blocked amygdala long-term potentiation. These findings indicate that amygdala depotentiation shares some molecular processes with learning and further suggest that different forms of synaptic plasticity in the basolateral amygdala mediate fear extinction. NeuroReport 20:517-520 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Responses of patients with persistent asthma to ambient air pollution may be different OSI-744 from those of general populations. For example, asthma medications may modify the effects of ambient air pollutants on peak expiratory flow (PEF). Few studies examined the association between air pollution and PEF in patients

with persistent asthma on well-defined medication regimens using asthma clinical trial data. Airway obstruction effects of ambient air pollutants, using 14,919 person-days of daily self-measured peak expiratory flow (PEF), were assessed from 154 patients with persistent asthma during the 16 wk of active treatment in the Salmeterol Off Corticosteroids Study trial. The three therapies were an inhaled corticosteroid, an inhaled long-acting -agonist, and placebo. The participants were nonsmokers aged 12 through 63 yr, recruited from 6 university-based ambulatory care centers from February 1997 to January 1999. Air pollution data were derived from the U.S. Environmental Protection Agency Aerometric Information Retrieval System. An increase of 10 ppb of ambient daily mean concentrations of NO2 was associated with a decrease in PEF of 1.53 L/min (95% confidence interval [CI] -2.93 to -0.

c.)] were evaluated in an open-field test and testing of the prepulse inhibition of acoustic startle reaction (PPI) 15 and 60 min after drug administration. The time disposition of mescaline 20 mg/kg s.c. in rat serum and brain homogenates was analyzed by gas chromatography-mass spectrometry.

Results Mescaline produced significant Anlotinib nmr inhibitory effects on locomotion in low doses and a biphasic effect with the highest dose. In the PPI test, only when tested

60 min after drug administration, all doses of mescaline disrupted PPI. Besides the experimental protocol, we have observed that approximately 50% of animals receiving 100 mg/kg died within 12 h post-injection. The serum levels of mescaline rapidly increased within 30 min and subsequently quickly decreased; however, the brain concentrations reached a maximum 1 h after administration and remained high for an additional 60 min.

Conclusions Mescaline had a delayed onset of the main behavioral changes in rats compared to other hallucinogens. Behavioral changes correlated with the pharmacokinetics of the drug.”
“Purpose: Radiological imaging is the mainstay of

diagnosing ureteropelvic junction obstruction. Current established radiological modalities can potentially differentiate check details the varying degrees of obstruction but they are limited in functionality, applicability and/or comprehensiveness. Of particular concern is that some tests require radiation, which has long-term consequences, especially in children.

Materials and Methods: learn more We investigated the novel use of Genhance (TM) 680 dynamic fluorescence imaging to assess ureteropelvic junction obstruction in 20 mice that underwent partial or complete unilateral ureteral obstruction. Ultrasound, mercaptoacetyltriglycine

renography, magnetic resonance imaging and fluorescence imaging were performed.

Results: Our model of partial and complete obstruction could be distinguished by ultrasound, mercaptoacetyltriglycine renography and magnetic resonance imaging, and was confirmed by histological analysis. Using fluorescence imaging distinct vascular and urinary parameters were identified in the partial and complete obstruction groups compared to controls.

Conclusions: Fluorescence imaging is a feasible alternative radiological imaging modality to diagnose ureteropelvic junction obstruction. It provides continuous, detailed imaging without the risk of radiation exposure.”
“Multifunctional agents with limited motor resources must decide what actions will best ensure their survival. Moreover, given that in an unpredictable world things don’t always work out, considerable advantage is to be gained by learning from experience – instrumental behaviour that maximises reward and minimises punishment.

Kidney International (2012) 82, 100-105; doi:10.1038/ki.2012.77; published online 28 March 2012″
“It is generally believed that the development of neuropathic pain primarily results from injuries to sensory afferent fibers. Recent studies found that injuries to the motor efferent fibers (e. g. ventral root transection) also contribute to the development of neuropathic pain. click here Furthermore, an increase in brain-derived neurotrophic factor (BDNF) synthesis has been found in the ventral root transection model, suggesting a possible role of BDNF in this model. To determine

the role of BDNF, we observed the effects of intrathecal antibody against BDNF treatment on ventral root transection-induced mechanical hyperalgesia. Paw withdrawal thresholds to mechanical stimuli were measured before and after surgery. The results showed that ventral root transection in rats produced a significant, lasting decrease of mechanical withdrawal thresholds, presenting the development of mechanical hyperalgesia. Intrathecal antibody against BDNF treatment markedly inhibited ventral root transection-induced

mechanical hyperalgesia in a dose-related manner. The findings suggest that BDNF-mediated signaling pathway within spinal cord may be involved in the development of neuropathic pain involving injuries to motor efferent fibers. NeuroReport 24:167-170 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. NeuroReport 2013, 24: 167-170″
“Objective: Despite clozapine’s unique effectiveness BIBW2992 in patients with schizophrenia, a number of adverse effects have been recognised including abnormalities in lipid and glucose metabolisms. A high clozapine level in red blood cells (RBCs) and disturbed anti-oxidant enzyme activities in blood from schizophrenic patients prompted check details us to investigate lipid status and anti-oxidant enzyme defence in the blood of chronic schizophrenic patients on long-term clozapine therapy.

Methods: Plasma lipids,

RBC anti-oxidant enzyme activities and haemoglobin (Hb) content were measured using established procedures in a group of eighteen chronically-medicated (average 630 days of therapy) schizophrenic patients receiving clozapine (average dose of 295 mg/day) and data were compared with those from a group of eighteen well-matched normal controls.

Results: Significantly higher levels of plasma triglycerides (by 47%, p<0.01) and total cholesterol and phospholipids (by 8% and 11%, respectively p<0.05) in patients were found. CuZn-superoxide dismutase (SOD1) activity was markedly higher (by 35%, p<0.001) while selenium-dependent glutathione peroxidase (GSH-Px1) activity was markedly lower (by 41%, p<0.001) in patients. In addition, metHb and HbA1c levels in patients were significantly higher (by 58% and 25%. respectively p<0.