(C) 2011 Elsevier Ltd All rights reserved “
“Objectives: Ou

(C) 2011 Elsevier Ltd. All rights reserved.”
“Objectives: Our objectives were (1) to determine whether elevated Mg(2+) in controlled hyperkalemic reperfusate without intervention during ischemia protects the juvenile heart against reperfusion injury; and (2) to identify the mechanism(s) underlying any protective effect of Mg(2+).

Methods: Langendorff-perfused

hearts from juvenile (11- to 14-day-old) guinea pigs were subjected to mild (30-minute) or severe (45-minute) learn more normothermic global ischemia and 35-minute reperfusion. Hearts were subjected to controlled hyperkalemic reperfusion without or with various concentrations of Mg(2+) (5, 10, 16, 23 mM). The mechanisms underlying the effect of Mg(2+) on intracellular Ca(2+) ([Ca(2+)] i) were also studied in isolated cardiomyocytes exposed to metabolic inhibition followed by washout using hyperkalemic solutions (reperfusion).

Results: Sixteen mM Mg(2+) conferred maximal cardioprotection as assessed by improved functional recovery and reduced cardiac injury; this was associated with a significant recovery of cardiac energetics and metabolism following both mild and severe ischemia. The Mg(2+)-induced protection was additive to that of hyperkalemia following mild ischemia and conferred protection following severe

ischemia when hyperkalemia alone had no significant effect. Elevated Mg(2+) in the hyperkalemic reperfusate of cardiomyocytes acutely prevented [Ca(2+)] i loading following mild metabolic inhibition and augmented the fall in [Ca(2+)] i following severe metabolic inhibition.

Conclusions: This work demonstrates for selleck compound the first time in juvenile hearts that elevated Mg(2+) during controlled hyperkalemic reperfusion rescues the heart following ischemia, and that this is likely to be facilitated

by reducing [Ca(2+)] i which, in turn, would aid metabolic recovery. (J Thorac Cardiovasc /www.selleck.co.jp/products/MG132.html Surg 2011;141:1529-37)”
“The present report describes a case of a 33-year old male patient with homozygous sickle cell disease (SCD) with comorbid psychotic symptoms. The systematical evaluation revealed an intimate association between acute SCD complications, associated with hematological abnormalities, and psychotic symptoms worsening. Clozapine was effective in controlling psychotic symptoms refractory to previous antipsychotic trials. (c) 2007 Elsevier Inc. All rights reserved.”
“Melatonin, a ubiquitous methoxyindole, is produced by and metabolized in the skin. Melatonin affects skin functions and structures through actions mediated by cell-surface and putative-nuclear receptors expressed in skin cells. Melatonin has both receptor-dependent and receptor-independent effects that protect against oxidative stress and can attenuate ultraviolet radiation-induced damage. The widespread expression and pleiotropic activity of the cutaneous melatoninergic system provides for a high level of cell-specific selectivity.

(C) 2009 Elsevier Ltd All rights reserved “
“Kaposi’s sarco

(C) 2009 Elsevier Ltd. All rights reserved.”
“Kaposi’s sarcoma-associated herpesvirus (KSHV) utilizes clathrin-mediated endocytosis for selleck its infectious entry into human foreskin fibroblast (HFF) cells (S. M. Akula, P. P. Naranatt, N.-S. Walia, F.-Z. Wang, B. Fegley, and B. Chandran, J. Virol. 77: 7978-7990, 2003). Here,

we characterized KSHV entry into primary human microvascular dermal endothelial (HMVEC-d) and human umbilical vein endothelial (HUVEC) cells. Similar to the results for HMVEC-d cells, KSHV infection of HUVEC cells also resulted in an initial high level and subsequent decline in the expression of the lytic switch gene, ORF50, while latent gene expression persisted. Internalized virus particles enclosed in irregular vesicles were observed by electron microscopy of infected HMVEC-d cells. At an early time of infection, colocalization of KSHV capsid with envelope was observed by immunofluorescence analysis, thus demonstrating endocytosis of intact enveloped virus

particles. Chlorpromazine, an inhibitor of clathrin-mediated endocytosis, and filipin (C(35)H(58)O(11)), a caveolar endocytosis inhibitor, did not have any effect on KSHV binding, entry (DNA internalization), or gene expression in HMVEC-d and HUVEC cells. In contrast to the results for HFF cells, virus entry and gene expression in both types of endothelial cells were significantly

blocked by macropinocytosis inhibitors (EIPA [5-N-ethyl-N-isoproamiloride] mTOR inhibitor and rottlerin [C(30)H(28)O(8)]) and by cytochalasin D, which affects actin polymerization. Inhibition of selleck compound lipid raft blocked viral gene expression in HMVEC-d cells but not in HUVEC or HFF cells. In HMVEC-d and HUVEC cells, KSHV induced the actin polymerization and formation of lamellipodial extensions that are essential for macropinocytosis. Inhibition of macropinocytosis resulted in the distribution of viral capsids at the HMVEC-d cell periphery, and capsids did not associate with microtubules involved in the nuclear delivery of viral DNA. Internalized KSHV in HMVEC-d and HUVEC cells colocalized with the macropinocytosis marker dextran and not with the clathrin pathway marker transferrin or with caveolin. Dynasore, an inhibitor of dynamin, did not block viral entry into endothelial cells but did inhibit entry into HFF cells. KSHV was not associated with the early endosome marker EEA-1 in HMVEC-d cells, but rather with the late endosome marker LAMP1, as well as with Rab34 GTPase that is known to regulate macropinocytosis. Silencing Rab34 with small interfering RNA dramatically inhibited KSHV gene expression. Bafilomycin-mediated disruption of endosomal acidification inhibited viral gene expression.

Urologists can use this nomogram to better inform patients of the

Urologists can use this nomogram to better inform patients of the potential need for epididymovasostomy and whether specialist referral is needed.”
“The neuregulin 1 (NRG1) receptor ErbB4 is involved in the development of cortical inhibitory GABAergic circuits and NRG1-ErbB4 signaling has been implicated in schizophrenia (SCZ). A magnetic resonance spectroscopy (H-1-MRS) study has demonstrated that a single-nucleotide polymorphism in ERBB4, rs7598440, influences human cortical GABA concentrations. Other work has highlighted the significant impact of this genetic variant on

expression of ERBB4 in the hippocampus and dorsolateral this website prefrontal cortex in human post mortem tissue. Our aim was to examine the association of rs7598440 with cerebrospinal fluid (CSF) GABA levels in healthy volunteers (n = 155). We detected a significant selleck chemical dose-dependent association of the rs7598440 genotype with CSF GABA levels (G-allele standardized beta = -0.23; 95% CIs: -0.39 to -0.07; P=0.0066). GABA concentrations were highest in A homozygous, intermediate in heterozygous, and lowest in G homozygous subjects. When excluding subjects on psychotropic medication (three subjects using antidepressants), the results did not change (G-allele standardized beta=-0.23; 95% CIs: -0.40

to -0.07; P=0.0051). The explained variance in CSF GABA by rs7598440 in our model is 5.2% (P=0.004). The directionality of our findings agrees with the aforementioned H-1-MRS and gene expression studies. Our observation therefore strengthens the evidence that the A-allele of rs7598440 in ERBB4 is associated with increased GABA concentrations in the human central nervous Unoprostone system (CNS). To our knowledge, our finding constitutes the first confirmation that CSF can be used to study genotype-phenotype correlations of GABA levels in the CNS. Such quantitative genetic analyses may be extrapolated to other CSF constituents relevant to SCZ in future studies. Neuropsychopharmacology (2012) 37, 2088-2092; doi:10.1038/npp.2012.57; published online

2 May 2012″
“Nanomedicine, or medicine using nanometric devices, has emerged in the past decade as an exhilarating domain that can help to solve a number of problems linked to unsatisfactory therapeutic responses of so-called ‘old drugs’. This dissatisfaction stems from inadequate biodistribution after a drug’s application, which leads to a limited therapeutic response but also to numerous side effects to healthy organs. The biodistribution of drugs encapsulated in a nanoobject that will act as a vector can be modified to tune its therapeutic efficacy. This review provides a general overview of existing colloidal nanovectors: liposomes, polymeric micelles, polymeric vesicles, polymeric nanoparticles (NPs), and dendrimers. We describe their characteristics, advantages and drawbacks, and discuss their use in the treatment of various diseases.

Our results revealed densely packed DCX-positive cells in the ent

Our results revealed densely packed DCX-positive cells in the entire extent of the subventricular zone from where cells migrated along the rostral migratory stream to the olfactory bulb. In the olfactory bulb, DCX-expressing cells were primarily present in the granular Compound C mw cell layer with radially orientated dendrites and in

the glomerular layer representing periglomerular cells. In the hippocampus, DCX-positive cells were identified in the subgranular and granular layers of the dentate gyrus and strongly labelled DCX-positive processes, presumably dendrites and axons of the newly generated granular cells, were observed in the CA3 regions. In addition, DCX immunoreactive cells were present in the olfactory tubercle, the piriform cortex and the endopiriform nucleus. While DCX-positive fibres have been previously observed in the anterior commissure of the hedgehog and mole, we were able to demonstrate

the presence Selleckchem GANT61 of DCX-positive cells presumably migrating across the anterior commissure. Taken together, the giant otter shrew reveals patterns of neurogenesis similar to that seen in other mammals; however, the appearance of possible neuronal precursor cells in the anterior commissure is a novel observation. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The HIV pandemic represents a major source of neurological morbidity worldwide. Emerging data from diverse populations indicate that HIV leads to significant neurocognitive impairments that reduce individuals’ ability to contribute to the well being of their families and society. HIV affects vulnerable populations with many comorbidities, but the virus contributes to neurocognitive impairment independent of these conditions. The neuropathological

substrate of HIV neurocognitive disorders is damage to synapses Epothilone B (EPO906, Patupilone) and dendrites, without major neuronal loss. This suggests the potential for substantial reversibility if synaptodendritic function can be restored. In the developed world, combination antiretroviral therapy (CART) leads to improved neurocognitive function as well as morbidity and mortality in HIV. CART is being used in increasing numbers of individuals in resource limited settings. New cases of severe dementia are now rare in populations where effective CART has been deployed. While some degree of neurocognitive improvement with CART is almost universal, many individuals do not achieve full restoration of their premorbid neurocognitive status, and milder degrees of impairment remain quite prevalent. Optimizing neurocognitive recovery is likely to require the development of better CNS penetrating antiretroviral regimens and the use of neuroprotective agents. (C) 2009 Elsevier Ltd. All rights reserved.

Two Ca glabrata, a Ca famata and Ca albicans as well as three

Two Ca. glabrata, a Ca. famata and Ca. albicans as well as three C. neoformans, a C. laurentii and Ca. albicans isolates had three virulence factors. Accordingly, 29 center dot

3% (n = 34) isolates possessed more than two virulence factors except capsule formation.


These results of this study indicate that feral pigeons harbour a variety of yeasts and are a reservoir of human pathogenic fungi.

Significance and Impact of the Study:

This study is the first time about the microflora (fungi) presents in faecal samples collected from a variety of public areas throughout Seoul, Korea.”
“In mammals, rewarding properties of drugs depend on their capacity to activate appetitive motivational states. With the underlying mechanisms strongly www.selleckchem.com/products/frax597.html conserved in evolution, invertebrates have recently emerged as a powerful new model in addiction research. In crayfish natural reward has proven surprisingly sensitive to human drugs of abuse, opening an unlikely avenue of research into the basic biological mechanisms of drug addiction. In a series of studies we first examined the presence of natural reward systems in crayfish, then characterized its sensitivity to a wide range of human drugs of abuse. A conditioned place preference (CPP) paradigm was

used to demonstrate that crayfish seek out those environments that had previously been paired with the psychostimulants cocaine and amphetamine, and AZD1480 the opioid morphine. The administration Florfenicol of amphetamine exerted its effects at a number of sites, including the stimulation of circuits for active exploratory behaviors (i.e., SEEKING). A further study examined morphine-induced reward, extinction and reinstatement in crayfish. Repeated intra-circulatory infusions of morphine served as a reward when paired with distinct visual or tactile cues. Morphine-induced CPP

was extinguished after repeated saline injections. Following this extinction phase, morphine-experienced crayfish were once again challenged with the drug. The priming injections of morphine reinstated CPP at all tested doses, suggesting that morphine-induced CPP is unrelenting. In an exploration of drug-associated behavioral sensitization in crayfish we concurrently mapped measures of locomotion and rewarding properties of morphine. Single and repeated intra-circulatory infusions of morphine resulted in persistent locomotory sensitization, even 5 days following the infusion. Moreover, a single dose of morphine was sufficient to induce long-term behavioral sensitization. CPP for morphine and context-dependent cues could not be disrupted over a drug free period of 5 days.

This work demonstrates that crayfish offer a comparative and complementary approach in addiction research.

They also performed better on a written calculation task when pro

They also performed better on a written calculation task when problems were presented as a monetary transaction compared to a standard arithmetic problem. A reference group of patients with Alzheimer’s disease

(AD) showed the reverse pattern. The findings provide convincing evidence that autobiographical relevance influences SD patients’ arithmetic performance. Moreover, they challenge current views on conceptual number knowledge as a unitary, abstract competence. (C) PF-6463922 purchase 2009 Elsevier Ltd. All rights reserved.”
“We study the plasticity of a delayed stochastic model of a genetic toggle switch as a multipotent differentiation pathway switch, at the single cell and cell population levels, by observing distributions of differentiation pathways choices of genetically homogeneous cell populations. Assuming a model of stochastic pathway determination of cell differentiation that is regulated by the proteins of the switch, we vary the proteins’ expression level and degradation rates, which cells are known to be able to regulate, to vary mean level , noise, and bias of the proteins’ expression levels. It is shown that small changes in each of these dynamical features significantly and distinctively affects the dynamics of the switch at the single cell level and thus,

the cell differentiation patterns. The regulation of SNX-5422 molecular weight these features allows cells to regulate their pluripotency and cell populations’ distribution of lineage choice, suggesting that the stochastic switch has high plasticity regarding differentiation pathway choice regulation, thus providing adaptability to environmental stresses and changes. (C) 2009 Elsevier Ltd. All rights reserved.”
“A comparison is made between orthologous proteins from a methanogen (Methanopyrus kandleri) and from a non-methanogen (Pyrococcus abyssi) in order to determine the amino

acid substitution pattern. This analysis makes it possible to establish which amino acids are significantly and asymmetrically utilised by these two organisms. A methanophily index (MI) based on this asymmetry makes it possible for any protein to be associated with a numerical value which, when calculated for the same orthologous protein from methanogenic and non-methanogenic Cediranib (AZD2171) organisms, turns out to have the power to discriminate between these two groups of organisms, even if only for about 20% of the analysed proteins. The MI can also be associated to the genetic code under the assumption that the frequency of synonymous codons specifying the amino acids in the genetic code also reflects the frequency with which amino acids appeared in ancestral proteins. Finally a t-test shows that the MI value associated to the genetic code is not different from the mean value of the MI deriving from methanogen proteins, but it differs from the mean MI of non-methanogen proteins. This might indicate that the genetic code evolved in a methanogenic ‘organism’. (C) 2009 Elsevier Ltd. All rights reserved.

Unmatched patients who underwent extracorporeal CPR had a higher

Unmatched patients who underwent extracorporeal CPR had a higher survival rate to discharge (log-rank p<0 . 0001) and a better 1-year survival than those who received conventional CPR (log rank p=0.007). Between the propensity-score matched groups, there was still a significant difference PLX4032 in survival to discharge (hazard ratio [HR] 0. 51, 95% CI 0.35-0.74, p<0.0001), 30-day survival (HR 0 .47, 95% CI

0 . 28-0.77, p=0.003), and 1-year survival (HR 0.53, 95% Cl 0.33-0.83, p=0.006) favouring extracorporeal CPR over conventional CPR.

Interpretation Extracorporeal CPR had a short-term and long-term survival benefit over conventional CPR in patients with in-hospital cardiac arrest of cardiac origin.

Funding National Science Council, Taiwan.”
“Background Although epidural anaesthesia and analgesia have numerous benefits, their effects on postoperative survival are unclear. We therefore undertook a population-based cohort study to determine whether perioperative epidural anaesthesia or analgesia is associated with improved 30-day survival.

Methods We used selleck products population-based linked administrative 6latabases to do a retrospective cohort study of 259037 patients, aged 40 years or older, who underwent selected elective intermediate-to-high risk non-cardiac surgical procedures between April 1, 1994, and March 31, 2004, in Ontario,

Canada. Propensity-score methods were used to construct a matched-pairs cohort that reduced important baseline differences between patients who received epidural anaesthesia or analgesia as opposed to those that did not. We then 4-Aminobutyrate aminotransferase determined the association of epidural anaesthesia with 30-day mortality within these matched-pairs.


Of the 259037 patients, 56556 (22%) received epidural anaesthesia. Within the matched-pairs cohort (n=88 188), epidural anaesthesia was associated with a small reduction in 30-day mortality (1 . 7% vs 2. 0%; relative risk 0 . 89, 95% Cl 0 . 81-0. 98, p=0. 02).

Interpretation Epidural anaesthesia and analgesia were associated with a small improvement in 30-day survival, but this effect should be interpreted cautiously. The estimate had borderline significance, despite a large sample size. Its absolute magnitude was also small, corresponding to a number needed to treat of 477. Our study, therefore, does not provide compelling evidence that epidural anaesthesia improves postoperative survival. Nonetheless, our results support the safety of perioperative epidural anaesthesia when used for indications other than improving survival (eg, improving postoperative pain relief, preventing postoperative pulmonary complications).

Funding Institute for Clinical Evaluative Sciences.”
“Modern management of acute myocardial infarction is built on a clinical evidence base drawn from many studies undertaken over the past three decades.

The detection of YMDD mutations in HBV-related HCC patients may h

The detection of YMDD mutations in HBV-related HCC patients may help guide the treatment of HCC. In this study, a simple, sensitive, reliable and cost-effective hybridization-fluorescence polarization assay for the detection of YMDD mutations in HCC was developed. A pair of general primers within the highly conserved region of the HBV polymerase gene was used in an asymmetric PCR. Three probes specific for the corresponding YMDD

mutations labeled with different fluorescent reporters hybridized to their target amplicons, and hybridization was indicated by higher fluorescence polarization. The hybridization-fluorescence polarization assay was capable of detecting YMDD mutations at a limit of detection of 10 copies per reaction, and the assay CHIR98014 was able to detect minor populations of viruses with primary YMDD mutations as low as 10%. The rates of primary YMDD mutations and the correlation between YMDD mutations and HBV genotypes in 251 HBV-related HCC patients were investigated using the AZD2171 manufacturer hybridization-fluorescence polarization assay. (c) 2012 Elsevier B.V. All rights reserved.”
“Suicidality is a major challenge for today’s health care. Evidence suggests that there are differences in cognitive functioning of suicidal patients but the knowledge about

the underlying neurobiology is limited. Brain imaging offers the advantage of a non-invasive in vivo direct estimation of detailed brain structure, regional brain functioning and estimation of molecular processes in the brain.

We have reviewed the literature on neuroimaging studies of the suicidal brain. This article contains studies on structural imaging such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) and functional imaging, consisting of Positron Emission Tomography (PET), Single Photon Emission DOCK10 Tomography (SPECT) and functional MRI (fMRI). We classified the results of the different imaging modalities in structural and functional imaging.

Within our research, we found no significant differences in the suicidal brain demonstrated by Computed Tomography.

Magnetic Resonance Imaging studies in subjects with a history of suicide attempt on the other hand deliver differing results, mostly pointing at a higher prevalence of white (especially deep white matter and periventricular) and grey matter hyperintensities in the frontal, temporal and/or parietal lobe and decreased volumes in the frontal and temporal lobe. There seems to be a trend towards findings of reduced grey matter volume in the frontal lobe. Overall, there is no consensus of opinion on structural imaging of the suicidal brain.

Research on functional imaging is further divided into studies in resting state, studies in activation conditions and studies on brain neurotransmitters, transporters and receptors.

In rats, systemic administration of pilocarpine induces a model o

In rats, systemic administration of pilocarpine induces a model of human temporal lobe epilepsy, wherein a brief period of status epilepticus (SE) triggers development of spontaneous recurrent seizures that appear after a latency of 2-3 weeks. Here we investigate changes in expression of A-type voltage-gated potassium (Kv) channels, which control neuronal excitability and regulate action potential propagation and neurotransmitter release, in the pilocarpine model of epilepsy.

Using immunohistochemistry, we examined the expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIP1 and KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine-treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in the molecular layer Idasanutlin in vivo of the dentate gyrus changes from being uniformly distributed across the molecular layer to concentrated in just the outer two-thirds. We also observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2 and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1 week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks. As such, these changes in Kv channel distribution parallel the acquisition of recurrent spontaneous seizures as observed in this model. We also found temporal changes in Kv1.4 immunoreactivity matching those in Timm’s stain,

being expanded in stratum lucidum of CA3 and in the inner third of the dentate molecular layer. Among pilocarpine-treated rats, changes were only observed in those DOK2 that entered SE. These changes in A-type Kv channel expression selleck inhibitor may contribute to hyperexcitability of dendrites in the associated hippocampal circuits as observed in previous studies of the effects of pilocarpine-induced SE. (C) 2008 IBRO. Published by Elsevier

Ltd. All rights reserved.”
“Background: Current evidence suggests that statin use plays an important role in improving adverse cardiovascular outcomes in patients with atherosclerosis. However, limited population-based data are available on use of statin therapy in these patients in Canada. We sought to study trends in statin use to treat these patients in Ontario during a 10-year period.

Methods: We conducted a population-based cross-sectional time series analysis between April 1, 1995, and March 31, 2004, using health care data front Ontario, Canada.

Results: During the study period, 343,154 elderly patients with atherosclerosis were identified. Of these, 235,615 (68.7%) had coronary artery diseases (CAD), 115,012 (33.5%) had cerebrovascular disease (CVD), and 23,886 (7.0%) had peripheral arterial disease (PAD). About 46% were women, and mean patient age was 77.1 (SD, 7.5) years. During the study period, the percentage of patients treated with a statin in each group increased considerably, front 9.8% to 55.3% in ill atherosclerotic patients (P < .01), from 11.8% to 61.2% in CAD patients (P < .01), front 5.3% to 41.

In this study, time-pregnant rats were dosed daily by gavage with

In this study, time-pregnant rats were dosed daily by gavage with chlorpyrifos this website (2.5 mg/kg) from gestational day 7 through the end of lactation on postnatal day 21 (PND 21), and offspring were weighed regularly from birth until brain harvest at PND 22 or young adulthood (PND 95-101). The chlorpyrifos exposure caused excess weight gain in males beginning at PND 45 and reaching levels 10.5% above control by PND 72, while volumetric measurements showed that the exposed males were also 12% larger than controls. The body weight response showed an inverted U-shaped relation to chlorpyrifos

dose. These data suggest delayed disturbances in body weight and density as previously unsuspected adverse consequences of developmental exposure to an environmental

pesticide. Although we do not regard our findings as definitive evidence that chlorpyrifos exposure is a risk factor for obesity, the potential implications nonetheless deserve serious consideration. (c) 2007 Elsevier Inc. All rights reserved.”
“The development of diagnostic assays for detecting beak and feather disease virus (BFDV) has traditionally https://www.selleckchem.com/products/pexidartinib-plx3397.html been hampered by the difficulty associated with producing suitable reagents, namely purified virus and polyclonal antibodies. In an effort to develop a consistent and standardised source of antibody, a monoclonal antibody to a recombinant BFDV capsid protein has been developed and its use in western blotting, immunohistochemistry (IHC), ELISA and haemagglutination-inhibition (HI) assays characterised. The antibody was specific for both the recombinant BFDV capsid protein and the whole virus and had similar optimal titres when used in western blotting and

IHC. The antibody also had HI activity and detected BFDV virus from three genera of psittacine birds, including the recently described cockatiel BFDV isolate. The monoclonal antibody should have widespread application in both research and the development of diagnostic assays for BFDV. (c) 2007 Elsevier B.V. All rights reserved.”
“Compound 48/80 (C48/80) is a synthetic condensation product of N-methyl-p-methoxyphenethyl am me with formaldehyde and is an experimental drug used since the 1950s to induce anaphylactic shock through histamine release. This study Oxymatrine was carried out to further elucidate the mechanism by which this drug induces nitric oxide (NO) release. Our specific goals were: (a) to verify if C48/80′s relaxation occurs through the stimulation of histamine receptors; (b) to evaluate the endothelium-dependent relaxation induced by C48/80; (c) to identify NO as the endothelium-relaxing factor released by C48/80; (d) to identify the NO synthase (NOS) responsible for NO release; and (e) to verify if the relaxation induced by C48/80 is calcium and cyclic guanidine monophosphate (cGMP) dependent.