, 2004). ROS was measured http://www.selleckchem.com/products/birinapant-tl32711.html essentially as described by Ackerley et al. (2006) excepting that incubation with H2DCF-DA was carried out for 30 min, and fluorescence of the dye was measured by a Hitachi F-3010 spectrofluorometer (excitation at 485 nm and emission at 530 nm). The specificity of H2DCF for different ROS species is limited (Setsukinai et al., 2003), and our assay could detect hydrogen peroxide (H2O2), hydroxyl radical (˙OH), and superoxide anion (). TSB-6 cells were grown in LB at 37 °C without chromate till OD600 nm of 0.25. Then, one-half of these cells were heat stressed by transferring to 65 °C. Both the control and heat-stressed cells were grown for another 24 h.

The cells were harvested and soluble extracts prepared as described previously. Ammonium sulfate was then added to the soluble extracts to 90% saturation. The mixture was centrifuged at 12 000 rpm for 30 min and the supernatant discarded. The pellet was dissolved in 20 mM sodium phosphate buffer and dialyzed against 20 mM sodium phosphate buffer, pH 7.0. For the first-dimension electrophoresis, IPG strips of 7 cm length

and nonlinear pH range 4–7 (Bio-Rad) were rehydrated with 150 μg protein in 125 μL of rehydration buffer (provided with the kit) for 16 h. Isoelectric focusing was carried out in a PROTEAN IEF Cell (Bio-Rad) at 4 kV for 1 h with linear voltage amplification and finally to 20 kVh with rapid RXDX-106 manufacturer amplification. Before SDS-PAGE in the second dimension, Mirabegron the focused strips were equilibrated

at room temperature first with a buffer containing 20% v/v glycerol, 0.375 M Tris–HCl, pH 8.8, 6 M urea, 2% (w/v) SDS, 130 mM DTT and then with a second buffer containing 20% (v/v) glycerol, 0.375 M Tris–HCl, pH 8.8, 6 M urea, 2% (w/v) SDS, and 135 mM iodoacetamide. Electrophoresis was carried out using 10% SDS polyacrylamide gels in a Mini-PROTEAN 3 system (Bio-Rad) at constant 200 V for 35 min. The gels were stained in 0.1% (w/v) Coomassie Brilliant Blue R-250. 2D gel images were obtained by VersaDoc™ (Model 4000) Imaging System (Bio-Rad). The spots were detected, analyzed, and assessed for reproducibility with PDQuest Advanced 2D Analysis software (version 8.0.1; Bio-Rad). Three independent experiments were performed with control and heat-stressed samples, and spots present in each of the three replicate gels of both samples were considered. Spots obtained from the control were taken as standard to determine the fold changes in the corresponding spots obtained from heat-stressed samples. Protein spots were excised from gels and subjected to in-gel digestion essentially as described by Shevchenko et al. (2006) using 25 ng μL−1 of trypsin and without the active extraction step. Mass spectrometry of the digested sample was carried out following a published protocol (Sinha & Chattopadhyay, 2011). Similarity searches to identify the proteins were performed using mascot search engine (version 3.5; Matrix Science, London, UK; www.matrixscience.com).

, 2005). While the direct D-wave recorded in the pyramidal tract is the result of direct activation of corticospinal axons, later I-waves reflect synchronous activity originated from trans-synaptic activation of cortical neurons. However, the fact that I-waves are modified by TBS does not prove that changes in synaptic plasticity are solely involved. Several studies have pointed toward the role of NMDA or GABA modulation; others have suggested a change in the Hydroxychloroquine cost expression of immediate early gene proteins (for a review, see Cardenas-Morales et al., 2010). The hypothetical LTP and LTD

effects of TBS are based on studies describing the induction of LTP in the rodent motor cortex or hippocampus; however, direct evidence in humans is still lacking. In this context, the combination of TMS with EEG offers new insights. Our results suggest that the effects of cTBS protocols, i.e. gamma rhythm triplets repeated at a theta rhythm, are not uniform across different populations of neurons. Moreover, the timing of response to cTBS might be specific to each system. Similar to Noh et al. (2012), we found that the effects on oscillations can be detected later than the effects on MEPs. Future studies

will need to explore why modulation of oscillations is delayed compared with modulation of MEPs. To summarize, systems-level effects involving cortical oscillators need to be considered when evaluating the TBS effects. Using real-time integration of TMS and EEG, we provide novel insights on the neural substrate of the effects

of cTBS. EPZ-6438 mouse We found that cTBS modulates TEPs, but also resting oscillations and TMS-induced oscillations, with opposite effects between cortical theta and beta oscillators. This suggests that the effects of TBS involve a complex, systems-level impact of TMS on brain function. Furthermore, it should be noted that the time courses GPX6 of all these TMS-induced modulations (MEPs, EEG after single-pulse TMS, EEG at rest) are different, which suggests that cTBS effects last longer than one can expect from MEP recordings. Future studies are needed to examine these observations at the individual level (for TEPs) and with populations from a different age range. If confirmed, TMS-induced potentials and oscillations might be useful tools to explore plasticity of areas outside the motor cortex where no MEPs can be recorded. This work was supported in part by grants from CIMIT (A.P.-L.), the National Center for Research Resources – Harvard Clinical and Translational Science Center (UL1 RR025758). A.P.-L. serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Neosync and Novavision, and is a listed inventor on issued and pending patents on the real-time integration of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) and magnetic resonance imaging (MRI). M.V. was supported by the Fyssen Foundation (France). W.-K.Y.

Pre-diagnosis treatment with antimalarial medications, or with medications having partial activity against Plasmodium species (such as azithromycin) occurred in 31% of patients. One patient, with travel to Africa, was empirically prescribed chloroquine by a U.S. physician to treat a suspected Plasmodium falciparum infection, three patients were taking azithromycin for presumptive respiratory tract infections,

and the remaining patients were either empirically self-treating with medications purchased off the shelf in Africa, or were prescribed antimalarials by a physician in Africa. Chloroquine and sulfadoxine pyramethamine were most common. There were no deaths in the study population. One patient experienced cardiac arrest beta-catenin tumor but survived. Another patient (newly arrived from a Liberian refugee camp) had a sibling that died at home 1 week before presenting; details of that out-of-hospital death were not available. Malaria was

accurately diagnosed on the day of initial presentation for 82% of the 92 patients for whom this information was available for review. At least three patients who were given their first treatment dose in the emergency department and then managed as outpatients were subsequently admitted after clinically worsening following failed attempts to fill their prescriptions at local pharmacies. Two patients were treated with exchange transfusions. Clinical and epidemiological RAD001 mouse analysis of the CNMC cohort did not find statistically significant indices of risk such as age, gender, purpose of travel, or pre-treatment with antimalarial medications for accurately predicting who, at the time of presentation, was at risk of severe malaria or to require hospitalization. A total of 306 inpatient cases for which malaria was the primary diagnosis were obtained Amobarbital from the PHIS database. Epidemiology and clinical findings from the PHIS hospitals compared to CNMC PHIS data during the same time period is summarized in Table 3. The CI for the entire dataset was 1.2 per 10,000 patient admissions [95% CI 1.1–1.3]. Of the 306 inpatient cases, 67% (n = 205) were of black race. Plasmodium falciparum infection was seen in 52% (n = 160)

of patients, and 39% had an unspecified species. Unspecified species may reflect coding variation in the database as opposed to the actual diagnosis and clinical management. Patients of black race comprised three-quarters of all P. falciparum cases (n = 119, 74%); however, all other races combined experienced the greatest number of non-P. falciparum infections (n = 22, 79%). As was seen at CNMC, the peak of malaria cases occurred in the summer months of July, August, and September, with a lower, secondary peak of malaria occurring in January. The hospital charges incurred by the 306 cases totaled US $5,360,951. Crude mean charges equaled $17,519 [95% CI $1,149–718,956; SD ± 46,346] with crude average daily charges equal to $4,247 [SD ± 2,459]. By malaria type, charges for P.

In the present study, we investigated the regional and cellular distribution of CC in normal, aging and pathological mouse brains. Immunoblotting failed to detect CC protein in whole brain tissues of normal mice, as previously described. However, low proteolytic activity of CC was detected in a brain region-dependent manner, and granular immunohistochemical signals were found in neuronal perikarya of particular brain regions, including the accessory olfactory bulb, the septum, CA2 of the hippocampus, a part of the cerebral cortex, the medial geniculate, and the inferior colliculus. In aged mice, the number of CC-positive neurons increased to some extent. The protein

level of CC and its proteolytic activity showed significant increases in particular brain regions of mouse models with Dabrafenib pathological conditions – the thalamus in cathepsin D-deficient mice, the hippocampus of ipsilateral brain hemispheres after hypoxic–ischemic brain injury, and peri-damaged portions of brains after penetrating injury. In such pathological conditions, the majority of the cells that were strongly immunopositive for CC were activated microglia. These lines of evidence suggest that CC is involved in normal neuronal function in certain brain regions, and also participates

Selleck beta-catenin inhibitor in inflammatory processes accompanying pathogenesis in the CNS. “
“Adult rats exposed to the DNA-methylating agent methylazoxymethanol on embryonic day 17 show a pattern of neurobiological deficits that model some of the neuropathological and behavioral changes observed in schizophrenia. Although it is generally assumed that these changes reflect targeted disruption of embryonic neurogenesis, it is unknown whether these effects generalise to other antimitotic agents administered at

different stages of development. In the present study, neurochemical, behavioral and electrophysiological techniques were used to determine whether exposure to the antimitotic agent Ara-C later in development recapitulates some of the changes observed in methylazoxymethanol (MAM)-treated animals and in patients with schizophrenia. Male rats exposed to Ara-C (30 mg/kg/day) at embryonic days 19.5 and 20.5 show reduced cell numbers and heterotopias in hippocampal CA1 and CA2/3 regions, Pregnenolone respectively, as well as cell loss in the superficial layers of the pre- and infralimbic cortex. Birth date labeling with bromodeoxyuridine reveals that the cytoarchitectural changes in CA2/3 are a consequence rather that a direct result of disrupted cortical neurogenesis. Ara-C-treated rats possess elevated levels of cortical dopamine and DOPAC (3,4-didyhydroxypheylacetic acid) but no change in norepinephrine or serotonin. Ara-C-treated rats are impaired in their ability to learn the Morris water maze task and showed diminished synaptic plasticity in the hippocampocortical pathway. These data indicate that disruption of neurogenesis at embryonic days 19.5 and 20.

Additionally, patients needed to have one or more of the following medical conditions at baseline in order to be included: diabetes, hyperlipidemia, hypertension, obesity, renal insufficiency, or a condition requiring chronic anticoagulation. Study patients’ records were reviewed to determine all chronic medical conditions at baseline, topics covered during the pre-travel visit, and any self-reported health problems or nonadherence to medications that occurred during travel. For the purposes of this investigation, medication nonadherence is defined as a patient stopping or running out of one or more medications during the travel period. In addition, the following markers of chronic disease management were compared

before and after travel using a two-sided paired t-test: hemoglobin A1c, LDL, SBP, DBP, www.selleckchem.com/screening/fda-approved-drug-library.html BMI, SCr, and INR. A linear regression analysis was performed to identify predictors of medication nonadherence, including the

following covariates: patient age, the number of medications, travel destination, duration of travel, and whether the patient received counseling on how to obtain medications to cover the duration of travel. selleck screening library A second linear regression was performed to identify factors associated with having a problem related to chronic conditions during travel, including the following covariates: patient age, travel destination, duration of travel, number of medications, documented nonadherence to medications, and whether or not the patient received counseling on chronic disease management during Casein kinase 1 the pre-travel visit. A total of 110 patients were included in our analysis (Figure 1). Patient demographics are summarized in Table 1. All patients traveled either to Asia (N = 62) or Africa (N = 48), and the median duration of travel was 59 days (range 21–303). Languages spoken are summarized in Table 1 and are representative of both country of origin and travel destinations in Asia and Africa. Key elements of pre-travel preparations are described in Table 2. A total

of 433 travel-related counseling points were documented in the medical record, averaging 4 counseling points per patient. Of these, 71% (N = 309) of all travel topics discussed were related to infectious disease prevention. Chronic disease and safety-related counseling topics comprised 16% (N = 69) and 13% (N = 55) of total health topics discussed at pre-travel visits, respectively. Table 2 further describes the percent of patients that received at least one piece of travel counseling advice in specific topic areas including: infectious disease, chronic disease, and safety. Sixty-three patients (57%) reported one or more health problems while traveling; 10 of these patients were sick enough that they sought care from a health care provider while abroad. Thirty-five patients (32% of travelers) experienced a health problem related to one or more chronic conditions diagnosed prior to travel (Table 3).

Grading: 1C Exceptions are: (i) PI monotherapy should be intensified to include (depending on tolerability, resistance and previous ARV history) one or more agents that cross the placenta. Grading: 2D (ii) The combination of stavudine and didanosine should not be prescribed in pregnancy. Grading: 1D Despite the lack of licence for the use of ART in pregnancy, with the exception of zidovudine in the third trimester, there is global consensus that

women who conceive on effective HAART should continue this throughout the pregnancy. Where the risk of treatment failure due to reduced or intermittent drug exposure with hyperemesis gravidum exceeds the risk of treatment interruption the Writing Group recommends the latter option although there are no data that specifically address this issue. The APR provides the

best data www.selleckchem.com/products/bay-57-1293.html on teratogenicity and first trimester ART exposure. This prospective database records rates of congenital birth defects in babies born to women with first-trimester exposure to ART in comparison with background rates of congenital birth defects and second and third trimester-only exposures to the same compounds. The congenital malformation rate observed in babies exposed to selleck compound a specified drug is reported once a minimum of 200 prospective first-trimester exposures to an individual ARV have been reported. In prospectively reported cases, zidovudine, lamivudine and ritonavir have been shown to have congenital malformation rates within the expected range and a congenital malformation rate >1.5-fold higher than the general Florfenicol population has been excluded. Among other currently used agents (abacavir, tenofovir,

emtricitabine, lopinavir, atazanavir nevirapine and efavirenz) there are now more than 200 prospective reports of first-trimester exposure with no signal of increased risk (and a greater than twofold higher rate than in the general population has been excluded) [49]. There are insufficient data to recommend routinely switching from efavirenz to another agent. The earlier recommendation that efavirenz be avoided in women who may conceive [50] was based on preclinical animal studies that had not been conducted on any other ART, the FDA reclassification of efavirenz to category D and the paucity of human data. Three of 20 offspring of cynomolgus macaques exposed to efavirenz in the first trimester had significant abnormalities at birth: one had anencephaly and unilateral anophthalmia; the second microphthalmia; and the third a cleft palate [51]. Subsequently four anecdotal cases of myelomeningocoele and two of Dandy Walker syndrome were reported following human first-trimester efavirenz exposure. No prospective data were available, causation was not proven and a lack of data on the number of cases reported compared with the number of exposures meant that the relative risk of the putative association could not be calculated.

, 2011; Marangolo et al., 2011, 2013) through additional

modulation of interhemispheric interactions via cathodic stimulation to the homologue contralesional area (Jung et al., 2011; Kang et al., 2011; You et al., 2011). Indeed, only after the real stimulation condition, articulatory errors significantly decreased and all patients were faster in repeating the stimuli compared to the sham condition. Most importantly, significant changes after therapy persisted at F/U and generalised to other tasks. Accordingly, most of the patients showed a significant improvement in different oral language tasks (picture description, noun and verb naming, word repetition and reading) administered before and after the treatment, an improvement which was still present 1 week after the therapy (see Table 2). This improvement revealed Inhibitor Library cell assay http://www.selleckchem.com/products/Maraviroc.html that the language treatment resulted in a positive effect on the production of stimuli not only treated but also belonging to other tasks. Indeed, after tDCS stimulation most patients were able to correctly produce the whole word and they showed

a reduction in phonological errors, the reduction being due to improvement in speech praxis. This is consistent with previous transcranial direct current stimulation–tDCS literature showing longer-term changes (at 1 month or more) in word retrieval and other language measures (Naeser et al., 2010, 2011; Marangolo et al., 2011, 2013). As far as

we know, this is the first study which has investigated the effects of bihemispheric stimulation on the recovery of language. As stated in the Introduction, several studies have already stressed the importance of associating specific language training with anodic unihemispheric tDCS stimulation over the perilesional language areas (Baker et al., 2010; Fiori et al., 2011; Fridriksson et al., 2011; Marangolo et al., 2013). This was based on the assumption that, in chronic patients, language recovery may be associated with the reactivation Protein kinase N1 of left-hemispheric perilesional structures (Warburton et al., 1999; Saur et al., 2006; Winhuisen et al., 2007). Although it is often assumed that the right homologue of Broca’s area takes over the function of the left if it is infarcted, the evidence for this is slender. Recent studies have stressed the importance of the left Broca’s area or adjacent tissue in the natural recovery from post-stroke aphasia (Saur et al., 2006, 2008). Coherently with this assumption, some studies have also shown that the suppression of the right homologue language areas through repetitive transcranial magnetic stimulation (Naeser et al., 2005, 2010, 2011) or unihemispheric cathodic tDCS (Jung et al., 2011; Kang et al., 2011; You et al., 2011), reducing the inhibition on the ipsilesional cortex exerted by the unaffected hemisphere via the transcallosal pathway, determines significant changes in language recovery.

Through pregnancy, it is routine to monitor LFT tests at each antenatal clinic appointment as a marker for potential obstetric complications

(HELLP, pre-eclampsia, acute fatty liver, etc.), particularly in the final trimester. Finally, in those diagnosed late and not receiving HBV treatment incorporated into cART, LFT flares may be seen shortly after delivery, which in some relates to HBeAg seroconversion and reappearance or a marked increase in HBV DNA levels. Where acute infection is suspected, testing for anti-HBc IgM is recommended. Acute HBV is uncommon during pregnancy and each case needs to be managed with specialist advice. Data suggest that lamivudine as part of cART does not completely protect against the development of acute HBV infection, although it is unknown whether

this is also the case Cell Cycle inhibitor with tenofovir with or without lamivudine/emtricitabine. Although there is a theoretical risk of high HBV DNA levels and the linked association with increased risk of transmission combined with the potential for acute hepatitis and threat to maternal and fetal health, the presumption would be that this would be abrogated by the patient already being on cART incorporating tenofovir and either emtricitabine or lamivudine. Where the woman is not on ART, a tenofovir-based ART regimen BGB324 purchase should be commenced immediately. 6.1.3 Where pegylated interferon or adefovir is being used to treat HBV in a woman who does not yet require HIV treatment and who discovers she is pregnant, treatment should be stopped and switched to a tenofovir-based cART regimen. Grading: 1C If a woman on pegylated interferon becomes pregnant it should be discontinued and changed to a tenofovir-based cART regimen because of the anti-proliferative effect of the drug. Few data are available on the risk of congenital malformation with first-trimester exposure to the newer therapies telbivudine (FDA category B) and entecavir (FDA Category C). The outcome of the pregnancy should be reported to the Interferon Pregnancy and Antiretroviral Pregnancy Registries. 6.1.4 Since there is no evidence of any adverse effect on maternal or neonatal health if women become

pregnant while taking antiretroviral Glutathione peroxidase therapy active against HBV, treatment should be continued. Grading: 1C For tenofovir, emtricitabine and lamivudine, APR [53] and the Development of Antiretroviral Therapy Study (DART) [190] have not identified any increased risk in prevalence or any specific pattern of anomaly, even when administered in the first trimester. Hence, when a patient becomes pregnant on an anti-HBV viral agent as part of their cART (tenofovir, lamivudine or emtricitabine), as for HIV management, cART should be continued as the potential risk to the fetus from drug exposure is outweighed by that of a hepatitis flare or liver disease progression if the drug(s) were to be discontinued in addition to HIV virological rebound and risk of MTCT.

Through pregnancy, it is routine to monitor LFT tests at each antenatal clinic appointment as a marker for potential obstetric complications

(HELLP, pre-eclampsia, acute fatty liver, etc.), particularly in the final trimester. Finally, in those diagnosed late and not receiving HBV treatment incorporated into cART, LFT flares may be seen shortly after delivery, which in some relates to HBeAg seroconversion and reappearance or a marked increase in HBV DNA levels. Where acute infection is suspected, testing for anti-HBc IgM is recommended. Acute HBV is uncommon during pregnancy and each case needs to be managed with specialist advice. Data suggest that lamivudine as part of cART does not completely protect against the development of acute HBV infection, although it is unknown whether

this is also the case HIF inhibitor with tenofovir with or without lamivudine/emtricitabine. Although there is a theoretical risk of high HBV DNA levels and the linked association with increased risk of transmission combined with the potential for acute hepatitis and threat to maternal and fetal health, the presumption would be that this would be abrogated by the patient already being on cART incorporating tenofovir and either emtricitabine or lamivudine. Where the woman is not on ART, a tenofovir-based ART regimen HM781-36B nmr should be commenced immediately. 6.1.3 Where pegylated interferon or adefovir is being used to treat HBV in a woman who does not yet require HIV treatment and who discovers she is pregnant, treatment should be stopped and switched to a tenofovir-based cART regimen. Grading: 1C If a woman on pegylated interferon becomes pregnant it should be discontinued and changed to a tenofovir-based cART regimen because of the anti-proliferative effect of the drug. Few data are available on the risk of congenital malformation with first-trimester exposure to the newer therapies telbivudine (FDA category B) and entecavir (FDA Category C). The outcome of the pregnancy should be reported to the Interferon Pregnancy and Antiretroviral Pregnancy Registries. 6.1.4 Since there is no evidence of any adverse effect on maternal or neonatal health if women become

pregnant while taking antiretroviral pentoxifylline therapy active against HBV, treatment should be continued. Grading: 1C For tenofovir, emtricitabine and lamivudine, APR [53] and the Development of Antiretroviral Therapy Study (DART) [190] have not identified any increased risk in prevalence or any specific pattern of anomaly, even when administered in the first trimester. Hence, when a patient becomes pregnant on an anti-HBV viral agent as part of their cART (tenofovir, lamivudine or emtricitabine), as for HIV management, cART should be continued as the potential risk to the fetus from drug exposure is outweighed by that of a hepatitis flare or liver disease progression if the drug(s) were to be discontinued in addition to HIV virological rebound and risk of MTCT.

With this in mind, we investigated whether changes in ADMA levels (Δ-ADMA) at an altitude of 4000 m can predict an individual’s susceptibility to AMS or HAPE. Twelve subjects spent two nights in a hypobaric chamber, the first night without exposure to altitude conditions and the second night at a simulated altitude of 4000 m. At identical

time points during both nights (after 2, 5, and 11 hours), we determined ADMA serum levels, PAP by Doppler echocardiography and estimated hypoxia c-Met inhibitor related symptoms by Lake Louise Score (LLS). Contrary to our initial hypothesis, subjects with a marked increase in ADMA at 4000 m showed PAP levels below the critical threshold for HAPE and were not affected by AMS. By contrast, subjects with a decrease in ADMA suffered from AMS and had PAP levels above 40 mmHg. After 2 hours of hypoxia we found a significant relationship between Δ-PAP t2 (Spearmans ρ = 0.30, p ≤ 0.05) respectively Δ-ADMA t2 (ρ = −0.92, p ≤ 0.05) and LLS. After 2 hours of hypoxia, the Δ-ADMA (positive or negative) can predict an LLS of >5 with a sensitivity of 80% and a specificity of 100% and can help assess

LBH589 research buy the risk of an increase in PAP to more than 40 mmHg and thus the risk of HAPE (ϕ coefficient: 0.69; p ≤ 0.05). Worldwide, 40 million tourists are at risk of getting acute mountain sickness (AMS) each year, because they travel to altitudes of higher than 2500 m (AMS-incidence at altitudes of 2500–3000

m: 10–30%).[1-4] In general, the following conditions are distinguished: AMS, high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). An increase in pulmonary artery pressure (PAP), which is subject to individual differences, plays a crucial role in the development of HAPE.[5] The risk of developing HAPE increases massively when PAP exceeds 40 mmHg.[6] The measurement of PAP by Doppler echocardiography usually allows individuals at Ureohydrolase risk of developing HAPE to be identified, especially in the setting of hypoxia.[7] For methodological reasons, however, Doppler echocardiography can be used only in individuals with (at least minor) tricuspid valve insufficiency. Although this insufficiency is often seen in association with an altitude-induced increase in PAP, high-altitude medical research has revealed the absence of tricuspid reflux in 5–30% of the subjects.[8] In addition, this method requires an experienced examiner and the availability of a suitable (mobile) system. This explains the need for simpler procedures. Against this background, the measurement of serum levels of asymmetric dimethylarginine (ADMA) may provide a new diagnostic approach. ADMA is a potent inhibitor of nitric oxide synthase (NOS). By increasing cyclic guanosine monophosphate (cGMP), nitric oxide (NO) causes smooth muscle relaxation and therefore induces rapid vasodilatation.