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‘Welfare chauvinism’ (or ‘welfare ethnocentrism,’ when directed against native-born ethnic minorities) is a declination of nativism within the social policy domain and a common element of populist radical right discourse. Previous studies have shown that this rhetoric can influence how people perceive the deservingness and entitlement of certain groups to welfare rights. In this study, we propose it has additional effects by evoking a purported lack of reciprocity in what concerns benefits from, and contributions to, the welfare system, such rhetoric can also justify and legitimize discrimination against out-groups in other domains that are unrelated to welfare. We use a pre-registered experiment embedded in a survey of a nationally representative sample of the Portuguese population to examine whether individuals who are exposed to the issue of illegitimate ‘takers’ of the welfare system become more likely to express discriminatory intentions regarding an out-group’s freedom of movement and establishment. We find that in the Portuguese context, where the populist radical right frequently portrays the Roma minority as welfare abusers, highlighting the issue of reciprocity can trigger a sizeable increase in discriminatory intentions against the Romani even in domains unrelated to welfare rights. [ABSTRACT FROM AUTHOR]

Corruption scandals and their investigation have been shown to undermine support not only for the allegedly involved public officials but also for political actors and institutions more generally. However, we know little about what happens when those investigations end up failing to result in punishments. Is citizens' trust in the legal authorities in charge of prosecuting and punishing corruption also undermined? Do those effects spill over to political actors, institutions, and even the political regime? We address these questions by taking advantage of an April 2021 judicial decision to drop corruption charges against former Portuguese Prime Minister José Sócrates during the fieldwork of a public opinion survey. We show that the decision had a substantial negative impact on public trust in the courts. Furthermore, although political trust was not immediately affected, its overall levels also became lower in comparison to periods before the judicial decision, suggesting a spillover effect. [ABSTRACT FROM AUTHOR]

Introduction: Suicide is one of the leading causes of death, with a trend for its increase in Brazil in past decades. This study aimed to review the characteristics of suicides in Brazilian postmortem studies. Methods: Studies investigating suicide deaths in Brazil, and based on autopsy or psychological autopsy were included. Proportions were pooled across studies with the use of random and fixed effects models. Results: 6777 references were retrieved from six databases (searches up to January, 2023), and 45 studies included. In autopsy studies (k = 37, n = 16,231), substance use at toxicological analysis was found in 36.42% of cases (95% CI: 30.05–43.32), previous suicide attempts in 23.92% (95% CI: 6.73–57.78). In psychological autopsy studies (k = 8, n = 139), previous suicide attempts were reported in 28.09% (95% CI: 19.74–38.28), psychiatric conditions/symptoms in 90.67% (95% CI: 67.79–97.82), family history of suicidality in 21.33% (95% CI: 13.5–32.03). Most suicide deaths were reported in males and took place at the victim's home, hanging was the most frequent suicide method. Included studies presented significant limitations in quality assessment. Conclusion: Future studies should present more robust methodology, including bigger samples, the use of controls, and validated methodology. [ABSTRACT FROM AUTHOR]

Objective: The term "mood stabilizer" is controversial in the literature and criticized for being imprecise and overly inclusive, having its retirement suggested to avoid misuse. Nevertheless, it continues to be employed as it may still carry important meaning. Methods: We employed document analysis for reviewing relevant definitions of mood stabilizer employed in the literature. Then, we clarify the meanings associated with the term by employing evolutionary concept analysis. Based on its results, we present a theoretical model for a mood stabilizer and further match it with evidence gathered from published meta‐analyses and other sources for drugs used in the treatment of bipolar disorder. Results: Concept analysis unearthed four attributes of a mood stabilizer that were nested into the following ascending hierarchy: "not worsening," "acute effects," "prophylactic effects," and "advanced effects." "Prophylactic effects" were often considered the core aspect of a legitimate mood stabilizer. Conclusion: The proposed model uses a hierarchy of attributes that take into account the complexity of the term and help to determine whether a drug is a mood stabilizer. Prophylaxis is pivotal to the concept, whose utility lies in implying a drug able to truly treat bipolar disorder, as opposed to merely targeting symptoms. Consistent use of the term could encourage investigation of drugs that modify long‐term outcomes and illness trajectory, instead of simply approaching symptom clusters. [ABSTRACT FROM AUTHOR]

The movement of personnel between roles in regulation, politics, and regulated industries is thought to affect the risks of politicization and industry capture of independent regulatory agencies. To test whether such movements are better explained by formal rules or by sector‐specific patterns, we employ an original dataset of the 152 appointees to 11 IRAs in Portugal over the last 3 decades. We find that variations in the formal independence of agencies have been of little consequence. Instead, revolving doors abound in the financial sector, with a disproportionate share of regulators of that sector coming from, and moving back, to the industry. In turn, appointment of regulators with political links to Portuguese IRAs seems related with legacies of sectoral public control. [ABSTRACT FROM AUTHOR]

Background: Studies on the electrocardiogram findings in African pregnant women are limited. There is no information available in the literature on the electrocardiographic parameters of pregnant Angolan women.Objectives: The aim of this study was to describe electrocardiographic findings in women with normal pregnancies in Bengo Province, Angola.Methods: This is a community-based study with a cross-sectional design conducted between September 2013 and March 2014 in Bengo. The study involved 114 black pregnant women, compared with a paired control group comprising of 120 black non-pregnant women, aged 15 to 42 years. A 12-lead electrocardiogram and a rhythm strip were recorded for all participants.Results: In this study, the mean age was 26.2 ± 7.3 years. Comparing pregnant women vs. non-pregnant, we found the following mean values: Heart rate (83 bpm vs. 74 bpm, p < .001), PR interval (146 ms vs. 151 ms, p = .034), QT interval (360 ms vs. 378 ms, p < .001), QTIc Fridericia (398 ms vs. 403, p = .017), QTIc Framingham (399 ms vs. 404 ms, p = .013) and T-wave axis (340 vs. 410 , p = .001).The main electrocardiographic changes found were: Sinus tachycardia (4.4% vs. 2.5%), T-wave inversion (14.9% vs. 1.7%), Minor ST segment depression (4.5% vs. 0%) and left ventricular hypertrophy (11.4% vs. 11.7%, p = .726).Conclusions: Pregnant Angolan women compared with controls, had several significantly higher values for heart rate, and significantly lower values of systolic blood pressure and diastolic blood pressure, PR interval, QT interval, QTc interval by Fridericia and Framingham and T-wave axis. Sinus tachycardia, T-wave inversion, and left ventricular hypertrophy, were the main electrocardiographic changes found. [ABSTRACT FROM AUTHOR]

We adopted the reverse‐transcriptase‐loop‐mediated isothermal amplification (RT‐LAMP) to detect severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2) in patient samples. Two primer sets for genes N and Orf1ab were designed to detect SARS‐CoV‐2, and one primer set was designed to detect the human gene Actin. We collected prospective 138 nasopharyngeal swabs, 70 oropharyngeal swabs, 69 salivae, and 68 mouth saline wash samples from patients suspected to have severe acute respiratory syndrome (SARS) caused by SARS‐CoV‐2 to test the RT‐LAMP in comparison with the gold standard technique reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR). The accuracy of diagnosis using both primers, N5 and Orf9, was evaluated. Sensitivity and specificity for diagnosis were 96% (95% confidence interval [CI]: 87–99) and 85% (95% CI: 76–91) in 138 samples, respectively. Accurate diagnosis results were obtained only in nasopharyngeal swabs processed via extraction kit. Accurate and rapid diagnosis could aid coronavirus disease 2019 (COVID‐19) pandemic management by identifying, isolating, and treating patients rapidly. [ABSTRACT FROM AUTHOR]

Background: Given the association of diabetic retinopathy (DR) and kidney disease, we investigated the urinary peptidome to presence and deterioration of DR in a post hoc analysis of trials investigating the effect of candesartan on progression of DR in type 1 and type 2 diabetes, respectively. Methods: Baseline urinary peptidomic analysis was performed on a random selection of 783 and 792 subjects in two randomized controlled trials, DIRECT‐Protect 1 and 2, respectively. End points were two‐step (RET2) and three‐step (RET3) change in Early Treatment of Diabetic Retinopathy Study protocol (ETDRS) defined level. Peptide levels were correlated to baseline EDTRS level in a discovery set of 2/3 of the participants from DIRECT‐Protect 1. The identified peptides were then validated cross‐sectionally in the remaining 1/3 from DIRECT‐Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT‐Protect 1 and 2 cohorts and significant peptides were tested longitudinally. Results: Follow‐up ranged 4.0–4.7 years. 24 peptides were associated with baseline DR in the discovery set. COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were associated with baseline DR in the validation set (Rho: −.223, p < 0.001 and Rho: −.141, p = 0.024). Neither was significantly associated with end points. Assessing the 24 identified peptides in the entire cohorts, several collagen peptides were associated with baseline DR and end points; however, there was no overlap across diabetes types. Conclusions: We identified several urinary peptides (mainly collagen) associated with the presence of DR, however they could not be conclusively associated with worsening of DR. [ABSTRACT FROM AUTHOR]

Trans‐4‐methoxy‐β‐nitrostyrene (T4MN) induced more potent vasorelaxant effects in resistance arteries from hypertensive rats than its parent drug, β‐nitrostyrene 1‐nitro‐2‐phenylethene (NPe). To better understand the influence of insertion of the electron‐releasing methoxy group in the aromatic ring of NPe, we investigated vasorelaxant effects of T4MN in isolated pulmonary artery and compared them with those of NPe in view of the potential interest of T4MN in pulmonary arterial hypertension. T4MN and NPe both caused concentration‐dependent vasorelaxation in pulmonary artery rings pre‐contracted with either phenylephrine (1 µmol/L) or KCl (60 mmol/L), an effect unaffected by endothelium removal. In endothelium‐intact preparations pre‐contracted with phenylephrine, the vasorelaxant effect of T4MN was more potent than that of NPe. However, unlike NPe, this effect was significantly reduced following pretreatment with 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) (10 µmol/L, a guanylate cyclase inhibitor) or tetraethylammonium (5 mmol/L, a potassium channel blocker). T4MN abolished the CaCl2‐induced contractions in pulmonary artery preparations stimulated with phenylephrine (PHE) under Ca2+‐free conditions in the presence of verapamil, to preferentially activate receptor‐operated calcium channels. From these findings, we propose that T4MN evokes endothelium‐independent vasorelaxant effects in isolated rat pulmonary artery, partially by inhibiting Ca2+ influx through L‐type Ca2+ channels, as well as by activating soluble guanylate cyclase and potassium channels. The present results suggest the therapeutic potential of T4MN in treating pulmonary arterial hypertension. [ABSTRACT FROM AUTHOR]

Previously, we showed that 1‐nitro‐2‐phenylethene, a nitrostyrene derivative of 1‐nitro‐2‐phenylethane, induced vasorelaxant effects in rat aorta preparations. Here, we studied mechanisms underlying the vasorelaxant effects of its structural analog, trans‐4‐chloro‐β‐nitrostyrene (T4CN), in rat aortic rings. Increasing concentrations of T4CN (0.54‐544.69 µm) fully and similarly relaxed contractions induced by phenylephrine (PHE, 1 µm) or KCl (60 mm) in endothelium‐intact aortic rings with IC50 values of 66.74 [59.66–89.04] and 79.41 [39.92–158.01] µm, respectively. In both electromechanical and pharmacomechanical couplings, the vasorelaxant effects of T4CN remained unaltered by endothelium removal, as evidenced by the IC50 values (108.35 [56.49–207.78] and 65.92 [39.72–109.40] µm, respectively). Pretreatment of endothelium‐intact preparations with L‐NAME, ODQ, glibenclamide, or TEA did not change the vasorelaxant effect of T4CN. Under Ca2+‐free conditions, T4CN significantly reduced the phasic contractions induced by caffeine or PHE, as well as the contractions due to exogenous CaCl2 in aortic preparations stimulated with PHE (in the presence of verapamil). These results suggest that in rat aortic rings, T4CN induced vasorelaxation independently from the activation of soluble guanylate cyclase/cGMP pathway, an effect that may be related to the electrophilicity of the substituted chloro‐nitrostyrene. This vasorelaxation seems to involve inhibition of both calcium influx from the extracellular milieu and calcium mobilization from intracellular stores mediated by IP3 receptors and by ryanodine‐sensitive Ca2+ channels. [ABSTRACT FROM AUTHOR]

Objective: Determining the existence of a relationship between judicial performance and citizens' trust in the legal system. Method: Cross‐classified multilevel models, using data from more than 20 European countries, 80 surveys, and 100,000 respondents, over a decade. Results: The longer the time that lower courts take, on average, to dispose of pending cases, the lower is the public's trust in their legal system. Conclusion: Judicial performance, operationalized as the ability of courts to avoid delays in the delivery of justice, is a significant correlate of citizens' evaluations of their country's legal system. [ABSTRACT FROM AUTHOR]

The aim of the study is to compare the acute effects of low- and moderate-intensity aerobic exercise on post-exercise blood pressure in active adults with high-normal/grade I hypertension. Thirteen physically active adults (67.0 ± 8.7 years) randomly completed two aerobic exercise sessions of 30 minutes at low (30% heart rate reserve [HRres]) and moderate (60% HRres) intensity. Blood pressure was assessed pre-session and every hour until 3 hours after. Systolic blood pressure decreased after both exercise intensities without significant differences between sessions at 1 hour after the session (30%: -10.0 ± 12.6% vs 60%: -11.4 ± 12.7 mm Hg, P > .05). Three hours after the 60% session, the systolic blood pressure remained significantly lower than baseline (139.9 ± 12.9 to 129.3 ± 11.9 mm Hg, P < .05), but without significant differences between sessions. No relevant changes were observed in diastolic and mean blood pressure. In conclusion, a single session of aerobic exercise acutely reduces systolic blood pressure in active adults with high-normal/grade I hypertension. [ABSTRACT FROM AUTHOR]

Ethnicity is an important determinant of blood pressure levels, being black individuals affected more than any other ethnic group. Arterial stiffening, an independent risk factor for hypertension, is also influenced by ethnicity. However, whether black individuals from different continents would have different patterns of arterial stiffening is still unknown. Thus, the authors aimed to compare pulse wave velocity (PWV) in black subjects living in Angola and Brazil. A total of 677 black individuals from two independent cross-sectional studies conducted in Brazil and Angola were included in this analysis. Carotid-to-femoral PWV was measured following the same protocols for both studies, as well as clinical and anthropometric variables. Adjusted PWV was higher in Brazilian blacks than in Angolans, regardless of sex (men from Brazil: 10.7 ± 1.8 vs men from Angola: 9.9 ± 1.8 m/s, P < .001; women from Brazil: 10.3 ± 1.5 vs women from Angola: 9.2 ± 1.3 m/s, P < .001). Although the cf-PWV was higher in Brazilian blacks, the age-related increase in cf-PWV was higher in Angolan men compared to Brazilians, but not in women. SBP showed the strongest association with cf-PWV, regardless of sex and country. However, age was associated with cf-PWV in all groups, except in Brazilian men. Our results clearly show a difference in PWV between two black populations, and highlight for sex differences in the hemodynamic parameters that might affect blood pressure levels in these populations. [ABSTRACT FROM AUTHOR]

The decarbonization of the economy, for which the contribution of power systems is significant, is a growing trend in Europe and in the world. In order to achieve the Paris Agreement's ambitious environmental goals, a substantial increase in the contribution of renewable sources to the energy generation mix is required. This trend brings about relevant challenges as the integration of this type of sources increases, namely in terms of the distribution system operation. In this paper, the challenges foreseen for future power systems are identified and the most effective approaches to deal with them are reviewed. The strategies include the development of Smart Grid technologies (meters, sensors, and actuators) coupled with computational intelligence that act as new sources of data, as well as the connection of distributed energy resources to distribution grids, encompassing the deployment of distributed generation and storage systems and the dissemination of electric vehicles. The impact of these changes in the distribution system as a whole is evaluated from a technical and environmental perspective. In addition, a review of management and control architectures designed for distribution systems is conducted. This article is categorized under:Energy Infrastructure > Systems and InfrastructureEnergy Infrastructure > Economics and Policy [ABSTRACT FROM AUTHOR]

A group of nitro compounds contains a benzene ring in a short aliphatic chain with the NO2 group, property that supposedly favors its vasodilator profile. In this study, we evaluated in isolated rat aorta the effects of 1‐nitro‐2‐propylbenzene (NPB), a nitro compound containing the NO2 in the aromatic ring. In aorta precontracted with KCl, NPB (1‐3000 μm) induced full endothelium‐independent relaxation. In endothelium‐intact preparations, phenylephrine‐induced contractions were fully relaxed by NPB, effect unaltered by N(ω)‐nitro‐L‐arginine methyl ester (L‐NAME) or 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ). In the concentration range of 30–300 μm, NPB slightly but significantly potentiated the phenylephrine‐induced contraction. Such potentiation was unaltered by the thromboxane‐prostanoid receptor antagonist seratrodast, but was abolished by endothelium removal or by preincubation of endothelium‐intact preparations with L‐NAME, ODQ or by ruthenium red and HC‐030031, blockers of subtype 1 of ankyrin transient receptor potential (TRPA1) channels. Verapamil exacerbated the potentiating effect of NPB. The potentiating effect was undetectable in preparations precontracted by 9,11‐dideoxy‐11α,9α‐epoxymethanoprostaglandin F2α (U‐46619). Relaxation was reduced by ruthenium red while it was enhanced by HC‐030031. In conclusion, NPB has vasodilator properties but with a mechanism of action distinct from its analogues. Contrary to other nitro compounds, its relaxing effects did not involve recruitment of the guanylyl cyclase pathway. NPB has also endothelium‐dependent potentiating properties on phenylephrine‐induced contractions, a phenomenon that putatively required a role of endothelial TRPA1 channels. The present findings reinforce the notion that the functional group NO2 in the aliphatic chain of these nitro compounds determines favorably their vasodilator properties. [ABSTRACT FROM AUTHOR]

Summary Government transparency has been discussed both as a way to decrease informational asymmetries between officeholders and citizens and as part of what makes for procedurally fair governance. These two different lines of argument generate predictions about how transparency should change voters' reactions to economic and policy outcomes. First, under high transparency, voters should respond less positively to fiscal expansions. Second, they should become more sensitive to incumbents' ability to deliver outcomes that generate benefits in the long‐run than to current tangible benefits. We test these arguments using municipality level data in Portugal. Controlling for variables that previous research has shown to drive electoral support for incumbents in local elections, only in the least transparent municipalities is support positively related with increases in local current expenditures, budget deficits, and municipal wages. Instead, where transparency is higher, voters are more likely to reward improvements in the quality of education. [ABSTRACT FROM AUTHOR]

A vast literature in social and organizational psychology suggests that support for authorities is driven both by the outcomes they deliver to people and by the extent to which they employ fair decision making processes. Furthermore, some of that literature describes a process‐outcome interaction, through which the effect of outcome favorability is reduced as process fairness increases. However, very few studies have been conducted to determine whether such interaction is also present in the explanation of support for political authorities. Here, we start by analyzing whether individual perceptions of the political system's procedural fairness moderate the well‐known individual‐level relationship between perceived economic performance and government approval. Then, we explore the implications of such process‐outcome interaction to the phenomenon of "economic voting," testing whether impartiality in governance moderates the effect of objective economic performance on aggregate incumbent parties' support. In both cases, we show that the interaction between processes and outcomes seems to extend beyond the organizational contexts where it has been previously observed, with important implications for the study of political support. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Is the responsiveness of isolated segments of the rat oesophagus to contractile or relaxant stimuli susceptible to acute luminal exposure of the oesophagus to an acid solution that contains pepsin and bile salt?What is the main finding and its importance?The study reveals that luminal acidity is an important factor that disrupts barrier function in the oesophagus to allow the diffusion of noxious agents, such as bile acid, that alter the contractile status of the oesophageal body, even in the absence of inflammation. We investigated whether the experimental simulation of duodenogastro‐oesophageal reflux alters the contractile responsiveness of rat oesophageal strips. After 30 min of luminal exposure to a solution at acid pH that contained pepsin and taurodeoxycholic acid, isolated strips of the rat oesophagus and gastro‐oesophageal junction were subjected to contractile or relaxing stimuli. Acid challenge decreased the responsiveness of oesophageal strips to contractile stimulation, especially in oesophageal preparations that were mounted following the circular orientation of the muscularis externa layer. The contractility of longitudinal preparations of the rat oesophagus appeared less susceptible to the deleterious effects of acid challenge. In contrast, the responsiveness of ring‐like preparations from the gastro‐oesophageal junction to contractile stimulation was unaltered by acid challenge. Taurodeoxycholic acid decreased the responsiveness of circular oesophageal preparations to KCl, an effect that was exacerbated by luminal acidity. On the contrary, although the relaxant ability of the rat oesophagus did not change, acid challenge increased the relaxant efficacy of sodium nitroprusside and isoprenaline in strips of the gastro‐oesophageal junction. A significant decrease in transepithelial electrical resistance was seen when the oesophageal mucosa was challenged at pH 1 but not at pH 4. Treatment with alginate blunted the deleterious effects of acid challenge on transepithelial electrical resistance and the responsiveness of oesophageal preparations to KCl. The present findings support the notion that luminal acidity is an important factor that disrupts barrier function in the oesophagus to allow the diffusion of noxious agents, such as bile acid, that alter the contractile status of the oesophagus. [ABSTRACT FROM AUTHOR]

Summary: β‐Phenylethylamine (β‐PEA) is a trace amine with chemical proximity to biogenic amines and amphetamines. It is an endogenous agonist of trace amine‐associated receptors (TAARs) that acts as a neuromodulator of classic neurotransmitters in the central nervous system. At high concentrations, β‐PEA contracts smooth muscle, and a role for TAARs in these responses has been postulated. The high dietary intake of trace amines has been associated with such symptoms as hypertension and migraine, especially after the intake of foods containing such compounds. In gastrointestinal tissues, TAAR expression was reported, although the effect of β‐PEA on gastric contractile behaviour is unknown. Here, isolated strips that were obtained from the rat gastric fundus were stimulated with high micromolar concentrations of β‐PEA. Under resting tonus, β‐PEA induced contractions. In contrast, when the strips were previously contracted with KCl, a relaxant response to β‐PEA was observed. The contractile effect of β‐PEA was inhibited by 5‐hydroxytryptamine (5‐HT) receptor antagonists (i.e., cyproheptadine and ketanserin) but not by the TAAR1 antagonist EPPTB. In gastric fundus strips that were previously contracted with 80 mmol/L KCl, the relaxant effect of β‐PEA intensified in the presence of 5‐HT receptor antagonists, which was inhibited by EPPTB and the adenylyl cyclase inhibitor MDL‐12,330A. The guanylyl cyclase inhibitor ODQ did not alter the relaxant effects of β‐PEA. In conclusion, β‐PEA exerted dual contractile and relaxant effects on rat gastric fundus. The contractile effect appeared to involve the recruitment of 5‐HT receptors, and the relaxant effect of β‐PEA on KCl‐elicited contractions likely involved TAAR1. [ABSTRACT FROM AUTHOR]

Carotid-femoral pulse wave velocity (PWV) has been used as the gold standard method to estimate arterial stiffness. However, its use in clinical practice is still limited because reference values for specific groups, such as black children, remain unknown. The authors aimed to investigate predictors and to propose preliminary reference values of PWV in this population. Prepubertal schoolchildren (N=157; mean age, 9.36±1.41 year) from Luanda (Angola) with normal blood pressure values and without obesity were included. Mean PWV was 5.73±0.68 m/s, with no difference between the sexes. Univariate regression analysis showed a significant (P<.05) positive correlation between PWV and height, age, body weight, lean body weight, and blood pressure. In multivariate analysis, however, only height remained an independent predictor of PWV [PWV=0.018×height (cm)+3.230]. Curves of PWV percentiles as a function of height are proposed, thus identifying normal PWV in black children. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Acute acidosis that results from short-term exercise is involved in delayed gastric emptying in rats and the lower responsiveness of gastric fundus strips to carbachol. Does extracellular acidosis decrease responsiveness to carbachol in tissues of sedentary rats? How?, What is the main finding and its importance? Extracellular acidosis inhibits cholinergic signalling in the rat gastric fundus by selectively influencing the Gq/11 protein signalling pathway., Acute acidosis that results from short-term exercise delays gastric emptying in rats and decreases the responsiveness to carbachol in gastric fundus strips. The regulation of cytosolic Ca2+ concentrations appears to be a mechanism of action of acidosis. The present study investigated the way in which acidosis interferes with gastric smooth muscle contractions. Rat gastric fundus isolated strips at pH 6.0 presented a lower magnitude of carbachol-induced contractions compared with preparations at pH 7.4. This lower magnitude was absent in carbachol-stimulated duodenum and KCl-stimulated gastric fundus strips. In Ca2+-free conditions, repeated contractions that were induced by carbachol progressively decreased, with no influence of extracellular pH. In fundus strips, CaCl2-induced contractions were lower at pH 6.0 than at pH 7.4 but only when stimulated in the combined presence of carbachol and verapamil. In contrast, verapamil-sensitive contractions that were induced by CaCl2 in the presence of KCl did not change with pH acidification. In Ca2+ store-depleted preparations that were treated with thapsigargin, the contractions that were induced by extracellular Ca2+ restoration were smaller at pH 6.0 than at pH 7.4, but relaxation that was induced by SKF-96365 (an inhibitor of store-operated Ca2+ entry) was unaltered by extracellular acidification. At pH 6.0, the phospholipase C inhibitor U-73122 relaxed carbachol-induced contractions less than at pH 7.4, and this phenomenon was absent in tissue that was treated with the RhoA kinase blocker Y-27632. Thus, extracellular acidosis inhibited pharmacomechanical coupling in gastric fundus by selectively inhibiting the Gq/11 protein signalling pathway, whereas electromechanical coupling remained functionally preserved. [ABSTRACT FROM AUTHOR]

Mechanisms underlying the vasorelaxant effects of trans-4-methyl-β-nitrostyrene (T4MeN) were studied in rat aortic rings. In endothelium-intact preparations, T4MeN fully and similarly relaxed contractions induced by phenylephrine ( PHE) ( IC50 = 61.41 [35.40-87.42] μmol/L) and KCl ( IC50 = 83.50 [56.63-110.50] μmol/L). The vasorelaxant effect of T4MeN was unchanged by endothelium removal, pretreatment with L- NAME, indomethacin, tetraethylammonium, ODQ or MDL-12,330A. Under Ca2+-free conditions, T4MeN significantly reduced with a similar potency: (i) phasic contractions induced by PHE, but not by caffeine; (ii) contractions due to CaCl2 in aortic preparations stimulated with PHE (in the presence of verapamil) or high KCl; (iii) contractions evoked by the restoration of external Ca2+ levels after depletion of intracellular Ca2+ stores in the presence of thapsigargin. In contrast, T4MeN was more potent at inhibiting contractions evoked by the tyrosine phosphatase inhibitor, sodium orthovanadate, than those induced by the activator of PKC, phorbol-12,13-dibutyrate. These results suggest that T4MeN induces an endothelium- independent vasorelaxation that appears to occur intracellularly through the inhibition of contractions that are independent of Ca2+ influx from the extracellular milieu but involve phosphorylation of tyrosine residues. [ABSTRACT FROM AUTHOR]

Intestinal mucositis (IM) is the critical side effect of irinotecan (CPT-11), which is the front-line drug used for the treatment of colorectal cancer. This study aimed to evaluate the effectiveness of latex proteins (LP) from Calotropis procera to prevent IM and diarrhea in animals. Swiss mice were treated daily with saline or LP (1, 5, or 50 mg/kg, i.v.) 24 h prior to CTP-11 (75 mg/kg/4 days, i.p) and for additional 6 days. Animal survival, body weight variation, and diarrhea were registered. After animal sacrifice (day 7 post first injection of CPT-11), intestinal samples were collected to study morphology and inflammatory parameters. Animals given LP exhibited improved parameters (survival, body weight, and absence of diarrhea) as compared with the CPT-11 control. The severity of IM observed in animals given CPT-11 was reduced in animals treated with LP. Treatment with LP also prevented the reduction in the villus/crypt ratio promoted by CPT-11. The rise in MPO activity and pro-inflammatory cytokines, over-contractility of the smooth muscle, and diarrhea were all abrogated in LP-treated mice. Markedly reduced immunostaining intensity for COX-2, TNF-α, IL-1β, iNOS, and NF-κB was observed in the intestinal tissue of animals treated with LP. The side-effects of CPT-11 were eliminated by LP treatment in experimental animals and improved clinical parameters characteristic of IM All known biochemical pathogenesis. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Hyperuricemia is associated with cardiovascular disease and its prevalence is unknown in black Africans. This study reports hyperuricemia distribution and its association with cardiovascular risk factors in a selected Angolan population. A cross-sectional study in 585 black Africans was performed. Hyperuricemia was defined as uric acid >7.0 mg/dL in men or >5.7 mg/dL in women. Overall prevalence was 25%. Hyperuricemia was associated with hypertension (odds ratio [OR], 2.20; confidence interval [CI], 95% 1.41-3.47), high waist circumference (OR, 1.67; CI, 95% 1.05-2.65), and metabolic syndrome (OR, 1.66; CI, 95% 1.07-2.57). Compared to those with uric acid levels in the first quartile, individuals in the fourth quartile showed higher body mass index, waist circumference, systolic blood pressure, and plasma levels of creatinine and triglycerides. Hypertension, high waist circumference, and metabolic syndrome were the major cardiovascular risk factors associated with hyperuricemia. [ABSTRACT FROM AUTHOR]

2-Nitro-1-phenyl-1-propanol ( NPP) is a nitro alcohol that is known as an intermediate in the synthesis of sympathomimetic agents, such as norephedrine. The present study investigated the vasoactive effects of NPP on rat aorta. In endothelium-intact aortic rings, NPP fully relaxed contractions that were induced by phenylephrine, KCl, and U-46619. The relaxant effects of NPP on phenylephrine-elicited contractions remained unaffected by NG-nitro- l-arginine methyl ester ( l-NAME), indomethacin, propranolol, tetraethylammonium, 4-aminopyridine, and glibenclamide. Conversely, pretreatment with 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ), cis- N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride (MDL-12,330A), and N-[2-( P-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89) reduced the ability of NPP to relax contractions that were elicited by phenylephrine. NPP inhibited the vasoconstrictor response that was induced by Ca2+ in aortic rings that were stimulated by pharmacomechanical or electromechanical coupling with phenylephrine and 60 mmol/L KCl, respectively, and after the depletion of intracellular Ca2+ stores. Such effects of NPP were significantly reversed by pretreatment with the guanylyl cyclase inhibitor ODQ and weakly influenced by the adenylyl cyclase inhibitor MDL-12,330A. In Ca2+-free medium, NPP inhibited transient contractions that were induced by phenylephrine but not caffeine. In homogenates of aortic rings, NPP increased cyclic guanosine 3′,5′-monophosphate ( cGMP) and cyclic adenosine 3′-5′-monophosphate levels, but this effect was statistically significant only for cGMP. In conclusion, in contrast to the vasoconstrictor amine norephedrine, NPP is a vasodilator in rat aorta, and its relaxant effects are likely attributable to cGMP production. [ABSTRACT FROM AUTHOR]

As semi-presidentialism has become increasingly common in European democracies, so have the debates about the consequences of several of its political and institutional features. In particular, in those regimes, cohabitation between presidents and cabinets of different parties and cabinet dismissal powers on the part of presidents are thought to be a source of inter-branch conflict and government instability. However, so far, most empirical work on government survival has failed to confirm any of these expectations. This article addresses this disjuncture between theory and empirical results by making a twofold contribution. First, it takes into account the internal diversity within semi-presidentialism, modeling the implications for government survival of different configurations between presidential powers' of cabinet dismissal, parliament dissolution and cohabitation in European semi-presidential systems. Second, it reconsiders traditional government survival using the competing risks framework by adding a distinction between two different types of non-electoral replacement: those where replacements imply a change in the party of the prime minister and those where they do not. Once such an approach is adopted, that presidential powers of parliamentary dissolution and cabinet dismissal indeed emerge as highly relevant for explaining government survival in these regimes. [ABSTRACT FROM AUTHOR]

Carvone is a monoterpene ketone that occurs naturally as ( R)-(-) and ( S)-(+) enantiomers in some essential oils that are used in the food and flavour industry and in folk medicine for the treatment of digestive disorders. However, the actions of carvone enantiomers on the gastrointestinal motility in vivo models are not well known. The effects of ( R)-(-)- and ( S)-(+)-carvone on gut motility were evaluated in mice by measuring gastric dye emptying and the rate of intestinal transit. It was also evaluated by measuring intragastric pressure monitored in vivo, and the contractile behaviour of gut strips from mice was studied in vitro. ( R)-(-)-carvone and ( S)-(+)-carvone caused gastric retention, reflected by decreased gastric dye emptying. These effects were accompanied by a reduction of the propulsive behaviour of the small intestine. The retarding effects of carvone on gastric emptying were also related to a decrease in the magnitude of intragastric pressure waves. The carvone-induced effects in vivo resembled those of the positive control, loperamide. In vitro, carvone relaxed sustained contractions induced by carbachol in strips of longitudinal gastric fundus and duodenum. In fundic strips under Ca2+-free conditions, ( S)-(+)-carvone inhibited both the phasic and tonic phases of carbachol-induced contractions and contractions caused by electrical field stimulation. Carvone inhibited duodenal tissues more than gastric tissues, especially when plasmalemmal Ca2+ influx was pharmacologically stimulated. Both enantiomers ( R)-(-)-carvone and ( S)-(+)-carvone exerted myorelaxant and antispasmodic effects on gut smooth muscle in vitro and inhibited gastrointestinal motility in awake mice. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the vascular effects of the E-isomer of methyl cinnamate (E- MC) in rat isolated aortic rings and the putative mechanisms underlying these effects. At 1-3000 μmol/L, E- MC concentration-dependently relaxed endothelium-intact aortic preparations that had been precontracted with phenylephrine ( PHE; 1 μmol/L), with an IC50 value (geometric mean) of 877.6 μmol/L (95% confidence interval ( CI) 784.1-982.2 μmol/L). These vasorelaxant effects of E- MC remained unchanged after removal of the vascular endothelium ( IC50 725.5 μmol/L; 95% CI 546.4-963.6 μmol/L) and pretreatment with 100 μmol/L NG-nitro- l-arginine methyl ester ( IC50 749.0 μmol/L; 95% CI 557.8-1005.7 μmol/L) or 10 μmol/L 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one ( IC50 837.2 μmol/L; 95% CI 511.4-1370.5 μmol/L). Over the concentration range 1-3000 μmol/L, E- MC relaxed K+-induced contractions in mesenteric artery preparations ( IC50 314.5 μmol/L; 95% CI 141.9-697.0 μmol/L) with greater potency than in aortic preparations ( IC50 1144.7 μmol/L; 95% CI 823.2-1591.9 μmol/L). In the presence of a saturating contractile concentration of K+ (150 mmol/L) in Ca2+-containing medium combined with 3 μmol/L PHE, 1000 μmol/L E- MC only partially reversed the contractile response. In contrast, under similar conditions, E- MC nearly fully relaxed PHE-induced contractions in aortic rings in a Ba2+-containing medium. In preparations that were maintained under Ca2+-free conditions, 600 and 1000 μmol/L E- MC significantly reduced the contractions induced by exogenous Ca2+ or Ba2+ in KCl-precontracted preparations, but not in PHE-precontracted preparations (in the presence of 1 μmol/L verapamil). In addition, E- MC (1-3000 μmol/L) concentration-dependently relaxed the contractions induced by 2 mmol/L sodium orthovanadate. Based on these observations, E- MC-induced endothelium-independent vasorelaxant effects appear to be preferentially mediated by inhibition of plasmalemmal Ca2+ influx through voltage-dependent Ca2+ channels. However, the involvement of a myogenic mechanism in the effects of E- MC is also possible. [ABSTRACT FROM AUTHOR]

Diffuse support for democracy, as captured in mass surveys, tends to be treated as impervious to regime performance. Such a finding is often presented as confirmation of the basic distinction between 'diffuse' and 'specific' support as proposed by David Easton. This study argues that this line of argument stems from an incomplete reading of important aspects of Easton's theorisation about the relationship between system outputs and diffuse support. Using multilevel models, evidence from more than 100 surveys in close to 80 countries, and different measures of democratic support, it is shown that government effectiveness is the strongest macro-level predictor of such support. In democratic regimes, government effectiveness, understood as the quality of policy-making formulation and implementation, is linked to higher levels of support for democracy. Furthermore, in non-democracies, effectiveness and support for democracy are, under some model specifications, negatively related. [ABSTRACT FROM AUTHOR]

Cardiovascular effects of the linalool-rich essential oil of Aniba rosaeodora (here named as EOAR) in normotensive rats were investigated. In anesthetized rats, intravenous (i.v.) injection of EOAR induced dose-dependent biphasic hypotension and bradycardia. Emphasis was given to the first phase (phase 1) of the cardiovascular effects, which is rapid (onset time of 1-3 s) and not observed in animals submitted to bilateral vagotomy or selective blockade of neural conduction of vagal C-fibre afferents by perineural treatment with capsaicin. Phase 1 was also absent when EOAR was directly injected into the left ventricle injection, but it was unaltered by i.v. pretreatment with capsazepine, ondansetron or HC030031. In conscious rats, EOAR induced rapid and monophasic hypotensive and bradycardiac (phase 1) effects that were abolished by i.v. methylatropine. In endothelium-intact aortic rings, EOAR fully relaxed phenylephrine-induced contractions in a concentration-dependent manner. The present findings reveal that phase 1 of the bradycardiac and depressor responses induced by EOAR has a vago-vagal reflex origin resulting from the vagal pulmonary afferents stimulation. Such phenomenon appears not to involve the recruitment of C-fibre afferents expressing 5HT3 receptors or the two chemosensory ion channels TRPV1 and TRPA1. Phase 2 hypotensive response appears resulting from a direct vasodilatory action. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study investigated the cardiovascular responses to the essential oil of Aniba canelilla (EOAC) and its main constituent 1-nitro-2-phenylethane (NP) in spontaneously hypertensive rats (SHRs). In anesthetized SHRs, intravenous (i.v.) bolus injections of EOAC (1-20 mg/kg) or NP (1-10 mg/kg) elicited dose-dependent hypotensive and bradycardiac effects, which were characterized in two periods (phases 1 and 2). The first rapid component (phase 1) evoked by EOAC and NP both at 10 mg/kg was absent after left ventricle injection, fully abolished by bilateral vagotomy and perineural treatment of both cervical vagus nerves with capsaicin (250 μg/mL) while remained unaltered by i.v. pretreatment with capsazepine (1 mg/kg) or ondansetron (30 μg/kg). In conscious SHRs, NP (5 and 10 mg/kg, i.v.) evoked rapid hypotensive and bradycardiac effects (phase 1) that were fully abolished by methylatropine (1 mg/kg, i.v.) pretreatment. In rat endothelium-containing mesenteric preparations, increasing concentrations (0.1-1000 μg/mL) of EOAC and NP relaxed the phenylephrine-induced contraction in a concentration-dependent manner. It is concluded that NP induces a vago-vagal bradycardiac and depressor reflex (phase 1) that apparently results from the stimulation of vagal pulmonary rather than cardiac C-fiber afferents. This effect does not appear to involve activation of either vanilloid TPRV1 or 5-HT3 receptors located on vagal sensory nerves. The phase 2 hypotensive response to i.v. NP seems to result, at least in part, from its direct vasodilatory effect on the peripheral smooth muscle. All in vivo and in vitro effects of EOAC are mostly attributed to the actions of its main constituent NP. [ABSTRACT FROM AUTHOR]

This study was undertaken to assess the effects of eugenol (EUG) on tracheal muscle (TM) and the putative mechanisms underlying these effects. Cumulatively increasing concentrations (1-1000 μ m) of EUG did not affect the resting tonus of TM. However, EUG (1-2000 μ m) reduced the contractions induced by electrical field stimulation (IC50 = 842.3 ± 52.7 μ m), an effect that was unaltered by either 10 μ m montelukast (IC50 = 816.1 ± 70.1 μ m) or 2 μ m indomethacin (IC50 = 693.1 ± 170.8 μ m). EUG also completely relaxed the sustained contractile responses to 80 mM K+ (IC50 = 597.3 ± 60.6 μ m) and 1 μ m carbamoylcholine (IC50 = 571.3 ± 148.8 μ m), an effect that was unaltered by indomethacin (2 μ m). Under Ca2+-free conditions, EUG reduced the ACh-induced contractions (IC50 = 703.4 ± 256.1 μ m), the CaCl2-induced contractions in preparations pretreated with 60 μ m ACh in the presence of nifedipine, and the Ba2+-induced contractions in preparations depolarized with K+. In tracheal preparations maintained in Ca2+-containing solution, EUG (300-2000 μ m) relaxed the contractile response to phorbol dibutyrate (1 μ m), an activator of protein kinase C. It is concluded that in TM, EUG induces a myogenic antispasmodic effect (not modulated by arachidonic acid derivatives) either through various mechanisms almost with the same pharmacological potency or via an action on a step common to all of them. These mechanisms seem to include blockade of voltage- and receptor-operated Ca2+ channels, IP3-induced Ca2+ release from sarcoplasmic reticulum and reduction of the sensitivity of contractile proteins to Ca2+. [ABSTRACT FROM AUTHOR]

Eucalyptol, also known as 1,8-cineole, is a monoterpene traditionally used to treat respiratory disorders due to its secretolytic properties. In addition to its myorelaxant effects, it also has anti-inflammatory actions in vitro. In this study, we aimed to evaluate the efficacy of acute treatment with 1,8-cineole on reducing airway inflammatory parameters. Ovalbumin (OVA)-sensitized guinea pigs were submitted to antigenic challenge (OVA) with or without pre-treatment with a single dose of 1,8-cineole administered by inhalation. Airway inflammatory parameters were reduced or absent in 1,8-cineole-treated animals as compared with untreated guinea pigs. Acute treatment with 1,8-cineole impaired the development of airway hyperresponsiveness to carbachol in isolated tracheal rings. Levels of the pro-inflammatory cytokines TNFα and IL-1β was lower in bronchoalveolar lavage fluid (BALF) of 1,8-cineol-treated guinea pigs than in untreated animals. 1,8-Cineole impaired the OVA-induced increase of the myeloperoxidase activity in BALF. 1,8-Cineole also prevented the reduction of the mucociliary clearance induced by the antigen presentation. The present investigation provides evidence that inhaled 1,8-cineole prevents hyperresponsiveness and inhibits inflammation in airways of ovalbumin-challenged guinea pigs. [ABSTRACT FROM AUTHOR]

This study investigates the effects of essential oil of Pterodon polygalaeflorus (EOPP) and β-caryophyllene (β-CAR). EOPP and β-CAR relaxed the basal tone of ileum smooth muscle in a concentration-dependent manner (ICs = 394.35 ± 62.12 and 68.65 ± 9.51 μg/mL respectively), an effect that was unaltered by hexamethonium, -nitroarginine methyl ester or indomethacin. Both EOPP and β-CAR evoked a concentration-dependent relaxation of ileum pre-contracted with KCl with an IC value of 107.78 ± 10.47 and 17.35 ± 0.75μg/mL, respectively. EOPP and β-CAR inhibited the contractions induced by acetylcholine (ACh) and by KCl. In ileal preparations, the CaCl-induced contractions were reduced by EOPP (300 μg/mL) and β-CAR (100 μg/mL). Furthermore, CaCl-induced contractions were also reduced by EOPP (300 μg/mL) and β-CAR (100 μg/mL) in ileal preparations pretreated with ACh under Ca-free condition and in the presence of verapamil. EOPP (100 and 300 μg/mL) and β-CAR (30 and 100 μg/mL) reduced the ACh-induced contractions of isolated rat ileum under Ca-free conditions. In the presence of high KCl and Ca-free conditions, EOPP (300 μg/mL) and β-CAR (100 μg/mL) reduced the contractions induced by barium. A similar effect was also observed with verapamil. It is concluded that (i) β-CAR is an important constituent involved in the myorelaxant and antispasmodic effects induced by EOPP; (ii) the inhibitory effect on intestinal contractility is myogenic and seems mainly mediated through an intracellular mechanism. However, the ability of EOPP and β-CAR to decrease Ca influx through cytoplasmic membrane could not be discounted. [ABSTRACT FROM AUTHOR]

The main purpose of this paper is to perform a sensitivity analysis where we quantify and analyse the effects on the mean of the profit on an Income Protection policy and two risk measures of changing the values of the transition intensities. All the calculations carried out are based on a multiple state model for Income Protection proposed in Continuous Mortality Investigation Committee (Continuous Mortality Investigation Reports 1991; 12). Within this model, we derive a formula for the mean of the profit, which enables to evaluate it more efficiently. In order to calculate the two risk measures we use the numerical algorithms for the calculation of the moments of the profit proposed by Waters (Insurance: Mathematics and Economics 1990; 9:101–113). We carry out the sensitivity analysis considering two different situations: in the first situation, we update the premium rates used to calculate the moments of the profit, according to the changes in the values of the transition intensities; in the second one, we do not update the premium rates. Both analyses are of practical interest to insurance companies selling Income Protection policies. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

1. 1,8-Cineole is a non-toxic small terpenoid oxide believed to have medicinal properties in folk medicine. It has been shown to have various pharmacological effects, including blockade of the compound action potential (AP). In the present study, using intracellular recording techniques, we investigated the effects of 1,8-cineole on the electrophysiological parameters of neurons of the superior cervical ganglion (SCG) in rats. 2. 1,8-Cineole (0.1–6 mmol/L) showed reversible and concentration-dependent effects on various electrophysiological parameters. At 3 and 6 mmol/L, but not at 0.1 and 1 mmol/L, 1,8-cineole significantly diminished the input resistance (Ri) and altered the resting potential (Em) to more positive values. At 6 mmol/L, 1,8-cineole completely blocked all APs within 2.7 ± 0.6 min ( n = 12). In neurons exposed to 3 and 1 mmol/L 1,8-cineole, the effects regarding excitability varied from complete AP blockade to minor inhibition of AP parameters. The depolarization of Em and the decrease in Ri induced by 6 mmol/L 1,8-cineole were unaltered by 200 µmol/L niflumic acid, a well known blocker of Ca2+-activated Cl− currents. 3. Significant correlations (Pearson correlation test) were found between changes in Em and decreases in AP amplitude ( r = –0.893; P < 0.00282) and maximum ascendant inclination ( r = –0.799; P < 0.0173), but not for maximum descendant inclination ( r = 0.598; P < 0.117). Application of current to restore the transmembrane potential equal to control Em values in the presence of 6 mmol/L 1,8-cineole resulted in the partial recovery of AP. 4. The present study shows that 1,8-cineole effectively blocks the excitability of SCG neurons, probably through various mechanisms, one of which acts indirectly via depolarization of the neuronal cytoplasmatic membrane. [ABSTRACT FROM AUTHOR]

1. 1,8-Cineole is a terpenoid constituent of essential oils with anti-inflammatory properties. It reduces the neural excitability, functions as an antinociceptive agent and has myorelaxant actions in guinea-pig airways. The aim of the present study was to investigate the mechanism underlying the myorelaxant effects of 1,8-cineole in guinea-pig isolated trachea from either naïve guinea-pigs or ovalbumin (OVA)-sensitized animals subjected to antigenic challenge. 2. Isometric recordings were made of the tone of isolated tracheal rings. Rings with an intact epithelium relaxed beyond basal tone in the presence of 1,8-cineole (6.5 × 10−6 to 2 × 10−2 mol/L) in a concentration-dependent manner ( P < 0.001,anova) with a pD2 value of 2.23 (95% confidence interval 2.10–2.37). Removal of the epithelium or pretreatment of intact tissue for 15 min with 50 µmol/L NG-nitro-l-arginine methyl ester, 5 mmol/L tetraethylammonium, 0.5 µmol/L tetrodotoxin or 5 µmol/L propranolol did not alter the potency (pD2) or the maximal myorelaxant effect (Emax) of 1,8-cineole. 3. 1,8-Cineole also significantly decreased the Schultz-Dale contraction induced by OVA, mainly in preparations from OVA-sensitized animals submitted to antigen challenge. 1,8-Cineole decreased tracheal hyperresponsiveness to KCl and carbachol caused by antigen challenge and almost abolished the concentration–response curves to KCl, whereas it had little effect on the concentration–response curves to carbachol. Under Ca2+-free conditions and in the presence of 10−4 mol/L acetylcholine, neither 1,8-cineole (6.5 × 10−3 mol/L) nor verapamil (1 × 10−5 mol/L) affected Ca2+-induced contractions, but they almost abolished Ba2+-induced contractions. 4. In conclusion, the findings of the present study show that 1,8-cineole is a tracheal myorelaxant that acts preferentially on contractile responses elicited electromechanically. [ABSTRACT FROM AUTHOR]

Previously, we reported that essential oil of Croton nepetaefolius (EOCN) decreases blood pressure in normotensive rats, an effect that seems resulting from its vasodilatory action directly upon vascular smooth muscle. In the present study, we aimed to study the role of endothelium–nitric oxide pathway in the mediation of vasodilatory effects of EOCN and two of its constituents, methyleugenol and α-terpineol, using rat isolated thoracic aorta and mesenteric vascular bed preparations. EOCN (1–300 μg/mL), in a concentration-dependent manner, relaxed isolated endothelium-intact aortic rings precontracted with KCl 60 mm, with an IC50 value of 26.7 (14.7–48.2) μg/mL. Either pretreatment of the tissue withl-NAME, a nitric oxide synthase inhibitor, or mechanical endothelium removal increased significantly the IC50 value to 66.6 (52.7–84.1) or 105.6 (91.3–122.2) μg/mL, respectively. In endothelium-intact aortic rings precontracted with norepinephrine, EOCN (10–200 μg/mL) produced a vasorelaxant action which was decreased by the pretreatment of the aortic rings with methylene blue, a guanylate cyclase inhibitor. In mesenteric bed preparations perfused under constant pressure, EOCN reverted the reduction of mesenteric flow caused by KCl (60 mm), an effect that was attenuated byl-NAME. Vasodilator responses to EOCN in mesenteric bed preparations were mimicked by methyleugenol and α-terpineol, and were also significantly reduced in the presence ofl-NAME. In conclusion, EOCN has vasorelaxant effects in both a resistance vascular bed and in a conduit artery. They seem attributed, at least in part, to the actions of its main constituents methyleugenol and α-terpineol and appear partially dependent upon the integrity of a functional vascular endothelium. Inhibition of other transduction pathways may be involved in the mediation of these effects. [ABSTRACT FROM AUTHOR]

Phosphodiesterase type-5 (PDE5) specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. The PDE5 inhibitor sildenafil is a well-known vasodilator that also has gastrointestinal myorelaxant properties. In the present study, we further investigated sildenafil-induced myorelaxation in rat isolated duodenum, assessing its interaction with nitric oxide (NO) synthase and K+ channel opening. The spontaneous contractions of duodenal strips were reversibly inhibited by sildenafil (0.1–300 μm) in a concentration-dependent manner [mean (95% confidence interval); EC50 = 6.8 (2.7–17.3) μm]. The sildenafil-induced myorelaxation was significantly decreased by the NO synthase inhibitor N-nitro-l-arginine methyl ester [increasing the EC50 value to 41.9 (26.1–67.3) μm]. Sodium nitroprusside or forskolin pretreatments enhanced the sildenafil-induced myorelaxation. In isolated strips pretreated with BaCl2 (0.2 mm), 4-aminopyridine (4-AP, 3 mm), or glybenclamide (1 μm), the sildenafil-induced EC50 value was significantly increased to 32.8 (19.1–56.4), 27.1 (15.2–48.3) and 20.1 (16.4–24.7) μm, respectively. Minoxidil (50 μm) or diazoxide (100 μm) also significantly attenuated the sildenafil-induced potency. In conclusion, the NO synthase/cyclic nucleotide pathway activation is involved in sildenafil-induced inhibition of spontaneous duodenal contractions. Its pharmacological action seems to be influenced by K+ channel opening, especially the voltage-sensitive ones, being inhibited by 4-AP and KATP channels, sensitive to glybenclamide. [ABSTRACT FROM AUTHOR]

Intravenous (i.v.) treatment of conscious DOCA-salt hypertensive rats with the essential oil of Ocimum gratissimum L. (Labiatae) (EOOG) induced a hypotensive effect that seems related to an active vascular relaxation rather than withdrawal of sympathetic tone. To corroborate this hypothesis, the present study examined the vascular effects of EOOG and its main constituent, eugenol (EUG) and the putative mechanisms underlying these effects. Additionally, the role of the vascular β2-adrenergic mechanism in the mediation of EOOG-induced hypotension has also been investigated. In conscious DOCA-salt hypertensive rats, the EOOG-induced hypotension was reversible and remained unchanged by i.v. pretreatment with propranolol (2 mg/kg). In isolated aorta preparations with intact endothelium from DOCA-salt hypertensive rats, EOOG (1–1000 μg/mL) and EUG (0.006–6 mm) relaxed the phenylephrine-induced contraction similarly with IC50 [geometric mean (95% confidence interval)] values of 226.9 (147.8–348.3) μg/mL and 1.2 (0.6–2.1) mm, respectively. Vasorelaxant effects of EOOG were significantly altered by removal of the vascular endothelium [IC50 = 417.2 (349.5–497.8) μg/mL]. In a calcium-free medium, the CaCl2-induced contractions were significantly reduced and even abolished by EOOG at 300 and 1000 μg/mL, respectively, whereas EOOG (1000 μg/mL) did not have any significant effect on caffeine-induced contractions. Similar results were obtained with EUG (1.8 and 6 mm) on both CaCl2- and caffeine-induced contractions, respectively. The data suggest that hypotensive responses to EOOG in DOCA-salt hypertensive rats are due to an active vascular relaxation, which is partly dependent upon the integrity of the vascular endothelium and seems predominantly mediated through an inhibition of plasmalemmal Ca2+ influx rather than Ca2+-induced Ca2+ release from the sarcoplasmic reticulum. [ABSTRACT FROM AUTHOR]

1. Antigenic challenge often induces hyperreactivity in asthmatic airway, although the precise mechanism(s) underlying this increased responsiveness is not entirely known. 2. Tracheae obtained from ovalbumin (OVA)-sensitized saline- or OVA-challenged rats were placed in 10 mL bath chambers for isometric recording of 5-hydroxytryptamine (5-HT)-induced contractions. 3. 5-Hydroxytryptamine induced a stronger contraction compared with control in antigen-challenged trachea under normal or Ca2+-free conditions. 4. In tracheae pretreated with the L-type Ca2+ channel blocker nifedipine (10−6 mol/L) or the Ca2+-activated Cl– channel blocker niflumic acid (10−4 mol/L), this hyperresponsiveness was not developed in either normal or Ca2+-free medium. 5. The increased contractile response to 5-HT in allergic rat isolated trachea may be related to a greater ionic (Ca2+ and Cl–) channel involvement. [ABSTRACT FROM AUTHOR]

1. Sildenafil citrate (Viagra™; Pfizer, Sandwich, Kent, UK), a phosphodiesterase 5 inhibitor, rises cGMP levels in smooth muscle cells. It relaxes both vascular and visceral smooth muscle. In order to assess the intestinal effects of sildenafil, we decided to investigate its actions on rat duodenal motor activityin vitro.2. In isolated duodenal segments maintained in Tyrode's solution, sildenafil exhibited a concentration-dependent antispasmodic effect on acetylcholine (ACh)-induced phasic contractions, with an IC50 value of 26.7 µmol/L (95% confidence interval (CI) 2.0–55.3 µmol/L).3. Sildenafil also relaxed the carbamylcholine (CCh)-induced sustained contraction with an IC50 of 16.2 µmol/L (95% CI 9.5–27.6 µmol/L). Sildenafil produced significant additional relaxation of 25.2 ± 8.1% of the CCh-induced contraction, beyond basal tone.4. Sildenafil reduced the amplitude of spontaneous duodenal contractions with an EC50 of 9.6 µmol/L (95% CI 5.7–16.2 µmol/L). This effect was significantly more potent than the effects of zaprinast and papaverine, which also reduced duodenal contractions with EC50 values of 91.6 µmol/L (95% CI 46.0–182.2 µmol/L) and 78.5 µmol/L (95% CI 37.1–166.3 µmol/L), respectively.5. In preparations treated previously with methylene blue (10 μmol/L) or 1H-[1,2,4]oxadiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 µmol/L), the EC50 values for the sildenafil effect were significantly increased to 39.0 µmol/L (95% CI 23.9–63.4 µmol/L) and 43.8 µmol/L (95% CI 24.5–78.3 µmol/L), respectively. These values were significantly greater than those obtained with sildenafil alone.6. In conclusion, sildenafil has myorelaxant and antispasmodic effects on rat duodenal segmentsin vitro.The contractile inhibitory effect of sildenafil on rat isolated duodenum is probably due to intracellular cGMP accumulation as a result of its decreased degradation. [ABSTRACT FROM AUTHOR]

The effects of essential oil ofCroton nepetaefolius(EOCN) on guinea-pig-isolated ileum were studied. We previously demonstrated that EOCN induced reversible relaxation of ileal tone artificially increased by high [K+] nutrient solution. This study aimed to elucidate whether these effects were caused by indirect, neural, or primarily by myogenic effect. EOCN (40 μg/mL) induced a relaxation of basal tone corresponding to approximately 38% of the reference contraction (K+ 60 mm), and was unaltered by 0.5 mmhexamethonium, 0.5 μmtetrodotoxin, 1 μmindomethacin, and 100 μml-nitroarginine methyl ester (l-NAME). Epinephrine- (100 μm) and EOCN-induced maximal relaxation of ileum pre-contracted with 60 mmKCl represented 16.8 ± 2.3% (n = 10) and 95.0 ± 6.4% (n = 6) of KCl-induced contraction, respectively. EOCN (200 μg/mL) had no effect on the transmembrane resting potential (Em) of ileum in nutrient solutions with normal (5 mm) and high (80 mm) [K+]. EOCN similarly inhibited the contractions induced by KCl, acetylcholine (ACh) and histamine (IC50 values of approximately 18, 28 and 21 μg/mL, respectively). EOCN also inhibited both the nifedipine-insensitive component of ACh-induced contraction and the contraction induced by ACh in Ca2+-free solution. EOCN accelerated the reversal of a KCl-induced tonic contraction upon withdrawal of Ca2+ from the extracellular medium. Our results suggest that EOCN induces relaxation of guinea-pig ileum by a direct action on smooth muscle via a mechanism largely independent of alterations of Em and Ca2+ influx, possibly at the level of the contractile apparatus. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response a letter regarding the pharmacological treatment of postpartum depression (PPD).

A letter to the editor is presented in response to an article on problems with single-factor solutions in factor analyses of low-end scores that was published in the October 2008 issue

A letter to the editor is presented regarding the article "Affective instability as rapid cycling: theoretical and clinical implications for borderline personality and bipolar spectrum disorders," by D. F. MacKinnon and R. Pies in the February 2006 issue.