Development of baroreflex function and hind limb vascular reactivity in the horse fetus

This study investigated, in vivo , the mechanisms underlying the development of cardiovascular function in the horse fetus, with particular relevance to baroreflex function and hind limb vascular arterial reactivity to constrictor agonists. Under general anaesthesia, vascular catheters were inserted and a Transonic flow probe was implanted around one of the metatarsal arteries of 13 horse fetuses, either at 0.6 of gestation ( n = 6) or at 0.9 of gestation ( n = 7, term ∼335 days). At least 5 days after surgery, pressor, vasoconstrictor and cardiac chronotropic responses to exogenous bolus doses of phenylephrine, angiotensin II and arginine vasopressin were recorded. Fetal cardiac baroreflex slopes were obtained using the peak pressor and heart rate responses to increasing doses of phenylephrine. Fetal treatment with phenylephrine, angiotensin II and vasopressin produced significant changes in arterial blood pressure, hind limb vascular resistance and heart rate. Pressor and vasopressor responses to all agonists were greater at 0.9 than at 0.6 of gestation; however, fetal cardiac baroreflex sensitivity decreased with advancing gestational age. Correlation analysis revealed that fetal plasma cortisol rather than gestational age was a greater determinant of pressor and vasopressor reactivity. In contrast, gestational age rather than cortisol better determined heart rate and baroreflex responsiveness in the equine fetus. The data show that development of cardiovascular function in the equine fetus occurs via cortisol-dependent and -independent pathways.     

Estrogen receptor transcription and transactivation: Structure-function relationship in DNA- and ligand-binding domains of estrogen receptors

Estrogen receptors are members of the nuclear receptor steroid family that exhibit specific structural features, ligand-binding domain sequence identity and dimeric interactions, that single them out. The crystal structures of their DNA-binding domains give some insight into how nuclear receptors discriminate between DNA response elements. The various ligand-binding domain crystal structures of the two known estrogen receptor isotypes (α and β) allow one to interpret ligand specificity and reveal the interactions responsible for stabilizing the activation helix H12 in the agonist and antagonist positions.     

Anti-CagA Reactivity in Helicobacter pylori-Negative Subjects (A Comparison of Three Different Methods)

Emerging evidence suggests that infection byCagA-positive Helicobacter pylori strains is related tothe development of more serious gastroduodenal diseases,thus conferring to the determination of anti-CagA antibodies a relevant clinical significance inserological screenings. The detection of anti-CagApositivity in sera negative for anti-H. pyloriantibodies raises the question of whether thisapparently nonsense result is merely due to a falsepositive reaction. To address this issue, we comparedthree different methods for the detection of anti-CagAantibodies. In all, 272 selected sera from patients with precisely defined H. pylori status(positive or negative concordance of five tests, ie,histology by Giemsa in both antrum and corpus, rapidurease test, culture, [¹³C]urea breath test,IgG ELISA) were tested for anti-CagA reactivity by threedifferent techniques (western immunoblotting, ELISA, andrecombinant immunoblotting assay). In order to assessthe sensibility and specificity of each tests, we considered as true anti-CagApositive sera those with two out of three positiveresults. Sera from 70% of H. pylori-positive patientsand 10% from H. pylori-negative patients turned out to be true positives foranti-CagA antibodies. The three methods showed similarexcellent results, in terms of both sensitivity andspecificity, always over 93%. It is confirmed that aproportion of patients with a negative conventionalserology against H. pylori possess anti-CagA antibodiesin their sera. In this paper we demonstrate that it canhappen even in patients without any biological signs of actual H. pylori infection. The possibilitythat this can be due to a false positive laboratoryresult is very likely ruled out by the accuracy of thethree methods used. The clinical management of these patients needs further study on largerseries.     

<Emphasis Type="Italic">In vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> evaluation of NCX 4040 cytotoxic activity in human colon cancer cell lines

Background  

Nitric oxide-releasing nonsteroidal antiinflammatory drugs (NO-NSAIDs) are reported to be safer than NSAIDs because of their lower gastric toxicity. We compared the effect of a novel NO-releasing derivate, NCX 4040, with that of aspirin and its denitrated analog, NCX 4042, in in vitro and in vivo human colon cancer models and investigated the mechanisms of action underlying its antitumor activity.     

Nitric oxide plays a role in the regulation of adrenal blood flow and adrenocorticomedullary functions in the llama fetus

The effect of temperature on isometric tension with and without the regulatory proteins tropomyosin and troponin was studied in bovine myocardium using a thin filament removal and reconstitution protocol. In control bovine myocardium, isometric tension increased linearly with temperature in the range 5–40 °C: isometric tension at 10 and 30 °C was 0.65 and 1.28 times that at 20 °C, respectively, with a Q ₁₀ of about 1.4. In actin filament-reconstituted myocardium without regulatory proteins, the temperature effect on isometric tension was less: isometric tension at 10 and 30 °C was 0.96 and 1.17 times that at 20 °C, respectively, with a Q ₁₀ of about 1.1. The temperature dependence of the apparent rate constants was studied using sinusoidal analysis. The temperature dependence of 2π b (rate constant of delayed tension phase) did not vary significantly with the regulatory proteins under the standard activating condition (5 m m MgATP, 8 m m P_i, 200 m m ionic strength, pCa 4.66, pH 7.00). Q ₁₀ for 2π b in control and actin filament-reconstituted myocardium was 3.8 and 4.0, respectively. There were two phases to the temperature dependence of 2π c (rate constant of quick recovery). In control and thin filament-reconstituted myocardium, Q ₁₀ for 2π c was approximately 5.5 in the low temperature range (≤ 25 °C) and 2.7 in the high temperature range (≥ 30 °C). In actin filament-reconstituted myocardium, Q ₁₀ for 2π c was 8.5 in the low temperature range and 3.6 in the high temperature range. The above results demonstrate that regulatory proteins augment the temperature dependence of isometric tension, indicating that the regulatory proteins may modify the actomyosin interaction.     

VErapamil plus antiarrhythmic drugs reduce atrial fibrillation recurrences after an electrical cardioversion (VEPARAF Study).

AIMS: To evaluate the impact, on atrial fibrillation (AF) recurrences, of verapamil addition to a class IC or III antiarrhythmic drug in patients, with persistent AF, who underwent an electrical cardioversion (EC). METHODS AND RESULTS: Three hundred sixty-three patients were randomized to receive four different pre-treatment protocols: oral amiodarone (group A), oral flecainide (group F), oral amiodarone plus oral verapamil (group A+V), oral flecainide plus oral verapamil (group F+V). Patients who showed an AF recurrence within 3 months were assigned to the alternative group and underwent a second EC after 48h. During 3 months of follow-up, 89 patients (27.5%) had an AF recurrence. By univariate analysis, verapamil reduced AF recurrences if added to amiodarone or flecainide (from 35% to 20%, P=0.004). Applying Cox proportional hazards regression model, only the younger age, the shorter duration of AF, and the use of verapamil were predictor of maintenance of sinus rhythm after cardioversion. In patients with primary AF recurrence, verapamil addition to group A and F patients, significantly decreased secondary AF recurrence rate as compared to group A+V and F+V patients who stopped the verapamil therapy (68% vs 88%, P=0.03). CONCLUSIONS: The addition of verapamil to class IC or III antiarrhythmic drug significantly reduced the AF recurrences, that were more frequent in older patients and in patients with longer lasting AF; moreover, verapamil was effective in reducing the secondary AF recurrences, too.     

PHoral: Effects of carnosine supplementation on quantity/quality of oral salivae in healthy volunteer and in subjects affected by common oral pathologies

Background:Diseases of the oral cavity (OC) with an infectious trigger such as caries and periodontal disease are extremely common in the general population and can also have effects at the cardiovascular level. The oral salivary flow, with its buffering capacity, is able to regulate the pH of the OC and, therefore, significantly contribute to the ecological balance of the microenvironment in which the oral microbiome (OM) develops. On the other side, when the quality/quantity of salivary flow is altered it is supposed the disruption of this balance with the potential increase in oral pathogens and triggered diseases. Among the endogenous substances able to exert a significant effect on the salivary flow and its characteristics, carnosine (Car), a dipeptide originally isolated in skeletal muscle, represents, thanks to the known buffering properties, a promising principle.Methods:We aimed this protocol to evaluate the quantitative/qualitative characteristics of the salivary flow in healthy volunteer subjects (n = 20) and in subjects suffering from common OC pathologies (n = 40), before and after 7 days of supplementation with SaliflussTM (Metis Healthcare srl, Milan, Italy), a Class I medical device on the market as 400 mg mucoadhesive oral tablets that has Car as the main ingredient.Discussion:Combining the characteristics of saliva with the OM and comparing them with OC pathologies, we expect to clarify their reciprocal relationship and, using quantitative proteomics techniques, to help clarify the mechanism of action of Car.     

Development and Validation of a Smoking Expectancies Measure for Adolescents Seeking to Quit Smoking

Background: A more comprehensive understanding of factors that affect smoking cessation outcomes among adolescents may help enhance treatment interventions. One promising but underexplored factor that may influence cessation success is teens’ specific expectancies or beliefs about smoking outcomes. The present study evaluated the validity and reliability of a new measure of expectancies and its association with cessation outcomes among 762 adolescent smokers participating in studies of the American Lung Association's Not On Tobacco cessation program. Methods: Self-report questionnaires were collected prior to and following participation in a smoking cessation program. Self-reported cigarette use was verified with expired-air carbon monoxide. A multistep exploratory and confirmatory factor analysis and reliability and validity analyses were performed. Results: Four theoretically related yet empirically independent factors were identified by the Smoking Expectancies Questionnaire (SEQ): (1) Positive Reinforcement, (2) Negative Reinforcement—Emotional Regulation, (3) Negative Reinforcement—Addiction and Withdrawal, and (4) Negative Outcomes/Risk. These factors could be subsumed by a single SEQ factor that reflected an overall concept of smoking expectancies relevant for adolescent smoking cessation. An overall SEQ Function score reflecting the balance between positive and negative expectancies predicted both preintervention cigarettes per day and cessation outcomes. Conclusions: A single, overall SEQ Function score may prove useful for understanding the associations among individual, social, and contextual factors in predicting treatment outcomes. Additionally, study findings may assist with modifying smoking expectancies among cessation program participants, thereby enhancing treatment outcomes with diverse youth smoking populations.