Cinnamaldehyde inhibits L-type calcium channels in mouse ventricular cardiomyocytes and vascular smooth muscle cells

Cinnamaldehyde (CA), a major component of cinnamon, is known to have important actions in the cardiovascular system, including vasorelaxation and decrease in blood pressure. Although CA-induced activation of the chemosensory cation channel TRPA1 seems to be involved in these phenomena, it has been shown that genetic ablation of Trpa1 is insufficient to abolish CA effects. Here, we confirm that CA relaxes rat aortic rings and report that it has negative inotropic and chronotropic effects on isolated mouse hearts. Considering the major role of L-type Ca²⁺ channels in the control of the vascular tone and cardiac contraction, we used whole-cell patch-clamp to test whether CA affects L-type Ca²⁺ currents in mouse ventricular cardiomyocytes (VCM, with Ca²⁺ as charge carrier) and in mesenteric artery smooth muscle cells (VSMC, with Ba²⁺ as charge carrier). We found that CA inhibited L-type currents in both cell types in a concentration-dependent manner, with little voltage-dependent effects. However, CA was more potent in VCM than in VSMC and caused opposite effects on the rate of inactivation. We found these divergences to be at least in part due to the use of different charge carriers. We conclude that CA inhibits L-type Ca²⁺ channels and that this effect may contribute to its vasorelaxing action. Importantly, our results demonstrate that TRPA1 is not a specific target of CA and indicate that the inhibition of voltage-gated Ca²⁺ channels should be taken into account when using CA to probe the pathophysiological roles of TRPA1.     

Comparative Evaluation of 11 Commercialized Rapid Diagnostic Tests for Detecting Trypanosoma cruzi Antibodies in Serum Banks in Areas of Endemicity and Nonendemicity

Chagas disease is one of the main public health issues in Latin America. Increasingly during the past few decades, Trypanosoma cruzi infection has been detected in North America, Europe, and the Western Pacific, mainly as a result of population movement. The limited availability of rapid serological diagnostic tests hinders rapid diagnosis and early treatment in areas of endemicity and nonendemicity. In collaboration with 11 national reference laboratories (NRLs) from different geographical areas, we evaluated the performances of commercialized serological rapid diagnostic tests (RDT) for T. cruzi infection. Eleven commercialized T. cruzi infection RDTs were evaluated on a total of 474 samples extensively tested with at least three different techniques for Chagas disease, maintained at controlled low temperatures, and stored in the serum banks of the 11 NRLs. We measured the sensitivity, specificity, and concordance of each RDT and provided an additional questionnaire to evaluate its ease of use. The selected RDTs in this study were performed under controlled laboratory conditions. Out of the 11 RDTs, we found 8 of them to be useful, with the cassette format favored over the strip. We did not observe significant differences in RDT performances in the different regions. Overall, the performance results were lower than those disclosed by the manufacturers. The results of this evaluation validate the possibility of using RDTs to diagnose Chagas disease, thereby decreasing the time to treatment at a primary health care facility for patients who are willing to be treated. Further studies should be conducted in the laboratory and in the field to confirm these data, expressly to evaluate reproducibility in resource-limited settings, or using whole blood in clinical settings in areas of endemicity and nonendemicity.     

Optimization and pharmacological characterization of receptor‐mediated Gi/o activation in postmortem human prefrontal cortex

The biochemical abnormalities in transmembrane signal transduction mediated through G protein‐coupled receptors (GPCRs) have been postulated as underlying pathophysiology of psychiatric diseases such as schizophrenia and mood disorders. In the present study, the experimental conditions of agonist‐induced [³⁵S]GTPγS binding in postmortem human brain membranes were optimized, and the responses induced by a series of agonists were pharmacologically characterized. The [³⁵S]GTPγS binding assay was performed in postmortem human prefrontal cortical membranes by means of filtration techniques, and standardized as to GDP concentration, membrane protein content, MgCl₂ and NaCl concentrations in assay buffer, incubation period and effect of white matter contamination. Under the standard assay conditions, the specific [³⁵S]GTPγS binding was stimulated by the addition of 15 compounds in a concentration‐dependent manner. Of these agonists, R(+)‐8‐OH‐DPAT, UK‐14,304, DAMGO and DPDPE showed apparently biphasic concentration‐response curves. As for these four responses, only higher‐potency site was pharmacologically characterized. The receptors involved in the responses investigated were 5‐HT_1A receptor (probed with R(+)‐8‐OH‐DPAT or 5‐HT), α_2A‐adrenoceptor (UK‐14,304 or (?)‐epinephrine), M₂/M₄ mAChRs (carbachol), adenosine A₁ receptor (adenosine), histamine H₃ receptor (histamine), group II mGlu (l ‐glutamate), GABA_B receptor (baclofen), μ‐opioid receptor (DAMGO or endomophin‐1), δ‐opioid receptor (DPDPE or SNC‐80) and NOP (nociceptin). Although dopamine also activated specific [³⁵S]GTPγS binding, this response was likely mediated via α_2A‐adrenoceptor, but not dopamine receptor subtypes. The present study provides us with fundamental aspects of the strategy for elucidation of probable abnormalities of neural signalling mediated by G proteins activated through multiple GPCRs in the brain of psychiatric patients.     

Management of Helicobacter pylori infection in Latin America: A Delphi technique-based consensus

AIM: To optimize diagnosis and treatment guidelines for this geographic region, a panel of gastroenterologists, epidemiologists, and basic scientists carried out a structured evaluation of available literature.METHODS: Relevant questions were distributed among the experts, who generated draft statements for consideration by the entire panel. A modified three-round Delphi technique method was used to reach consensus. Critical input was also obtained from representatives of the concerned medical community. The quality of the evidence and level of recommendation supporting each statement was graded according to United States Preventive Services Task Force criteria.RESULTS: A group of ten experts was established. The survey included 15 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 50% in the first round, 73.3% in the second round and 100% in the third round. Main consensus recommendations included: (1) when available, urea breath and stool antigen test (HpSA) should be used for non-invasive diagnosis; (2) detect and eradicate Helicobacter pylori (H. pylori) in all gastroscopy patients to decrease risk of peptic ulcer disease, prevent o retard progression in patients with preneoplastic lesions, and to prevent recurrence in patients treated for gastric cancer; (3) further investigate implementation issues and health outcomes of H. pylori eradication for primary prevention of gastric cancer in high-risk populations; (4) prescribe standard 14-d triple therapy or sequential therapy for first-line treatment; (5) routinely assess eradication success post-treatment in clinical settings; and (6) select second- and third-line therapies according to antibiotic susceptibility testing.CONCLUSION: These achievable steps toward better region-specific management can be expected to improve clinical health outcomes.     

A multicentre observational study of the effectiveness,safety and economic impact of nivolumab on non-small-cell lung cancer in real clinical practice

International Journal of Clinical Pharmacy - Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective...     

Negative Pressure Wound Therapy With Low Pressure and Gauze Dressings to Treat Diabetic Foot Wounds

This study was a prospective cohort study to evaluate negative pressure wound therapy (NPWT) with low pressure and a gauze dressing to treat diabetic foot wounds. Thirty patients with diabetic foot wounds were consented to a prospective study to evaluate wound closure and complications to evaluate NPWT with low pressure (80 mmHg) and a gauze dressing interface (EZCare, Smith and Nephew) for up to 5 weeks. NPWT was changed 3 times a week. Study subjects were evaluated once a week for adverse events and wound measurements. Of study subjects, 43% attained at least a 50% wound area reduction after 4 weeks of therapy. Our results suggest that a high rate of wound closure could be expected with low pressure and a gauze interface.     

Bleeding risk stratification in an era of aggressive management of acute coronary syndromes

Major bleeding is currently one of the most common non-cardiac complications observed in the treatment of patients with acute coronary syndrome (ACS). Hemorrhagic complications occur with a frequency of 1% to 10% during treatment for ACS. In fact, bleeding events are the most common extrinsic complication associated with ACS therapy. The identification of clinical characteristics and particularities of the antithrombin therapy associated with an increased risk of hemorrhagic complications would make it possible to adopt prevention strategies, especially among those exposed to greater risk. The international societies of cardiology renewed emphasis on bleeding risk stratification in order to decide strategy and therapy for patients with ACS. With this review, we performed an update about the ACS bleeding risk scores most frequently used in daily clinical practice.     

Dispersion of γ-Alumina Nano-Sized Spherical Particles in a Calamitic Liquid Crystal. Study and Optimization of the Confinement Effects

We report an experimental study on confined systems formed by butyloxybenzylidene octylaniline liquid crystal (4O.8) + γ-alumina nanoparticles. The effects of the confinement in the thermal and dielectric properties of the liquid crystal under different densities of nanoparticles is analyzed by means of high resolution Modulated Differential Scanning Calorimetry (MDSC) and broadband dielectric spectroscopy. First, a drastic depression of the N-I and SmA-N transition temperatures is observed with confinement, the more concentration of nanoparticles the deeper this depression is, driving the nematic range closer to the room temperature. An interesting experimental law is found for both transition temperatures. Second, the change in shape of the heat capacity peaks is quantified by means of the full width half maximum (FWHM). Third, the confinement does not noticeably affect the molecular dynamics. Finally, the combination of nanoparticles and the external applied electric field tends to favor the alignment of the molecules in metallic cells. All these results indicate that the confinement of liquid crystals by means of γ-alumina nanoparticles could be optimum for liquid crystal-based electrooptic devices.