Clinical Efficacy of Phosphodiesterase‐5 Inhibitor Tadalafil in Eisenmenger Syndrome—A Randomized,Placebo‐controlled,Double‐blind Crossover Study

Objectives. In a randomized double‐blind crossover trial, we compared the efficacy of phosphodiesterase‐5 (PDE‐5) inhibitor tadalafil with placebo in patients of Eisenmenger Syndrome (ES). The primary end point was the change in 6‐minute walk test distance (6 MWD). Secondary end points were the effect of the drug on systemic oxygen saturation (SO₂), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), effective pulmonary blood flow (EPBF), and World Health Organization (WHO) functional class. Background. ES is a disorder with limited treatment options. Uncontrolled studies have shown PDE‐5 inhibitors to be beneficial in patients of ES. Methods. Twenty‐eight symptomatic adult patients of ES with weight ≥30 kg in WHO class II and III were enrolled. Patients were given 40 mg of tadalafil or matching placebo for 6 weeks followed by crossover to the other drug after a washout period of 2 weeks. Assessment of WHO class, exercise capacity by 6 MWD, and various hemodynamic parameters by cardiac catheterization was done at baseline, after 6 weeks and at the end of the study. Results. All patients completed the study. There was significant increase in 6 MWD following drug administration compared with baseline (404.18 ± 69.54 m vs. 357.75 ± 73.25 m, P < .001). Compared with placebo, tadalafil produced significant decrease in PVR (?7.32 ± 1.58, P < .001), resulting in significant increase in EPBF (0.12 ± 0.05, P= .03), SO₂ % (1.72 ± 0.58, P= .007), and WHO functional class (1.96 ± 0.18 vs. 2.14 ± 0.44, P= .025), with no significant change in SVR (P= NS). Conclusion. In this first short‐term placebo‐controlled trial of tadalafil in patients of ES, the drug was well tolerated and significantly improved exercise capacity, functional class, SO₂, and pulmonary hemodynamics. http://www.clinicaltrial.gov/ct2/show/NCT01200732?term=NCT01200732&rank=1     

Peptide contents of neuropeptide Y, vasoactive intestinal polypeptide, and beta-calcitonin gene-related peptide and their messenger ribonucleic acids after dexamethasone treatment in the isolated rat islets of Langerhans

A number of neuropeptides including neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), and beta-calcitonin gene related peptide (beta-CGRP) are known to influence insulin secretion. In order to investigate whether they might have a local autocrine/paracrine effect within the islets of Langerhans we screened isolated islets by Northern blot analysis and RIA for a number of peptides and found evidence for the presence of messenger RNA (mRNA) encoding NPY, VIP, and beta-CGRP. Dexamethasone treatment for 12 days increased the content of NPY, VIP, and beta-CGRP significantly from 1.3 +/- 0.3 to 19.8 +/- 1.6; 0.25 +/- 0.03 to 0.91 +/- 0.1; 2.2 +/- 0.2 to 4.8 +/- 0.1 fmol/islet respectively, mean +/- SEM (n = 4, P less than 0.05) and remained elevated 24 h after recovery. However when the results were normalized and expressed as a ratio of insulin content only NPY and VIP were significantly raised. Five days post treatment VIP was still significantly elevated compared to controls. mRNA for NPY increased 10-fold and for VIP increased 2 1/2 times after dexamethasone whereas mRNA for beta-CGRP was not significantly different from controls. Neither capsaicin nor 6-hydroxydopamine affected islet content or message of NPY, VIP, and beta-CGRP. Immunoreactive NPY and its mRNA were detected in two cultured beta-cell lines, HIT T-15 and RIN m5F cells whereas VIP and beta-CGRP were undetectable. The local islet synthesis of neuropeptides, which are known to influence islet hormone release pharmacologically, suggests the possibility that they may play a role in intraislet paracrine regulation.     

Copper sulfide nanostructures: synthesis and biological applications

Over the past few years, considerable attention has been paid to biomedical applications of copper sulfide nanostructures owing to their enhanced physiochemical and pharmacokinetics characteristics in comparison to gold, silver, and carbon nanomaterials. The small-sized Cu_xS_y nanoparticles have the advantage to absorb efficiently in the near-infrared region (NIR) above 700 nm and the absorption can be tuned by altering their stoichiometries. Moreover, their easy removal through the kidneys overpowers the issue of toxicity caused by many inorganic substances. The low cost and selectivity further add to the advantages of Cu_xS_y nanostructures as electrode materials in comparison to relatively expensive materials such as silver and gold nanoparticles. This review is mainly focused on the synthesis and biomedical applications of Cu_xS_y nanostructures. The first part summarizes the various synthetic routes used to produce Cu_xS_y nanostructures with varying morphologies, while the second part targets the recent progress made in the application of small-sized Cu_xS_y nanostructures as biosensors, and their analysis and uses in the cure of cancer. Photoacoustic imaging and other cancer treatment applications are discussed. Research on Cu_xS_y nanostructures will continue to increase over the next few decades, and great opportunities lie ahead for potential biomedical applications of Cu_xS_y nanostructures.

Over the past few years, considerable attention has been paid to biomedical applications of copper sulfide nanostructures owing to their enhanced physiochemical and pharmacokinetics characteristics in comparison to gold, silver, and carbon nanomaterials.     

Level of happiness and its determining factors in pregnant women: a cross-sectional study

Objective: This study aimed to estimate the prevalence of happiness and screen its determinant factors in pregnant Iranian women. Background: The psychological health status of a mother during pregnancy has a huge impact on clinical outcomes of pregnancy. Recent studies have demonstrated associations between mothers’ level of happiness and pregnancy outcomes such as low birth weight and intrauterine growth restriction. However, the data on determinant factors of maternal happiness are limited. Methods: Healthy pregnant women referring to a prenatal clinic in Tehran between 2013 and 2014 were recruited. We used the Persian version of the standard Oxford Happiness Questionnaire to assess level of happiness. In addition, personal, marital, pregnancy-related and psychological data were collected. Univariable and multivariable logistic analyses were conducted to investigate the determinant factors of happiness. Results: Two hundred pregnant women completed the questionnaire. One hundred and thirty women (68.5%) were categorised as happy. At a screening P value level of 0.2, univariable analysis selected maternal age (odds ratio [OR] = 8.3, P = 0.03), smoking (OR = 4.8, P = 0.01), level of education (OR = 1.78, P = 0.07), use of antidepressants (OR = 1.78, P = 0.17), and order of child (OR = 1.6, P = 0.18) for the multivariable model. The final multivariable logistic model demonstrated that maternal age (OR = 7.7, P = 0.01 for mothers aged 21–25; OR = 7.2, P = 0.01 for mothers aged 26–30; OR = 5.4, P = 0.03 for mothers aged 31–35; and OR=6.6, P = 0.05 for mothers aged 36–40 vs. mothers aged 20 or below) and smoking (OR = 5.4, P = 0.01 for mothers who had never smoked vs. mothers who had given up smoking) were independent correlates of happiness. Conclusion: Our observations suggest probable associations of maternal age and smoking with level of happiness in pregnancy. Further prospective longitudinal studies could investigate the causality inference of these associations.     

Anti-inflammatory effect of Algerian date fruit (Phoenix dactylifera)

From ages, dates are consumed by humans for its beneficial health and nutritional values. The aim of this study was to evaluate anti-inflammatory effect of Algerian date fruit (Phoenix dactylifera). A quantity of 50?mg/kg of the P. dactylifera extract was analyzed in vivo using the formalin-induced paw edema test in mice. The inflammation level was detected by the measure of the edema size, also the dosage of C-reactive protein (CRP) and homocysteine levels in the blood. The results showed a highly significant decrease in the edema size and the level of the homocysteine in the blood (P?=?.000) and significant decrease in CRP values (P?in vivo and directs the importance of further research and development of novel anti-inflammatory agents.     

Children’s recognition of pictorial signs and symbols

This study aimed to examine children’s recognition of common signs. A group of 449 children ages 4–5 years old were recruited from preschools in three Jordanian cities. The children were presented with a collection of common signs found in public spaces and asked to identify the sign’s meaning. Results revealed a low frequency of correctly recognising a sign’s meaning, as reflected in the total score. Signs were categorised as guided, warning, or public. Results showed that the most frequently identified signs were guided signs, with the mosque sign in particular being mostly often correctly identified. Results also showed that the least recognised sign was the elevator sign. Additionally, findings revealed that sign recognition differed significantly depending on the child’s gender, age, and location. The results of this study highlight the lack of knowledge children have about common public signs.     

Antimicrobial,anticancer, and antioxidant compounds from Premna resinosa growing in Saudi Arabia

Context: Premna resinosa (Hochst.) Schauer (Lamiaceae) is used in many places to treat bronchitis, respiratory illness and convulsions of the rib cage.

Objective: This study evaluates the anticancer, antimicrobial and antioxidant activities of P. resinosa, and isolates some responsible constituents.

Materials and methods: The methanol extract of P. resinosa aerial parts and its fractions (n-hexane, dichloromethane, ethyl acetate and n-butanol) were tested. Antimicrobial activity was tested using microdilution method against three Gram-positive and four Gram-negative bacteria. The tested concentrations ranged from 4000 to 7.8?μg/mL and MIC values were determined after 24?h incubation. Anticancer activity was evaluated against three human cancer cell lines (Daoy, HepG2 and SK-MEL28) using MTT assay. Antioxidant activity was investigated by DPPH scavenging method and β-carotene-linoleic acid assay.

Results: The greatest antimicrobial activity was exhibited by n-hexane fraction (MIC 10?μg/mL) against Staphylococcus aureus, Enterococcus faecalis, and Shigella flexneri. The n-hexane fraction induced the greatest cytotoxic activity against Daoy, HepG2, and SK-MEL28 cell lines with IC₅₀ values of 9.0, 8.5 and 13.2, respectively. Moreover, the dichloromethane and ethyl acetate fractions showed the highest antioxidant potential. A bioassay-guided fractionation led to the isolation and characterization of seven compounds for the first time, namely, quercetin (1), 3-methoxy quercetin (2), kaempferol (3), 3-methoxy kaempferol (4), myricetin 3,7,3′-trimethyl ether (5), lupeol (6), and stigmasterol (7).

Conclusion: Our results indicate that P. resinosa is a source for antimicrobial and cytotoxic compounds. However, further work is required to isolate other active principles and to determine the mechanism of action.