Sustained release and enhanced oral bioavailability of rivaroxaban by PLGA nanoparticles with no food effect

Journal of Thrombosis and Thrombolysis - The purpose of the currents study was to enhance bioavailability of rivaroxaban (RXB) and reduce the food effect. RXB loaded PLGA nanoparticles...     

“Abortion—It Is My Own Body”: Women's Narratives About Influences on Their Abortion Decisions in Ghana

Globally, abortion has emerged as a critical determinant of maternal morbidity and mortality. The Ghana government amended the country's abortion law in 1985 to promote safe abortion. This article discusses the findings of a qualitative study that explored the decision-making experiences of 28 female abortion seekers aged between 15 and 30 years in Ghana. Key findings from the study are that individuals claimed autonomy in their abortion decisions; underlying the abortion decisions were pragmatic concerns such as economic difficulties, child spacing, and fear of parental reaction. In conclusion, we examine the health implications of Ghanaian women's abortion decisions.     

The Caenorhabditis elegans INX‐4/Innexin is required for the fine‐tuning of temperature orientation in thermotaxis behavior

Innexins in invertebrates are considered to play roles similar to those of connexins and pannexins in vertebrates. However, it remains poorly understood how innexins function in biological phenomena including their function in the nervous systems. Here, we identified inx‐4, a member of the innexin family in C. elegans, by a forward screening of thermotaxis‐defective mutants. The inx‐4 mutants exhibited abnormal migration to a temperature slightly higher than the cultivation temperature, called mild thermophilic behavior. Rescue experiments revealed that INX‐4 acts in the major thermosensory neuron AFD to regulate thermotaxis behavior. INX‐4::GFP fusion protein localized exclusively along axons in AFD neurons. In addition, over‐expression of INX‐4 in AFD neurons induced a cryophilic behavior, which is opposite to inx-4 mutants. Our findings suggest that INX‐4/Innexin in AFD may fine‐tune the execution of thermotaxis behavior when moving to desired temperatures.     

Modulation of Tissue Inflammatory Response by Histamine Receptors in Scorpion Envenomation Pathogenesis: Involvement of H4 Receptor

The inflammatory response caused by scorpion venoms is a key event in the pathogenesis of scorpion envenomation. This response was assessed in the cardiac, pulmonary, and gastric tissues of envenomed mice. The results reveal an increase of permeability in cardiac, pulmonary, and gastric vessels accompanied by an edema-forming, inflammatory cell infiltration, and imbalanced redox status. These effects are correlated with severe tissue alterations and concomitant increase of metabolic enzymes in sera. Pretreatment of mice with antagonists of H1, H2, or H4 receptors markedly alleviated these alterations in the heart and lungs. Nevertheless, the blockade of the H3 receptor slightly reduced these disorders. Histamine H2 and H4 receptors were the most pharmacological targets involved in the gastric oxidative inflammation. These findings could help to better understand the role of histamine in scorpion venom-induced inflammatory response and propose new therapy using as targets the H4 receptor in addition to histamine H1 and H2 receptors to attenuate the induced inflammatory disorders encountered in scorpion envenoming.     

Therapeutic potential of mesenchymal stem cell transplantation in a nitrofen-induced congenital diaphragmatic hernia rat model

Purpose

The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model.

Methods

Pregnant rats were exposed to nitrofen on embryonic day 9.5 (E9.5). MSCs were isolated from the enhanced green fluorescent protein (eGFP) transgenic rat lungs. The MSCs were transplanted into the nitrofen-induced E12.5 rats via the uterine vein, and the E21 lung explants were harvested. The study animals were divided into three: the control group, the nitrofen-induced left CDH (CDH group), and the MSC-treated nitrofen-induced left CDH (MSC-treated CDH group). The specimens were morphologically analyzed using HE and immunohistochemical staining with proliferating cell nuclear antigen (PCNA), surfactant protein-C (SP-C), and α-smooth muscle actin.

Results

The alveolar and medial walls of the pulmonary arteries were significantly thinner in the MSC-treated CDH group than in the CDH group. The alveolar air space areas were larger, while PCNA and the SP-C positive cells were significantly higher in the MSC-treated CDH group, than in the CDH group. MSC engraftment was identified on immunohistochemical staining of the GFP in the MSC-treated CDH group.

Conclusions

MSC transplantation potentially promotes alveolar and pulmonary artery development, thereby reducing the severity of pulmonary hypoplasia.     

Effect of sodium deficiency on growth of surgical infants: a retrospective observational study

Background/aim

Sodium is thought to be critical to growth. Infants who have an ileostomy may suffer from growth faltering, as sodium losses from stomas may be excessive. Urinary sodium measurements may indicate which patients could benefit from sodium supplementation; however, there is no consensus on what level of urinary sodium should be the cutoff for intervention. Our aim was to determine whether there is a relationship between urinary sodium and growth in infants undergoing ileostomy, colostomy and cystostomy.

Methods

Following audit approval, a retrospective observational study of patient notes and chemical pathology data was carried out. All infants <1 year of age that had an ileostomy, colostomy, or cystostomy procedure between February 1997 and January 2014 were included. Patients’ weights, urinary and serum sodium and potassium levels and clinical variables were recorded until discharge. Weights were converted to Z-scores for analysis.

Results

Forty patients were identified whose notes were available for review and who had at least three urinary sodium measurements. During their hospital stay, 11 (28 %) maintained weight within normal limits (Z-scores ?2 to +2, 15 (38 %) were moderately malnourished (?3 to ?2) and 14 (35 %) severely malnourished (30 mmol litre. Electrolyte data were not normally distributed so that correlations between electrolytes and growth were tested using the non-parametric Spearman rank correlation coefficient. Urinary sodium levels positively correlated with growth (r = 0.3071, p < 0.0001), as did serum sodium levels (r = 0.2620, p = 0.0059) whereas there was no relationship between urine or serum potassium and growth.

Conclusions

Poor growth is frequent in this group of patients and appears to be linked with sodium levels. Further work is necessary to draw up guidelines for appropriate sodium supplementation.     

Superior Proton Exchange Membrane Fuel Cell (PEMFC) Performance Using Short-Side-Chain Perfluorosulfonic Acid (PFSA) Membrane and Ionomer

Optimization of the ionomer materials in catalyst layers (CLs) which sometimes is overlooked has been equally crucial as selection of the membranes in membrane electrode assembly (MEA) for achieving a superior performance in proton exchange membrane fuel cells (PEMFCs). Four combinations of the MEAs composed of short-side-chain (SSC) and long-side-chain (LSC) perfluorosulfonic acid (PFSA) polymers as membrane and ionomer materials have been prepared and tested under various temperatures and humidity conditions, aiming to investigate the effects of different side chain polymer in membranes and CLs on fuel cell performance. It is discovered that SSC PFSA polymer used as membrane and ionomer in CL yields better fuel cell performance than LSC PFSA polymer, especially at high temperature and low RH conditions. The MEA with the SSC PFSA employed both as a membrane and as an ionomer in cathode CL demonstrates the best cell performance amongst the investigated MEAs. Furthermore, various electrochemical diagnoses have been applied to fundamentally understand the contributions of the different resistances to the overall cell performance. It is illustrated that the charge transfer resistance (R_ct) made the greatest contribution to the overall cell resistance and then membrane resistance (R_m), implying that the use of the advanced ionomer in CL could lead to more noticeable improvement in cell performance than only the substitution as the membrane.     

Markovnikov-addition of H-phosphonates to terminal alkynes under metal- and solvent-free conditions

An addition of H-phosphonates to aryl alkynes was realized under solvent- and metal-free conditions, affording Markovnikov-selective α-vinylphosphonates in moderate to good yields. A wide range of aryl alkynes could be applied for the reaction. A tentative mechanism of addition–substitution was proposed based on in situ³¹P {¹H} NMR studies.

Synthesis of α-vinylphosphonates from terminal alkynes and H-phosphonates as only the Markovnikov-regioisomer under metal- and solvent-free conditions.

Vinyl phosphorus compounds are of high importance because of their wide application in the fields of biological metabolism,¹ functional materials,² and as synthetic blocks of organophosphorus compounds.³ Some reviews have documented the preparations and applications of the vinyl phosphorus.⁴ Normally, the compounds can be acquired from alkynes, via the addition with H–P species. Aromatic ketones and aldehydes are also used as the sources of vinyl phosphorus, via multi-step conversions.^1b,5 The recently developed methods to obtain vinyl phosphorus involving H–P species include decarboxylation of cinnamic acid,⁶ dehydrogenation of active alkene,⁷ and dehydration of alcohols.⁸The addition of H–P species to alkynes is undoubtedly the most effective and atom economical method. The addition was usually catalysed by metals.^4e,9 One of the authors has reported palladium and rhodium catalysed additions of H–P species to alkynes.^9a–d Similar additions could be realized by catalysis with copper, nickel, molybdenum and ytterbium (Chart 1).¹⁰ The metal-catalysed procedures also include Suzuki reaction and others.¹¹ Although much progress has been made in this area, problems associated with narrow substrate scope, the need to use expensive transition metals and a stoichiometric amount of additives, and poor regio- and stereo-control have encouraged researchers to search for new and more efficient methods.Open in a separate windowChart 1Comparison of the construction of C(sp²)–P bonds to our current work.Recently, triflic anhydride (Tf₂O) has been applied for electrophilic activation of amides and P O species, and the activated intermediates could be used for the substitutions with various nucleophilic reagents.^7b,12 The conversions of P O species to C(sp²)–P bonds are quite rare. Miura and coauthors have reported a Tf₂O promoted activation of secondary phosphine oxides, which is applied for phosphination and intramolecular cyclization with alkynes.¹³ However, the scopes are limited with inner-alkynes. The application of H-phosphonates was not reported for the reaction (Chart 1).Herein we enclosed a novel Tf₂O promoted reaction of terminal alkyne with H-phosphonates. Vinyl phosphonates were afforded under metal- and solvent-free conditions, in excellent Markovnikov-regio selectivity.Phenylacetylene (1a) was initially treated with diethyl phosphite (2a) in the presence of Tf₂O in a molar ratio of 1 : 1 : 1. To our delight, diethyl 1-phenyl ethenylphosphonate (3aa), a Markovnikov addition product, was obtained in high regio-selectivity but in poor yield (10%). The reaction conditions were subsequently optimized with 1a and 2a. Considering Tf₂O was moisture sensitive, all experiments were performed under nitrogen. Two equivalents 2a was used to ensure 1a was consumed as much as possible. The conversion and isolated yield were calculated based on 1a (