Expression of Gsalpha,connexin-43, connexin-26, and EP1, 3, and 4 receptors in myometrium of prelabor singleton versus multiple gestations and the effects of mechanical stretch and steroids on Gsalpha

OBJECTIVE: We tested the hypothesis that multiple pregnancies would be associated with altered expression of the following three groups of proteins that are key regulators of myometrial function: (i) Gsalpha, (ii) connexins-43 and 26, and (iii) prostanoid EP1, EP3, and EP4 receptors. METHODS: An in vitro model was used to determine the effects of mechanical stretch on myometrial cell Gsalpha expression. Then the effects of the steroid hormones beta-estradiol and progesterone were tested on Gsalpha expression in vitro. All in vitro studies were performed using myometrium from nonlaboring women. RESULTS: There were no differences in the expression of Gsalpha, prostaglandin E2 receptors, or gap junction proteins in myometrium of singleton versus multiple pregnancies. Mechanical stretch did not alter Gsalpha expression in vitro, and Gsalpha expression was unaffected by steroid hormones. CONCLUSION: These results suggest that the methods whereby stretch can promote myometrial contraction are complex or require additional factors than those tested here. Alternatively, cases of multiple gestation that do not result in preterm labor perhaps compensate for the increased stretch by preventing aberrant expression of the proteins investigated in this study.     

Control of dendritic cell cross-presentation by the major histocompatibility complex class I cytoplasmic domain

Dendritic cells (DCs) can present extracellularly derived antigens in the context of major histocompatibility complex (MHC) class I molecules, a process called cross-presentation. Although recognized to be important for priming of T cell responses to many viral, bacterial and tumor antigens, the mechanistic details of this alternative antigen-presentation pathway are poorly understood. We demonstrate here the existence of an endolysosomal compartment in DCs where exogenously derived peptides can be acquired for presentation to T cells, and show that the MHC class I cytoplasmic domain contains a tyrosine-based targeting signal required for routing MHC class I molecules through these compartments. We also report that transgenic mice expressing H-2K(b) with a tyrosine mutation mount inferior H-2K(b)-restricted cytotoxic T lymphocyte responses against two immunodominant viral epitopes, providing evidence of a crucial function for cross-priming in antiviral immunity.     

Surface characterization and platelet adhesion studies on fluorocarbons prepared by plasma-induced graft polymerization

It is believed that the interactions between the biological environment and biomaterial surface are the key factors influencing its biocompatibility. Therefore, plasma processing, which can vary the surface properties without altering the bulk properties, has been considered as one of the important techniques for improving a materials' biocompatibility. In this investigation, plasma-induced grafting polymerization of vinylidene fluoride (VDF) and chlorotrifluoroethylene (CTFE), instead of direct plasma polymerization, was attempted with an aim to improve the substrate blood compatibility. Contact angle measurement indicated both fluorocarbon-grafted Pdyethylenes (PEs) are hydrophobic. Due to the additional fluorine and chlorine atoms on the CTFE chain, the PCTFE-grafted PE exhibited a higher hydrophobicity than the PVDF-grafted one. ESCA analysis has revealed that these two plasma-induced fluorocarbon deposits contain almost no CFx (x > 2) binding on the surface layer, indicating the grafting polymerization mainly follows the free radical mechanism instead of the molecule-highly-fragmented reaction steps commonly seen in the direct plasma polymerization treatment. In addition, ATR-FTIR has shown the surface chemical configuration of these PVDF- and PCTFE-grafted PEs to be very similar to those of the bulk samples of PVDF and PCTFE. The surface roughness decreased after oxygen plasma treatment and was further reduced by VDF and CTFE grafting polymerization. In vitro platelet adhesion testing indicated these two fluorocarbon grafted PEs are less platelet-activating than the nontreated PE control and oxygen plasma activated one.     

Case illustrations of long QT syndrome

Long QT syndrome (LQTS) is a rare potentially life-threatening condition. Physicians must remain vigilant and consider LQTS as a possible etiology in patients with a history of syncope. Prolongation of the QT interval on electrocardiogram (ECG) is an essential component for the diagnosis of LQTS, despite the limitations of this technique. Experience of analyzing the ECG and calculating corrected QTc still remain relevant and are the mainstay diagnostic tools. Often, the first sign of the problem is observed after careful evaluation of the resting ECG for the hallmark of the disorder. Unfortunately, more than 60% of physicians-even cardiologists-have been known to misinterpret the QT interval on ECG. The cases discussed in this article highlight the variable clinical presentation of prolonged QT interval and the need to be highly vigilant in clinical evaluation.     

Effects of liquisolid formulations on dissolution of naproxen

The aim of this study was to investigate the use of liquisolid technique in improving the dissolution profiles of naproxen in a solid dosage form. This study was designed to evaluate the effects of different formulation variables, i.e. type of non-volatile liquid vehicles and drug concentrations, on drug dissolution rates. The liquisolid tablets were formulated with three different liquid vehicles, namely Cremophor^® EL (polyoxyl 35 castor oil), Synperonic^® PE/L61 (poloxamer 181, polyoxyethylene-polyoxypropylene copolymer) and poly ethylene glycol 400 (PEG400) at two drug concentrations, 20%w/w and 40%w/w. Avicel^® PH102 was used as a carrier material, Cab-o-sil^® M-5 as a coating material and maize starch as a disintegrant. The empirical method as introduced by Spireas and Bolton (1999) [1] was applied strictly to calculate the amounts of coating and carrier materials required to prepare naproxen liquisolid tablets. Quality control tests, i.e. uniformity of tablet weight, uniformity of drug content, tablet hardness, friability test, disintegration and dissolution tests were performed to evaluate each batch of prepared tablets. In vitro drug dissolution profiles of the liquisolid formulations were studied and compared with conventional formulation, in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.2) without enzyme. Stability studies were carried out to evaluate the stability of the tablets under humid conditions. Differential scanning calorimetry and Fourier transform infrared were used to investigate physicochemical interaction between naproxen and the excipients. It was found that liquisolid tablets formulated with Cremophor^® EL at drug concentration of 20%w/w produced high dissolution profile with acceptable tablet properties. The stability studies showed that the dissolution profiles of liquisolid tablets prepared with Cremophor^® EL were not affected by ageing significantly. Furthermore, DSC revealed that drug particles in liquisolid formulations were completely solubilised.