Ventricular defibrillating properties of catecholamine uptake inhibitors.

Ventricular fibrillation (VF) is a fatal event in humans unless electrical defibrillation is applied within minutes. Recent publications describe spontaneous termination of VF in various animals and even in humans. Certain drugs can transfer a fatal, sustained VF (SVF) into a self-terminating, transient VF (TVF). Based on results obtained in animals of various species and ages, we have suggested that the occurrence of TVF requires a high cardiac catecholamine level at the time of VF. According to our hypothesis, drugs which decrease catecholamine reuptake by the sympathetic nerve terminals will increase the ability of the heart ventricles to defibrillate spontaneously. In the present study, we examined the effects of desipramine, maprotiline, mianserin, iprindole, cocaine and amphetamine on the type of VF in cats exhibiting SVF prior to the treatment. The results show that the ability of these compounds to transfer SVF to TVF is closely related to their potency to inhibit catecholamine reuptake. The establishment of the catecholamine related mechanisms of TVF may lead to the development of a new class of antiarrhythmic-defibrillatory drugs.     

Lowry protein assay using an automatic microtiter plate spectrophotometer

The method of protein determination reported by Lowry et al. (1951, J. Biol. Chem. 193, 265-275) has been adapted for use with 96-well microtiter plates and an automatic microplate spectrophotometer. The spectrophotometer has been interfaced with a computer which plots the standard curve and calculates the protein content of each sample. The adapted method offers advantages over previously reported methods in that it is more rapid and uses a smaller sample volume (100 microliters) for samples containing 3-300 micrograms/ml (0.3-30 micrograms/assay) of protein. The method of Bensadoun and Weinstein (1976, Anal. Biochem. 70, 241-252) for precipitating microgram amounts of protein away from substances which interfere with the Lowry assay has also been adapted to this microplate procedure. These techniques should be particularly useful for laboratories where large numbers of samples containing a wide range of protein concentrations are assayed.     

Ciliary neurotrophic factor prevents neuronal degeneration and promotes low affinity NGF receptor expression in the adult rat CNS.

Recombinant human ciliary neurotrophic factor (CNTF) was infused for 2 weeks into the lateral ventricle of fimbria-fornix transected adult rats, and its effects were compared with those of purified mouse nerve growth factor (NGF). We provide evidence that CNTF can prevent degeneration and atrophy of almost all injured medial septum neurons (whereas NGF protects only the cholinergic ones). CNTF is also involved in up-regulation of immunostainable low affinity NGF receptor (LNGFR) in cholinergic medial septum and neostriatal neurons and in a population of lateral septum neurons. In contrast to NGF, CNTF did not stimulate choline acetyltransferase in the lesioned septum and normal neostriatum (pointing to different mechanisms for the regulation of choline acetyltransferase and LNGFR), cause hypertrophy of septal or neostriatal cholinergic neurons, or cause sprouting of LNGFR-positive (cholinergic) septal fibers.     

Streptococcus pneumoniae carriage in the Gaza strip

Background

Pneumococcal infections cause major morbidity and mortality in developing countries. We report the epidemiology of S. pneumoniae carriage in a developing region, the Gaza strip, and evaluate the theoretical coverage of carriage strains by pneumococcal conjugate vaccines (PCVs).

Methodology

In 2009 we conducted a cross-sectional survey of S. pneumoniae carriage in healthy children and their parents, living throughout the Gaza strip. Data were collected and nasopharyngeal swabs were obtained. Antibiotic susceptibilities were determined by Vitek-2 and serotypes by the Quellung reaction.

Principal Findings

S. pneumoniae carriage was detected in 189/379 (50%) of children and 30/376 (8%) of parents. Carriage prevalence was highest in children <6 months of age (63%). Significant predictors for child carriage were number of household members and DCC attendance. The proportion of pediatric and adults isolates with serotypes included in PCV7 were 32% and 20% respectively, and 46% and 33% in PCV13 respectively. The most prominent non-vaccine serotypes (NVT) were 35B, 15B/C and 23B. Penicillin-nonsusceptible strains were carried by70% of carriers, penicillin-resistant strains (PRSP) by 13% and Multi-drug-resistant (MDR) by 30%. Of all PRSP isolates 54% belonged to serotypes included in PCV7 and 71% in the PCV13. Similarly, 59% and 73% of MDR-SP isolates, would theoretically be covered by PCV7 and PCV13, respectively.

Conclusions

This study demonstrates that, PCV13-included strains were carried by 46% and 33% of pediatric and adult subjects respectively. In the absence of definitive data regarding the virulence of the NVT strains, it is difficult to predict the effect of PCVs on IPD in this region.     

Cholinergic neuronotrophic factors: III. Developmental increase of trophic activity for chick embryo ciliary ganglion neurons in their intraocular target tissues

Between stages 34 and 40 in the chick embryo, the ciliary ganglion (CG) undergoes a 50% loss of neurons. Such neuronal death is a common feature in neural development and it has been proposed that neurons are dependent for survival on trophic support from their target tissues. Using an in vitro bioassay it was previously shown in this laboratory that trophic activity for CG neurons is highly concentrated in eye structures containing CG target tissues. In the present study we have found that trophic activity in the eye increases markedly between stages 37 and 39, the time when neuronal death in the ciliary ganglion is ending. Thus, a developmental increase in trophic activity within the eye may be involved in determining neuronal survival in the CG. Furthermore, this study provides the first indication that the trophic content of target tissue is itself developmentally regulated.     

Human bone marrow-derived stem cells acquire epithelial characteristics through fusion with gastrointestinal epithelial cells

Bone marrow-derived mesenchymal stem cells (MSC) have the ability to differentiate into a variety of cell types and are a potential source for epithelial tissue repair. Several studies have demonstrated their ability to repopulate the gastrointestinal tract (GIT) in bone marrow transplanted patients or in animal models of gastrointestinal carcinogenesis where they were the source of epithelial cancers. However, mechanism of MSC epithelial differentiation still remains unclear and controversial with trans-differentiation or fusion events being evoked. This study aimed to investigate the ability of MSC to acquire epithelial characteristics in the particular context of the gastrointestinal epithelium and to evaluate the role of cell fusion in this process. In vitro coculture experiments were performed with three gastrointestinal epithelial cell lines and MSC originating from two patients. After an 8 day coculture, MSC expressed epithelial markers. Use of a semi-permeable insert did not reproduce this effect, suggesting importance of cell contacts. Tagged cells coculture or FISH on gender-mismatched cells revealed clearly that epithelial differentiation resulted from cellular fusion events, while expression of mesenchymal markers on fused cells decreased over time. In vivo cell xenograft in immunodeficient mice confirmed fusion of MSC with gastrointestinal epithelial cells and self-renewal abilities of these fused cells. In conclusion, our results indicate that fusion could be the predominant mechanism by which human MSC may acquire epithelial characteristics when in close contact with epithelial cells from gastrointestinal origin . These results could contribute to a better understanding of the cellular and molecular mechanisms allowing MSC engraftment into the GIT epithelium.