Epidermal growth factor suppresses renal tubular apoptosis following ureteral obstruction

Objectives. Acute unilateral ureteral obstruction (UUO) results in ipsilateral hydronephrosis characterized by a decrease in epidermal growth factor (EGF) mRNA expression and EGF protein levels in the distal renal tubules. UUO results in programmed cell death with increases in the characteristic markers of apoptosis. To suppress the apoptotic response during UUO, recombinant EGF was administered during renal obstruction and the ensuing molecular and histologic changes were studied.Methods. Mature Sprague-Dawley rats underwent left ureteral obstruction and the kidneys were harvested at 24, 48, and 72 hours. Markers of apoptosis included DNA laddering pattern on agarose gel electrophoresis, in situ gap labeling of fragmented DNA for quantitative apoptotic body determination, polyadenylated mRNA expression of SGP-2, and in situ hybridization for sulfated glycoprotein-2 (SGP-2) mRNA. Studies were repeated in rats following administration of 10, 20, and 40 μg of subcutaneous recombinant EGF on a daily basis after UUO.Results. Subcutaneous injection of EGF into unilaterally obstructed rats promotes renal tubular epithelial cell regeneration, as demonstrated by increased cortical mitotic activity. Systemic EGF supplementation in these unilaterally obstructed rats also resulted in a decrease in the intensity of the DNA laddering pattern associated with renal tubular apoptosis. An in situ labeling procedure to identify apoptotic nuclei in the ureterally obstructed kidneys revealed a 50% reduction in apoptosis after EGF administration. Northern blot analysis and in situ hybridization for SGP-2 mRNA or clusterin gene product also revealed a decreased expression in the obstructed and EGF-treated renal parenchyma.Conclusions. These data suggest that EGF, apart from its known role as a mitogenic substance for renal tubular epithelial cells, is also a critical in vivo renal cell survival factor for the developmentally mature kidney.     

Experimental arthritis induced by a clinical Mycoplasma fermentans isolate

Background  

Mycoplasma fermentans has been associated with rheumatoid arthritis. Recently, it was detected in the joints and blood of patients with rheumatoid arthritis, but it is not clear yet how the bacteria enter the body and reach the joints. The purpose of this study was to determine the ability of M. fermentans to induce experimental arthritis in rabbits following inoculation of the bacteria in the trachea and knee joints.     

Membrane properties of an unusual intrinsically oscillating, wide-field teleost retinal amacrine cell

In the retina, amacrine cells modulate the transfer of information from bipolar to ganglion cells. The nature of the modulation depends on the synaptic input and the membrane properties of the cells. In the retina of white bass, we identified a class of bistratified, wide-field amacrine cell characterized by immunopositive labelling for GABA and calmodulin. In isolation, the cells presented resting membrane potentials averaging -69 mV although some cells settled at more depolarized values (-30 mV). Injection of depolarizing current pulses induced oscillatory membrane responses. When elicited from depolarized cells, the oscillations were short-lived (< 40 ms). For the most part, the oscillatory potentials of hyperpolarized cells remained unattenuated throughout the depolarizing pulse. The frequency of the oscillations increased logarithmically with mean membrane potential, ranging from 74 to 140 Hz. Cells exhibiting depolarized membrane potentials oscillated at twice that rate. When the membrane potential of these cells was hyperpolarized to -70 mV, the oscillations became unattenuated and slowed. We found the cells expressed voltage-gated sodium, potassium and calcium currents and calcium-dependent potassium currents. We demonstrate that the oscillatory potentials arose as a result of the interplay between calcium and potassium currents. The cells responded to local application of GABA and glycine, both of which modulate the oscillatory potentials. Glutamate and its analogues depolarized the cell and induced oscillatory potentials. Our results indicate that oscillatory responses of a type of wide-field amacrine cell are an intrinsic feature of the cell and not due to circuit properties.     

Parvalbumin-immunoreactive neurons in the cerebral cortex of the lizardPodarcis hispanica

An antibody against the calcium binding protein parvalbumin selectively labels a set of neurons in the cerebral cortex of lizards. Golgi-like immunostained bipolar, multipolar and pyramid-like neurons appear mainly located in the inner plexiform layers. Parvalbumin-immunoreactive (PARV-IR) puncta are concentrated in the cell layer of the dorsal and dorsomedial cortices showing a basket-like distribution. The morphology and distribution of PARV-IR neurons and puncta overlap GABA-immunostaining in the cerebral cortex of lizards. Thus, it is likely that PARV-IR neurons are a subset of the cortical GABAergic neurons of lizards.     

Immunogenicity and safety of a novel yeast Hansenula polymorpha-derived recombinant Hepatitis B candidate vaccine in healthy adolescents and adults aged 10–45 years

The aim was to determine whether the immunogenicity of an investigational hepatitis B vaccine (spHB) is at least as high as that of a licensed control vaccine, Engerix B^®, and to evaluate its safety before inclusion in new pediatric combination vaccines. Two randomized, controlled, blind-observer, Phase 3 trials were performed: one in Argentina (344 participants aged 10–15 years, 10 μg HBsAg/dose) and one in Uruguay (344 participants aged 16–45 years, 20 μg HBsAg/dose). Both vaccines were given in a 0, 1, 6 month schedule to all participants with a baseline anti-Hep B antibody titer <0.6 mIU/mL. Antibody titers were measured pre-dose 1, 1 month after dose 2, pre-dose 3, and 1 month after dose 3. Statistical non-inferiority analyses were performed on seroprotection rates (SP) post-dose 3 (% with anti-Hep B titers ≥10 mIU/mL; delta non-inferiority limit of −10%). In both studies, SP for the spHB vaccine was 100% and the spHB vaccine was non-inferior in terms of SP to the licensed control vaccine. GMTs post-dose 3 were approximately 1.8- and 4.1-fold higher for spHB in the 10–15 year and 16–45 year age groups, respectively. Reactogenicity was low for each vaccine, after each dose. This highly immunogenic hepatitis B candidate vaccine was selected for further investigation as a component of new pediatric combination vaccines.     

An alternative to the neoliberal model in health: the case of Venezuela.

The authors present a synthesis of the proposals put forth by the health sector of Venezuela during the framing of the new Venezuelan Constitution. They summarize the background to the National Constituent Assembly and the legal framework typical of the health sector at that time, identify the methodological aspects that substantiated the health topics included in the new Constitution, and analyze the articles that shape the current constitutional health framework in Venezuela, summarizing their most important features and comparing them with neoliberal health proposals.