Increased transvascular transport of WGA-peroxidase after chronic perinatal stress in the hippocampal microvasculature of the rat

Brain endothelial ultrastructural properties contribute to maintain proper blood-brain barrier (BBB) function. Several physiological and pathological conditions have been shown to alter BBB permeability to blood-borne molecules, acute and chronic stress among them. In the rat, early life stress increased transvascular transport of Evans blue, however, the route of tracer extravasation is not fully known; therefore the aim of the present experiment was to describe the ultrastructural changes in endothelial cells subsequent to chronic perinatal stress in order to ascertain the route for transvascular transport of an electrodense tracer. Pregnant Wistar rats and their litters were used. Four pregnant rats were subjected to forced swimming between gestational days 10 to 20. After delivery, half of the control litters underwent 180 min maternal separation from postnatal day 2 to 20. Controls were kept free of any stress manipulation. At sacrifice between postnatal days 1 to 30 subjects were given intracardially the lectin wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). WGA-HRP stained hippocampi were processed for ultrastructural analysis, transmission electron micrographs were obtained and endothelial ultrastructural parameters quantified using the ImageJ software. Both stress procedures accelerated gross microvessel development by decreasing capillary wall thickness and endothelial microvilli. However, early-life stress also neutralized endothelial glycocalyx, increased vesicle-mediated transport and tended to promote the formation of secondary lysosomes containing endocytosed WGA-HRP vesicles, all parameters of altered endothelial cell function. Tight junction development in both stress groups was similar to the control pups.     

First egg protein with a neurotoxic effect on mice

While many invertebrates sequester toxic compounds to endow eggs with chemical defences, here we show, for the first time to our knowledge, the identification of a neurotoxin of proteinaceous nature localized inside an egg. Egg extracts from the freshwater apple snail Pomacea canaliculata displayed a neurotoxic effect in mice upon intraperitoneal injection (i.p.) (LD50, 96h 2.3mg/kg). Egg protein and total lipids were analysed separately and the only fraction displaying a highly toxic effect (LD50, 96h 0.25mg/kg, i.p.) was further purified to homogeneity as an oligomeric glyco-lipoprotein of 400kDa and two subunits biochemically and immunologically indistinguishable from the previously described perivitellin PV2. The neurotoxin was heat sensitive and there was evidence of circulating antibody response to sublethal i.p. doses on mice. Clinical signs, histopathological and immunocytochemical studies revealed damage mostly in mice spinal cord. Experiments showed chromatolysis and a decreased response to calbindin D-28K associated with a significant increase of TUNEL-positive cells in the dorsal horn neurons. These results suggest that calcium buffering and apoptosis may play a role in the neurological disorders induced by the toxin in mammalian central nervous system. This is the first report of a mollusc neurotoxin genetically encoded outside the cone-snail species.     

Hydrops fetalis associated with Noonan syndrome]

A case of Noonan syndrome associated with hydrops fetalis has been reported; it is recalled that morphological anomalies common to both Turner and Noonan syndromes depend on similar lymphatic anomalies. In the present case it is therefore proposed that the malformations of Noonan syndrome and hydrops fetalis proceed from the same lymphatic anomalies.     

Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure

Zidovudine (AZT) was the first nucleoside analogue licensed for the treatment of HIV infection. Efforts have continuously been made to improve the therapeutic characteristics of this drug, most of them focussed on prodrugs design. Here we describe the anti-HIV-1 activity and cytotoxicity of six novel AZT derivatives namely 3'-azido-3'-deoxy-5'-O-oxalyl-N-valinethymidine, 3'-azido-3'-deoxy-5'-O-oxalyl-N-leucinethymidine, 3'-azido-3'-deoxy-5'-O-oxalyl-N-isoleucinethymidine, 3'-azido-3'-deoxy-5'-O-oxalyl-N-phenylalaninethymidine, 3'-azido-3'-deoxy-5'-O-oxalylthymidine acid, 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine and 5-chloro-6-hydroxy-5,6-dihydro-3'-azido-3'-deoxythymidine which were perfectly characterized. AZT-Val, AZT-Leu, AZT-iLeu, AZT-Phen, AZT-Ac and AZT-Iso have shown a similar or higher selectivity index than that of AZT itself, in one or both of the different cell cultures used (PBMC and MT2). However, AZT-ClOH showed no anti-HIV activity. These results suggest that using amino acids in the design of AZT derivatives improves AZT activity.     

Integrating gender and number information in Spanish word pairs: an ERP study

The aim of the current study was to explore the integration processes of gender and number morphological features, since it has been proposed that grammatical gender and number features might be associated with different strength with the word stem in lexical representation. Event related potentials (ERPs) were recorded using a 128-channel sensor net while twenty-four volunteers read Spanish word pairs and performed a syntactic judgment task. The word pairs which could agree or disagree in gender or number or in gender and number at the same time, were formed by a noun and an adjective (e.g. faro-alto [lighthouse-high]). A negativity around 400 msec with posterior distribution, which has been related to lexical integration processes, was found in response to both gender and number violations. No differences were found between gender disagreement, number disagreement and the double disagreement. Therefore, ERPs suggest that integration of gender and number features may not be different, and that the detection of disagreement may work under a binary state, since the double disagreement condition did not differ from the others. In addition, a subsequent component (identified as P3) showed delayed latencies in the gender disagreement condition as compared to the number disagreement condition, while the double disagreement conditions showed a shorter peak latency than the other two disagreement conditions and similar to the agreement condition. The variations in the latency of the P3 component, which has been related to categorization processes, suggest that these processes are quickly triggered by the accumulation of two incongruent as compared to one disagreement features, and that reanalysis is costlier in the case of gender disagreement as compared to the number disagreement.     

Urinary retinol-binding protein as a prognostic marker in glomerulopathies

Tubulointerstitial involvement seems to have a decisive influence on the progression of glomerular diseases. We have prospectively evaluated the levels of urinary retinol-binding protein (urRBP), a marker of proximal tubular dysfunction, in patients with different glomerulopathies (GPs) and correlated these levels with disease progression. By studying 238 patients with GPs, we found that urRBP tend to be lower in minimal change disease, glomerular hematuria and poststreptococcal glomerulonephritis as compared to focal segmental glomerulosclerosis, membranous nephropathy and membranoproliferative glomerulonephritis. By following 149 patients for up to 10 years, we have concluded that high levels of urRBP can identify patients who will progress with loss of renal function (defined as doubling of serum creatinine level) and that a urRBP level >1 mg/l was an efficient and independent indicator of poor prognosis as shown by multivariate analysis. This prediction was possible at a time when serum creatinine and creatinine clearance were still in the normal range. Our data suggest that this laboratory test adds important clinical information to the follow-up of GPs.