Effect of cortical spreading depression on the levels of mRNA coding for putative neuroprotective proteins in rat brain.

Previous studies have demonstrated that cortical spreading depression (CSD) induces neuronal tolerance to a subsequent episode of ischemia. The objective of the present investigation was to determine whether CSD alters levels of mRNA coding for putative neuroprotective proteins. Unilateral CSD was evoked in male Wistar rats by applying 2 mol/L KCl over the frontal cortex for 2 hours. After recovery for 0, 2, or 24 hours, levels of several mRNA coding for neuroprotective proteins were measured bilaterally in parietal cortex using Northern blot analysis. Levels of c-fos mRNA and brain-derived neurotrophic factor (BDNF) mRNA were markedly elevated at 0 and 2 hours, but not 24 hours after CSD. Tissue plasminogen activator (tPA) mRNA levels were also significantly increased at 0 and 2 hours, but not 24 hours after CSD. Levels of the 72-kDa heat-shock protein (hsp72) mRNA were not significantly increased by CSD, except for a small elevation (20%) at 2 hours recovery. Levels of the 73-kDa heat-shock cognate (hsc73) mRNA were slightly, but significantly, increased at 2 and 24 hours of recovery. Finally, levels of mRNA for protease nexin-1 and glutamine synthetase were not significantly altered by CSD at any time studied. The current results support the hypothesis that neuronal tolerance to ischemia after CSD may be mediated by increased expression of FOS, BDNF, or tPA, but not by increased expression of hsp72, hsc73, nexin-1, or glutamine synthetase.

Distribution of thorny excrescences on CA3 pyramidal neurons in the rat hippocampus.

Thorny excrescences are the postsynaptic components of synapses between mossy fibers of granule cells and dendrites of CA3 pyramidal neurons in the hippocampal formation. Very little quantitative data on the number and distribution of excrescences in adult rats are available because, first, the vast majority are grouped into clusters and it is not possible to identify single excrescences within these clusters at the light microscope level. Second, clusters are of varying lengths and are distributed over hundreds of micrometers, making ultrastructural analysis prohibitively time-consuming. Here, by using three-dimensional analysis techniques at the light microscope level, we quantified the number, length, and distribution of excrescence clusters on proximal and midfield pyramidal neurons in the rat. Results indicated that proximal neurons had similar numbers of clusters on their apical and basal trees, and that cluster length was also similar. In contrast, midfield neurons had more apical than basal clusters, and apical clusters were longer. For neurons in both regions, basal clusters were located about 50% closer to somata. Overall, proximal neurons had more clusters than did midfield neurons, but the clusters were shorter; thus, proximal and midfield neurons had about the same total cluster length, and presumably the same number of single excrescences. Based on these data and on published ultrastructural measurements of single excrescences, we estimated an average of 41 excrescences/neuron, and suggest that a pyramidal neuron can be contacted by a maximum of 41 mossy fiber boutons, each from a different granule cell.

Preconditioning with cortical spreading depression does not upregulate Cu/Zn-SOD or Mn-SOD in the cerebral cortex of rats.

Previous studies have demonstrated that preconditioning the brain with cortical spreading depression (CSD) induces tolerance to a subsequent episode of ischemia. In other models of preconditioning, induction of ischemic tolerance has been associated with increased expression of the antioxidant enzyme, superoxide dismutase (SOD). The objective of the present study was to determine whether CSD upregulates Cu/Zn-SOD or Mn-SOD. CSD was induced in one hemisphere by applying 2 M KCl to the frontal cortex in Wistar rats. After 2 or 24 h of recovery, Cu/Zn-SOD and Mn-SOD mRNA levels were determined in both hemispheres using Northern blot analysis. In separate rats, Cu/Zn-SOD and Mn-SOD protein levels were determined 24 and 72 h after CSD using Western blot analysis. In addition, total SOD, Cu/Zn-SOD and Mn-SOD enzymatic activities were measured 24 and 72 h after CSD using spectrophotometric and zymographic assays. At the times investigated, no significant differences in mRNA or protein levels for Cu/Zn-SOD or Mn-SOD were observed between the ipsilateral and contralateral cortex. Further, there were no significant differences in Cu/Zn-SOD or Mn-SOD enzymatic activities between the two hemispheres at 24 or 72 h after CSD. In addition, CSD did not alter the activities of Cu/Zn-SOD or Mn-SOD in either hemisphere, relative to those in unoperated animals. Taken together, these results fail to support the hypothesis that CSD-induced tolerance is mediated through the upregulation of Cu/Zn-SOD or Mn-SOD.

Dose-dependent induction of mRNAs encoding brain-derived neurotrophic factor and heat-shock protein-72 after cortical spreading depression in the rat.

Previous studies have demonstrated that cortical spreading depression (CSD) increases the expression of putative neuroprotective proteins. The objective of the present study was to elucidate the relationship between the number of episodes of CSD and steady-state levels of mRNAs encoding brain-derived neurotrophic factor (BDNF), heat-shock protein-72 (hsp72) and c-fos. Wistar rats were administered one, five, or twenty-five episodes of CSD evoked by application of 2 M KCl to the frontal cortex of one hemisphere. Animals were permitted to recover for 30 min, 2 h or 24 h prior to sacrifice. Total RNA was isolated from the parietal cortex of each hemisphere and analyzed using Northern blots. At 30 min recovery, levels of BDNF mRNA were not significantly elevated after 1 episode of CSD, but were increased 4-fold after five episodes of CSD and 11-fold after twenty-five episodes of CSD, relative to levels in the contralateral hemisphere. At 2 h recovery, BDNF mRNA levels increased 2-, 3- and 9-fold, respectively. At 24 h, BDNF mRNA had returned to control levels in all groups. Thus, CSD increased levels of BDNF mRNA in a dose-dependent fashion at the early recovery times. Hsp72 mRNA was below the level of detection after 1 and 5 episodes of CSD. However, after twenty-five episodes of CSD, hsp72 mRNA levels were increased in the ipsilateral hemisphere at 30 min and 2 h recovery. Unlike levels of BDNF and hsp72 mRNA, levels of c-fos mRNA were increased nearly to the same extent at 30 min and 2 h after one, five or twenty-five episodes of CSD before returning to control by 24 h recovery. These results demonstrate that CSD triggers a dose-dependent increase in the expression of genes encoding neuroprotective proteins, which may mediate tolerance to ischemia induced by CSD.

Temporal and spatial patterns of malaria reinfection in northeastern Venezuela.

We stratified the risk of malaria transmission (Plasmodium vivax) in 35 villages along a coastal range in northeastern Venezuela (51 km2) where the main vector is the mosquito Anopheles aquasalis. After 20 years without local malaria transmission, reinfection of the entire area occurred from May to December 1985 by local (continuous) and jump (discontinuous) dispersal. Epidemiologic, environmental, and vector variables were investigated with the aid of a Geographic Information System. Risk factors for malaria transmission were human population density, proximity to pre-adult mosquito habitats (< 500 m), and the number of pre-adult habitats nearby. Most inhabitants, immature mosquito habitats, and malaria cases were located at low elevations and on gentle slopes. High prevalence of malaria during the dry seasons was associated with the presence of permanent bodies of water containing An. aquasalis. Occurrence of a La Niña event in 1988 (wet and cool phase of the El Niño Southern Oscillation) triggered malaria transmission to unusually high levels, consolidating infection in the area, and rendering traditional control efforts useless. We recommend tracking malaria persistence per village and associated risk factors as methods to reduce the cost of malaria control programs.

Novastan anticoagulation during renal stent implant in a patient with heparin-induced thrombocytopenia.

We describe a case of a 70-year-old male who underwent coronary artery bypass surgery which was complicated by multiple thrombotic events associated with HIT. The thrombotic events were treated with intravenous argatroban (Novastan). During the hospitalization the patient was found to require percutaneous bilateral renal artery revascularization for acute renal failure. The revascularization procedure was successfully accomplished with a high dose argatroban regimen. We present our report of a successful anticoagulation strategy during a peripheral intervention in a patient with HIT and the laboratory data which support this strategy.

Genetic divergence among Venezuelan populations of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae).

Lutzomyia longipalpis (Lutz & Neiva) is the primary vector of visceral leishmaniasis in Venezuela. An analysis of alleles at seven enzyme-encoding loci among four populations from different geographic and epidemiological regions revealed strong genetic substructuring. Isozyme analysis indicated that L. longipalpis in Venezuela is a complex of at least two subspecies. Possible differences in population size during their evolutionary histories, varying colonization histories and geological events may explain discrepancies in the patterns of variation observed at genetic markers between these four populations.

Genetic markers for the identification of two tick species, Amblyomma dissimile and Amblyomma rotundatum.

Genetic markers are described for 2 species of reptile and amphibian ticks, Amblyomma dissimile and Amblyomma rotundatum, by allozyme electrophoresis. Fixed allelic differences in 4 out of the 8 examined loci allowed the unequivocal separation of both of these species. A strong correlation was found between these genetic markers and the relative size of the spurs in coxae IV but not with the punctuation pattern of the scutum. Moreover, no overlap was found in the distribution of relative spur sizes between samples of both species. The percent polymorphic loci and the mean percent heterozygosity per locus for A. rotundatum was considerably lower than that for A. dissimile. Differences in the amount of genetic variability may be related to their modes of reproduction.

Population genetic structure of a three-host tick, Amblyomma dissimile, in eastern Venezuela.

Patterns of genetic variation for the tick Amblyomma dissimile were analyzed from a total of 200 ticks collected on 12 toads (Bufo marinus), 14 snakes (Boa constrictor), and 8 lizards (Iguana iguana) at 11 localities. The analyses were performed on electrophoretic data from 8 isozyme loci. Mean heterozygosity per locus was 6% (+/-3.1) per population. Differences in allelic frequencies among ticks from different individual hosts were the major source of genetic variability in this study. Host species was a smaller source of genetic variation. Genetic distances between localities varied according to which host species was present in each locality, and these appeared to be related to the extent of habitat overlap between host species. The smallest genetic distances between samples from different host species were recorded for I. iguana and B. constrictor. In contrast, the genetic distances between tick samples from B. marinus and either of the reptile species were significantly larger than between tick samples from this amphibian species. Ecological variables or the geographic distance did not explain the local patterns of differentiation observed in A. dissimile. Major genetic differences between island and mainland sites (0.03702) suggested an association between genetic distances and geographic isolation. The consistency between patterns of genetic variation and those of host home range overlap suggests that host dispersion is the main force structuring the genetic variation within this tick species.

The first report of successful carotid stent implant using argatroban anticoagulation in a patient with heparin-induced thrombocytopenia and thrombosis syndrome: a case report.

We report the first successful carotid stent implant in a patient with heparin-induced thrombocytopenia and thrombosis syndrome who presented with recurrent neurologic deficits secondary to severe carotid stenosis. Argatroban anticoagulation was used for the carotid stent deployment. We also present laboratory data that document effective procedural anticoagulation.

Correlated morphologic and genetic diversity among Lutzomyia longipalpis (Diptera: Psychodidae) collections in Venezuela.

Diversity among Lutzomyia longipalpis populations in Venezuela was characterized using 2 methods: larval mouthpart morphology-morphometry and isoenzyme electrophoresis. Analysis of the results suggested the presence of 2 morpho-genotypes. The mentum, maxillary comb, mandibular ventral teeth, and adenylate kinase and hexokinase enzyme-encoding loci suggested that a population from the northwestern Coriano System (Curarigua) is a distinct lineage within the L. longipalpis complex. Three widely separated populations from the Llanos (savanna), Andes, and northcentral Coastal Cordillera showed no significant substructure. These studies provide morphologic markers that are congruent with genetic data and suggest that the morphologic markers may be used to characterize and differentiate populations within this species complex.

Enfermedad de Darier sementaria tipo 1 / Segmental Darier disease type 1

La enfermedad de Darier segmentaria es una variante rara de esta patológica. Se caracteriza por una (..) (AU)

Segmental Darier disease is an unusual form of this condition. It is characterized by the localized (..) (AU)