Acute and delayed vasoconstriction after subarachnoid hemorrhage: local cerebral blood flow, histopathology, and morphology in the rat basilar artery.

The decreased local cerebral blood flow (LCBF) and cerebral ischemia that occur after subarachnoid hemorrhage (SAH) may be caused by acute and/or delayed vasospasm. In 36 Sprague-Dawley (350-450 g) rats SAH was induced by transclival puncture of the basilar artery. Mean arterial blood pressure (MABP), LCBF, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were measured in all rats for 30 min before and 60 min after SAH was induced. One set of control (n : 7) and experimental animals (n : 7) was sacrificed after the 60 min of initial post-hemorrhage measurements were recorded. Four days after SAH induction, LCBF and MABP were measured again for 60 min in subgroups of surviving experimental rats (n : 7) and control rats (n : 7). Histopathologic and morphologic examinations of the basilar artery were performed in each subgroup. There was a sharp drop in LCBF just after SAH was induced (55.50 +/- 11.46 mlLD/min/100 g and 16.1 +/- 3.6 mlLD/min/100 g for baseline and post-SAH, respectively; p < 0.001). The flow then gradually increased but had not returned to pre-SAH values by 60 min (p < 0.05). At 4 days after SAH induction, although LCBF was lower than that observed in the control group and pre-SAH values, it was not significantly different from either of these flow rates (p > 0.05). ICP (baseline 7.05 +/- 0.4 mmHg) increased acutely to 75.2 +/- 7.1 mmHg, but returned to normal levels by 60 min after SAH. CPP (baseline 84.5 +/- 6.3 mmHg) dropped accordingly (to 18.6 +/- 3.1 mmHg), and then increased, reaching 72.2 +/- 4.9 mmHg at 60 min after SAH (p > 0.05). Examinations of the arteries revealed decreased inner luminal diameter and distortion of the elastica layer in the early stage. LCBF in nonsurviver rats (n : 8) was lower than that in the animals that survived (p < 0.01). At 4 days post-hemorrhage, the rats' basilar arteries showed marked vasculopathy. The findings showed that acute SAH alters LCBF, ICP, and CPP, and that decreased LCBF affects mortality rate. Subsequent vasculopathy occurs in delayed fashion, and this was observed at 4 days after the hemorrhage event.     

Sandfly-Borne Phlebovirus Isolations from Turkey: New Insight into the Sandfly fever Sicilian and Sandfly fever Naples Species

BackgroundMany studies have presented virus sequences which suggest the existence of a variety of putative new phleboviruses transmitted by sandflies in the Old World. However, in most of these studies, only partial sequences in the polymerase or the nucleoprotein genes were characterised. Therefore to further our understand of the presence and potential medical importance of sandfly-borne phleboviruses that circulate in southern Anatolia, we initiated field campaigns in 2012 and 2013 designed to identify, isolate and characterise phleboviruses in sandflies in this regionConclusions/SignificanceThe results indicate that a variety of phleboviruses are co-circulating in this region of southern Anatolia. Based on our studies, these new viruses clearly belong to genetic groups that include several human pathogens. However, whether or not Toros and Zerdali viruses can infect humans and cause diseases such as sandfly fever remains to be investigated.     

Signaling Crosstalk of FHIT,p53, and p38 in etoposide-induced apoptosis in MCF-7 cells

Fragile histidine trail (FHIT) is a tumor suppressor in response to DNA damage which has been deleted in various tumors. However, the signaling mechanisms and interactions of FHIT with regard to apoptotic proteins including p53 and p38 in the DNA damage-induced apoptosis are not well described. In the present study, we used etoposide-induced DNA damage in MCF-7 as a model to address these crosstalks. The time course study showed that the expression of FHIT, p53, and p38MAPK started after 1 hour following etoposide treatment. FHIT overexpression led to increase p53 expression, p38 activation, and augmented apoptosis following etoposide-induced DNA damage compared to wild-type cells. However, FHIT knockdown blocked p53 expression, delayed p38 activation, and completely inhibited etoposide-induced apoptosis. Inhibition of p38 activity prevented induction of p53, FHIT, and apoptosis in this model. Thus, activation of p38 upon etoposide treatment leads to increase in FHIT and p53 expression. In p53 knockdown MCF-7, the FHIT induction was hampered but p38 activation was induced in lower doses of etoposide. In p53 knockdown cells, inhibition of p38 induced FHIT expression and apoptosis. Our data demonstrated that the exposure of MCF-7 cells to etoposide increases apoptosis through a mechanism involving the activation of the p38-FHIT-p53 pathway. Moreover, our findings suggest signaling interaction for these pathways may represent a promising therapy for breast cancer.     

Effect of Proteasome Inhibitor on Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1) Expressions in Rat Model of Atherosclerosis

Background:The effect of proteasome inhibitors on atherosclerosis is known to vary depending on the atherosclerosis stage. Previous studies have shown that the highest proteasome expression in atherosclerotic lesions is at the progression stage. Adhesion molecules play a role in the progression stage of atherosclerosis, but no studies have analyzed the effect of proteasome inhibitors on the expression of adhesion molecules at this stage.Methods:This experimental study aimed to analyze the effect of a proteasome inhibitor, namely bortezomib, on the vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule1 (ICAM-1) expressions in blood vessels of rat model of atherosclerosis at the progression stage. This study used 18 male Wistar rats divided into three groups, i.e. group I that is the control group given standard feed, group II induced by atherosclerosis, and group III induced by atherosclerosis and given bortezomib. Atherosclerosis induction was performed using vitamin D3 (700,000 IU/kg) orally by gastric intubation on the 1st day and atherogenic feed given for four days. Bortezomib 50 µg/kgBW/day was administered intra-peritoneally. The expression of VCAM-1 and ICAM-1 molecules was measured using immunohistochemistry and analyzed quantitatively using Adobe Photoshop software.Results:The statistical test showed differences in VCAM-1 expression between atherosclerosis + Bortezomib group and atherosclerosis group, but there were no differences in the expression of ICAM-1 and atherosclerotic lesions between the groups.Conclusion:Administration of bortezomib 50μg/kg for four days in progressive atherosclerosis model rats can inhibit VCAM-1 expression, although it does not affect ICAM-1 expression and cannot inhibit atherosclerotic lesion formation.Key Words: Atherosclerosis, Bortezomib, Proteasome, VCAM-1, ICAM-1     

Presumptive monosomy 21 with neuronal migration disorder re-diagnosed as de novo unbalanced translocation t(18p;21q) by fluorescence in situ hybridisation

We present clinical and cytogenetic data of a one year old boy with partial monosomy for both 21q and 18p, resulting from a de novo unbalanced translocation. The initial diagnosis of a seemingly full monosomy 21 was revised after fluorescence in situ hybridisation (FISH) with whole chromosome painting probes and a locus-specific chromosome 21 probe. The karyotype was reinterpreted as 45,XY,der(18)t(18;21)(p11.2;q22.1),-21. This karyotype, to our knowledge, has not been previously described. The boy presented with a spectrum of clinical features previously described for (partial) monosomy 18p only, for monosomy 21q only, or for both of these aneusomies. The radiological finding of a neuronal migration disorder with localised polymicrogyria (cortical dysplasia) has not been described for either monosomy before.     

Genome structural variation discovery and genotyping

Comparisons of human genomes show that more base pairs are altered as a result of structural variation - including copy number variation - than as a result of point mutations. Here we review advances and challenges in the discovery and genotyping of structural variation. The recent application of massively parallel sequencing methods has complemented microarray-based methods and has led to an exponential increase in the discovery of smaller structural-variation events. Some global discovery biases remain, but the integration of experimental and computational approaches is proving fruitful for accurate characterization of the copy, content and structure of variable regions. We argue that the long-term goal should be routine, cost-effective and high quality de novo assembly of human genomes to comprehensively assess all classes of structural variation.