Acute cerebral vascular injury after subarachnoid hemorrhage and its prevention by administration of a nitric oxide donor

OBJECT: Structural changes in brain parenchymal vessels occur within minutes after subarachnoid hemorrhage (SAH). These changes include platelet aggregation, activation of vascular collagenases, and destruction of perivascular collagen IV. Because collagen IV is an important component of the basal lamina, the authors attempted to further define changes in vascular structure (length and luminal diameter) and their relationship to vascular permeability immediately after SAH. In addition, the authors explored whether such alterations were attenuated by administration of a nitric oxide (NO) donor. METHODS: Endovascular perforation was used to induce SAH in rats. Two sets of experiments were performed. The first established changes in vascular structure and permeability (collagen IV and endothelial barrier antigen [EBA] dual immunofluorescence) during the first 24 hours after SAH. In the second, the investigators examined the effects of an NO donor on vascular structure, permeability, and collagenase activity (in situ zymography). In this second study, animals received intravenous infusion of the NO donor S-nitrosoglutathione (GSNO, 1 microM/8 microl/min) 15 minutes after induction of SAH and were killed 3 hours after SAH onset. Controls were naive unoperated animals for the first study and saline-infused SAH animals for the second. The authors found a time-dependent decrease in area fraction, length, and luminal diameter of collagen IV- and EBA-immunofluorescent vessels after SAH. The greatest change occurred at 3 hours after onset of SAH. Administration of GSNO was associated with striking preservation of collagen IV and EBA immunofluorescence compared with saline treatment. Zymography indicated decreased collagenase activity in GSNO-treated SAH animals compared with saline-treated SAH animals. CONCLUSIONS: These results demonstrate changes in the structure and permeability of brain parenchymal microvessels after SAH and their reversal by treatment with an NO donor.     

Demographic and Health-related Risk Factors of Subclinical Vitamin A Deficiency in Ethiopia

The study was conducted to determine the demographic and health-related risk factors of subclinical vitamin A deficiency in Ethiopia. Blood samples were collected from 996 children in 210 clusters across the nation for analysis of serum retinol. Interviews were conducted with the respective mothers of the 996 children on presumed risk factors of vitamin A deficiency. A higher subclinical vitamin A deficiency was associated with: not receiving vitamin A supplement over the year, having been ill during the two weeks preceding the survey, no or incomplete vaccination, belonging to a mother with high parity, and low levels of awareness of vitamin A. Moreover, being from Muslim household was strongly associated with higher levels of subclinical vitamin A deficiency. Among the risk factors identified, low levels of vaccination, high parity, and low levels of maternal awareness of vitamin A contributed to higher risks of vitamin A deficiency among Muslim children. The findings underscore the need for creation of strengthened awareness of family planning and importance of vitamin A, promotion of vaccination and child health, intensification of vitamin A supplementation, and in-depth investigation on factors contributing to increased vulnerability of Muslim children.Key words: Cross-sectional studies, Risk factors, Serum retinol, Vitamin A, Vitamin A deficiency, Xerophthalmia, Ethiopia     

Characterization of two mouse models of metastatic pheochromocytoma using bioluminescence imaging

Pheochromocytoma is the most common tumor of the adrenal medulla in adults. The lack of sensitive animal models of pheochromocytoma has hindered the study of this tumor and in vivo evaluation of antitumor agents. In this study we generated two sensitive luciferase models using bioluminescent pheochromocytoma cells: an experimental metastasis model to monitor tumor spreading and a subcutaneous model to monitor tumor growth and spontaneous metastasis. These models offer a platform for sensitive, non-invasive and real-time monitoring of pheochromocytoma primary growth and metastatic burden to follow the course of tumor progression and for testing relevant antitumor treatments in metastatic pheochromocytoma.     

Stress responsivity and HPA axis activity in juveniles: results from a home-based CO2 inhalation study

OBJECTIVE: A previous laboratory-based study found elevated cortisol levels in anxious children susceptible to CO(2)-induced panic, but the effects of parent diagnosis were not considered. The current home-based study tested the hypothesis that parental panic disorder and offspring response to CO(2) are associated with elevated cortisol levels in juvenile offspring. METHOD: A total of 131 offspring (ages 9-19) of parents with panic disorder, major depression, and no mental disorder underwent CO(2) inhalation. Parent and child diagnoses were assessed. Salivary cortisol was assayed before and after CO(2) inhalation. RESULTS: Neither parents with panic disorder, parents with major depression, or offspring anxiety predicted offspring cortisol levels. Independent of parent and child diagnoses, anxiety response to CO(2) predicted elevated cortisol levels in offspring. CONCLUSIONS: As in adults, anxiety response to CO(2) in juveniles is associated with elevated cortisol levels, but elevated cortisol levels are not related to parent or child diagnoses.     

Stent Migration and Folding in the Subclavian Vein during Subclavian Hemodialysis Catheter Placement

The role of stent placement in hemodialysis (HD) access intervention continues to evolve. As more stents are placed, new and unusual complications are coming to light. We describe a case in which an unsuccessful attempt to place a left subclavian dialysis catheter resulted in the inadvertent migration and folding of a previously deployed subclavian stent. Attempts to remove the stent with a snare were unsuccessful. Patency was restored to the access circuit by placing a new stent through the struts of the folded one. Clinical vascular practice guidelines for vascular access on the use of fluoroscopy for temporary HD catheter placement may need to be re-evaluated with the reported increase in stent placement in the US HD population.     

HIV and intestinal parasites in adult TB patients in a teaching hospital in Northwest Ethiopia

The level of HIV infection and intestinal parasitoses among TB patients was assessed in a hospital-based cross-sectional study involving 257 patients in Gondar, Ethiopia. In TB patients, our study reported co-infection with HIV (52.1%) and intestinal parasites (40.9%) The high prevalence of HIV and intestinal parasites indicates an increased morbidity inTB patients and emphasized the importance of continued HIV sero-surveillance, stool analysis and treatment.     

Prevalence of bacterial pathogens in children with acute respiratory infection in Addis Ababa

A study was conducted in the Ethio-Swedish Children's Hospital and different schools and kindergartens in Addis Ababa to determine the prevalence of bacterial agents that are associated with acute respiratory infection in children from 1998-1999. A total of 883 subjects were studied, out of which 77% were cases from the Ethio-Swedish Children's Hospital and 23% were controls from different schools and kindergartens. From each case and control throat and nasopharyngeal specimens were collected. Culture and different biochemical tests were used to isolate the potential bacterial pathogens. Clinical findings like cough, difficult breathing and fever were correlated with laboratory findings. S. pneumoniae and H. influenzae type b were the most commonly isolated bacteria in both throat and nasopharyngeal specimens; 74% and 70% in the cases and 2% and 5% in the control groups, respectively. This paper discusses the association between throat and nasopharyngeal carriership of bacteria and acute respiratory infection in children in Addis Ababa.     

Estimation of the von Willebrand factor-cleaving protease in plasma using monoclonal antibodies to vWF

A protease present in plasma cleaves von Willebrand factor (vWF) at the peptide bond 842Tyr-843Met of the mature subunit. To quantify this vWF-cleaving protease activity in plasma we have developed a simple method based on the estimation by IRMA of the degradation of a constant amount of wild type recombinant vWF used as substrate, by serial dilutions of test plasma used as protease provider. vWFAg was estimated by two-site IRMA using as first coating antibody a monoclonal antibody (MoAb) whose epitope is localized on the C-terminal side of the cleavage site, and as second labeled antibody a pool of MoAbs specific for the N-terminal side. Because the proteolytic process leads to the progressive separation of the C- and N-terminal portions of the vWF subunit such an IRMA also shows a progressive apparent loss of vWFAg. In contrast, the levels of vWFAg estimated after proteolysis by regular IRMA remained essentially constant. Results obtained with this new method were compared with the analysis by SDS-agarose gel electrophoresis of the multimeric pattern of proteolyzed WT-rvWF and no significant difference was noted testing a series of 28 plasmas. As compared with normal pooled plasma, 14 normal individuals and 13 patients with various types of vWD had normal levels of protease activity (44-178%) by both methods. The validity of the method was confirmed by showing a lack of detectable protease activity in a patient with chronic relapsing thrombotic thrombocytopenic purpura. In conclusion our method appears as a useful tool for the quantification of the vWF-cleaving protease activity in plasma. Its sensitivity and specificity are similar to those of SDS-gel electrophoresis. However, this new IRMA has the major advantages of being much simpler and faster, and open to most research laboratories in the field.     

Rb+ efflux through functional activation of cardiac KCNQ1/minK channels by the benzodiazepine R-L3 (L-364,373)

The slow delayed rectifier K+ current, Iks, encoded by KCNQ1 (KvLQT1)/KCNE1 (mink) genes, contributes to cardiac action potential repolarization and determines the heartbeat rate. Mutations in either KCNQ1 or KCNE1 that reduce Iks cause long-QT syndrome (LQTS), a disorder of ventricular repolarization that results in cardiac arrhythmia and sudden death. A well-recognized potential treatment for LQTS caused by reduction of Iks is to enhance functional activation of cardiac KCNQ1/KCNE1 channels. In the present study, we generated a stable Chinese hamster ovary cell line that expresses KCNQ1/KCNE1 channels confirmed by electrophysiology. Using a pharmacological tool compound R-L3 (L-364,373 [(3-R)-1,3-dihydro-5-(2-fluorophenyl)-3-(1H-indol- 3-ylmethyl)-1-methyl-2H-1,4-benzodiazepin-2-one]), which activates KCNQ1/mink channels, we then developed and validated a non-radioactive rubidium (Rb+) efflux assay that directly measures the functional activity of KCNQ1/KCNE1 channels by atomic absorption spectroscopy. Our results show that the validated Rb+ efflux assay can be used for screening of KCNQ1/KCNE1 openers that potentially treat LQTS in both inherited and acquired forms. In addition, the assay also can be used for evaluation of possible long-QT liability during cardiac selectivity of new chemical entities.