No phenotype associated with established lipopolysaccharide model for cerebral palsy

OBJECTIVE: Cerebral palsy (CP) is associated with childhood spasticity, seizures, and paralysis. Oligodendrocyte damage resulting in periventicular leukomalacia (PVL) in the developing brain has been implicated. Animal models of CP have used prenatal hypoxia and infection with histopathology of PVL as the end point. To evaluate whether this histologic end point is associated with a CP phenotype, we reproduced a lipopolysaccharide (LPS) model for PVL, 1 and evaluated developmental, behavioral, and motor outcomes. STUDY DESIGN: On gestational day 15, Fischer 344 rats were intracervically injected with .1 mg/kg LPS (n = 5) or saline (n = 4). After delivery, evaluation for developmental milestones was performed on days 1 to 21 (LPS = 45; control = 30 pups). Males were also tested at 2.5 months using open-field, rotarod, and anxiety tests. On day 21, 2 pups/litter were perfused for immunohistochemistry, and stained with 2 oligodendrocyte antibodies: 2', d'-cyclic nucleotide phosphodiesterase (CNP), and myelin proteolipid protein (PLP) with relative densities of staining assessed using NIH Image software. Statistical analysis included Mann-Whitney U and analysis of variance (ANOVA). RESULTS: LPS pups demonstrated decreased CNP (P = .04) and PLP (P = .06) staining, replicating the model. There was no difference seen in neonatal weight, righting, negative geotaxis, cliff aversion, rooting, forelimb grasp, audio startle, air righting, eye opening, and activity. Surprisingly, LPS-exposed neonatal rats mastered forelimb placement (P < .01) and surface righting (P = .02) earlier than control rats. There were no differences between adult groups in open field distance traveled (P = .8), open-field locomotion time (P = .6), rotarod (P = .6), or anxiety (P = .7). CONCLUSION: Histologic evidence of white matter damage can be replicated using an LPS model for intrauterine inflammation. Significant phenotypic differences consistent with the motor and cognitive damage sequelae of such lesions (ie, CP) were not demonstrated. When evaluating animal models, it is important to assess not only biochemical markers for human disease, but also clinically relevant phenotypes.     

Human immunodeficiency virus/acquired immunodeficiency syndrome knowledge and risk factors in Ethiopian military personnel

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-related knowledge and behaviors were assessed in face-to-face structured interviews with 314 Ethiopian military personnel. A significant finding of this research was the association between HIV/AIDS knowledge and risky sexual behavior. That is, military personnel who had inaccurate knowledge about HIV/AIDS transmission and prevention were 3.4 times as likely to engage in combined sexual risk behaviors compared with personnel with accurate knowledge, after controlling for age, military rank, and marital status (odds ratio, 3.4; 95% confidence interval, 1.86-6.22). This finding highlights the potential value of educational programs in slowing the spread of HIV/AIDS in sub-Saharan Africa.     

Vascular responsiveness to dimethylaminoethyl methacrylate and its degradation products

The increasing use of acrylate-based resins in dentistry has raised questions about the biocompatibility of these substances with oral tissues. The focus of the present investigation was to assess the responsiveness of blood vessels to the resin polymerization accelerating agent dimethylaminoethyl methacrylate (DMAEMA) and its degradation products dimethylethanolamine (DME) and methacrylic acid (MAA), using the rat aortic ring preparation as a tissue model. DMAEMA induced concentration-dependent relaxation of norepinephrine (NE)-contracted aortic rings with and without endothelium. N-nitro-L-arginine methyl ester (L-NAME) selectively inhibited the endothelium-dependent relaxation induced by DMAEMA, suggesting the release of nitric oxide from the endothelium by DMAEMA. Both indomethacin and glybenclamide attenuated the vasorelaxation elicited by DMAEMA in the presence as well as in the absence of endothelium, providing evidence for the role of vasorelaxant prostanoid(s) and K(ATP) channel activation in the responses observed. On the other hand, while MAA was without any apparent effect on the rat aorta, DMAEMA at high and DME at relatively low concentrations caused contraction of the tissues with and without endothelium in the absence of NE. The DME-induced contraction was inhibited by indomethacin, suggesting the involvement of contractile arachidonic acid metabolite(s) in the action of DME. This observation was supported by the findings of increased thromboxane A(2) (TXA(2)) production in aortic rings incubated with DME. Taken together, the data suggest that both DMAEMA and its degradation product, DME, are vasoactive, inducing vasorelaxation and contraction by various mechanisms that may involve the release of nitric oxide from the endothelium, the activation of smooth muscle K(ATP) channels, and the generation of vasorelaxant prostanoid(s) and TXA(2). These effects may play a role in tissue homeostasis and certain adverse conditions associated with the use of dental resin materials containing DMAEMA and/or DME.     

Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome

Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.     

Occupational environment as perceived by workers at a textile mill in Bahir Dar, northwest Ethiopia

This cross sectional study was conducted among textile mill workers in Bahir Dar town in 1995/96. The main objective of the study was to investigate how workers perceive their work environment and explore their state of satisfaction with their work. A pretested questionnaire was administered by trained health workers to 394 production workers. The majority of the workers (53.6%) claimed the work environment to be hot. For 66.8%, the physical conditions around the working departments was worst during the hot season. The work place was perceived as dusty and noisy by 47.2% and 36.0% of the respondents respectively. The distribution of adverse environmental complaint by work department was not the same. A higher proportion of the workers in the spinning department complained of inadequate air movement (64.5%) and dusty work place (53.3%); whereas those in the weaving department complained the work place to be hot and noisy (60.5%, 53.5% respectively). Aprons were used by 95.7%, but other personal protectors such as ear protectors, gloves and goggles were used rarely. In general, 228 (57.9%) workers were satisfied but the rest were dissatisfied with their work environment. In order to improve the hygienic conditions in the work place, 71.2% suggested use of different kinds of personal protectors. In conclusion, personal protectors should always be used, environmental hygiene should be conducted and health education should be provided to workers.     

Role of cardiac resynchronization in end-stage heart failure patients requiring inotrope therapy

BackgroundOutcomes among inotrope-treated heart failure (HF) patients receiving cardiac resynchronization therapy (CRT) have not been well characterized, particularly in those requiring intravenous inotropes at the time of implant.MethodsWe analyzed 759 consecutive CRT-defibrillator recipients who were categorized as never on inotropes (NI; n = 585), weaned from inotropes before implant (PI; n = 124), or on inotropes at implant (II; n = 50). Survival free from heart transplant or ventricular assist device and overall survival were compared using the Social Security Death Index. A patient cohort who underwent unsuccessful CRT implantation and received a standard defibrillator (SD; n = 94) comprised a comparison group. Propensity score analysis was used to control for intergroup baseline differences.ResultsCompared with the other cohorts, II patients had more comorbidities. Both survival endpoints differed significantly (P < .001) among the 4 cohorts; II patients demonstrated shorter survival than NI patients, with the PI and SD groups having intermediate survival. After adjusting for propensity scores, overall differences and patterns in survival endpoints persisted (P < .01), but the only statistically significant pairwise difference was overall survival between the NI and II groups at 12 months (hazard ratio 2.95, 95% confidence interval 1.05-8.35). CRT recipients ever on inotropes (PI and II) and SD patients ever requiring inotropes (n = 17) experienced similar survival endpoints. Among II patients, predictors of hospital discharge free from inotropes after CRT included male gender, older age, and ability to tolerate β-blockade.ConclusionsInotrope-dependent HF patients show significantly worse survival despite CRT than inotrope-naïve patients, in part because of more comorbid conditions at baseline. CRT may not provide a survival advantage over a standard defibrillator among patients who have received inotropes before CRT. Weaning from inotropes and initiating neurohormonal antagonists before CRT should be an important goal among inotrope-dependent HF patients.     

Blockage of VIP during mouse embryogenesis modifies adult behavior and results in permanent changes in brain chemistry

Vasoactive intestinal peptide (VIP) regulates growth and development during the early postimplantation period of mouse embryogenesis. Blockage of VIP with a VIP antagonist during this period results in growth restriction, microcephaly, and developmental delays. Similar treatment of neonatal rodents also causes developmental delays and impaired diurnal rhythms, and the adult brains of these animals exhibit neuronal dystrophy and increased VIP binding. These data suggest that blockage of VIP during the development of the nervous system can result in permanent changes to the brain. In the current study, pregnant mice were treated with a VIP antagonist during embryonic days 8 through 10. The adult male offspring were examined in tests of novelty, paired activity, and social recognition. Brain tissue was examined for several measures of chemistry and gene expression of VIP and related compounds. Glial cells from the cortex of freated newborn mice were plated with neurons and examined for VIP binding and their ability to enhance neuronal survival. Treated adult male mice exhibited increased anxiety-like behavior and deficits in social behavior. Brain tissue exhibited regionally specific changes in VIP chemistry and a trend toward increased gene expression of VIP and related compounds that reached statistical significance in the VIP receptor, VPAC-1, in the female cortex. When compared to control astrocytes, astrocytes from treated cerebral cortex produced further increases in neuronal survival with excess synaptic connections and reduced VIP binding. In conclusion, impaired VIP activity during mouse embryogenesis resulted in permanent changes to both adult brain chemistry/cell biology and behavior with aspects of autism-like social deficits.     

Pastoralism and delay in diagnosis of TB in Ethiopia

Background  

Tuberculosis (TB) is a major public health problem in the Horn of Africa with Ethiopia being the most affected where TB cases increase at the rate of 2.6% each year. One of the main contributing factors for this rise is increasing transmission due to large number of untreated patients, serving as reservoirs of the infection within the communities. Reduction of the time between onset of TB symptoms to diagnosis is therefore a prerequisite to bring the TB epidemic under control. The aim of this study was to measure duration of delay among pastoralist TB patients at TB management units in Somali Regional State (SRS) of Ethiopia.     

Antenatal care services utilization and factors associated in Jimma Town (south west Ethiopia)

BACKGROUND: Antenatal care is potentially one of the most effective health intervention for preventing maternal morbidity and mortality particularly in places where the general health status of women is poor. OBJECTIVE: to assess antenatal care service utilization and factors associated with antenatal care non attendance. METHODS: A community based cross-sectional study was conducted among pregnant women from January 26 to February 06, 2006 in Jimma Town, Jimma zonal administration south west Ethiopia. Structured interviewer administered questionnaire was used for data collection. The data collected on study variables were tabulated in frequency tables and significance of association between variables was tested using chi2--test of significance. RESULT: A total of 360 pregnant women were enrolled in the study. The study, revealed that about 76.7% of the women have attended antenatal care and 23.3% have not attended at all. Literacy status, income, Gravidity, Religion and occupation showed statistically significant association (P < 0.05) with utilization of antenatal care. But marital status, Ethnicity and parity showed no statistically significant association (P > 0.05) with antenatal care utilization. The study showed that about 42.8% of the attendants have made their first antenatal visit in the 3rd trimester of pregnancy. Out of the total only 6.5% the studied women had the recommended four visits. Women in the age group 15-24 are more likely to attend ANC 2.75 times larger than that of women in the age group 25-34 (OR = 2.74, 95% CI: 1.37, 4.38). Similarly others (students and farmers) are about four times likely to attend ANC than House wife's (OR = 4.06. 95% CI: 1.50, 11.40). CONCLUSION: Even if there was high antenatal care utilization the pattern of follow up was in appropriate in most cases as the majority of pregnant women started using the service around 7-9 months with decreasing number in the 1st and 2nd trimester of pregnancy. Effective behavior change communication is needed to bring about proper antenatal care services utilization. Improving the quality of the service delivery and effective monitoring at, evaluation is critically important for improving the utilization of antenatal care services.