Sex, stress and social status: Patterns in fecal testosterone and glucocorticoid metabolites in male Ethiopian wolves

Ethiopian wolves, Canis simensis, live in large multi-male family packs, where males are philopatric and do not disperse. Within a pack, mating and breeding is largely monopolized by the dominant male and female, although extra-pack copulations are common, and subordinate males may sire pups in neighboring packs. Regardless of paternity, all males in a pack help rear the pups. We non-invasively studied patterns in fecal testosterone and glucocorticoid metabolite concentrations using radioimmunoassays of fecal samples collected from nine wild male Ethiopian wolves between August 2007 and February 2008. We tested the predictions of the Challenge Hypothesis, namely that fecal testosterone metabolite concentrations would be higher during the annual mating season, which is the portion of the reproductive cycle when mating and increased aggression typically occur, and lower when there were pups in the pack for which to care. Contrary to the predictions of the Challenge Hypothesis, we did not detect patterns in fecal testosterone metabolite concentrations associated with reproductive stage during our study period. Similarly, we found no patterns associated with reproductive stage in male fecal glucocorticoid metabolite concentrations. Dominant males had higher average fecal testosterone and glucocorticoid metabolite concentrations than did subordinates, which may be related to higher rates of aggression and mate guarding in dominant males of group-living canids, a pattern also reported in African wild dogs, Lycaon pictus.     

Apple juice concentrate prevents oxidative damage and impaired maze performance in aged mice

Oxidative stress contributes to age-related cognitive decline. In some instances, consumption of fruits and vegetables rich in antioxidant can provide superior protection than supplementation with purified antioxidants. Our prior studies have shown that supplementation with apple juice concentrate (AJC) alleviates oxidative damage and cognitive decline in a transgenic murine model compromised in endogenous antioxidant potential when challenged with a vitamin-deficient, oxidative stress-promoting diet. Herein, we demonstrate that AJC, administered in drinking water, is neuroprotective in normal, aged mice. Normal mice aged either 9-10 months or 2-2.5 years were maintained for 1 month on a complete diet or a diet lacking folate and vitamin E and containing iron as a pro-oxidant, after which oxidative damage was assayed by thiobarbituric acid-reactive substances and cognitive decline as assayed by performance in a standard Y-maze. Mice 9-12 months of age were unaffected by the deficient diet, while older mice demonstrated statistically-increased oxidative damage and poorer performance in a Y maze test. Supplementation with AJC prevented these neurodegenerative effects. These data are consistent with normal aged individuals being susceptible to neurodegeneration following dietary compromise such as folate deficiency, and a hastened onset of neurodegeneration in those individuals harboring a genetic risk factor such as ApoE deficiency. These findings also support the efficacy of antioxidant supplementation, including consumption of antioxidant-rich foods such as apples, in preventing the decline in cognitive performance that accompanies normal aging.     

Tuberculosis defaulters from the "dots" regimen in Jimma zone, southwest Ethiopia

A cross-sectional study was conducted among patients with tuberculosis on the DOTS regimen in the four teaching health centers of Jimma zone to determine rate of defaulting and factors associated with it. All tuberculosis patients registered and treated using DOTS regimen in the 4 teaching health centers (THC's) from the second half of 1999 to December 30, 2000 were included in the study. A sub-sample of one hundred and fourteen 114 (56.2%) defaulters were traced at their homes and interviewed to elicit their reasons for defaulting. The study showed that overall rate of defaulting was 6.7%. The default rate from the DOTS regimen was found to be quite low when compared to the rate of defaulting from the standard regimen in Jimma zone. Socio-economic factors including distance of patients' residence from the health institution, lack of money for paying transportation and poor awareness about the disease were the major reasons contributing to poor compliance and defaulting. Designing community based strategies for DOTS regimen in order to make the drug available within the vicinity of the grass root community and strong information education and communication activities need to be employed in order to reduce the defaulter rate and improve the quality of treatment of tuberculosis cases by the DOTS regimen.     

Differential EphA2 epitope display on normal versus malignant cells

The EphA2 receptor tyrosine kinase is overexpressed in many different types of human cancers where it functions as a powerful oncoprotein. Dramatic changes in the subcellular localization and function of EphA2 have also been linked with cancer, and in particular, unstable cancer cell-cell contacts prevent EphA2 from stably binding its ligand on the surface of adjoining cells. This change is important in light of evidence that ligand binding causes EphA2 to transmit signals that negatively regulate tumor cell growth and invasiveness and also induce EphA2 degradation. On the basis of these properties, we have begun to target EphA2 on tumor cells using agonistic antibodies, which mimic the consequences of ligand binding. In our present study, we show that a subset of agonistic EphA2 antibodies selectively bind epitopes on malignant cells, which are not available on nontransformed epithelial cells. We also show that such epitopes arise from differential cell-cell adhesions and that the stable intercellular junctions of nontransformed epithelial cells occlude the binding site for ligand, as well as this subset of EphA2 antibodies. Finally, we demonstrate that antibody targeting of EphA2 decreases tumor cell growth as measured using xenograft tumor models and found that the mechanism of antibody action relates to EphA2 protein degradation in vivo. Taken together, these results suggest new opportunities for therapeutic targeting of the large number of different cancers that express EphA2 in a manner that could minimize potential toxicities to normal cells.     

Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells. 2. Aryl modifications of 4-(aryloxy)thieno[2,3-c]pyridines with fine-tuning at C-2 carbamides

The elevated expression of cell adhesion molecules (CAMs) on the lumenal surface of vascular endothelial cells is a critical early event in the complex inflammatory process. The adhesive interactions of these CAMs that include E-selectin, ICAM-1, and VCAM-1 with their counter-receptors on leukocytes, such as integrins of the alpha(L)beta(2) family, result in migration of the leukocytes to the site of inflammation and cause tissue injury. Pharmaceutical agents that could suppress the induced expression of one or more of these cell adhesion molecules would provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A-205804 (1), a potent and selective inhibitor of the induced expression of E-selectin and ICAM-1 over VCAM-1, was further modified with emphasis at the C-4 and C-2 positions to identify a more potent drug candidate with a good pharmacokinetic profile and physical properties. Replacement of the C-4 sulfur linkage in 1 with an oxygen atom eliminated one of the two major metabolites for this lead molecule. The para-position of the 4-phenoxy group of the thieno[2,3-c]pyridine lead is found to be very critical for a higher in vitro potency and selectivity of E-selectin and ICAM-1 over VCAM-1 expression. This position is presumably close to the solvent-accessible region of the target protein-inhibitor complex. An attempt to install a water-solubilizing group at the para-position of the phenoxy group to increase the aqueous solubility of this lead series through various linkages failed to provide an ideal inhibitor. Only small substituents such as fluorine are tolerated at the meta- and ortho-positions of the 4-phenoxy to retain a good in vitro potency. Bromo, trifluoromethyl, pyrazol-1-yl, and imidazol-1-yl are among the better substituents at the para-position. With fine-tuning at the C-2 position we discovered a series of very potent (IC(50) < 5 nM for ICAM-1) and selective (>200-fold vs VCAM-1) inhibitors with a good pharmacokinetic profile. Demonstrated efficacy in a rat rheumatoid arthritis model and in a mice asthma model with selected compounds is also reported.     

Sleep-related breathing disorder in children with vagal nerve stimulators

The effects of vagal nerve stimulation on sleep-related breathing have not been well-described in children. Vagal nerve stimulation was reported to cause decreases in airflow during sleep, although most studies reported this condition to be clinically insignificant. We present a retrospective case series of nine children who underwent polysomnography after vagal nerve-stimulator placement. All children, except for one, had sleep-disordered breathing after stimulator implantation. We describe in further detail a child who manifested severe, obstructive sleep apnea postimplantation, with apneas occurring regularly and consistently with stimulator activity, resulting in an elevated apnea-hypopnea index of 37 per hour. Polysomnography was repeated with the stimulator turned off, and revealed complete resolution of the stimulator-related sleep apnea. With the vagal nerve stimulator back on, continuous positive airway pressure treatment was effective in normalizing the apnea-hypopnea index. This study demonstrates that severe and clinically significant disturbances in sleep-related breathing may occur with vagal nerve stimulators. Obstructive apneas of this severity, related to vagal nerve stimulators, were not previously described in pediatric patients. This effect on sleep-related breathing warrants further investigation and care in managing pediatric patients.     

A nanoemulsion of an anti-oxidant synergy formulation reduces tumor growth rate in neuroblastoma-bearing nude mice

Neuroblastoma, the most common form of childhood cancer, may arise from a biochemical block of cellular differentiation and a resultant continuation of a proliferative state. Neuroblastoma often spontaneously reverts by undergoing partial differentiation and ultimate degeneration and may be associated with the generation of reactive oxygen species (ROS). We have recently reported in neuroblastoma cell culture studies that an anti-oxidant synergy formulation (ASF) can induce differentiation and buffer neuronal degeneration and oxidative stress in cultured cortical neurons and in central nervous system tissue of apolipoprotein E-deficient mice. The objective of the present study was to investigate whether a subcutaneous injection and/or transdermal application of a nanoemulsion preparation of ASF would reduce tumor growth rate in a neuroblastoma xenograph mouse model. The results indicate that whereas suspensions of ASF were ineffective in decreasing tumor growth rate in the neuroblastoma mouse model, tumor growth rate was similarly reduced an average 65% by either subcutaneous injection or transdermal application of an ASF nanoemulsion preparation to the tumor. In conclusion, the data suggest that subcutaneous and/or transdermal application of an ASF nanoemulsion preparation is effective in reducing tumor growth rate in this neuroblastoma mouse model.     

Magnitude and pattern of injury in jimma university specialized hospital, South west ethiopia

Background

Injury statistics in Ethiopia provides little knowledge about its magnitude and related information needed for prevention. This study, therefore, aims to determine the magnitude and pattern of injury in Jimma University Specialized Hospital (JUSH).

Methods

A retrospective review of records of all injured patients seen at surgical outpatient department from April 09, 2010 to January 07, 2011; was conducted in January 2011. Data were collected using a structured checklist that was developed by adapting the World Health Organization instrument. Five degree holder nurses collected the data while investigators closely supervised. Socio demographic characteristics of the patients and injury related information were collected. Data were analyzed using SPSS for windows version 16.0.

Results

Of 13500 patients who visited surgical outpatient department of JUSH during the study period, 1102(8.2%) were injury cases. The commonest mechanism of injury was blunt assault, 341(30.9%), followed by road traffic accident, 334(30.3). Fracture was the leading outcome of injury, 454(41.2%), followed by bruise or skin laceration, 404(36.7%). Significantly more males had cut, (AOR=2.0; 95% CI=1.2, 3.3) and stab, (AOR=3.0; 95% CI=1.6, 5.7), injuries compared to females. Conversely, significantly fewer males had burn, (AOR=0.4, 95% CI=0.2, 0.8) and road traffic accident, (AOR=0.7, 95% CI=0.5, 0.9), than females. Most, 715(95.8%), patients were presented to the hospital within one week. The commonest functional limitations were; difficulty to use hands, 312(28.3%) and difficulty to use legs, 217(19.7%). Eighty three, (7.5%) of the patients died and road traffic accident alone accounted for almost half, 179 (49.7%), of the severe injuries.

Conclusion

The magnitude of injury in the hospital was considerably high. Age and sex were predictors of injury. Appropriate prevention strategies should be designed and implemented against assault, road traffic accident and cut by sharp tool.