Thoracic aortic dissection in a patient with autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease is one of the most common hereditary diseases, and frequently has well defined extrarenal manifestations. Very few cases of aortic aneurysms associated with this disorder are described in literature. We report a 42-year-old male with autosomal dominant polycystic kidney disease presenting with dissecting aneurysm of the thoracic aorta.     

Individual and county level predictors of asthma related emergency department visits among children on Medicaid: A multilevel approach

Objective: Disparities in asthma outcomes are well documented in the United States. Interventions to promote equity in asthma outcomes could target factors at the individual and community levels. The objective of this analysis was to understand the effect of individual (race, gender, age, and preventive inhaler use) and county-level factors (demographic, socioeconomic, health care, air-quality) on asthma emergency department (ED) visits among Medicaid-enrolled children. This was a retrospective cohort study of Medicaid-enrolled children with asthma in 29 states in 2009. Multilevel regression models of asthma ED visits were constructed utilizing individual-level variables (race, gender, age, and preventive inhaler use) from the Medicaid enrollment file and county-level variables reflecting population and health system characteristics from the Area Resource File (ARF). County-level measures of air quality were obtained from Environmental Protection Agency (EPA) data. Results: The primary modifiable risk factor at the individual level was found to be the ratio of long-term controller medications to total asthma medications. County-level factors accounted for roughly 6% of the variance in the asthma ED visit risk. Increasing county-level racial segregation (OR=1.04, 95% CI=1.01-1.08) was associated with increasing risk of asthma ED visits. Greater supply of pulmonary physicians at the county level (OR=0.81, 95% CI=0.68-0.97) was associated with a reduction in risk of asthma ED visits. Conclusions: At the patient care level, proper use of controller medications is the factor most amenable to intervention. There is also a societal imperative to address negative social determinants, such as residential segregation.     

Yohimbine Depresses Excitatory Transmission in BNST and Impairs Extinction of Cocaine Place Preference Through Orexin-Dependent,Norepinephrine-Independent Processes

The alpha2 adrenergic receptor (α₂-AR) antagonist yohimbine is a widely used tool for the study of anxiogenesis and stress-induced drug-seeking behavior. We previously demonstrated that yohimbine paradoxically depresses excitatory transmission in the bed nucleus of the stria terminalis (BNST), a region critical to the integration of stress and reward pathways, and produces an impairment of extinction of cocaine-conditioned place preference (cocaine-CPP) independent of α₂-AR signaling. Recent studies show yohimbine-induced drug-seeking behavior is attenuated by orexin receptor 1 (OX₁R) antagonists. Moreover, yohimbine-induced cocaine-seeking behavior is BNST-dependent. Here, we investigated yohimbine-orexin interactions. Our results demonstrate yohimbine-induced depression of excitatory transmission in the BNST is unaffected by alpha1-AR and corticotropin-releasing factor receptor-1 (CRFR₁) antagonists, but is (1) blocked by OxR antagonists and (2) absent in brain slices from orexin knockout mice. Although the actions of yohimbine were not mimicked by the norepinephrine transporter blocker reboxetine, they were by exogenously applied orexin A. We find that, as with yohimbine, orexin A depression of excitatory transmission in BNST is OX₁R–dependent. Finally, we find these ex vivo effects are paralleled in vivo, as yohimbine-induced impairment of cocaine-CPP extinction is blocked by a systemically administered OX₁R antagonist. These data highlight a new mechanism for orexin on excitatory anxiety circuits and demonstrate that some of the actions of yohimbine may be directly dependent upon orexin signaling and independent of norepinephrine and CRF in the BNST.     

Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats

OBJECTIVE: Carica papaya is an important fruit with its seeds used in the treatment of ulcer in Nigeria. This study investigated the anti-ulcerogenic and antioxidant activities of aqueous extract of Carica papaya seed against indomethacin-induced peptic ulcer in male rats.METHODS: Thirty male rats were separated into 6 groups(A–F) of five rats each. For 14 d before ulcer induction with indomethacin, groups received once daily oral doses of vehicle(distilled water), cimetidine 200 mg/kg body weight(BW), or aqueous extract of C. papaya seed at doses of 100, 150 or 200 mg/kg BW(groups A, B, C, D, E and F, respectively). Twenty-four hours after the last treatment, groups B, C, D, E and F were treated with 100 mg/kg BW of indomethacin to induce ulcer formation. RESULTS: Carica papaya seed extract significantly(P<0.05) increased gastric p H and percentage of ulcer inhibition relative to indomethacin-induced ulcer rats. The extract significantly(P<0.05) decreased gastric acidity, gastric acid output, gastric pepsin secretion, ulcer index and gastric secretion volume relative to group B. These results were similar to that achieved by pretreatment with cimetidine. Specific activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase in the extract-treated groups(D, E and F) were increased significantly over the group B(P<0.05). Pretreatment with the seed extract protected rats from the indomethacin-mediated decrease in enzyme function experienced by the group B. Similarly, indomethacin-mediated decrease in reduced glutathione level and indomethacin-mediated increase in malondialdehyde were reversed by Carica papaya extract. CONCLUSION: In this study, pretreatment with aqueous extract of Carica papaya seed exhibited antiulcerogenic and antioxidant effects, which may be due to the enhanced antioxidant enzymes.     

Antiplasmodial activity-aided isolation and identification of quercetin-4’-methyl ether in Chromolaena odorata leaf fraction with high activity against chloroquine-resistant Plasmodium falciparum

The present study was undertaken to evaluate the antiplasmodial activity of Chromolaena odorata leaf extract and gradient fractions through in vivo and in vitro tests, aimed at identifying its antiplasmodial constituents. Sub-fractions obtained from the most active gradient fraction were further tested for cytotoxicity against THP-1 cells, chloroquine-sensitive (HB3) and chloroquine-resistant (FCM29) Plasmodium falciparum. Our results showed the dichloromethane gradient fraction was most effective, significantly (P?50 of 4.8 and 6.74 μg/ml against P. falciparum HB3 and FCM29, respectively. Cytotoxicity of DF11 was estimated to be above 50 μg/ml, and its separation by column chromatography yielded a flavonoid which was characterized as 3, 5, 7, 3’ tetrahydroxy-4’-methoxyflavone from its spectroscopic data. It significantly suppressed infection (65.43–81.48 %) in mice at 2.5–5 mg/kg doses and compared favourably with the effects of chloroquine and artemisinin. It may therefore serve as a useful phytochemical and antiplasmodial activity marker of C. odorata leaves, which exhibit potential for development as medicine against malaria.     

Differential expression of perlecan receptors, α‐dystroglycan and integrin β1, before and after invasion of oral squamous cell carcinoma

J Oral Pathol Med (2011) 40 : 552–559 Objectives: The deposition of perlecan, a heparan sulfate proteoglycan, is enhanced within oral carcinoma in situ (CIS) foci, while it dynamically switches from CIS foci to the stromal space in squamous cell carcinoma (SCC). Because α‐dystroglycan and integrin β1 have been identified as two of the perlecan receptors, we wanted to determine their differential distributions before and after invasion of oral SCC. Methods: Eighty‐two surgical tissue specimens of oral SCC containing different precancerous stages were examined by immunohistochemistry for perlecan, α‐dystroglycan, integrin β1, and Ki‐67. In addition, α‐dystroglycan mRNA signals were localized by in situ hybridization. Results: In normal epithelia, α‐dystroglycan and integrin β1 were localized on the cell membrane of basal cells, while perlecan was faintly present in the intercellular spaces of parabasal cells. In epithelial dysplasia and CIS, α‐dystroglycan and perlecan were well co‐localized in the epithelial layer, especially in its lower half, and this co‐localization was mostly overlapped with Ki‐67‐positive (+) cell zones. However, in SCC, α‐dystroglycan was localized neither within carcinoma cell nests nor in the stroma, while perlecan disappeared from SCC foci but emerged in the stromal space, leaving integrin β1+ and Ki‐67+ cells only to the periphery of SCC foci. α‐Dystroglycan mRNA signals were basically identical to the α‐dystroglycan protein localizations. Conclusion: The findings suggest that α‐dystroglycan and integrin β1 act as perlecan receptors in oral precancerous lesions prior to invasion, and that the perlecan signals via the two different receptors function in cellular differentiation and proliferation of CIS cells, respectively.