Modulation of ceramide content and lack of apoptosis in the chronically hypoxic neonatal rat heart.

To assess the effect of chronic hypoxia on cardiomyocyte apoptosis, we used an animal model that mimics cyanotic heart disease. Rats were placed in a hypoxic environment at birth, and oxygen levels were maintained at 10% in an air-tight Plexiglas chamber. Controls remained in room air. Animals were killed, and the hearts were harvested at 1 and 4 wk. Significant polycythemia developed in the hypoxic rats at 1 and 4 wk. Right ventricular mass in the hypoxic rats was 192% and 278% that of controls, and hypoxic left ventricular mass was 140% and 178% that of the controls at 1 and 4 wk, respectively. The increase in cardiac mass was paralleled by only mild hypertrophy (10 to 20%). Contrary to previous reports showing increased apoptosis in response to hypoxia in cultured cardiomyocytes, there was no difference in the number of apoptotic cardiomyocytes between the chronically hypoxic rats and controls, as assayed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Hoechst staining. We then examined the role of the sphingolipid ceramide because of its reported role in the stress response, growth suppression, and apoptosis. We found that the right ventricular ceramide content was significantly decreased in the hypoxic rats to 73% of control levels at the age of 4 wk. We suggest that the decrease in the ceramide content in the hypoxic right ventricular rat heart may be an adaptive response to chronic hypoxia and pulmonary hypertension. Lower ceramide levels may help suppress apoptosis and allow compensatory right ventricular cardiomyocyte proliferation.     

Prothrombotic states associated with retinal venous occlusion in young adults

Background. The etiology of retinal venous occlusion in young patients is not well understood although thrombosis does occur histologically. A search for the risk factors that may lead to thrombosis is highly desirable may contribute to our understanding of the pathogenesis of this complication and may improve our therapeutic strategies. Methods. We studied 17 patients with retinal venous occlusion. All patients were under 45 years of age (mean 37.8 ± 7.1). Antiphospholipid antibodies (APAs) and certain hemostatic factors were determined. The results obtained in these patients were compared to those of normal controls. Results. We found APAs in 8 out of 17 patients compared to 5 out of 60 controls (p = 0.0002). In patients with major trunk occlusion, there was a trend for the presence of APAs in those with poor visual acuity at presentation. Deficiencies of the coagulation inhibitor proteins C and S and antithrombin III activities were detected in 6 patients, and reduced levels of Factor XII were found in 4 patients. Levels of hematocrit, erythrocyte sedimentation rate, Fibrinogen, ₁-globulin, and ₂-globulin were significantly higher in patients compared to the controls (p = 0.019; 0.014; 0.0001; 0.011; 0.047), indicating increased blood viscosity in patients with retinal venous occlusion. Conclusion: Prothrombotic changes in the form of APAs and/or deficiencies of coagulation inhibitors and Factor XII may contribute to the etiology of retinal venous occlusion in young adults. Young patients with retinal venous occlusion should be evaluated for these prothrombotic states.     

Radiographic assessment of degenerative lumbar spinal stenosis: is MRI superior to CT?

Objective

To determine the reliability and dependability of magnetic resonance imaging (MRI) and computerized tomography (CT) in the assessment of lumbar spinal stenosis and correlate the qualitative assessment to both a quantitative assessment and functional outcome measures.

Summary of background data

Multiple studies have addressed the issue of CT and MRI imaging in lumbar spinal stenosis. None showed superiority of one modality.

Methods

We performed a standardized qualitative and quantitative review of CT and MRI scans of 54 patients. Intra-observer and inter-observer reliability was determined between three reviewer using Kappa coefficient. Agreement between the two modalities was analyzed. ODI and SF-36 outcomes were correlated with the imaging assessments.

Results

Almost perfect intra-observer reliability for MRI was achieved by the two expert reviewers (κ = 0.91 for surgeon and κ = 0.92 for neuro-radiologist). For CT, substantial intra-observer agreement was found for the surgeon (κ = 0.77) while the neuro-radiologist was higher (κ = 0.96). For both CT and MRI the standardized qualitative assessment used by the two expert reviewers had a better inter-observer reliability than that between the expert reviewers and the general reporting radiologist, who did not utilize a standardized assessment system. When the qualitative assessment was compared directly, CT overestimated the degree of stenosis 20–35 % of the time (p < 0.05) while MRI overestimated the degree of stenosis 2–11 % of the time (p < 0.05). No correlation was found between qualitative and quantitative analysis with functional status.

Conclusions

This study directly demonstrates that MRI is a more reliable tool than CT, but neither correlates with functional status. Both experience of the reader and the standardization of a qualitative assessment are influential to the reliability.

     

Recording Adverse Events Following Joint Arthroplasty: Financial Implications and Validation of an Adverse Event Assessment Form

Background

In Ireland, funding of joint arthroplasty procedures has moved to a pay-by-results national tariff system. Typically, adverse clinical events are recorded via retrospective chart-abstraction methods by administrative staff. Missed or undocumented events not only affect the quality of patient care but also may unrealistically skew budgetary decisions that impact fiscal viability of the service. Accurate recording confers clinical benefits and financial transparency. The aim of this study was to compare a prospectively implemented adverse events form with the current national retrospective chart-abstraction method in terms of pay-by-results financial implications.

Antiobesity and antihyperglycaemic effects of Adiantum capillus-veneris extracts: in vitro and in vivo evaluations

Context: Adiantum capillus-veneris L. (Adiantaceae) hypocholesterolemic activity is therapeutically praised.

Objectives: Pharmacological modulation of pancreatic triacylglycerol lipase (PL) and α-amylase/α-glucosidase by A. capillus-veneris are evaluated.

Materials and methods: Using positive controls (acarbose, orlistat, guar gum, atorvastatin, glipizide and metformin) as appropriate, crude aqueous extracts (AEs) of A. capillus-veneris aerial parts were tested via a combination of in vitro enzymatic (0.24–100?mg/mL), acute in vivo carbohydrate tolerance tests (125, 250 or 500?mg/kg body weight [b.wt]) and chronic in vivo studies (500?mg/kg b.wt) in high cholesterol diet (HCD) fed Wistar rats.

Results: Like acarbose, A. capillus-veneris as well as chlorogenic acid, with respective IC₅₀ values (mg/mL) of 0.8?±?0.0 and 0.2?±?0.0, were identified as in vitro potent dual inhibitors of α-amylase/α-glucosidase. Unlike guar gum, A. capillus-veneris had no glucose diffusion hindrance capacity. Equivalent to orlistat, A. capillus-veneris and its phytoconstituents inhibited PL in vitro with an ascending order of PL- IC₅₀ values (μg/mL): ferulic acid; 0.48?±?0.06?A. capillus-veneris; 1600?±?100. Incomparable to acarbose or metformin and glipizide, A. capillus-veneris (125, 250 and 500?mg/kg b.wt) lacked antihyperglycaemic efficacies in acute starch- or glucose-evoked postprandial hyperglycaemia increments in normoglycaemic overnight fasting rats. Superior to atorvastatin; A. capillus-veneris exerted significant antiobesity (p?p?Discussion and conclusion: A. capillus-veneris, modulating pancreatic digestive enzymes, may be advocated as a combinatorial diabesity prevention/phytotherapy agent.     

Female-Headed Households Associated with Lower Childhood Stunting Across Culturally Diverse Regions of Pakistan: Results from a Cross-Sectional Household Survey

Objectives Early childhood stunting adversely influences long-term cognitive and health outcomes. There is limited evidence on whether female empowerment within households could reduce its prevalence. We investigated this relationship in Punjab, Pakistan, which has high stunting rates and a sizeable proportion of female-headed households, and whether this relationship differed across three provincial regions with diverse cultural attitudes towards the role of women in society. Methods Using cross-sectional data from the 2011 Multiple Indicator Cluster Survey, we identified 13,412 children aged 1–4 from 8985 two-parent households in three culturally distinct regions in Punjab, Pakistan. Logistic regression models assessed whether the likelihood of stunting was associated with female-headed households, a proxy for female empowerment, and whether this relationship differed by region. Regressions controlled for child- and household-level covariates. Results Children had 26% lower odds of stunting among female-headed households (OR 0.74, CI 0.60, 0.90). The interaction term for female-headed households and child stunting by provincial region was not statistically significant, suggesting that the relationship holds across the three culturally distinct regions. Conclusions for Practice Female empowerment was associated with lower rates of stunting among young children, and the results did not vary by provincial region. This suggests that women can play important roles as agents of change, even in areas where females have limited freedoms. Greater investments in public education and awareness campaigns to improve health literacy might have important spillover effects for child health and improve the success of existing public health interventions targeting childhood stunting.     

(+)-Catechin-5-galloyl Ester as a Novel Natural Polyphenol from the Bark of Acacia nilotica of Sudanese Origin1

From the bark of ACACIA NILOTICA subsp. TOMENTOSA a novel polyphenol, (+)-catechin-5-galloyl ester ( 5), was isolated along with gallic acid ( 1), its methyl ester ( 2), naringenin ( 3), and (+)-catechin ( 4). The structure of 5 was determined by use of mass spectrometry as well as (1)H- and (13)C-NMR spectroscopy.     

Synthesis and Biological Evaluation of Ether-Linked Derivatives of Phosphatidylinositol

The synthesis of two novel glycero-3-phosphoinositol ether lipid analogues, rac-l-O-octadecyl-2-O methylglycero-3-phospho-myo-inositol 6 (an ether lipid analogue of rac-l-O-octadecyl-2-O-methylglycero-3-phosphocholine; ET-18-OMe) and rac-l-O-octadecyl-2-O-acetylglycero-3-phospho-myo-inositol 11 (an ether lipid analogue of platelet-activating factor), is described. The two target compounds and the synthetic intermediates were evaluated for inhibition of HL60, BG1, and BG3 human malignant cells in vitro and inhibition of protein kinase C. Tumor inhibitory activity was found for compounds 6 and 11 in all systems but not for their synthetic intermediates. However, compounds 6 and 11 as well as the synthetic intermediates 5 and 13, but not 9, exhibited protein kinase C inhibitory activity.