Recombinant factor VIIa enhances deposition of platelets with congenital or acquired alpha IIb beta 3 deficiency to endothelial cell matrix and collagen under conditions of flow via tissue factor-independent thrombin generation

A novel approach to treat bleeding episodes in patients with Glanzmann thrombasthenia (GT) and perhaps also in patients receiving alpha IIb beta 3 inhibitors is the administration of recombinant factor VIIa (rFVIIa). The mechanism of action of rFVIIa in these patients is, however, still unclear. We studied the effect of rFVIIa-mediated thrombin formation on adhesion of alpha IIb beta 3-deficient platelets under flow conditions. Adhesion of alpha IIb beta 3-deficient platelets to the extracellular matrix (ECM) of stimulated human umbilical vein endothelial cells or to collagen type III was studied using a model system with washed platelets and red cells. When alpha IIb beta 3-deficient platelets were perfused over the surface at arterial shear rate for 5 minutes, a low surface coverage was observed (GT platelets, mean +/- SEM, 37.5% +/- 5.0%; normal platelets preincubated with an RGD-containing peptide, 7.4% +/- 2.1%). When rFVIIa, together with factors X and II, was added to the perfusate, platelet deposition significantly increased (GT platelets, mean +/- SEM, 67.0% +/- 4.3%; normal platelets preincubated with an RGD-containing peptide, 48.2% +/- 2.9%). The same effect was observed when normal platelets were pretreated with the commercially available anti-alpha IIb beta 3 drugs abciximab, eptifibatide, or tirofiban. It was shown that tissue factor-independent thrombin generation (presumably induced by binding of rFVIIa to adhered platelets) was responsible for the increase in platelet deposition. In conclusion, defective adhesion of alpha IIb beta 3-deficient platelets to ECM can be restored by tissue factor-independent rFVIIa-mediated thrombin formation. The enhanced generation of platelet procoagulant surface facilitates fibrin formation, so that lack of platelet aggregate formation might be compensated for.     

Prevalence of diabetes and prediabetes and their risk factors among Bangladeshi adults: a nationwide survey

Objective

To estimate the prevalence of diabetes and prediabetes in Bangladesh using national survey data and to identify risk factors.

Methods

Sociodemographic and anthropometric data and data on blood pressure and blood glucose levels were obtained for 7541 adults aged 35 years or more from the biomarker sample of the 2011 Bangladesh Demographic and Health Survey (DHS), which was a nationally representative survey with a stratified, multistage, cluster sampling design. Risk factors for diabetes and prediabetes were identified using multilevel logistic regression models, with adjustment for clustering within households and communities.

Findings

The overall age-adjusted prevalence of diabetes and prediabetes was 9.7% and 22.4%, respectively. Among urban residents, the age-adjusted prevalence of diabetes was 15.2% compared with 8.3% among rural residents. In total, 56.0% of diabetics were not aware they had the condition and only 39.5% were receiving treatment regularly. The likelihood of diabetes in individuals aged 55 to 59 years was almost double that in those aged 35 to 39 years. Study participants from the richest households were more likely to have diabetes than those from the poorest. In addition, the likelihood of diabetes was also significantly associated with educational level, body weight and the presence of hypertension. The prevalence of diabetes varied significantly with region of residence.

Conclusion

Almost one in ten adults in Bangladesh was found to have diabetes, which has recently become a major public health issue. Urgent action is needed to counter the rise in diabetes through better detection, awareness, prevention and treatment.     

Ameliorative effect of vitamin C on the haematological changes induced by exposure of chlorpyriphos and lead acetate in Wistar rats

The present study was designed to evaluate the effects of chlorpyriphos, lead acetate and vitamin C alone and in combinations, on various haematological parameters in Wistar rats. Rats of 150–200 g body weight were divided into eight groups of six animals each and were subjected to various daily oral treatment regimes for 98 days. Group C served as control receiving only corn oil, group CP received chlorpyriphos at 5.5 mg/kg in corn oil and group L received lead acetate at100?ppm in water, whereas animals in group CP + L received a combination of chlorpyriphos at 5.5 mg/kg in corn oil and lead acetate at 100 ppm in water. Group VC received vitamin C at 100 mg/kg in water; group CP + VC received a combination of chlorpyriphos at 5.5 mg/kg and vitamin C at 100 mg/kg; group L + VC received lead acetate at 100 ppm in water and vitamin C at 100 mg/kg and group CP + L + VC received chlorpyriphos at 5.5 mg/kg, lead acetate at 100 ppm in water and vitamin C at 100 mg/kg. Blood samples were collected on days 0, 30, 60 and 98 post exposure and analysed for packed cell volume (PCV), total erythrocyte count (TEC), haemoglobin (Hb), erythrocyte sedimentation rate (ESR), total leucocyte count (TLC) and differential leucocyte count. A significant decrease in TEC, PCV and Hb and a significant increase in ESR values were observed. However, lead acetate caused an increase in TLC while chlorpyriphos resulted in a decrease in TLC. Both of these toxicants potentiated toxicity of each other. The study demonstrated that treatment of chlorpyriphos- and lead-treated rats with vitamin C significantly altered some of the important haematological parameters revealing the protective effect of this vitamin against haematological alterations induced by chlorpyriphos and lead.     

Extracts of Musa basjoo induce growth inhibition and changes in the protein expression of cell cycle control molecules in human colorectal cancer cell lines

Musa basjoo (MB) is a species of the banana plant belonging to the genus Musa that has been used as a folk medicine. However, evidence-based biological activities and the molecular mechanism of action of MB are unknown. Thus, the aim of the present study was to examine whether the crude dried leaf extracts of MB inhibit the growth of colorectal (HT29 and HCT116) and other types (HepG2, MCF-7 and PC-3) of human cancer cell lines. Crude extracts of MB inhibited the growth of cells with IC₅₀ values of 136 µg/ml (acetone extract, HT29), 51 µg/ml (acetone extract, HCT116), 45 µg/ml (acetone extract, HepG2), 40 µg/ml (acetone extract, MCF-7), 29 µg/ml (acetone extract, PC-3), 175 µg/ml (methanol extract, HT29), 137 µg/ml (methanol extract, HCT116), 102 µg/ml (methanol extract, HepG2), 85 µg/ml (methanol extract, MCF-7), and 85 µg/ml (methanol extract, PC-3) in colony formation assays, and 126 µg/ml (acetone extract, HT29), 68 µg/ml (acetone extract, HCT116), 260 µg/ml (methanol extract, HT29), and 216 µg/ml (methanol extract, HCT116) in MTT assays. Thin layer chromatography analysis revealed the potential existence of aromatic compounds in the acetone extract of MB. Flow cytometric analysis indicated that the percentage of cells in G1 increased, and this was associated with a concomitant decrease of cells in the S and/or G2-M phases of the cell cycle. When colorectal cancer cells were treated with acetone extract of MB, there was a marked decrease in the levels of expression of the cyclin D1, cyclin E, cdk2 and cdk4 proteins and a marked increase in the levels of the expression of the p21^CIP1, p27^KIP1, and p53 proteins, but those of apoptosis-associated protein PARP did not change. There was a tendency for acetone extract of MB to inhibit xenograft tumor growth in mice. Collectively, the crude extracts of MB contain active components that exert growth inhibition of human cancer cells. This is the first systematic study of the anticancer activity of MB and may broaden insights into the possible clinical approach of specific herbal medicines.     

Bronchial artery embolization in the management of hemoptysis: technical aspects and long-term results

Seventy-five patients with hemoptysis were treated with bronchial artery embolization (BAE). The procedure was performed with Hexabrix (sodium methylglucamine ioxaglate), Mikaelson catheters, and Gelfoam particles. Angiographic evaluation of the bronchial artery anatomy revealed ten different configurations, which are described. The embolization attempt failed in three cases (4%); eight additional patients (10.7%) were excluded from the series because of inadequate data. In the remaining 64 patients, 41 underwent BAE alone and 23 underwent either chemotherapy or surgery in addition to embolization. Immediate control of hemoptysis was achieved in 49 of 64 patients (76.6%). Long-term control of hemoptysis was achieved in 46 of the 56 patients included in the long-term follow-up (82.1%). Eight of the 64 patients were lost to follow-up, which ranged from one to 47 months (mean 24.8 months). Hemoptysis recurred in 12 of 56 patients (severe in 10, mild in 2) (21.4%). Twelve patients died (21.4%), five of them due to hemoptysis (8.9%). None of the patients who died of hemoptysis had responded to initial BAE. It is concluded that BAE is an effective treatment for immediate control of life-threatening hemoptysis, allowing long-term control of bleeding in the majority of patients.     

Prevalence and Factors Associated with Concomitant Chinese Medicine Use by Rheumatoid Arthritis Patients in A Multi-Ethnic Asian Population

Objective:To determine the prevalence,factors associated with and patterns of concomitant Chinese medicine(CM)with Western treatment use among patients with rhe...     

An increase in S-glutathionylated proteins in the Alzheimer's disease inferior parietal lobule, a proteomics approach

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neurofibrillary tangles, senile plaques, and loss of synapses. Many studies support the notion that oxidative stress plays an important role in AD pathogenesis. Previous studies from our laboratory employed redox proteomics to identify oxidatively modified proteins in the AD inferior parietal lobule (IPL) and hippocampus. The proteins were consistent with biochemical or pathological alterations in AD and have been central to further investigations of the disease. The present study focused on the identification of specific targets of protein S-glutathionylation in AD and control IPL by using a redox proteomics approach. For AD IPL, we identified deoxyhemoglobin, alpha-crystallin B, glyceraldehyde phosphate dehydrogenase (GAPDH), and alpha-enolase as significantly S-glutathionylated relative to these brain proteins in control IPL. GAPDH and alpha-enolase were also shown to have reduced activity in the AD IPL. This study demonstrates that specific proteins are sensitive to S-glutathionylation, which most likely is due to their sensitivity to cysteine oxidation initiated by the increase in oxidative stress in the AD brain.