Nutritional status in patients with rheumatoid arthritis.

A nutritional assessment of 50 patients with rheumatoid arthritis (RA) showed evidence of malnutrition in 13 (26%), while all 50 control subjects had normal nutritional status. Of the anthropometric measurements the body-mass index and triceps skinfold thickness values in men and women were significantly reduced in RA patients compared with controls. Upper arm muscle circumference was significantly less in male but not female rheumatoid patients. In addition all six biochemical determinants of nutrition assayed-serum albumin, transferrin, retinol-binding protein, thyroxine-binding prealbumin, zinc, and folic acid-were significantly lower in the RA group of patients. Malnourished patients had more active disease than the remaining RA patients, with significantly higher ESR, C-reactive protein, and alpha 1 antichymotrypsin measurements. Significant inverse correlations were found between some biochemical measurements of nutrition and indices of disease activity. Our results suggest that in RA the severity of disease adversely affects the nutritional status.     

Concomitant inhibition of DNA methyltransferase and BCL-2 protein function synergistically induce mitochondrial apoptosis in acute myelogenous leukemia cells

DNA methylation and BLC-2 are potential therapeutic targets in acute myeloid leukemia (AML). We investigated pharmacologic interaction between the DNA methyltransferase inhibitor 5-azacytidine (5-AZA) and the BCL-2 inhibitor ABT-737. Increased BCL-2 expression determined by reverse phase protein analysis was associated with poor survival in AML patients with unfavorable cytogenetics (n?=?195). We found that 5-AZA, which itself has modest apoptotic activity, acts synergistically with ABT-737 to induce apoptosis. The 5-AZA/ABT-737 combination enhanced mitochondrial outer membrane permeabilization, as evidenced by effective conformational activation of BAX and ?ψ_m loss. Although absence of p53 limited apoptotic activities of 5-AZA and ABT-737 as single agents, the combination synergistically induced apoptosis independent of p53 expression. 5-AZA down-regulated MCL-1, known to mediate resistance to ABT-737, in a p53-independent manner. The 5-AZA/ABT-737 combination synergistically induced apoptosis in AML cells in seven of eight patients. 5-AZA significantly reduced MCL-1 levels in two of three samples examined. Our data provide a molecular rationale for this combination strategy in AML therapy.     

Sustained Simultaneous Delivery of Metronidazole and Doxycycline From Polycaprolactone Matrices Designed for Intravaginal Treatment of Pelvic Inflammatory Disease

Poly(?-caprolactone) (PCL) intravaginal matrices were produced for local delivery of a combination of antibacterials, by rapidly cooling a mixture of drug powders dispersed in PCL solution. Matrices loaded with different combinations of metronidazole (10%, 15%, and 20% w/w) and doxycycline (10% w/w) were evaluated in vitro for release behavior and antibacterial activity. Rapid “burst release” of 8%-15% of the doxycycline content and 31%-37% of the metronidazole content occurred within 24 h when matrices were immersed in simulated vaginal fluid at 37°C. The remaining drug was extracted gradually over 14 days to a maximum of 65%-73% for doxycycline and 62%-71% for metronidazole. High levels of antibacterial activity up to 89%-91% against Gardnerella vaginalis and 84%-92% against Neisseria gonorrhoeae were recorded in vitro for release media collected on day 14, compared to “nonformulated” metronidazole and doxycycline solutions. Based on the in vitro data, the minimum levels of doxycycline and metronidazole released from PCL matrices in the form of intravaginal rings into vaginal fluid in vivo were predicted to exceed the minimum inhibitory concentrations for N. gonorrhea (reported range 0.5-4.0 μg/mL) and G. vaginalis (reported range 2-12.8 μg/mL) respectively, which are 2 of the major causative agents for pelvic inflammatory disease.     

First Nation Elders’ perspectives on healthy ageing in NSW,Australia

Objectives : Healthy ageing has been unattainable for many of Australia’s First Nation people, driven by an earlier onset of chronic disease when compared to the general Australian population. Our objective was to examine the perspectives of Australian First Nation people about healthy ageing. Methods : We used a conversational method to gather knowledge from older First Nation people from established communities in New South Wales, Australia. Discussions were audio recorded and transcribed and analysed using an Indigenous research standpoint methodology. Eight yarning circles were held in six locations with 76 participants aged 45 years and over. Results : Key issues around healthy ageing were identified; particularly, what the impact of chronic disease means to individuals. Study participants reported that healthy ageing is essential to continue to share knowledge of their history and culture. Conclusion : This article highlights the need for culturally appropriate healthy ageing programs addressing issues related to chronic disease among First Nation communities. Implications for public health : Research into what constitutes healthy ageing for older First Nation people is necessary for the development of culturally appropriate chronic disease interventions.