Reduction of abdominal fat and chronic disease factors by lifestyle change in migrant Asian Indians older than 50 years

The objective of this study was to assess the impact of a group diet and physical activity intervention on body composition, blood lipid profile and insulin resistance in migrant Asian Indian volunteers. Total body and abdominal fat, waist girth, serum glucose, insulin and lipids were measured one month before and immediately prior to an intervention designed to encourage increased physical activity and improved diet. Measurements were repeated after a 5-month period of altered exercise and dietary habits. Over this period monthly group education sessions were held on diet and physical activity and the importance of lifestyle changes to reduce risk factors for chronic disease. Forty one (21M, 20F) volunteers (aged > 50 y) were recruited from Asian Indian community groups in urban Auckland, New Zealand. Body weight, total and percentage body fat, waist girth and abdominal fat decreased in men following the intervention (p < 0.006) while these changes were not statistically significant in women. In both men and women high density lipoprotein (HDL) levels increased and LDL and total cholesterol/HDL ratio decreased (p < 0.002) without changes in serum glucose, insulin and triglycerides. Reduction in systolic and diastolic blood pressure was associated with an increase in HDL cholesterol in women (r = 0.63, p = 0.003, r = 0.48, p = 0.03) but not in men (r = 0.09, p = 0.69, r = 0.04, p = 0.86). Over a five month period, an Asian Indian community group diet and physical activity intervention resulted in significant reductions in total and abdominal body fat and blood lipid risk factors but not in insulin sensitivity or resistance.     

Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-kappaB ligand pathway

Bone is a common site of cancer metastasis. Breast, prostate, and lung cancers show a predilection to metastasize to bone. Recently, we reported that the chemokine interleukin 8 (IL-8) stimulates both human osteoclast formation and bone resorption. IL-8 mRNA expression was surveyed in a panel of human breast cancer lines MDA-MET, MDA-MB-231, MDA-MB-435, MCF-7, T47D, and ZR-75, and the human lung adenocarcinoma cell line A549. IL-8 mRNA expression was higher in cell lines with higher osteolytic potential in vivo. Human osteoclast formation was increased by MDA-MET or A549 cell-conditioned medium, but not by MDA-MB-231. Pharmacologic doses of receptor activator of nuclear factor-kappaB (RANK)-Fc or osteoprotogerin had no effect on the pro-osteoclastogenic activity of the conditioned medium; however, osteoclast formation stimulated by conditioned medium was inhibited 60% by an IL-8-specific neutralizing antibody. The data support a model in which tumor cells cause osteolytic bone destruction independently of the RANK ligand (RANKL) pathway. Tumor-produced IL-8 is a major contributor to this process. The role of secreted IL-8 isoforms was examined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, which detected distinct IL-8 isoforms secreted by MDA-MET and MDA-231 cells, suggesting different pro-osteoclastogenic activities of the two IL-8-derived peptides. These data indicate that (a) osteoclast formation induced by MDA-MET breast cancer cells and A549 adenocarcinoma cells is primarily mediated by IL-8, (b) cell-specific isoforms of IL-8 with distinct osteoclastogenic activities are produced by tumor cells, and (c) tumor cells that support osteoclast formation independent of RANKL secrete other pro-osteoclastogenic factors in addition to IL-8.     

Cardiac risk stratification of breast cancer patients in a cardio-oncology clinic

Breast Cancer Research and Treatment - Identification of women with DCIS who have a very low risk of local recurrence risk (LRR) after breast-conserving surgery (BCS) is needed to de-escalate...     

Cholesterol-conjugated poly(D,L-lactide)-based micelles as a nanocarrier system for effective delivery of curcumin in cancer therapy

Polymeric micelles have been widely explored preclinically as suitable delivery systems for poorly soluble chemotherapeutic drugs in cancer therapy. The present study reported the development of cholesterol (Ch)-conjugated poly(D,L-Lactide) (PLA)-based polymeric micelles (mPEG–PLA-Ch) for effective encapsulation and delivery of curcumin (CUR) at the tumor site. Cholesterol conjugation dramatically affected the particle size and improved drug loading (DL) and encapsulation efficiency (EE). mPEG–PLA-Ch-CUR showed bigger hydrodynamic diameter (104.6?±?2.1?nm, and 169.3?±?1.52?nm for mPEG–PLA and mPEG–PLA-Ch, respectively) due to increased size of the hydrophobic core. The newly developed polymer exhibited low critical micelles concentration (CMC) (25?μg/mL) which is close to lipid-based polymer, PEG-phosphatidyl ethanolamine (12.5?μg/mL) compared to mPEG–PLA (50?μg/mL). mPEG–PLA-Ch micelles exhibited relatively higher EE (93.74?±?1.6%) and DL (11.86?±?0.8%) compared to mPEG–PLA micelles (EE 91.89?±?1.2% and DL 11.06?±?0.8%). mPEG–PLA-Ch micelles were internalized by the cancer cells effectively and exhibited higher cytotoxicity compared to free CUR in both, murine melanoma (B16F10) and human breast cancer (MDA-MB-231) cells. mPEG–PLA-Ch exhibited satisfactory hemocompatibility indicating their potential for systemic application. Further, mPEG–PLA-Ch-CUR demonstrated higher rate of reduction of tumor volume in B16F10-xenografted tumor-bearing mice compared to free CUR. At the end of 22 days, the tumor reduced to 1.87-fold (627.72?±?0.9?mm³ versus 1174.68?±?1.64?mm³) compared to the treatment with free CUR. In conclusion, the experimental data in vitro and in vivo indicated that the newly developed CUR-mPEG–PLA-Ch micelles may have promising applications in solid tumors.     

Sluggish glucose tolerance in tuberculosis patients.

OBJECTIVE: To examine glucose tolerance in sputum-positive non-treated pulmonary tuberculosis (TB) patients as part of a general metabolic profile. Subjects. Sixty-three sputum-positive non-treated patients (male and female) attending the pulmonary clinic at Mthatha General Hospital in the Eastern Cape and 89 apparently healthy sex and age-matched volunteers. METHODS: Sixty-three untreated TB patients who came to the Mthatha General Hospital's pulmonary clinic with classic symptoms of TB, confirmed by sputum analysis, were recruited for the study. Eighty-nine apparently healthy sex and age-matched volunteers served as the control group. Anthropometric measurements were taken using an electronic scale. Standard oral glucose tolerance tests (OGTTs) were performed in both groups in the morning after an overnight fast. Anticoagulant-treated blood was analysed for glucose and insulin using Peridochrome Glucose (Boehringer Mannheim, Mannheim, Germany) and radioimmunoassay (RIA) (Diagnostic Products Corporation, Los Angeles, USA) respectively. RESULTS: There was sluggish response to glucose and insulin in the TB patient group compared with the control group. Glucose and insulin levels were significantly higher in patients at 0, 30, 60, 120, and 180 minutes. Analysis of variance gave the following p-values, viz. p = 0.0000, 0.0004, 0.0000, 0.0000 and 0.0000 for glucose, and p = 0.0317, 0.0071, 0.0000, 0.0005 and 0.0000 for insulin respectively. CONCLUSIONS: The results of this study suggest an altered glucose/insulin metabolism in TB patients. This might play an important role in the clinical course of the disease.     

Chronic rhinofacial mucormycosis caused by Mucor irregularis (Rhizomucor variabilis) in India

In this article, we describe a chronic case of rhinofacial mucormycosis caused by Mucor irregularis, formerly known as Rhizomucor variabilis var. variabilis, a rare mycotic agent in humans. The infection caused progressive destruction of the nasal septum and soft and hard palate, leading to collapse of the nose bridge and an ulcerative gaping hole. The mucoralean mold cultured from a nasal biopsy specimen was determined by multilocus DNA sequence data to be conspecific with M. irregularis.     

Studies on Condensed Triazines as Chemotherapeutic Agents,II. Synthesis of 1,2,4-Triazino[5,6-b]indoles and Related Compounds

1,2,4-Triazino[5,6-b]indoles and their derivatives are prepared by the cyclisation of isatin 3-thiosemicarbazone (1) followed by condensation and displacement reactions. Condensations of 3-hydrazino-1,2,4-triazino[5,6-b]indole (4) with ethoxymethylenemalononitrile, ethyl ethoxymethylenecyanoacetate, acetylacetone and methyl bis(methylmercapto)methylenecyanoacetate yield the corresponding 3-pyrazolo-1,2,4-triazino[5,6-b]indoles 6–9. The hydrazine 4 is further transformed into the higher heterocycles 10–12 on reaction with formic, acetic or nitrous acids.