Obesity: epidemiology and possible prevention

Obesity can be defined as the excessive accumulation of fat in adipose tissue, to the extent that health may be impaired. The most widely used measures of total and abdominal adiposity are the body mass index and waist circumference. Obesity is now a global public health problem, with about 315 million people world-wide estimated to fall into the WHO-defined obesity categories with a body mass index (BMI) of 30 or above.The primary causes of the rapid global rise in obesity rates lie in the profound environmental and societal changes now affecting large parts of the world and creating societies in which physical activity is low and the availability of high-fat, energy-dense foods has increased. Strategies aimed at preventing weight gain and obesity have not been successful to date but are likely to be more cost effective, and to have a greater positive impact on long-term control of body weight than treating obesity once it has developed.     

Probiotics to enhance anti-infective defences in the gastrointestinal tract

Several clinical studies have demonstrated the therapeutic and/or prophylactic efficacy of specific probiotics against acute viral gastroenteritis and antibiotic-associated diarrhoea (including Clostridium difficile infection). Emerging evidence also suggests beneficial effects against Helicobacter pylori infection. The evidence of efficacy against traveller's diarrhoea remains, however, inconclusive. The precise mechanisms by which probiotics potentiate host gastrointestinal defences and mediate protection are not fully known. There is evidence to suggest, however, that probiotics might contribute to host defence by reinforcing non-immunological defences and stimulating both specific and non-specific host immune responses. Little is known about the relative importance of the probiotic-stimulated mechanisms in host protection. This review summarises the evidence for the anti-infective effects of probiotics and discusses the effect of orally delivered probiotics on non-immunological and immunological defence mechanisms in the host, especially in the gastrointestinal tract.     

Stability of frozen methacholine solutions in unit-dose syringes for bronchoprovocation

OBJECTIVE: Methacholine solutions < 0.25 mg/mL must be prepared fresh daily, while concentrations > or = 0.25 mg/mL must be prepared at 2-week intervals according to US Food and Drug Administration-required labeling. The purpose of this report was to determine whether freezing methacholine solutions in unit-dose syringes would allow less frequent preparation. DESIGN: Diluent containing 0.5% sodium chloride, 0.275% sodium bicarbonate, and 0.4% phenol was used to prepare 11 concentrations of methacholine ranging from 0.031 to 32.0 mg/mL. Three milliliters of each dilution was placed into 5-mL polypropylene syringes and immediately frozen. Methacholine concentrations were determined using a validated high-performance liquid chromatography assay after preparation (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 5, and 6 months. On the day of analysis, the samples were allowed to thaw to room temperature. An additional set of each dilution was stored at room temperature for 24 h after thawing and then analyzed for methacholine. RESULTS: Samples > or = 0.062 mg/mL analyzed immediately after thawing retained > or = 90% of labeled potency for at least 6 months, while the 0.031-mg/mL sample retained 90% potency for 4 months. Most samples analyzed 24 h after thawing lost potency. CONCLUSION: If prepared and stored in unit-dose syringes frozen, methacholine solutions containing 0.062 to 32.0 mg/mL can be prepared at 6-month intervals, and solutions containing 0.031 mg/mL can be prepared at 4-month intervals. Once thawed, unused methacholine solutions should be discarded.     

Chronic and Acute Prenatal and Postnatal Ethanol Exposure on Lymphocyte Subsets from Offspring Thymic, Splenic, and Intestinal Intraepithelial Sources

The overall objective of this study was to analyze the effects of a combined prenatal and postnatal (entire gestational human chronic drinking model) ethanol exposure on T-cell development in mice. Specifically, this study evaluated the effects of chronic exposure to prenatal ethanol on lymphocyte makeup and proliferative capabilities of postnatal offspring's (4 and 12 weeks) peripheral lymphoid tissues. Chronic exposure regimens were conducted over the entire gestational period and through postnatal day 14 or 21. Thymus, spleen, and intestinal intraepithelial lymphocytes were harvested and analyzed by flow cytometry for percentages of T-cell subsets. Splenic lymphocytes were also analyzed for their ability to proliferate in response to a T-cell mitogen. Limited effects of chronic ethanol exposure were seen.     

Involvement of nicotinamide adenine dinucleotide in the action of cholera toxin in vitro.

NAD is a necessary cofactor for the activation of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) by cholera toxin. Lysates of certain types of cell that hydrolyze their endogenous store of NAD after cell disruption respond poorly or not at all to cholera toxin. Lysates of pigeon erythrocytes, which lack enzymes that degrade NAD, provide a convenient and reproducible system for assaying the activity of cholera toxin in vitro and allow investigation of the mechanism of action of the toxin upon broken cells.     

Enhanced green fluorescent protein targeted to the Sca-1 (Ly-6A) locus in transgenic mice results in efficient marking of hematopoietic stem cells in vivo

OBJECTIVE: Hematopoietic stem cells are important clinically, both as targets of disease and as reagents for cellular therapy. Studies in hematopoietic stem cell biology have been hampered by difficulties in purifying and manipulating these cells. To facilitate these studies, we sought to develop a system for targeting genes of interest to the hematopoietic stem cell compartment in transgenic mice. MATERIALS AND METHODS: We used Sca-1, a glycosyl phosphatidylinositol-anchored protein expressed on the surface of all hematopoietic stem cells in commonly used inbred mouse strains. We created a mutant Sca-1 allele in which the enhanced green fluorescent protein (EGFP) cDNA is integrated into the Sca-1 locus by homologous recombination in embryonic stem cells. RESULTS: EGFP protein is detectable in all hematopoietic tissues of mice heterozygous for the mutant Sca-1 allele. Growth and development of these mice are normal. No adverse effects of long-term, high-level EGFP expression were noted. Sca-1 positive cells coexpress EGFP in all tissues and lineages examined, as predicted by the targeting strategy. Sca-1 and EGFP expression are coordinately up-regulated in splenocytes from mutant mice. The Lin(-)EGFP(+) bone marrow population contains all progenitor activity in Sca-1(+)(/EGFP) mice. The Lin(-)EGFP(+) bone marrow cells are equivalent to Lin(-)Sca-1(+) cells in long-term repopulation and serial transplantation assays. CONCLUSION: The hematopoietic stem cell compartment appears to be targeted in Sca-1(+)(/EGFP) mutant mice. This system should be useful for studying the normal biology of hematopoietic stem cells and for targeting other genes to this cellular compartment.     

Recurrent hemoperitoneum in women receiving continuous ambulatory peritoneal dialysis

Of 27 women in the reproductive age group receiving continuous ambulatory peritoneal dialysis for more than 3 months, 4 of 7 who menstruated developed recurrent hemoperitoneum. Tubal ligation had been done in 3 of these 4 women. There were 37 episodes of hemoperitoneum; 22 occurred at midcycle and 15 with menstruation. One patient required repeated blood transfusion, but after oral anovulant therapy no further bleeding occurred and no transfusion was required. Two patients needed laparotomy: one for heavy intraperitoneal bleeding originating from a luteal cyst, and the other for severe lower abdominal pain from follicular and luteal cysts. Ultrasound examinations suggested the presence of small ovarian cysts in the two remaining patients. Recurrent midcycle hemoperitoneum in women on continuous ambulatory peritoneal dialysis may be triggered by ovulation and associated ovarian cyst formation. Suppression of ovulation should be considered.