Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults

BACKGROUND: Epidemiologic studies have found whole-grain intake to be inversely associated with the risk of type 2 diabetes and heart disease. OBJECTIVE: We tested the hypothesis that whole-grain consumption improves insulin sensitivity in overweight and obese adults. DESIGN: This controlled experiment compared insulin sensitivity between diets (55% carbohydrate, 30% fat) including 6-10 servings/d of breakfast cereal, bread, rice, pasta, muffins, cookies, and snacks of either whole or refined grains. Total energy needs were estimated to maintain body weight. Eleven overweight or obese [body mass index (in kg/m(2)): 27-36] hyperinsulinemic adults aged 25-56 y participated in a randomized crossover design. At the end of each 6-wk diet period, the subjects consumed 355 mL (12 oz) of a liquid mixed meal, and blood samples were taken over 2 h. The next day a euglycemic hyperinsulinemic clamp test was administered. RESULTS: Fasting insulin was 10% lower during consumption of the whole-grain than during consumption of the refined-grain diet (mean difference: -15 +/- 5.5 pmol/L; P = 0.03). After the whole-grain diet, the area under the 2-h insulin curve tended to be lower (-8832 pmol.min/L; 95% CI: -18720, 1062) than after the refined-grain diet. The rate of glucose infusion during the final 30 min of the clamp test was higher after the whole-grain diet (0.07 x 10(-4) mmol.kg(-1).min(-1) per pmol/L; 95% CI: 0.003 x 10(-4), 0.144 x 10(-4)). CONCLUSION: Insulin sensitivity may be an important mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart disease.     

Alterations in cell proliferation and apoptosis in colon cancers with microsatellite instability

Colon cancers with microsatellite instability (MSI) demonstrate a host immune response characterized by tumor infiltrating lymphocytes (TILs) that may exert effects upon tumor cell apoptosis and cell proliferation. Accordingly, we compared rates of apoptosis and cell proliferation in colon cancers with defective DNA mismatch repair and their association with phenotypic features and clinical outcome. Primary Astler-Coller stage B2 and C colon carcinomas (n = 329) were analyzed for MSI and for hMLH1 and hMSH2 protein expression. Apoptosis (TUNEL assay) and p53 expression were also analyzed by immunohistochemistry, and TILs were quantified by morphology. DNA ploidy and proliferation (PI: S phase + G(2)M) were evaluated using flow cytometry. MSI-H (n = 58) colon cancers showed increased TILs that were significantly associated with increased apoptosis, higher apoptosis to proliferation (AI/PI) ratios, reduced proliferative indices (PI) and diploid DNA content. Increased TILs (p = 0.036) and reduced PI (p = 0.042), but not AI or AI/PI, were associated with improved disease-free survival. Tumors with MSI-H (p = 0.032) or loss of hMLH1 or hMSH2 proteins (p = 0.040), or diploidy (p = 0.0015), had better adjusted overall survival rates. Interestingly, similar rates of cell turnover and overlapping survival rates were found in diploid MSS/MSI-L tumors and in MSI-H cases. In conclusion, higher apoptosis/proliferation ratios and reduced cell proliferation are phenotypic features of MSI-H tumors that are associated with increased TILs, indicating an activated immune response that may contribute to their favorable survival rates.     

Neuromuscular adaptations to concurrent strength and endurance training

PURPOSE: The purpose of this study was to examine muscle morphological and neural activation adaptations resulting from the interaction between concurrent strength and endurance training. METHODS: Thirty sedentary healthy male subjects were randomly assigned to one of three training groups that performed 10 wk of 3-d x wk(-1) high-intensity strength training (S), cycle endurance training (E), or concurrent strength and endurance training (CC). Strength, quadriceps-muscle biopsies, computed tomography scans at mid-thigh, and surface electromyogram (EMG) assessments were made before and after training. RESULTS: S and CC groups demonstrated similar increases (P < 0.0001) in both thigh extensor (12 and 14%) and flexor/adductor (7 and 6%) muscle areas. Type II myofiber areas similarly increased (P < 0.002) in both S (24%) and CC (28%) groups, whereas the increase (P < 0.004) in Type I area with S training (19%) was also similar to the nonsignificant (P = 0.041) increase with CC training (13%). Significant increases (P < 0.005) in maximal isometric knee-extension torque were accompanied by nonsignificant (P 0.38) in the EMG/torque relation across 20 to 100% maximal voluntary contractions occurred in any group. A small 3% increase (P < 0.01) in thigh extensor area was the only change in any of the above variables with E training. CONCLUSIONS: Findings indicate 3-d x wk(-1) concurrent performance of both strength and endurance training does not impair adaptations in strength, muscle hypertrophy, and neural activation induced by strength training alone. Results provide a physiological basis to support several performance studies that consistently indicate 3-d x wk(-1) concurrent training does not impair strength development over the short term.     

The effect of early caloric restriction on colonic cellular growth in rats

Although the inhibitory effect of caloric restriction on tumorigenesis is substantial and well known, the pertinent mechanisms remain to be determined. We recently suggested that the risk of cancer may be directly related to the total number of dividing cells within an affected organ. This study evaluates the effects of early caloric restriction on the cellular growth of the colon. The experiment began one day postpartum and ended six weeks later with the killing of all animals. It consisted of two consecutive periods: a) three weeks of suckling and b) three weeks postweaning. Animals whose food was restricted only during the suckling period showed normal colons when killed at six weeks. Caloric restriction (40%) for three weeks postweaning resulted in colons of lower weight with fewer cells (less total DNA) and reduced total DNA synthesis ([³H]thymidine uptake, dpm/colon) when compared with animals fed ad libitum postweaning. Conversely, only rats fed ad libitum from birth through the first three weeks after weaning demonstrated an increase (21%) in the rate of DNA synthesis (dpm/mg DNA) compared with other animals. In addition, the colonic crypts showed no differences in the number of cells or the number of dividing cells, as determined by autoradiography. By contrast, the total number of crypts (and/or the number of mucosal cells between crypts) are reduced, and hence the total number of colonic mucosal cells dividing at any given time are similarly decreased. The reduced number of dividing cells in the colons of these animals (i.e., those restricted postweaning) could explain previous data suggesting that they are resistant to the induction of colon cancer.     

Prerequisites for global child and adolescent mental health

The epidemiology of the mental and physical health of children and adolescents the world over reflects: the genomes they inherit (and the modifications those genes undergo in utero); the pregnancies that led to their births, whether their mothers survive those pregnancies, and whether their births were welcome; the parents, the neighbors, and the neighborhoods they 'inherit' along with their genomes; when and where they live (by cohort, by country, and by province); the air they breathe; the water they drink; what and how much they eat; the schools they attend (and by whom they are taught what and for how long); the energy they expend; the family status in the social order; the friends they have; and last but not least, the amount and kind of medical and psychiatric care they receive.     

Mometasone furoate nasal spray: a review of safety and systemic effects.

The development of corticosteroids that are delivered directly to the nasal mucosa has alleviated much of the concern about the systemic adverse effects associated with oral corticosteroid therapy. However, given the high potency of these drugs and their widespread use in the treatment of allergic rhinitis, it is important to ensure that intranasal corticosteroids have a favourable benefit-risk ratio. One agent that typifies the systemic safety found in the majority of intranasal corticosteroids is mometasone furoate nasal spray, a potent and effective treatment for seasonal and perennial allergic rhinitis and nasal polyposis. Mometasone furoate does not reach high systemic concentrations or cause clinically significant adverse effects. Results from pharmacokinetic studies in adults and children suggest that systemic exposure to mometasone furoate after intranasal administration is negligible. This is probably because of the inherently low aqueous solubility of mometasone furoate, which allows only a small fraction of the drug to cross the nasal mucosa and enter the bloodstream, and because a large amount of the administered drug is swallowed and undergoes extensive first-pass metabolism. There is no clinical evidence that mometasone furoate nasal spray suppresses the function of the hypothalamus-pituitary-adrenal axis when the drug is administered at clinically relevant doses (100-200 microg/day); consequently, mometasone furoate nasal spray has not been associated with growth inhibition in children. The safety and tolerability of mometasone furoate nasal spray have been rigorously assessed in clinical trials involving approximately 4,500 patients, with epistaxis, headache and pharyngitis being the most common adverse effects associated with treatment in adolescents and adults.The clinical effectiveness of mometasone furoate nasal spray, coupled with its agreeable safety and tolerability profile, confirms its favourable benefit-risk ratio.     

Nonalcoholic Fatty Liver Disease: Pathogenesis, Identification, Progression, and Management

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases in the absence of significant alcohol consumption, and its incidence is paralleling the increasing numbers of overweight and obese individuals worldwide. This review discusses the pathogenesis of NAFLD, including the roles potentially played by specific adipokines, such as TNF-α, leptin, and adiponectin. Clinical features, diagnosis, and potential methods of management are also addressed to assist practitioners with the management of this growing population of patients.     

Debate on the conservative and aggressive treatment options for the optimal management of indolent non-Hodgkin's lymphoma

Indolent non-Hodgkin's lymphoma (NHL) is currently considered to be an incurable disease, with a median survival of 6-8 years. In the absence of a cure, the variety of therapeutic options available for patients with indolent NHL range from 'watchful waiting' to high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT). There is no current consensus on standard treatment. Conventional chemotherapy is clearly not curative, and many clinicians prefer to delay chemotherapy until the patient develops overt symptoms that require treatment. On the one hand, long-term studies indicate that 'watchful waiting' has no effect on overall survival. On the other hand, aggressive treatment strategies, such as HDT with ASCT, may increase disease-free survival in some patients, particularly when used early in the treatment algorithm, but are also associated with potential toxicity. Thus the selection of therapy for each patient involves balancing the benefit of the treatment with any side effects and detriment to quality of life. The development of innovative therapies for indolent NHL, such as monoclonal antibodies with or without chemotherapy, requires a reassessment of the treatment choices. Good clinical responses and time to progression have so far been achieved in clinical trials of rituximab and other agents including radiolabelled antibodies, but in view of the long median survival of patients with indolent NHL, it will be some years before it can be conclusively demonstrated whether such treatments have an effect on the natural history of the disease or produce a cure. This issue raises an important question: outside the setting of a clinical trial, should patients be treated aggressively with therapies that do not yet have proven curative ability? This article considers the evidence and relative merits for the conservative approach to indolent NHL, where patients are treated according to symptoms in order to maintain a normal quality of life wherever possible, and for the aggressive approach, where the lymphoma is targeted soon after the diagnosis.     

Enriched environment delays the onset of hippocampal damage after global cerebral ischemia in rats

An enriched environment has been shown to improve cognitive, behavioral and histopathological outcome after focal cerebral ischemia and head trauma. The purpose of this study was to determine the effect of an enriched environment on histopathology following global cerebral ischemia. Wistar rats (21 weeks of age) were placed in different environments [standard cages (SC) or enriched environment (EE) cages] for 2 months before and either 6 days or 2 months after ischemia. Rats underwent 10 min of global ischemia by bilateral carotid artery occlusions plus hypotension. Five groups (n=4-5 in each group) were studied: (1) rats kept in SC before and 2 months after ischemia; (2) rats kept in SC before ischemia but transferred to an EE for 2 months after ischemia; (3) rats kept in EE before and after ischemia for 2 months; (4) rats kept in SC before and 6 days after ischemia; (5) rats kept in EE before and 6 days after ischemia. At 7 days or 2 months after ischemia, brains were perfusion-fixed, and ischemic injury was assessed by counting numbers of normal neurons in the hippocampal CA1 sector. Physiological variables showed no inter-group differences. Rats housed in EE for 2 months before and for 6 days (but not 2 months) after global ischemia showed significantly better preservation of pyramidal neurons in the hippocampal CA1 area when compared to control animals (middle CA1, 20.5+/-5.4 vs. 2.8+/-0.6; lateral CA1, 31.5+/-7.2 vs. 2.6+/-0.6, respectively). The present data suggest that housing in EE for 2 months before and 6 days after ischemia can delay the onset of damage to hippocampal pyramidal neurons, which eventually occurs despite 2-month EE.