Changes in thigh muscle volume predict bone mineral density response to lifestyle therapy in frail,obese older adults

Summary

We studied the relationships among strength, muscle mass, and bone mineral density (BMD) with lifestyle change. Lifestyle therapy consisted of exercise, diet, and diet plus exercise. Diet was by caloric restriction to induce and maintain a weight loss of 10 % from baseline body weight. Exercise attenuated weight loss-induced muscle and bone losses. Exercise improved strength despite muscle loss in patients on diet and exercise. Changes in strength did not correlate with changes in BMD. However, changes in thigh muscle volume correlated with, and predicted changes in hip BMD.

Introduction

Losses of hip BMD and lean body mass are major complications of lifestyle therapy in frail, obese older adults; however, the contribution of mechanical strain loss from muscle loss is poorly defined. We determined the effect of changes in thigh muscle volume and muscle strength on BMD in frail, obese older adults undergoing lifestyle therapy aimed at intentional weight loss with or without exercise.

Methods

One hundred seven obese older adults were randomized to control, diet, exercise, and diet–exercise groups for 1 year. Thigh muscle volume was measured by magnetic resonance imaging, BMD by DXA, knee strength by dynamometry, total strength by one-repetition maximum (1-RM), and bone markers by immunoassay.

Results

Thigh muscle volume decreased in the diet group (?6.2?±?4.8 %) and increased in the exercise group (2.7?±?3.1 %), while it was not significantly different from the control in the diet–exercise group. Changes in hip BMD followed similar pattern as those in thigh muscle volume. Knee extension and flexion increased in the exercise group (23?±?20 %; 25?±?19 %) and diet–exercise group (20?±?19 %; 20.6?±?27 %) but were unchanged in the control and diet groups. Changes in thigh muscle volume correlated with changes in hip BMD (r?=?0.55, P?=?<0.001) and were an independent predictor of changes in hip BMD (β?=?0.12, P?=?0.03) in the multiple regression analyses after accounting for demographic factors and changes in weight and physical activity. There were no correlations between BMD changes and knee strength, 1-RM, and sclerostin changes.

Conclusions

Changes in thigh muscle volume predict hip BMD changes in obese older patients undergoing lifestyle therapy. The effect of exercise in attenuating thigh muscle loss when added to diet may in part account for the reduction in weight loss-induced bone loss in the diet–exercise group.     

Naratriptan: biological profile in animal models relevant to migraine

The biological profile of naratriptan (N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethane-sulphona-mide), a novel 5HT_1B/1D receptor agonist, was investigated in a variety of experimental models of relevance to migraine. Naratriptan has high affinity for human recombinant 5HT_1B and 5HT_1D receptors (pKi = 8.70.03 and 8.30.1, respectively) and causes contractions of dog isolated basilar and middle cerebral artery (EC₅₀ values of 0.11 and 0.07 M, respectively). Naratriptan causes small contractions of human isolated coronary arteries (EC₅₀ value of 0.17 M; maximum contraction equivalent to 33% of 5HT maximum). In anaesthetized dogs, naratriptan causes selective vasoconstriction of the carotid arterial bed (CD₅₀ dose = 193 g kg⁻¹) and, in anaesthetized rats, naratriptan selectively inhibits neurogenic plasma protein extravasation in the dura (ID₅₀ = 4.1 g kg⁻¹). In a variety of antinociceptive tests, naratriptan has no effect even at high doses. In conscious rats and dogs, naratriptan has high oral bioavailability (71% and 95%, respectively). The data show that naratriptan is a selective agonist at 5HT_1B/1D receptors, with a pharmacological profile very similar to that of sumatriptan, albeit 2-3 fold more potent. These observations, coupled with high oral bioavailability in animals, suggest that naratriptan has the profile of an orally effective anti-migraine drug.     

A highly sensitive and specific chemiluminescent enzyme-linked immunosorbent assay for diagnosis of active Trypanosoma cruzi infection

BACKGROUND: Chagas' disease is transmitted to man either by the bite of insects harboring Trypanosoma cruzi or by the transfusion of blood from infected donors. The conventional serologic testing as presently used in blood banks in South America is unsatisfactory, because of a high number of inconclusive and false-positive results. Other methods such as polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) with recombinant antigens have been proposed, but inherent difficulties have so far precluded their adoption in the large-scale screening required by blood banks. STUDY DESIGN AND METHODS: A highly sensitive and specific chemiluminescent ELISA using a purified trypomastigote glycoconjugate antigen and a complex epimastigote antigen was devised for the diagnosis of active T. cruzi infection. RESULTS: Chemiluminescent ELISA was 100-percent sensitive in the diagnosis of 100 cases of confirmed Chagas' disease. Inconclusive results and false-positive reactions were eliminated in a panel of 115 sera.The specificity of the chemiluminescent ELISA was 100 percent with a purified trypomastigote glycoconjugate antigen and 99.7 percent with a complex epimastigote antigen when applied to 1000 normal human sera and 288 heterologous sera from patients with other infections, including leishmaniasis, and vaccinated individuals. CONCLUSION: The chemiluminescent ELISAs provide a test that is highly sensitive (purified trypomastigote glycoconjugate and complex epimastigote antigens) and specific (purified trypomastigote glycoconjugate antigen) for Chagas' disease diagnosis. It can be used in blood bank screening and to monitor the treatment of patients undergoing chemotherapy.     

Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training

We reported that weight loss induces bone loss which is prevented by exercise training; however, the mechanism for this observation remains unclear. Sclerostin, an inhibitor of bone formation, has been found to increase in states of unloading and may mediate the changes in bone metabolism associated with weight loss and exercise. The objective of the study was to determine the effect of lifestyle intervention in obese older adults on sclerostin levels, and on hip geometry parameters. A total of 107 obese (body mass index [BMI] ≥ 30 kg/m²) older (≥65 years) adults were randomly assigned to control, diet, exercise, and combined diet‐exercise for 1 year. Sclerostin levels were measured by ELISA at baseline, 6 months, and 12 months, while hip geometry parameters were obtained from bone mineral density (BMD) images done by dual‐energy X‐ray absorptiometry using hip structure analysis at baseline and 12 months. Both the diet and diet‐exercise groups had significant decreases in body weight (?9.6% and ?9.4%, respectively), whereas weight was stable in the exercise and control groups. Sclerostin levels increased significantly and progressively in the diet group (6.6% ± 1.7% and 10.5% ± 1.9% at 6 and 12 months, respectively, all p < 0.05), whereas they were unchanged in the other groups; in particular, they were stable in the diet‐exercise group (0.7% ± 1.6% and 0.4% ± 1.7% at 6 and 12 months, respectively, all p = 0.05). Hip geometry parameters showed significant decreases in cross‐sectional area, cortical thickness, and BMD; and increases in buckling ratio at the narrow neck, intertrochanter, and femoral shaft. These negative changes on bone geometry were not observed in the diet‐exercise group. Significant correlations between changes in sclerostin and changes in certain hip geometry parameters were also observed (p < 0.05). In conclusion, the increase in sclerostin levels with weight loss that was prevented by exercise may partly mediate the negative effects of weight loss on bone metabolism and the osteoprotective effect of exercise training. © 2012 American Society for Bone and Mineral Research.     

Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties

Human protein S (HPS), a regulator of hemostasis, is a vitamin K- dependent plasma protein with potential clinical utility. We have obtained high-level expression of the cDNA for HPS in two mammalian cell lines. Both cell lines secreted single chain recombinant HPS (rHPS) in serum-free medium as determined by Western blot analysis. The ability of the rHPS from both cell lines to act as a cofactor for human protein C (HPC) was determined; the rHPS secreted from the human 293 cell line had an activity six times that of the rHPS from the AV12-664 Syrian hamster cell line. Furthermore, the relative specific cofactor activity of rHPS from the 293 cell line was actually 2.5-fold higher than that of single-chain human plasma-derived HPS. Essentially all of the rHPS secreted from the 293 cell line exhibited a calcium-dependent elution profile on anion exchange chromatography, whereas only 25% to 35% of the hamster cell-derived rHPS exhibited this profile. However, the calcium-eluted rHPS from the AV12 cell line had a high specific cofactor activity, equivalent to that of the 293-derived rHPS. A NaCl- elutable rHPS fraction (calcium nondependent) was isolated from the recombinant AV12-664 cell line, further purified, and found to have reduced activity, only 40% that of the calcium-dependent rHPS. The only observable difference in the calcium-dependent and nondependent rHPS molecules was in the content of gamma-carboxyglutamic acid (Gla); the calcium-dependent material contained approximately 10 mol Gla/mol protein whereas the calcium-nondependent material contained only approximately 8 mol Gla/mol of protein. In addition, the calcium- nondependent rHPS had reduced ability to interact with phospholipid vesicles as evidenced by an eightfold increase in the apparent kd. Our data demonstrate the isolation of rHPS with high specific activity, and show that a reduction in as few as two Gla residues dramatically decreases its functional cofactor activity for HPC, due to a reduction in ability to interact with the phospholipid bilayer.     

Caloric restriction but not exercise-induced reductions in fat mass decrease plasma triiodothyronine concentrations: a randomized controlled trial

Caloric restriction (CR) decreases circulating triiodothyronine (T(3)) concentration. However, it is not known if this effect is due to body fat mass reductions or due to CR, per se. The purpose of this study was to test the hypothesis that plasma T(3) concentration decreases with CR-induced reductions in fat mass but not in response to similar decreases in fat mass that are induced by exercise. Sedentary, nonobese 50- to 60-year-old men and women with no clinical evidence of cardiovascular or metabolic disease and not taking thyroid medications were randomly assigned to 12 months of caloric restriction (n = 18) or exercise-induced weight loss (n = 17) or to a control group (n = 9). Body weight and composition and plasma concentrations of the thyroid hormones T(3), thyrotropin (TSH), thyroxine (T(4)), and free thyroxine (FT(4)) were measured at baseline and 12 months. Fat mass changed significantly in the CR (-6.3 +/- 1.0 kg) and exercise (-5.5 +/- 1.0 kg) groups but not in the control group (-0.6 +/- 1.4 kg). The changes were not significantly different between the CR and exercise groups. Plasma T(3) concentration decreased in the CR group (-9.8 +/- 2.0 ng/dL, p < 0.0001) but not in the exercise (-3.8 +/- 2.1 ng/dL, p = 0.07) or control (-1.3 +/- 2.8 ng/dL, p = 0.65) groups. TSH, T(4), and FT(4) did not change in any of the study groups. Twelve months of CR decreased circulating T(3) concentrations in middle-aged adults. This effect does not appear to be attributable to changes in body fat mass because a comparable decrease in T(3) concentration was not observed in response to an exercise-induced fat mass reduction.     

Food label reading and understanding in parts of rural and urban Zimbabwe

Background

Overweight and obesity prevalence is rapidly rising in developing countries. The reading and understanding of nutrition information on food packages has been shown to improve food choices and instill healthy eating habits in individuals.

Objective

The aim of this study was to describe the prevalence of food label usage and understanding among urban and rural adults in Zimbabwe and its association with demographic and socio economic factors.

Methods

A cross sectional study was conducted on 320 adults (147 urban and 173 rural) using a validated questionnaire adapted from previous similar studies. Data were analysed using SPSS-17 statistical software.

Results

A high proportion (77.2%) of the respondents read food labels. Food label reading differed significantly by educational status (p<0.05), employment status (p<0.05) and locality (p<0.05). Only 40.9% of food label readers mostly understood the information on the food labels. More urban shoppers (86.1%) read food labels than their rural counterparts (66.7%). A significant number of participants (80.6%) indicated they would like to be educated on the meaning of food labels and 80.3% preferred the nutrition information on food labels to be simplified.

Conclusion

The study found above average reported reading of nutrition information on food labels with partial understanding. Efforts should be made to determine how all consumers could be made to understand the nutrition information on food labels and use it effectively in decision making.