Calcium and dairy product modulation of lipid utilization and energy expenditure

Objective: The purpose of this study was to investigate the impact of dietary calcium or dairy product intake on total energy expenditure (TEE), fat oxidation, and thermic effect of a meal (TEM) during a weight loss trial. Methods and Procedures: The intervention included a prescribed 500‐kcal deficit diet in a randomized placebo‐controlled calcium or dairy product intervention employing twenty‐four 18 to 31‐year‐old (22.2 ± 3.1 years, mean ± s.d.) overweight women (75.5 ± 9.6 kg). TEM and fat oxidation were measured using respiratory gas exchange after a meal challenge, and TEE was measured by doubly labeled water. Fat mass (FM) and lean mass (fat‐free mass (FFM)) were measured by dual‐energy X‐ray absorptiometry. Subjects were randomized into one of these three intervention groups: (i) placebo (<800 mg/day calcium intake); (ii) 900 mg/day calcium supplement; (iii) three servings of dairy products/day to achieve an additional 900 mg/day. Results: There were no group effects observed in change in TEE; however, a group effect was observed for fat oxidation after adjusting for FFM (P = 0.02). The treatment effect was due to an increase in fat oxidation in the calcium‐supplemented group of 1.5 ± 0.6 g/h, P = 0.02. Baseline 25‐hydroxyvitamin D (25OHD) was positively correlated with TEM (R = 0.31, P = 0.004), and trended toward a correlation with fat oxidation (P = 0.06), independent of group assignment. Finally, the change in log parathyroid hormone (PTH) was positively correlated with the change in trunk FM (R = 0.27, P = 0.03). Discussion: These results support that calcium intake increases fat oxidation, but does not change TEE and that adequate vitamin D status may enhance TEM and fat oxidation.     

The Transmembrane Protein of the Human Endogenous Retrovirus - K (HERV-K) Modulates Cytokine Release and Gene Expression

Numerous copies of endogenous retroviruses are present in the genome of mammals including man. Although most of them are defective, some, e.g., the human endogenous retroviruses HERV-K, were found to be expressed under certain physiological conditions. For instance, HERV-K is expressed in germ cell tumours and melanomas as well as in the placenta. Most exogenous retroviruses including the human immunodeficiency virus HIV-1 induce severe immunodeficiencies and there is increasing evidence that the transmembrane envelope (TM) proteins of these retroviruses may be involved. We show here that HERV-K particles released from a human teratocarcinoma cell line, a recombinant TM protein and a peptide corresponding to a highly conserved so-called immunosuppressive domain in the TM protein of HERV-K inhibit the proliferation of human immune cells, induce modulation of the expression of numerous cytokines, and modulate the expression of cellular genes as detected by a microarray analysis. The changes in cytokine release and gene expression induced by the TM protein of HERV-K are similar to those found previously induced by the TM protein of HIV-1. These data suggest that the mechanism of immunosuppression may be similar for different retroviruses and that the expression of the TM protein in tumours and in the placenta may suppress immune responses and thus prevent rejection of the tumour and the embryo.     

Fat mass deposition during pregnancy using a four-component model.

Estimates of body fat mass gained during human pregnancy are necessary to assess the composition of gestational weight gained and in studying energy requirements of reproduction. However, commonly used methods of measuring body composition are not valid during pregnancy. We used measurements of total body water (TBW), body density, and bone mineral content (BMC) to apply a four-component model to measure body fat gained in nine pregnant women. Measurements were made longitudinally from before conception; at 8-10, 24-26, and 34-36 wk gestation; and at 4-6 wk postpartum. TBW was measured by deuterium dilution, body density by hydrodensitometry, and BMC by dual-energy X-ray absorptiometry. Body protein was estimated by subtracting TBW and BMC from fat-free mass. By 36 wk of gestation, body weight increased 11.2 +/- 4.4 kg, TBW increased 5.6 +/- 3.3 kg, fat-free mass increased 6.5 +/- 3.4 kg, and fat mass increased 4.1 +/- 3.5 kg. The estimated energy cost of fat mass gained averaged 44,608 kcal (95% confidence interval, -31, 552-120,768 kcal). The large variability in the composition of gestational weight gained among the women was not explained by prepregnancy body composition or by energy intake. This variability makes it impossible to derive a single value for the energy cost of fat deposition to use in estimating the energy requirement of pregnancy.     

Correlation between brain/plasma ratios and efficacy in neuropathic pain models of selective metabotropic glutamate receptor 1 antagonists

We have discovered a novel, potent, and selective triazafluorenone series of metabotropic glutamate receptor 1 (mGluR1) antagonists with efficacy in various rat pain models. Pharmacokinetic and pharmacodynamic profiles of these triazafluorenone analogs revealed that brain/plasma ratios of these mGluR1 antagonists were important to achieve efficacy in neuropathic pain models. This correlation could be used to guide our in vivo SAR (structure-activity relationship) modification. For example, compound 4a has a brain/plasma ratio of 0.34, demonstrating only moderate efficacy in neuropathic pain models. On the other hand, antagonist 4b with a brain/plasma ratio of 2.70 was fully efficacious in neuropathic pain models.     

Effects of external beam radiation on in vitro formation of Abeta1-42 fibrils and preformed fibrils

Plaques containing fibrillar amyloid-beta (Abeta) are a characteristic finding in Alzheimer's disease. Although plaque counts correlate poorly with the extent of cognitive deficits in this disorder, fibrillar Abeta can promote neuronal damage through a variety of mechanisms. External beam radiotherapy has been reported to be an effective treatment for tracheobronchial amyloidosis, in which amyloid is deposited as submucosal plaques and tumor-like masses in the trachea and/or bronchi. Radiotherapy's effectiveness in this disorder is thought to be due to its toxicity to plasma cells, but direct effects of radiotherapy on amyloid may also be involved. On this basis, whole-brain radiotherapy has been suggested as a treatment for Alzheimer's disease. The objective of this study was to determine the effects of external beam radiation on preformed Abeta1-42 fibrils and on the formation of these fibrils. Using the Thioflavin-T assay, no effects of radiation were found on either of these parameters. Our results in this in vitro study suggest that whole-brain irradiation is unlikely to directly reduce plaque counts in the Alzheimer's disease brain. This treatment might still lower plaque counts indirectly, but any potential benefits would need to be weighed against its possible neurotoxic effects, which could induce further cognitive deficits.     

Complex Biventricular Pacing - A Case Series

It is established that cardiac resynchronisation therapy (CRT) reduces mortality and hospitalisation and improves functional class in patients with NYHA class 3-4 heart failure, an ejection fraction of ≤ 35% and a QRS duration of ≥ 120ms. Recent updates in the American guidelines have expanded the demographic of patients in whom CRT may be appropriate. Here we present two cases of complex CRT; one with a conventional indication but occluded central veins and the second with a novel indication for CRT post cardiac transplant.     

Determinants for Membrane Association of the Hepatitis C Virus NS2 Protease Domain

Hepatitis C virus (HCV) nonstructural protein 2 (NS2) is required for HCV polyprotein processing and particle assembly. It comprises an N-terminal membrane domain and a C-terminal, cytosolically oriented protease domain. Here, we demonstrate that the NS2 protease domain itself associates with cellular membranes. A single charged residue in the second α-helix of the NS2 protease domain is required for proper membrane association, NS2 protein stability, and efficient HCV polyprotein processing.     

Biological control of rice sheath blight using hyphae-associated bacteria: development of an <Emphasis Type="Italic">in planta</Emphasis> screening assay to predict biological control agent performance under field conditions

A pathogenicity assay for in planta screening of biological control agents (BCAs) towards sheath blight in rice was developed, and used to evaluate a panel of Rhizoctonia solani Kühn hyphae-associated bacteria for their ability to control sheath blight under screenhouse conditions. The best performing BCA, Burkholderia sp. strain A-7.3, was selected for field trials. Disease incidence and disease severity were significantly reduced leading to a significant grain yield increase of 7%. Furthermore, R. solani sclerotia formation and sclerotia viability were significantly reduced, thus lowering the reservoir for primary infections in the next crop cycle. The paper presents a reliable pathogenicity assay that can be used to test BCA performance under different scenarios e.g. plant variety and soil conditions, and help predict translation of results obtained under screenhouse conditions to field performance. Furthermore, it supports the hypothesis that hyphae-associated bacteria are a promising source of niche-specific BCAs towards fungal pathogens.     

A review of haliday species ofMicroctonus [Hym.: Braconidae,Euphorinae]

A neotype based on aWesmael specimen is designated forMicroctonus aethiops (Nees).M. aethiops of authors is described asaethiopoides, new species. Lectotypes are designated forM. secalis (Haliday) andcerealium (Haliday). The namecerealium is suppressed as a synonym of the namesecalis and the types ofsecalis andbrevicollis (Haliday) are redescribed.