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Objective Glucagon-like peptide-1 (GLP-1) analogs are attractive options for the treatment of type II diabetes and obesity because of their incretin and anorexigenic effects. Peripheral administration of the GLP-1R agonist Exendin-4 (Ex-4) also increases glucocorticoid secretion in rodents and humans, but whether the released glucocorticoids interact with Ex-4's anorexigenic effect remains unclear. Methods To test this, we used two experimental approaches that suppress corticosterone secretion and then assessed Ex-4 effects on eating in adult male rats. First, we combined acute and chronic low dose dexamethasone treatment with Ex-4. Second, we ablated hindbrain catecholamine neurons projecting to the hypothalamus with anti-dopamine-β-hydroxylase-saporin (DSAP) to block Ex-4-induced corticosterone secretion. Results Combining dexamethasone and Ex-4 produced a larger acute anorexigenic effect than Ex-4 alone. Likewise, chronic dexamethasone and Ex-4 co-treatment produced a synergistic effect on eating and greater body weight loss in diet-induced obese rats than Ex-4 alone. DSAP lesions not only blunted Ex-4's ability to increase corticosterone secretion, but potentiated the anorexigenic effect of Ex-4, indicating that Ex-4-dependent corticosterone secretion opposes Ex-4's actions. Consistent with the enhancement of Ex-4's anorexigenic effect, DSAP lesion altered Ex-4-dependent changes in neuropeptide Y, preproglucagon, and corticotropin releasing hormone gene expression involved in glucocorticoid feedback. Conclusions Our findings demonstrate that limiting glucocorticoid secretion and actions with low dose dexamethasone or DSAP lesion increases Ex-4's ability to reduce food intake and body weight. Novel glucocorticoid receptor based mechanisms, therefore, may help enhance GLP-1-based obesity therapies., Highlights • Blocking HPA axis by low dose dexamethasone increased the anorexigenic property of Ex-4. • Dexamethasone/Ex-4 co-treatment reduced food intake and body weight in diet-induced obese rats more than Ex-4 alone. • A brain lesion model identified a potential central interaction between glucocorticoids and GLP-1 in food intake control.

Intestinal lymph supposedly provides a readout for the secretion of intestinal peptides. We here assessed how mesenteric lymph duct (MLD) lymph levels of glucagon-like peptide (GLP-1), insulin, and metabolites [glucose and triglycerides (TG)] evolve after isocaloric high- and low-fat diet (HFD and LFD) meals and how they compare with hepatic portal vein (HPV) plasma levels. Moreover, we examined the effects of intraperitoneally administered GLP-1 (1 or 10 nmol/kg) on these parameters. At 20 min after the HFD meal onset, GLP-1 levels were higher in MLD lymph than in HPV plasma. No such difference occurred with the LFD meal. Intraperitoneal injections of 10 nmol/kg GLP-1 before meals enhanced the meal-induced increases in MLD lymph and HPV plasma GLP-1 levels except for the MLD lymph levels after the HFD meal. Intraperitoneal injection of 1 nmol/kg GLP-1 only increased HPV plasma GLP-1 levels at 60 min after the HFD meal. GLP-1 injections did not increase the MLD lymph or HPV plasma GLP-1 concentrations beyond the physiological range, suggesting that intraperitoneal GLP-1 injections can recapitulate the short-term effects of endogenous GLP-1. Dipeptidyl peptidase IV (DPP-IV) activity in MLD lymph was lower than in HPV plasma, which presumably contributed to the higher levels of GLP-1 in lymph than in plasma. Insulin and glucose showed similar profiles in MLD lymph and HPV plasma, whereas TG levels were higher in lymph than in plasma. These results indicate that intestinal lymph provides a sensitive readout of intestinal peptide release and potential action, in particular when fat-rich diets are consumed.

We present the design, synthesis, and characterization of a novel photocaged glutamine derivative (modified on the side chain of glutamine), and describe its use in enhancing peptide stability and solubility. Our results demonstrate that this approach can be used to develop molecular switches to control the folding and β-sheet formation of amyloidogenic peptides.

This article concerns some realistic scenarios for evaluation of the electromagnetic (EM) field and for better comprehension of its behavior outdoors and indoors spaces having a place nearby powerful EM sources or base stations (CBS) [1]. Following scenarios are marked: As soon as closed or semi-open objects could be as a resonator with some Q-factor, we consider numerical study of EMC problems related to the resonance enhancement of the EM field inside vehicles. Then, finding field?s propagation outdoors (nearby and around some obstacles) and field?s distribution indoors are presented. Eventually, the motivation of this article is to investigate possible negative impact of the EM field on human during exposure in a wide range of the frequencies mainly through the temperature rise. All these simulated scenarios are an integral part of all cities and consequently are taken for consideration.

Temperature rise evaluation in human body exposed to RF energy is becoming increasingly important topic related to the future development of the RF exposure safety standards. Therefore the validation of the existing methods like FDTD used in such complex multidisciplinary studies is very important. The accuracy of the FDTD solution of the bio-heat equation which is most often used in this type if studies have been analyzed based on the developed program package. The effect of stair case geometry representation in FDTD grid has been investigated by comparing the test case with analytical solution. In addition comparison was made with the published results. Preliminary data show that in case of constant temperature boundary conditions FDTD results slightly differ from the analytical solution during the transition state of the heat transfer process while there is a much better agreement in steady state regime. In case of convective boundary conditions the steady state temperature distribution at the convective boundary obtained by FDTD method also differ insignificantly from the FEM results reported in literature and temperature values inside the model are almost identical with that from FEM models. The results point to the conclusion that the error in FDTD simulations may be attributed to faster heat exchange which is due to the difference of surface area between the smooth and stair case boundaries of the modeled structures. These results are similar to those reported in T. Samaras et al. (2006). The impact on temperature inside the body far from the boundary is less than 1% while at the boundary is in the range of 4-7% for the models with 0.5 mm grid resolution and tissue like thermal properties

This paper presents an approach to estimate the main characteristics (specific absorption rate (SAR), total absorbed EM power and temperature rise) related to human exposure to EM energy. The assessment is done numerically using a proprietary software package, which is based on the finite difference time domain (FDTD) method and the method of auxiliary sources (MAS) (used here for partially homogeneous models). The general goal is to provide an efficient and sufficiently accurate method to assess human exposure to EM fields in a wide frequency range and for different types of exposure conditions: far field exposure (from cellular base stations) and near field exposure (from personal wireless communication devices). Dependence of exposure on different posture and EM field distribution inside the body is considered.

This paper contains the results of computer simulations performed for several realistic scenarios of electromagnetic (EM) field evaluation near the cellular base station (CBS) and some analysis of obtained results. The motivation of this study is exposure assessment of EM energy on biological objects. There are scenarios of field distribution indoors, near the hill, obstacle like a wall and finally the field distribution inside the human body is computed. These scenarios are general and frequently encountering in practice inside space covered by wireless networks. Using the reasonable computational resources and keeping the accuracy of the solution acceptable for problems involving the electrically large objects the method of auxiliary sources (MAS) (R. Zaridze et al., 2002) (D. Kakulia et al., 2004) is used to simulate the EM field for the cases mentioned above.