Drugs That Cause Weight Gain

Among drugs which cause weight gain, the tricyclic antidepressant medications are a drug class producing persistent and problematic body weight gain in many treated patients. Major depressive illness is often associated with reductions in appetite and body weight, and treatment with antidepressants effectively restores mood, appetite and weight. However, a frequent complaint of patients treated with tricyclic drugs is of excessive and unwanted weight gain, oftentimes resulting in medication noncompliance. The incidence of weight gain during acute and chronic treatment with different, frequently prescribed antidepressant drugs will be reviewed, as will the possible mechanisms by which such drugs alter caloric intake and expenditure, contributing to drug-induced weight gain.     

Adoptive Transfer of Lymphocytes Isolated from Simian Immunodeficiency Virus SIVmac239Δnef-Vaccinated Macaques Does Not Affect Acute-Phase Viral Loads but May Reduce Chronic-Phase Viral Loads in Major Histocompatibility Complex-Matched Recipients

The live attenuated simian immunodeficiency virus (SIV) SIVmac239Δnef is the most effective SIV/human immunodeficiency virus (HIV) vaccine in preclinical testing. An understanding of the mechanisms responsible for protection may provide important insights for the development of HIV vaccines. Leveraging the uniquely restricted genetic diversity of Mauritian cynomolgus macaques, we performed adoptive transfers between major histocompatibility complex (MHC)-matched animals to assess the role of cellular immunity in SIVmac239Δnef protection. We vaccinated and mock vaccinated donor macaques and then harvested between 1.25 × 10⁹ and 3.0 × 10⁹ mononuclear cells from multiple tissues for transfer into 12 naive recipients, followed by challenge with pathogenic SIVmac239. Fluorescently labeled donor cells were detectable for at least 7 days posttransfer and trafficked to multiple tissues, including lung, lymph nodes, and other mucosal tissues. There was no difference between recipient macaques'' peak or postpeak plasma viral loads. A very modest difference in viral loads during the chronic phase between vaccinated animal cell recipients and mock-vaccinated animal cell recipients did not reach significance (P = 0.12). Interestingly, the SIVmac239 challenge virus accumulated escape mutations more rapidly in animals that received cells from vaccinated donors. These results may suggest that adoptive transfers influenced the course of infection despite the lack of significant differences in the viral loads among animals that received cells from vaccinated and mock-vaccinated donor animals.     

Medical and Social Determinants of Subsequent Labour Market Marginalization in Young Hospitalized Suicide Attempters

Background

Individuals with a history of suicide attempt have a high risk for subsequent labour market marginalization. This study aimed at assessing the effect of individual and parental factors on different measures of marginalization.

Methods

Prospective cohort study based on register linkage of 5 649 individuals who in 1994 were 16–30 years old, lived in Sweden and were treated in inpatient care for suicide attempt during 1992–1994. Hazard ratios (HRs) for labour market marginalization defined as long-term unemployment (>180 days), sickness absence (>90 days), or disability pension in 1995–2010 were calculated with Cox regression.

Results

Medical risk factors, particularly any earlier diagnosed specific mental disorders (e.g., schizophrenia: HR 5.4 (95% CI: 4.2, 7.0), personality disorders: HR 3.9, 95% CI: 3.1, 4.9), repetitive suicide attempts (HR 1.6, 95% CI: 1.4, 1.9) were associated with a higher relative risk of disability pension. Individual medical factors were of smaller importance for long-term sickness absence, and of only marginal relevance to long-term unemployment. Country of birth outside Europe had an opposite effect on disability pension (HR 0.6, 95% CI: 0.4, 0.8) and long-term unemployment (HR 1.5, 95% CI: 1.3, 1.8). Female sex was positively correlated with long-term sickness absence (HR 1.6, 95% CI: 1.4, 1.7), and negatively associated with long-term unemployment (HR: 0.8, 95% CI: 0.7, 0.9).

Conclusions

As compared to disability pension, long-term sickness absence and unemployment was more strongly related to socio-economic variables. Marginalization pathways seemed to vary with migration status and sex. These findings may contribute to the development of intervention strategies which take the individual risk for marginalization into account.     

Reduction potential variations in azurin through secondary coordination sphere phenylalanine incorporations

Recent evidence has shown that the properties of metal binding sites can be tuned by more than the ligands in the primary coordination sphere. We investigated the incorporation of four phenylalanine residues into the secondary coordination sphere of the small soluble blue copper protein azurin. The locations for placement of these residues in azurin were based on the structure of the highly hydrophobic blue copper protein rusticyanin, which is known to have a significantly higher reduction potential than azurin. Using site-directed mutagenesis, these residues in close proximity to the copper binding site were mutated to large hydrophobic phenylalanine residues individually and in combination. We also added the Met121Leu mutation on top of the Phe mutations to construct a total of 13 variants. We found little change in the UV-visible absorption and EPR data for these proteins, however modest increases in reduction potential were observed with increases by as much as 30 mV per Phe residue. Furthermore, we observed the increases in potential to be additive.     

Body image and quality of life in post massive weight loss body contouring patients

Objective: Because post‐bariatric surgery patients undergo massive weight loss, the resulting skin excess can lead to both functional problems and profound dissatisfaction with appearance. Correcting skin excess could improve all these corollaries, including body image. Presently, few data are available documenting body image and weight‐related quality of life in this population. Research Methods and Procedures: Eighteen patients who underwent both bariatric surgery and body contouring completed our study. Both established surveys and new surveys designed specifically for the study were used to assess body perception and ideals, quality of life, and mood. Patients were surveyed at the following time‐points: pre‐body contouring (after massive weight loss) and both 3 and 6 month post‐body contouring. Statistical testing was performed using Student's t test and ANOVA. Results: The mean age of the patients was 46 ± 10 years (standard deviation). Quality of life improved after obesity surgery and was significantly enhanced after body contouring. Three months after body contouring, subjects ascribed thinner silhouettes to both current appearance and ideal body image. Body image also improved with body contouring surgery. Mood remained stable over 6 months. Discussion: Body contouring after surgical weight loss improved both quality‐of‐life measurements and body image. Initial body dissatisfaction did not correlate with mood. Body contouring improved body image but produced dissatisfaction with other parts of the body, suggesting that as patients become closer to their ideal, these ideals may shift. We further developed several new assessment methods that may prove useful in understanding these post‐surgical weight loss patients.     

Remarkable Diversity in the Enzymes Catalyzing the Last Step in Synthesis of the Pimelate Moiety of Biotin

Biotin synthesis in Escherichia coli requires the functions of the bioH and bioC genes to synthesize the precursor pimelate moiety by use of a modified fatty acid biosynthesis pathway. However, it was previously noted that bioH has been replaced with bioG or bioK within the biotin synthetic gene clusters of other bacteria. We report that each of four BioG proteins from diverse bacteria and two cyanobacterial BioK proteins functionally replace E. coli BioH in vivo. Moreover, purified BioG proteins have esterase activity against pimeloyl-ACP methyl ester, the physiological substrate of BioH. Two of the BioG proteins block biotin synthesis when highly expressed and these toxic proteins were shown to have more promiscuous substrate specificities than the non-toxic BioG proteins. A postulated BioG-BioC fusion protein was shown to functionally replace both the BioH and BioC functions of E. coli. Although the BioH, BioG and BioK esterases catalyze a common reaction, the proteins are evolutionarily distinct.     

Epithelial Adhesion Mediated by Pilin SpaC Is Required for Lactobacillus rhamnosus GG-Induced Cellular Responses

Lactobacillus rhamnosus GG is a widely used probiotic, and the strain''s salutary effects on the intestine have been extensively documented. We previously reported that strain GG can modulate inflammatory signaling, as well as epithelial migration and proliferation, by activating NADPH oxidase 1-catalyzed generation of reactive oxygen species (ROS). However, how strain GG induces these responses is unknown. Here, we report that strain GG''s probiotic benefits are dependent on the bacterial-epithelial interaction mediated by the SpaC pilin subunit. By comparing strain GG to an isogenic mutant that lacks SpaC (strain GGΩspaC), we establish that SpaC is necessary for strain GG to adhere to gut mucosa, that SpaC contributes to strain GG-induced epithelial generation of ROS, and that SpaC plays a role in strain GG''s capacity to stimulate extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in enterocytes. In addition, we show that SpaC is required for strain GG-mediated stimulation of cell proliferation and protection against radiologically inflicted intestinal injury. The identification of a critical surface protein required for strain GG to mediate its probiotic influence advances our understanding of the molecular basis for the symbiotic relationship between some commensal bacteria of the gut lumen and enterocytes. Further insights into this relationship are critical for the development of novel approaches to treat intestinal diseases.     

Heritable variation in reaction norms of metabolism and activity across temperatures in a wild-derived population of white-footed mice (Peromyscus leucopus)

Heritable variation in metabolic traits is likely to affect fitness. In this study, white-footed mice from wild-derived photoresponsive [R, infertile in short day length (SD)] and non-photoresponsive (NR, fertile in SD) selection lines were maintained under short-day (SD 8Light:16Dark), sub-thermoneutral conditions (22 or 12 °C). Mice had significantly higher levels of food intake and resting metabolic rates (RMR) at low temperature. RMR differed significantly between lines (greater in NR mice). In contrast to previous work under thermoneutral conditions, there was no significant difference in overall activity or average daily metabolic rates (ADMR) of mice from the two lines. Reduced activity may reflect behavioral changes under cooler conditions (e.g., nest building) reducing the overall energetic cost of fertility (for NR mice). There was no significant difference in maximal rate of oxygen consumption ( $\dot V \text{O}_{\text {2max}} $ ) between lines. R mice had significantly greater brown adipose tissue and white abdominal fat mass due to both line and temperature. Reaction norms for intake, resting metabolism (RMR/BMR) and level of activity from current (12 and 22 °C) and previously published data (28 °C) demonstrate independent effects of genetics (line) and environment (temperature) for resting metabolism, but a clear interaction between these for activity. The results suggest that fertility under winter conditions imposes metabolic costs that are related to the level of reproductive development. Under the coldest conditions tested, however, mice that remained fertile in SD reduced activity, ADMR and food requirements, decreasing the differential between selection lines. Heritable variation in reaction norms suggests a genetic by environment effect that could be subject to selection.