Effects of Sibutramine on Binge Eating,Hunger, and Fullness in a Laboratory Human Feeding Paradigm

Objective : The purpose of this study was to evaluate the effects of sibutramine vs. placebo on binge‐eating behavior, hunger, and satiety in patients who had problems with binge eating. Research Methods and Procedures : Seven adult subjects who had problems with binge eating (mean age, 42 years) were randomly assigned to receive alternating sibutramine and placebo in a double‐blind placebo‐controlled crossover study. This involved two 4‐week dosing periods separated by a 2‐week washout. Results : Subjects lost weight on sibutramine but not on placebo. There was a significant difference in the number of kilocalories consumed between the sibutramine and placebo conditions, with a significant reduction of intake during binge‐eating episodes on sibutramine. Discussion : Sibutramine suppresses intake during binge‐eating episodes. This effect is demonstrable in a human feeding laboratory paradigm.     

Low incidence of polyploids and high uniformity of karyotypes displayed by Delphinium (Ranunculaceae) in the Hengduan Mountains region of south‐west China

The chromosome numbers and morphology in 92 populations belonging to 49 species and three varieties in the genus Delphinium L. (Ranunculaceae), mostly from the Hengduan Mountains region of south‐west China, were studied. Forty seven species and three varieties were diploid, with 2n = 16, one species was tetraploid, with 2n = 32, and one species had diploid and tetraploid cytotypes. Three species had B chromosomes, representing the first time the occurrence of B chromosomes has been reported in the genus. The karyotypes of all the diploid species were quite uniform, commonly bimodal, and usually consisted of one pair of large median‐centromeric (m), one pair of large submedian‐centromeric (sm), five pairs of medium‐sized subterminal‐centromeric (st), and one pair of smaller sm (rarely st) chromosomes. The low incidence of polyploids in Delphinium from the Hengduan Mountains region indicates that polyploidy has played a minor role in the speciation of this highly diversified genus in the region. © 2008 The Linnean Society of London, Botanical Journal of the Linnean Society, 2008, 158 , 172–188.     

Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology.     

Promoter hypermethylation using 24-gene array in early head and neck cancer: Better outcome in oral than in oropharyngeal cancer

Silencing of tumor suppressor genes (TSGs) by DNA promoter hypermethylation is an early event in carcinogenesis and a potential target for personalized cancer treatment. In head and neck cancer, little is known about the role of promoter hypermethylation in survival. Using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) we investigated the role of promoter hypermethylation of 24 well-described genes (some of which are classic TSGs), which are frequently methylated in different cancer types, in 166 HPV-negative early oral squamous cell carcinomas (OSCC), and 51 HPV-negative early oropharyngeal squamous cell carcinomas (OPSCC) in relation to clinicopathological features and survival. Early OSCC showed frequent promoter hypermethylation in RARB (31% of cases), CHFR (20%), CDH13 (13%), DAPK1 (12%), and APC (10%). More hypermethylation (≥ 2 genes) independently correlated with improved disease specific survival (hazard ratio 0.17, P = 0.014) in early OSCC and could therefore be used as prognostic biomarker. Early OPSCCs showed more hypermethylation of CDH13 (58%), TP73 (14%), and total hypermethylated genes. Hypermethylation of two or more genes has a significantly different effect on survival in OPSCC compared with OSCC, with a trend toward worse instead of better survival. This could have a biological explanation, which deserves further investigation and could possibly lead to more stratified treatment in the future.     

Relative accuracy of spatial predictive models for lynx Lynx canadensis derived using logistic regression-AIC,multiple criteria evaluation and Bayesian approaches

We compared probability surfaces derived using one set of environmental variables in three Geographic Information Systems (GIS) -based approaches: logistic regression and Akaike's Information Criterion (AIC),Multiple Criteria Evaluation (MCE),and Bayesian Analysis (specifically Dempster-Shafer theory). We used lynx Lynx canadensis as our focal species,and developed our environment relationship model using track data collected in Banff National Park,Alberta,Canada,during winters from 1997 to 2000. The accuracy of the three spatial models were compared using a contingency table method. We determined the percentage of cases in which both presence and absence points were correctly classified (overall accuracy),the failure to predict a species where it occurred (omission error) and the prediction of presence where there was absence (commission error). Our overall accuracy showed the logistic regression approach was the most accurate (74.51% ). The multiple criteria evaluation was intermediate (39.22%),while the Dempster-Shafer (D-S) theory model was the poorest (29.90%). However,omission and commission error tell us a different story: logistic regression had the lowest commission error,while D-S theory produced the lowest omission error. Our results provide evidence that habitat modellers should evaluate all three error measures when ascribing confidence in their model. We suggest that for our study area at least,the logistic regression model is optimal. However,where sample size is small or the species is very rare,it may also be useful to explore and/or use a more ecologically cautious modelling approach (e.g. Dempster-Shafer) that would over-predict,protect more sites,and thereby minimize the risk of missing critical habitat in conservation plans.     

Momentary affect surrounding loss of control and overeating in obese adults with and without binge eating disorder

Research suggests that loss of control (LOC) while eating (the sense that one cannot control what or how much one is eating) is a more salient feature of binge eating than the amount of food consumed. This study examined the unique contributions of LOC and episode size to negative affect surrounding eating episodes in binge eating disorder (BED) and obesity. Twenty-two obese adults with (n = 9) and without (n = 13) BED completed daily records of eating patterns and mood using ecological momentary assessment (EMA). Linear mixed modeling revealed that across groups, greater premeal self-reported LOC was associated with higher premeal negative affect independent of episode size. For individuals with BED, greater premeal self-reported LOC was associated with higher postmeal negative affect, regardless of the amount of food eaten, whereas for obese controls, the combination of LOC and consumption of large amounts of food was associated with lower postmeal negative affect. Results indicate that LOC, but not the quantity of food consumed, is associated with momentary distress related to aberrant eating in BED. Findings also highlight the need for further research investigating the emotional context surrounding aberrant eating in obese individuals without BED.     

The oxygen delivery response to acute hypoxia during incremental knee extension exercise differs in active and trained males

Background

It is well known that hypoxic exercise in healthy individuals increases limb blood flow, leg oxygen extraction and limb vascular conductance during knee extension exercise. However, the effect of hypoxia on cardiac output, and total vascular conductance is less clear. Furthermore, the oxygen delivery response to hypoxic exercise in well trained individuals is not well known. Therefore our aim was to determine the cardiac output (Doppler echocardiography), vascular conductance, limb blood flow (Doppler echocardiography) and muscle oxygenation response during hypoxic knee extension in normally active and endurance-trained males.

Methods

Ten normally active and nine endurance-trained males (VO_2max = 46.1 and 65.5 mL/kg/min, respectively) performed 2 leg knee extension at 25, 50, 75 and 100% of their maximum intensity in both normoxic and hypoxic conditions (FIO₂ = 15%; randomized order). Results were analyzed with a 2-way mixed model ANOVA (group × intensity).

Results

The main finding was that in normally active individuals hypoxic sub-maximal exercise (25 – 75% of maximum intensity) brought about a 3 fold increase in limb blood flow but decreased stroke volume compared to normoxia. In the trained group there were no significant changes in stroke volume, cardiac output and limb blood flow at sub-maximal intensities (compared to normoxia). During maximal intensity hypoxic exercise limb blood flow increased approximately 300 mL/min compared to maximal intensity normoxic exercise.

Conclusion

Cardiorespiratory fitness likely influences the oxygen delivery response to hypoxic exercise both at a systemic and limb level. The increase in limb blood flow during maximal exercise in hypoxia (both active and trained individuals) suggests a hypoxic stimulus that is not present in normoxic conditions.

     

Impact of Weight Loss and Regain on Quality of Life: Mirror Image or Differential Effect?

Objective: To compare the impact of weight regain and weight loss on health‐related quality of life. Research Methods and Procedures: Subjects were 122 (106 women, 16 men) overweight and obese participants in a weight reduction program (phentermine‐fenfluramine and dietary counseling) who had initially lost at least 5% of their total body weight and then regained at least 5% of their weight during the follow‐up period. Follow‐up periods ranged from 10 to 41 months (mean, 28 months). Participants completed the Impact of Weight on Quality of Life‐Lite, an obesity‐specific health‐related quality of life (HRQOL) measure, at 3‐month intervals. Results: Mean BMI at baseline was 40.9 ± 6.6 kg/m² (range, 29.2 to 63.7 kg/m²). Average weight loss from entry was 18.8 ± 6.7% (range, 6.0% to 43.7%), and average regain was 10.1 ±4.4% of baseline weight (range, 5.0% to 30.6%). The effects of weight regain on HRQOL mirrored the effects of weight loss—rates of HRQOL change were similar in magnitude but different in direction for comparable weight loss and regain. Those with more severe initial impairments in HRQOL experienced greater improvements in HRQOL during weight loss as well as greater deterioration during weight regain than those with less severe impairments. Discussion: Weight loss and regain produced mirror image changes in HRQOL. The initial severity of HRQOL impairment had a greater impact on the magnitude of HRQOL change than the direction of weight change. Findings underscore the importance of maintaining weight loss for the purposes of retaining obesity‐specific HRQOL benefits.