Topiramate in the treatment of compulsive sexual behavior: case report

BACKGROUND: Among the multiple mechanisms of action of topiramate, AMPA/kainate antagonism may be particularly interesting for the treatment of disorders characterized by conditioned cognitive and behavioral cue reactivity. CASE PRESENTATION: We report the case of a patient consulting primarily for obesity and cue triggered snacking, who responded well on topiramate at doses up to 50 mg. Coincidentally he reported on an improvement of compulsive nonparaphilic sexual behaviors (consumption of prostitution), which was also strongly triggered by environmental cues. Both addictive behaviors (snacking and consumption of prostitution) reoccurred after discontinuation of topiramate and again responded reintroduction of the drug. CONCLUSION: The present case report of topiramate's effect on comorbid obesity and nonparaphilic addiction could be interpreted as a further indication that topiramate acts on the common pathway underlying conditioned behaviors and seems to be a treatment of behavioral disorders associated with environmental cues

Evaluation of the efficacy and tolerability of miglitol in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylureas

The objective of this study is to examine the efficacy and tolerability of miglitol with respect to improving glycemic control in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylurea treatment. This was a randomized, double-blinded, placebo-controlled, multicenter study. A total of 105 patients were randomized to receive 24 weeks of treatment with miglitol (n = 52; titrated from 50 mg to 100 mg 3 times daily) or placebo (n = 53). Concomitant sulfonylurea treatment and diet remained unchanged. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline at 24 weeks. Secondary endpoints were changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and postprandial serum insulin (PSI). The miglitol treatment group showed significantly greater reductions in HbA1c and PPG levels compared with the placebo group. With respect to adverse events, abdominal discomfort, diarrhea, and hypoglycemia occurred with similar frequency in both groups. Results of this study indicate that miglitol significantly improves metabolic control in Chinese patients with type 2 diabetes mellitus. Miglitol is safe and well tolerated, with the exception of abdominal discomfort. Therefore, miglitol may be a useful adjuvant therapy for Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylurea treatment

Perceived neighborhood safety and incident mobility disability among elders: the hazards of poverty

<p>Abstract</p> <p>Background</p> <p>We investigated whether lack of perceived neighborhood safety due to crime, or living in high crime neighborhoods was associated with incident mobility disability in elderly populations. We hypothesized that low-income elders and elders at retirement age (65 – 74) would be at greatest risk of mobility disability onset in the face of perceived or measured crime-related safety hazards.</p> <p>Methods</p> <p>We conducted the study in the New Haven Established Populations for Epidemiologic Studies of the Elderly (EPESE), a longitudinal cohort study of community-dwelling elders aged 65 and older who were residents of New Haven, Connecticut in 1982. Elders were interviewed beginning in 1982 to assess mobility (ability to climb stairs and walk a half mile), perceptions of their neighborhood safety due to crime, annual household income, lifestyle characteristics (smoking, alcohol use, physical activity), and the presence of chronic co-morbid conditions. Additionally, we collected baseline data on neighborhood crime events from the New Haven Register newspaper in 1982 to measure local area crime rates at the census tract level.</p> <p>Results</p> <p>At baseline in 1982, 1,884 elders were without mobility disability. After 8 years of follow-up, perceiving safety hazards was associated with increased risk of mobility disability among elders at retirement age whose incomes were below the federal poverty line (HR 1.56, 95% CI 1.02 – 2.37). No effect of perceived safety hazards was found among elders at retirement age whose incomes were above the poverty line. No effect of living in neighborhoods with high crime rates (measured by newspaper reports) was found in any sub-group.</p> <p>Conclusion</p> <p>Perceiving a safety hazard due to neighborhood crime was associated with increased risk of incident mobility disability among impoverished elders near retirement age. Consistent with prior literature, retirement age appears to be a vulnerable period with respect to the effect of neighborhood conditions on elder health. Community violence prevention activities should address perceived safety among vulnerable populations, such as low-income elders at retirement age, to reduce future risks of mobility disability.</p

Neighborhood conditions, diabetes, and risk of lower-body functional limitations among middle-aged African Americans: A cohort study

<p>Abstract</p> <p>Background</p> <p>The relationship between presence of diabetes and adverse neighborhood and housing conditions and their effect on functional decline is unclear. We examined the association of adverse neighborhood (block face) and housing conditions with incidence of lower-body functional limitations among persons with and those without diabetes using a prospective population-based cohort study of 563 African Americans 49-65 years of age at their 2000-2001 baseline interviews.</p> <p>Methods</p> <p>Participants were randomly sampled African Americans living in the St. Louis area (response rate: 76%). Physician-diagnosed diabetes was self reported at baseline interview. Lower-body functional limitations were self reported based on the Nagi physical performance scale at baseline and the three-year follow-up interviews. The external appearance of the block the respondent lived on and five housing conditions were rated by study interviewers. All analyses were done using propensity score methods to control for confounders.</p> <p>Results</p> <p>109 (19.4%) of subjects experienced incident lower-body functional limitations at three-year follow-up. In adjusted analysis, persons with diabetes who lived on block faces rated as fair-poor on each of the five conditions had higher odds (7.79 [95% confidence interval: 1.36-37.55] to 144.6 [95% confidence interval: 4.45-775.53]) of developing lower-body functional limitations than the referent group of persons without diabetes who lived on block faces rated as good-excellent. At least 80 percent of incident lower-body functional limitations was attributable to the interaction between block face conditions and diabetes status.</p> <p>Conclusions</p> <p>Adverse neighborhood conditions appear to exacerbate the detrimental effects on lower-body functioning associated with diabetes.</p

Socioeconomic position and incident mobility impairment in the Cardiovascular Health Study

Background We investigated if personal socioeconomic position (SEP) factors and neighborhood characteristics were associated with incident mobility impairment in the elderly. Methods We used data from the Cardiovascular Health Study, a longitudinal, population-based examination of coronary heart disease and stroke among persons aged 65 and older in the United States. Results Among 3,684 persons without baseline mobility impairment, lower baseline SEP was associated with increased risk of incident mobility disability during the 10-year follow-up period, although the strengths of these associations varied by socioeconomic indicator and race/sex group. Conclusion Among independent-living elderly, SEP affected development of mobility impairment into later life. Particular effort should be made to prevent or delay its onset among the elderlyhttp://deepblue.lib.umich.edu/bitstream/2027.42/57781/1/Socioeconomic Position and Incident Mobility Impairment in the Cardiovascular Health Study.pd

On the Action of Cyclosporine A, Rapamycin and Tacrolimus on M. avium Including Subspecies paratuberculosis

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) may be zoonotic. Recently the "immuno-modulators" methotrexate, azathioprine and 6-MP and the "anti-inflammatory" 5-ASA have been shown to inhibit MAP growth in vitro. We concluded that their most plausible mechanism of action is as antiMAP antibiotics. The "immunosuppressants" Cyclosporine A, Rapamycin and Tacrolimus (FK 506) treat a variety of "autoimmune" and "inflammatory" diseases. Rapamycin and Tacrolimus are macrolides. We hypothesized that their mode of action may simply be to inhibit MAP growth. METHODOLOGY: The effect on radiometric MAP (14)CO(2) growth kinetics of Cyclosporine A, Rapamycin and Tacrolimus on MAP cultured from humans (Dominic & UCF 4) or ruminants (ATCC 19698 & 303) and M. avium subspecies avium (ATCC 25291 & 101) are presented as "percent decrease in cumulative GI" (%-DeltacGI.) PRINCIPAL FINDINGS: The positive control clofazimine has 99%-DeltacGI at 0.5 microg/ml (Dominic). Phthalimide, a negative control has no dose dependent inhibition on any strain. Against MAP there is dose dependent inhibition by the immunosuppressants. Cyclosporine has 97%-DeltacGI by 32 microg/ml (Dominic), Rapamycin has 74%-DeltacGI by 64 microg/ml (UCF 4) and Tacrolimus 43%-DeltacGI by 64 microg/ml (UCF 4) CONCLUSIONS: We show heretofore-undescribed inhibition of MAP growth in vitro by "immunosuppressants;" the cyclic undecapeptide Cyclosporine A, and the macrolides Rapamycin and Tacrolimus. These data are compatible with our thesis that, unknowingly, the medical profession has been treating MAP infections since 1942 when 5-ASA and subsequently azathioprine, 6-MP and methotrexate were introduced in the therapy of some "autoimmune" and "inflammatory" diseases

A systematic review of longitudinal studies on the association between depression and smoking in adolescents

<p>Abstract</p> <p>Background</p> <p>It is well-established that smoking and depression are associated in adolescents, but the temporal ordering of the association is subject to debate.</p> <p>Methods</p> <p>Longitudinal studies in English language which reported the onset of smoking on depression in non clinical populations (age 13-19) published between January 1990 and July 2008 were selected from PubMed, OVID, and PsychInfo databases. Study characteristics were extracted. Meta-analytic pooling procedures with random effects were used.</p> <p>Results</p> <p>Fifteen studies were retained for analysis. The pooled estimate for smoking predicting depression in 6 studies was 1.73 (95% CI: 1.32, 2.40; p < 0.001). The pooled estimate for depression predicting smoking in 12 studies was 1.41 (95% CI: 1.21, 1.63; p < 0.001). Studies that used clinical measures of depression were more likely to report a bidirectional effect, with a stronger effect of depression predicting smoking.</p> <p>Conclusion</p> <p>Evidence from longitudinal studies suggests that the association between smoking and depression is bidirectional. To better estimate these effects, future research should consider the potential utility of: (a) shorter intervals between surveys with longer follow-up time, (b) more accurate measurement of depression, and (c) adequate control of confounding.</p

Acute Effects of Nicotine Amplify Accumbal Neural Responses during Nicotine-Taking Behavior and Nicotine-Paired Environmental Cues

Nicotine self-administration (SA) is maintained by several variables, including the reinforcing properties of nicotine-paired cues and the nicotine-induced amplification of those cue properties. The nucleus accumbens (NAc) is implicated in mediating the influence of these variables, though the underlying neurophysiological mechanisms are not yet understood. In the present study, Long-Evans rats were trained to self-administer nicotine. During SA sessions each press of a lever was followed by an intravenous infusion of nicotine (30 µg/kg) paired with a combined light-tone cue. Extracellular recordings of single-neuron activity showed that 20% of neurons exhibited a phasic change in firing during the nicotine-directed operant, the light-tone cue, or both. The phasic change in firing for 98% of neurons was an increase. Sixty-two percent of NAc neurons additionally or alternatively showed a sustained decrease in average firing during the SA session relative to a presession baseline period. These session decreases in firing were significantly less prevalent in a group of neurons that were activated during either the operant or the cue than in a group of neurons that were nonresponsive during those events (referred to as task-activated and task-nonactivated neurons, respectively). Moreover, the session decrease in firing was dose-dependent for only the task-nonactivated neurons. The data of the present investigation provide supportive correlational evidence for two hypotheses: (1) excitatory neurophysiological mechanisms mediate the NAc role in cue-maintenance of nicotine SA, and (2) a differential nicotine-induced inhibition of task-activated and task-nonactivated neurons mediates the NAc role in nicotine-induced amplification of cue effects on nicotine SA

Natural Reward Experience Alters AMPA and NMDA Receptor Distribution and Function in the Nucleus Accumbens

Natural reward and drugs of abuse converge upon the mesolimbic system which mediates motivation and reward behaviors. Drugs induce neural adaptations in this system, including transcriptional, morphological, and synaptic changes, which contribute to the development and expression of drug-related memories and addiction. Previously, it has been reported that sexual experience in male rats, a natural reward behavior, induces similar neuroplasticity in the mesolimbic system and affects natural reward and drug-related behavior. The current study determined whether sexual experience causes long-lasting changes in mating, or ionotropic glutamate receptor trafficking or function in the nucleus accumbens (NAc), following 3 different reward abstinence periods: 1 day, 1 week, or 1 month after final mating session. Male Sprague Dawley rats mated during 5 consecutive days (sexual experience) or remained sexually naïve to serve as controls. Sexually experienced males displayed facilitation of initiation and performance of mating at each time point. Next, intracellular and membrane surface expression of N-methyl-D-aspartate (NMDA: NR1 subunit) and α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA: GluA1, GluA2 subunits) receptors in the NAc was determined using a bis(sulfosuccinimidyl)suberate (BS3) protein cross-linking assay followed by Western Blot analysis. NR1 expression was increased at 1 day abstinence both at surface and intracellular, but decreased at surface at 1 week of abstinence. GluA2 was increased intracellularly at 1 week and increased at the surface after 1 month of abstinence. Finally, whole-cell patch clamp electrophysiological recordings determined reduced AMPA/NMDA ratio of synaptic currents in NAc shell neurons following stimulation of cortical afferents in sexually experienced males after all reward abstinence periods. Together, these data show that sexual experience causes long-term alterations in glutamate receptor expression and function in the NAc. Although not identical, this sex experience-induced neuroplasticity has similarities to that caused by psychostimulants, suggesting common mechanisms for reinforcement of natural and drug reward