Stimulation of defecation: effects of coffee use and nicotine on rectal tone and visceral sensitivity

OBJECTIVE: Coffee and cigarette use is believed to induce bowel movements, although the literature is controversial and precise measurements of rectal tone and sensitivity with a barostat have never been performed. The aim of this study was to assess the effects of coffee and nicotine on rectal tone, compliance and sensitivity. MATERIALS AND METHODS: Sixteen healthy volunteers were recruited for the coffee (n = 8) and nicotine (n = 8) experiments. The experiments were randomly performed in a placebo-controlled crossover design on separate days. In the coffee experiment, 280 ml strong coffee or warm water was drunk and in the nicotine experiment, nicotine (2 mg) or placebo was given sublingually. A rectal barostat procedure was carried out. A flaccid bag, mounted on a catheter, was inserted in the rectum. Continuous pressure distension was exerted to register basal visceral sensitivity and compliance. After rectal adaptation, the stimulus was given. Rectal tone was measured for 1 h, after which continuous pressure distension was repeated. RESULTS: Rectal tone increased by 45% 30 min after coffee intake (p = 0.031) and by 30% after water intake (p = 0.032), but the effects of coffee and water were not significantly different. Rectal tone did not change significantly after administration of nicotine (7%) or placebo (10%). There was no difference in compliance and visceral sensitivity between coffee and water or nicotine and placebo. CONCLUSIONS: Both coffee and warm water have an effect on defecation by increasing rectal tone, but nicotine (2 mg) did not affect rectal tone. Coffee and nicotine did not influence sensitivity or compliance.     

Social contextual factors associated with entry into opiate agonist treatment among injection drug users

We tested hypotheses that social living arrangement and drug use in one's network are independently associated with entry into opiate agonist treatment modalities. Injection drug users (IDUs) attending the Baltimore Needle Exchange Program who received a referral for drug abuse treatment were studied. Baseline interviews, HIV testing, and the Addiction Severity Index (ASI) were administered. Agency records were used to confirm entry into a treatment program offering opiate agonist maintenance therapy within 30 days of the baseline interview. Logistic regression was used to identify predictors of treatment entry. To date, of 245 IDUs, 39% entered such a program. Multivariate logistic regression models controlling for age and intervention status revealed that compared to individuals who lived alone, in a controlled, or nonstable environment (e.g., streets, abandoned house, transitional housing program, or boarding house), individuals who lived with a sexual partner were 3 times more likely to enter treatment (adjusted Odds Ratio [aOR]=3.04; p=0.013) and those who lived with family or friends were almost 3 times more likely to enter treatment (aOR=2.72; p=0.016). In the bivariate analyses, a marginal association was observed between being responsible for children or others and entry into treatment (p=0.066); however, this association was not significant in the multivariate model. Findings from this study suggest that supportive living environments may facilitate entry into treatment and may be helpful in devising appropriate and targeted interventions to encourage drug treatment entry.     

Different dietary fatty acids are associated with blood lipids in healthy South African men and women: The PURE study

Background

Preliminary data from the baseline Prospective Urban Rural Epidemiology (PURE) study in South Africa indicated a higher prevalence of dyslipidemia than previous South African studies. The intake of specific individual dietary fatty acids may affect blood lipids differently than sub-groups of fat (i.e. polyunsaturated fatty acids). We investigated the dietary intake of different individual fatty acids and their associations with blood lipids, in relation to urbanization and gender.

Methods

Cross-sectional data analysis within the PURE baseline study of healthy subjects (n = 1950, 35–70 years) from rural and urban areas. Dietary data were collected and blood lipid analysis performed.

Results

Intake of individual fatty acids was significantly higher in urban than rural dwellers. However, the intake of n-3 PUFAs was below recommendations in all groups. Total cholesterol and LDL were higher in females than in males, with no rural?urban differences. Intake of alpha-linolenic acid (ALA) was positively associated with total cholesterol (β = 0.143) and triglycerides (β = 0.256) in males. The risk for having elevated LDL also increased with increased intake of ALA (OR 1.49, 95% CI 1.04, 2.14) in males. In females, arachidonic acid and eicosapentaenoic acid (EPA) were positively associated with total cholesterol and arachidonic acid was also positively associated with LDL, whereas docosahexaenoic acid was negatively associated with total cholesterol and LDL.

Conclusions

These results suggest that specific individual dietary fatty acids may affect blood lipids in males differently than in females irrespective of rural or urban dwelling. The positive association between ALA and total cholesterol and triglycerides in males is a concern, because current advice aims to improve the dietary linoleic acid to ALA ratio by increasing ALA intake.     

Attention‐network specific alterations of structural connectivity in the undamaged white matter in acute neglect

Visual neglect results from dysfunction within the spatial attention network. The structural connectivity in undamaged brain tissue in neglect has barely been investigated until now. In the present study, we explored the microstructural white matter characteristics of the contralesional hemisphere in relation to neglect severity and recovery in acute stroke patients. We compared age‐matched healthy subjects and three groups of acute stroke patients (9 ± 0.5 days after stroke): (i) patients with nonrecovered neglect (n = 12); (ii) patients with rapid recovery from initial neglect (within the first week post‐stroke, n = 7), (iii) stroke patients without neglect (n = 17). We analyzed the differences between groups in grey and white matter density and fractional anisotropy (FA) and used fiber tracking to identify the affected fibers. Patients with nonrecovered neglect differed from those with rapid recovery by FA‐reduction in the left inferior parietal lobe. Fibers passing through this region connect the left‐hemispheric analogues of the ventral attention system. Compared with healthy subjects, neglect patients with persisting neglect had FA‐reduction in the left superior parietal lobe, optic radiation, and left corpus callosum/cingulum. Fibers passing through these regions connect centers of the left dorsal attention system. FA‐reduction in the identified regions correlated with neglect severity. The study shows for the first time white matter changes within the spatial attention system remote from the lesion and correlating with the extent and persistence of neglect. The data support the concept of neglect as disintegration within the whole attention system and illustrate the dynamics of structural‐functional correlates in acute stroke. Hum Brain Mapp 35:4678–4692, 2014. © 2014 Wiley Periodicals, Inc .     

High-level gait and balance disorders in the elderly: a midbrain disease?

The pathophysiology of gait and balance disorders in elderly people with ‘higher level gait disorders’ (HLGD) is poorly understood. In this study, we aimed to identify the brain networks involved in this disorder. Standardised clinical scores, biomechanical parameters of gait initiation and brain imaging data, including deep white matter lesions (DWML) and brain voxel-based morphometry analyses, were assessed in 20 HLGD patients in comparison to 20 age-matched controls. In comparison to controls, HLGD patients presented a near-normal preparatory phase of gait initiation, but a severe alteration of both locomotor and postural parameters of first-step execution, which was related to ‘axial’ hypokinetic-rigid signs. HLGD patients showed a significant grey matter reduction in the mesencephalic locomotor region (MLR) and the left primary motor cortex. This midbrain atrophy was related to the severity of clinical and neurophysiologically determined balance deficits. HLGD patients also showed a reduction in speed of gait, related to ‘appendicular’ hypokinetic-rigid signs and frontal-lobe-like cognitive deficits. These last two symptoms were correlated with the severity of DWML, found in 12/20 HLGD patients. In conclusion, these data suggest that the gait and balance deficits in HLGD mainly result from the lesion or dysfunction of the network linking the primary motor cortex and the MLR, brain regions known to be involved in the control of gait and balance, whereas cognitive and ‘appendicular’ hypokinetic-rigid signs mainly result from DWML that could be responsible for a dysfunction of the frontal cortico-basal ganglia loops.     

The NLRP1 and CARD8 inflammasomes

Inflammasomes are multiprotein complexes that activate inflammatory cytokines and induce pyroptosis in response to intracellular danger-associated signals. NLRP1 and CARD8 are related germline-encoded pattern recognition receptors that form inflammasomes, but their activation mechanisms and biological purposes have not yet been fully established. Both NLRP1 and CARD8 undergo post-translational autoproteolysis to generate two non-covalently associated polypeptide chains. NLRP1 and CARD8 activators induce the proteasome-mediated destruction of the N-terminal fragment, liberating the C-terminal fragment to form an inflammasome. Here, we review the danger-associated stimuli that have been reported to activate NLRP1 and/or CARD8, including anthrax lethal toxin, Toxoplasma gondii, Shigella flexneri and the small molecule DPP8/9 inhibitor Val-boroPro, focusing on recent mechanistic insights and highlighting unresolved questions. In addition, we discuss the recently identified disease-associated mutations in NLRP1 and CARD8, the potential role that DPP9’s protein structure plays in inflammasome regulation, and the emerging link between NLRP1 and metabolism. Finally, we summarize all of this latest research and consider the possible biological purposes of these enigmatic inflammasomes.