Differential effects of energy balance on experimentally-induced colitis

AIM:To characterize the influence of diet-induced changes in body fat on colitis severity in SMAD3-/mice.METHODS:SMAD3-/-mice (6-8 wk of age) were randomly assigned to receive a calorie restricted (30% of control;CR),control (CON),or high fat (HF) diet for 20 wk and were gavaged with sterile broth or with Helicobacter hepaticus (H.hepaticus) to induce colitis.Four weeks after infection,mice were sacrificed and the cecum and colons were processed for histological evaluation.RESULTS:Dietary treatment significantly influenced body composition prior to infection (P 0.05),with CR mice having less (14% ± 2%) and HF-fed mice more body fat (32% ± 7%) compared to controls (22% ±4%).Differences in body composition were associated with alterations in plasma levels of leptin (HF CON CR) and adiponectin (CON HF ≥ CR) (P 0.05).There were no significant differences in colitis scores between CON and HF-fed mice 4 wk post-infection.Consistent with this,differences in proliferation and inflammation markers (COX-2,iNOS),and infiltrating cell types (CD3 + T lymphocytes,macrophages) were not observed.Unexpectedly,only 40% of CR mice survived infection with H.hepaticus,with mortality observed as early as 1 wk following induction of colitis.     

Increased presence of effector lymphocytes during Helicobacter hepaticus-induced colitis

AIM: To identify and characterize drosophila mothers against decapentaplegic (SMAD)3-dependent changes in immune cell populations following infection with Helicobacter hepaticus (H. hepaticus).METHODS: SMAD3^-/- (n = 19) and colitis-resistant SMAD3^+/- (n = 24) mice (8-10 wk of age) were infected with H. hepaticus and changes in immune cell populations [T lymphocytes, natural killer (NK) cells, T regulatory cells] were measured in the spleen and mesenteric lymph nodes (MsLNs) at 0 d, 3 d, 7 d and 28 d post-infection using flow cytometry. Genotype-dependent changes in T lymphocytes and granzyme B⁺ cells were also assessed after 28 d in proximal colon tissue using immunohistochemistry.RESULTS: As previously observed, SMAD3^-/-, but not SMAD3^+/- mice, developed colitis, peaking at 4 wk post-infection. No significant changes in T cell subsets were observed in the spleen or in the MsLNs between genotypes at any time point. However, CD4⁺ and CD8⁺/CD62L^lo cells, an effector T lymphocyte population, as well as NK cells (NKp46/DX5⁺) were significantly higher in the MsLNs of SMAD3^-/- mice at 7 d and 28 d post-infection. In the colon, a higher number of CD3⁺ cells were present in SMAD3^-/- compared to SMAD3^+/– mice at baseline, which did not significantly change during infection. However, the number of granzyme B⁺ cells, a marker of cytolytic lymphocytes, significantly increased in SMAD3^-/- mice 28 d post-infection compared to both SMAD3^+/- mice and to baseline values. This was consistent with more severe colitis development in these animals.CONCLUSION: Data suggest that defects in SMAD3 signaling increase susceptibility to H. hepaticus-induced colitis through aberrant activation and/or dysregulation of effector lymphocytes.     

Topical anaesthesia of the skin: a review

The ability to provide painless venepuncture and venous cannulation is a major advance in paediatric practice. Topical local anaesthesia of the skin can allow such procedures to be carried out with little or no discomfort in children of all ages. This has obvious psychological benefits for children, particularly those subjected to repeated procedures. The techniques for anaesthetizing the skin to be effective and safe must be based upon an understanding of the anatomy and physiology of the skin, the pharmacology of local anaesthetic agents and their behaviour when applied to the skin. Although eutectic mixture of local anaesthetics (EMLA cream) (Astra Pharmaceuticals) is the market leader, promising new preparations are being evaluated with the aim of decreasing the onset time of effective analgesia. New clinical applications for topical anaesthesia of the skin are appearing and it is likely that these will be increasingly used in the future.     

Relationship of physical activity vs body mass index with type 2 diabetes in women

CONTEXT: Physical inactivity and body mass index (BMI) are established independent risk factors in the development of type 2 diabetes; however, their comparative importance and joint relationship with diabetes are unclear. OBJECTIVE: To examine the relative contributions and joint association of physical activity and BMI with diabetes. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 37 878 women free of cardiovascular disease, cancer, and diabetes with 6.9 years of mean follow-up. Weight, height, and recreational activities were reported at study entry. Normal weight was defined as a BMI of less than 25; overweight, 25 to less than 30; and obese, 30 or higher. Active was defined as expending more than 1000 kcal on recreational activities per week. MAIN OUTCOME MEASURE: Incident type 2 diabetes, defined as a new self-reported diagnosis of diabetes. RESULTS: During the follow-up, 1361 cases of incident diabetes occurred. Individually, BMI and physical activity were significant predictors of incident diabetes. Compared with normal-weight individuals, the multivariate-adjusted hazard ratio (HR) was 3.22 (95% confidence interval [CI], 2.69-3.87) for overweight individuals and 9.09 (95% CI, 7.62-10.8) for obese individuals. For overall activity (kilocalories expended per week), compared with the least active first quartile, the multivariate-adjusted HRs were 0.91 (95% CI, 0.79-1.06) for the second quartile, 0.86 (95% CI, 0.74-1.01) for the third, and 0.82 (95% CI, 0.70-0.97) for the fourth (P for trend =.01). In the combined analyses, overweight and obese participants, whether active or inactive, had significantly elevated risks, compared with normal-weight active individuals. The multivariate-adjusted HRs were 1.15 (95% CI, 0.83-1.59) for normal-weight inactive, 3.68 (95% CI, 2.63-5.15) for overweight active, 4.16 (95% CI, 3.05-5.66) for overweight inactive, 11.5 (95% CI, 8.34-15.9) for obese active, and 11.8 (95% CI, 8.75-16.0) for obese inactive participants. CONCLUSIONS: Although BMI and physical inactivity are independent predictors of incident diabetes, the magnitude of the association with BMI was greater than with physical activity in combined analyses. These findings underscore the critical importance of adiposity as a determinant of diabetes.     

Vitamin B 1, B 2 and B 6 deficiency in neurological disorders

Summary The activities of the red blood cell enzymes transketolase, glutathione reductase, and glutamic oxaloacetate transaminase were measured with and without in vitro addition of their respective coenzyme components thiamine, riboflavin, and pyridoxine in a group of patients with neurological disorders which may have been caused by malnutrition, intestinal malabsorption, hepatic failure or neoplasms arising outside the nervous system. The incidence of thiamine deficiency was 31%, of riboflavin deficiency 22% and of pyridoxine deficiency 6%.Alcoholics in particular suffered from deficiencies of vitamin B 1, and B 2. There was a correlation of vitamin B 1 and B 2 deficiency and signs of a cerebellar and/or brainstem lesion. The most frequent symptoms in this connection were gait disturbances and oculomotor signs like spontaneous and gaze nystagmus, disturbed eye tracking, diminished optokinetic nystagmus, decreased ability to suppress vestibular nystagmus by fixation. These signs hardly ever occured in alcoholic patients who showed no deficiency of vitamin B 1, B 2 or B 6. Whenever they do appear, a vitamin B supplementation has to be performed in order to prevent the manifestation of Wernicke's encephalopathy, cerebral or cerebellar atrophy.Alcoholics showed the same incidence of polyneuropathy, whether they suffered from a deficiency of B vitamins or not.Deficiencies of vitamin B 1, B 2 or B 6 were also found in patients with intestinal malabsorption and polyneuropathy, diabetic polyneuropathy, optic atrophy, myelopathy and cerebellar ataxia of unknown etiology, neurological manifestations of neoplasms arising outside the nervous system, B 12 myeloencephalopathy and Thévenard's syndrome.

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Zusammenfassung Bei Patienten mit neurologischen Erkrankungen, die möglicherweise als Folge einer Malnutrition, einer intestinalen Malabsorption, einer Lebererkrankung oder eines paraneoplastischen Syndroms aufgetreten waren, wurden die Aktivitäten der Erythrocytenenzyme Transketolase, Glutathionreduktase und Glutamat-Oxalacetat-Transaminase vor und nach Aktivierung mit ihren entsprechenden Coenzym-Komponenten Thiamin, Riboflavin oder Pyridoxin gemessen. Ein Thiaminmangel kam in 31%, ein Riboflavinmangel in 22% und ein Pyridoxinmangel in 6% der Fälle vor.Besonders Alkoholkranke litten unter einem Vitamin-B 1- und -B 2-Mangel. Zwischen Vitamin-B 1- und Vitamin-B 2-Mangelzuständen und Kleinhirn-und/oder Hirnstammsymptomen fand sich eine enge Beziehung. Die häufigsten Zeichen waren in diesem Zusammenhang Gangataxie und oculomotorische Symptome wie Spontan- oder Blickrichtungsnystagmus, gestörte Blickfolge, verminderter optokinetischer Nystagmus, gestörte Fixationssuppression des vestibulären Nystagmus. Bei Alkoholkranken ohne einen Vitamin-B 1-, -B 2- oder -B 6-Mangel kamen diese Symptome selten vor. Bei ihrem Auftreten müssen B-Vitamine gegeben werden, um der Manifestation einer Wernicke-Encephalopathie, einer Hirn- oder Kleinhirnatrophie vorzubeugen.Eine Polyneuropathie kam in etwa gleicher Häufigkeit bei Alkoholikern mit und ohne Mangel an B-Vitaminen vor.Ein Mangel an Vitamin B 1, B 2 oder B 6 wurde auch bei Patienten mit intestinaler Malabsorption und Polyneuropathie, diabetischer Polyneuropathie, Opticusatrophie, Myelopathie und cerebellarer Ataxie unbekannter Ätiologie, paraneoplastischem Syndrom, B 12-Myelo-Encephalopathie und Thévenard-Syndrom gefunden.

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Abbreviations EGOT erythrocyte glutamic oxaloacetate transaminase - EGR erythrocyte glutathione reductase - FAD flavin-adenine dinucleotide, vitamin B 2 - ETK erythrocyte transketolase - MDH malate dehydrogenase - PALP pyridoxal-5-phosphate, vitamin B 6 - TPP thiamine pyrophosphate, vitamin B 1