Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.

BACKGROUND: Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known. OBJECTIVE: Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy-prone infants. METHODS: In a randomized double-blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C-reactive protein (CRP), total IgA and IgE, food-specific IgA, IgG, and IgE, IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years. RESULTS: Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL-10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17-0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16-0.87), P=0.023] at age 2 years, when adjusted with probiotic use. CONCLUSION: The association of CRP with a decreased risk of eczema at 2 years of age in allergy-prone children supports the view that chronic, low-grade inflammation protects from eczema. Probiotic-induced low-grade inflammation was characterized by elevation of IgE, IgA, and IL-10, the changes typically observed in helminth infection-associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.

Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use.

BACKGROUND: Children with high body mass index (BMI) at preschool age are at risk of developing obesity. Early identification of factors that increase the risk of excessive weight gain could help direct preventive actions. The intestinal microbiota and antibiotic use have been identified as potential modulators of early metabolic programming and weight development. To test if the early microbiota composition is associated with later BMI, and if antibiotic use modifies this association, we analysed the faecal microbiota composition at 3 months and the BMI at 5-6 years in two cohorts of healthy children born vaginally at term in the Netherlands (N = 87) and Finland (N = 75). We obtained lifetime antibiotic use records and measured weight and height of all children. RESULTS: The relative abundance of streptococci was positively and the relative abundance of bifidobacteria negatively associated with the BMI outcome. The association was especially strong among children with a history of antibiotic use. Bacteroides relative abundance was associated with BMI only in the children with minimal lifetime antibiotic exposure. CONCLUSIONS: The intestinal microbiota of infants are predictive of later BMI and may serve as an early indicator of obesity risk. Bifidobacteria and streptococci, which are indicators of microbiota maturation in infants, are likely candidates for metabolic programming of infants, and their influence on BMI appears to depend on later antibiotic use.

Efficient enantioselective separation of drug enantiomers by immobilised antibody fragments.

There is an increasing need for methods for efficient enantioselective separation and purification of chiral drugs. Genetic engineering provides the means for generating recombinant antibodies exhibiting extremely high specificity for even small molecular mass compounds. Here, recombinant antibody fragments have been generated for the drug diarylalkyltriazole that contains two chiral centres. Immobilised antibody fragments has been used successfully for efficient, step-wise separation of two enantiomers of the drug. Owing to the antibody specificity, one enantiomer came out in the flow-through, while the bound enantiomer could be specifically eluted. One of the antibodies tolerated solvents required both for dissolving the target molecules and for their elution for extended times and was shown to function over multiple cycles of the separation process.

Body mass index and physical fitness as determinants of serum lipoprotein levels in middle-aged men.

The aim of the present study was to analyse to what extent serum lipoproteins are determined by overweight and physical fitness. Fifty-eight middle-aged males were divided into lean, overweight and obese subgroups according to their body mass indices, which characterization was also well in accordance with two skinfold thicknesses. Maximal oxygen consumption per body weight was lowest in the obese. HDL cholesterol was decreased in the obese compared to the lean. HDL cholesterol correlated separately significantly with maximal oxygen consumption and body mass index when all the three groups were combined. Physical fitness was a less dominant determinant of HDL cholesterol than body mass index. The importance of physical fitness as a determinant of HDL cholesterol was less marked in the obese than in the lean and overweight suggesting a need for certain level of physical activity before it can influence serum lipoprotein levels.

Physical training of obese middle-aged persons.

The aim of this study was to find out how individually prescribed moderate physical training influences aerobic power and body weight in obese middle-aged men and women. 210 persons with poor physical fitness and body mass index (BMI) over 25 kg/m2 were accepted. Of these 169 persons were without regular medication and in this group 95 persons trained actively for the complete follow-up period of 17 months while 74 persons dropped out during the study. Maximal oxygen consumption was estimated indirectly before training and after 2, 5, 11 and 17 months of training. The exercise physiologist prescribed an individual training program, which was checked every six weeks. The most popular sports were walking and skiing. Initial aerobic power was poor in both sexes (3.1 +/- 0.1 l/min in men and 2.3 +/- 0.1 l/min in women, mean +/- SE). In the actively training group it increased significantly after two months and remained on this improved level for the rest of the observation period (total increase 14% in men and 11% in women). Initial BMI was 29.8 +/- 0.5 kg/m2 in men and 29.1 +/- 0.4 kg/m2 in women. The greatest change in body weight in the actively training group also took place during the first months. The mean decrease of body weight was 4.8 +/- 0.8 kg in men and 3.3 +/- 0.6 kg in women after 17 months. In conclusion, obese middle-aged men and women initially in poor physical condition can benefit from an individually prescribed training program resulting in significantly increased aerobic power and a minor loss of overweight.

Physical training of middle-aged men with borderline hypertension.

The aim of the study was to clarify the feasibility of physical training for middle-aged borderline-hypertensive males. Blood pressure of 59 subjects was followed for nine months, whereafter 25 persons were classified as borderline-hypertensive and 34 persons as normotensive. Both groups were randomly allocated into training and control groups. Training lasted for four months, of which the first two included supervised bicycle ergometer exercise. During the last two months training was unsupervised. After training estimated maximal oxygen consumption increased significantly both in borderline-hypertensive and normotensive men. After training resting diastolic blood pressure decreased significantly both in training and control groups. This finding supports the importance of sufficiently long follow-up of blood pressure before eventual drug therapy when blood pressure is mildly elevated. Diastolic blood pressure during 50-minute ergometer exercise was decreased after four months of training in borderline-hypertensives and did not any longer differ from that of normotensives. Individually prescribed physical training is worth regarding as one treatment modality for middle-aged borderline-hypertensive patients.

Interaction of NPSR1 genotypes and probiotics in the manifestation of atopic eczema in early childhood

BACKGROUND: Neuropeptide S Receptor (NPSR1) gene has been associated with multiple allergic phenotypes in several patient populations. OBJECTIVE: We analysed the effect of the NPSR1 genotypes in the development of asthma, rhinitis, eczema, or food allergy in children randomly receiving either probiotic or placebo treatment. METHODS: 796 children born to families at high risk for allergic diseases were examined by a paediatrician at the age of three months, six months, two years, and five years. Asthma, rhinitis, eczema, and food allergy were diagnosed according to international guidelines. Treatment with probiotics (double-blinded and placebo controlled) was begun with mothers at 35 weeks of gestation age and continued after the birth of infants up to the age of six months. Association and additive inheritance models were used in genetic analyses. RESULTS: Distribution of the hopo546333 was suggestive in the group of patients with atopic eczema at two years. The hopo546333_G was found more often in those with eczema in the placebo group (p = 0.048, after Bonferroni correction) and the hopo546333_A was found more often in those with eczema and probiotics compared to those with eczema and placebo treatment. None of the NPSR1 tagging SNPs was associated with asthma, IgE-mediated asthma, or sensitisation. Allergic disease in both parents doubled the risk for IgE-mediated allergic disease (OR 2.1). CONCLUSIONS: The NPSR1 gene SNP hopo546333 showed a suggestive association for high IgE-associated atopic eczema at two years

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Effects of histamine H(3)-ligands on the levodopa-induced turning behavior of hemiparkinsonian rats.

Histamine H(3)-receptors act as heteroreceptors on many neurons. The effects of H(3)-ligands (an agonist, R-alpha-methylhistamine and an antagonist, thioperamide) on levodopa-induced turning behavior in a rat model of Parkinson's disease were quite similar to those seen with alpha(2)-adrenoceptor ligands (dexmedetomidine and atipamezole). R-alpha-methylhistamine clearly reduced contralateral turning behavior but the increase of turning behavior after thioperamide was less clear. The lack of effect of H(3)-ligands, in contrast to alpha(2)-ligands, on the amphetamine-induced ipsilateral turning behavior points to different roles or neuronal distribution of these two presynaptic receptors. We propose that in this lesion model, H(3)-receptors modify those pathways participating striatal outflow.