Effects of trans- and n-3 unsaturated fatty acids on cardiovascular risk markers in healthy males. An 8 weeks dietary intervention study

BACKGROUND: Studies of long-term intake of industrially produced trans fatty acids (TFA) and n-3 polyunsaturated fatty acids (PUFA) suggest opposite effects on cardiovascular disease risk. Common mechanisms of action are probable. OBJECTIVE: To examine the effects on cardiovascular risk markers of dietary enrichment with TFA or n-3 PUFA. DESIGN: Randomized, double-blind, parallel intervention trial. SETTING: Department of Human Nutrition, The Royal Veterinary and Agricultural University. SUBJECTS: In all, 87 healthy males included, 79 completed. INTERVENTION: Subjects were randomly assigned to 8 weeks of a daily intake of 33 g of experimental fats from either partially hydrogenated soy oil containing 20 g of TFA, 12 g of fish oil with approximately 4 g of n-3 PUFA and 21 g of control fat, or 33 g of control fat. The experimental fats were incorporated into bakery products. Plasma lipids, blood pressure, heart rate variability (HRV), arterial dilatory capacity, compliance, and distensibility were recorded before and after intervention and at follow-up 12 weeks after the intervention. RESULTS: High-density lipoprotein cholesterol (HDL-C) decreased in the TFA group and triglycerides and mean arterial blood pressure decreased in the n-3 PUFA group compared to the control group. HRV, arterial dilatory capacity, compliance, and distensibility were unchanged. CONCLUSION: The results indicate that the association between coronary heart disease risk and intake of TFA and n-3 PUFA relates only modestly to changes in traditional risk markers. SPONSORSHIP: Danish Medical Research Council (Grant no. 22-01-0390), Center of Advanced Food Research (Copenhagen, Denmark) (Grant no. KVL-R-2001-107), the Danish Heart Association (Grant no. 99-2-3-45-22748), Novozymes (Bagsvaerd, Denmark), Aarhus Olie (Aarhus, Denmark), and from private sources. The experimental fats were provided by Pronova Biocare (Aalesund, Norway) and Aarhus Olie (Aarhus, Denmark).     

Breastfeeding and risk of atopic dermatitis, by parental history of allergy, during the first 18 months of life

The role of breastfeeding in allergic diseases remains controversial. The authors studied the association between breastfeeding and development of atopic dermatitis during the first 18 months of life among children with and without a parental history of allergy. A cohort study of 15,430 mother-child pairs enrolled in The Danish National Birth Cohort was carried out between 1998 and 2000. Data on breastfeeding, atopic dermatitis, and potential confounders was obtained from telephone interviews conducted during pregnancy and when the children were 6 and 18 months of age. The cumulative incidence of atopic dermatitis was 11.5% at 18 months of age. Overall, current breastfeeding was not associated with atopic dermatitis (incidence rate ratio (IRR) = 0.91, 95% confidence interval (CI): 0.80, 1.04). Exclusive breastfeeding for at least 4 months was associated with an increased risk of atopic dermatitis in children with no parents with allergies (IRR = 1.29, 95% CI: 1.06, 1.55) but not for children with one (IRR = 1.11, 95% CI: 0.94, 1.31) or two (IRR = 0.88, 95% CI: 0.69, 1.13) parents with allergies (test for homogeneity, p = 0.03). The authors found no overall effects of exclusive or partial breastfeeding on the risk of atopic dermatitis. However, the effect of exclusive breastfeeding for 4 months or more depended on parental history of allergic diseases.     

Ibotenic acid and thioibotenic acid: a remarkable difference in activity at group III metabotropic glutamate receptors

In this study, we have determined and compared the pharmacological profiles of ibotenic acid and its isothiazole analogue thioibotenic acid at native rat ionotropic glutamate (iGlu) receptors and at recombinant rat metabotropic glutamate (mGlu) receptors expressed in mammalian cell lines. Thioibotenic acid has a distinct pharmacological profile at group III mGlu receptors compared with the closely structurally related ibotenic acid; the former is a potent (low microm) agonist, whereas the latter is inactive. By comparing the conformational energy profiles of ibotenic and thioibotenic acid with the conformations preferred by the ligands upon docking to mGlu1 and models of the other mGlu subtypes, we propose that unlike other subtypes, group III mGlu receptor binding sites require a ligand conformation at an energy level which is prohibitively expensive for ibotenic acid, but not for thioibotenic acid. These studies demonstrate how subtle differences in chemical structures can result in profound differences in pharmacological activity.     

A review of the second-generation antihistamine ebastine for the treatment of allergic disorders

Ebastine is a once-daily, non-sedating, selective, long-acting, second-generation antihistamine. The use of ebastine is indicated in patients suffering from intermittent and persistent allergic rhinitis and chronic idiopathic urticaria. Ebastine 10 mg/day, appears as effective as other second-generation antihistamines, such as cetirizine and loratadine. Ebastine 20 mg/day is indicated in patients with moderate and severe allergic symptoms. No cardiovascular effects of ebastine are described, although there is a pharmacokinetic interaction when ketoconazole or macrolides are co-administered. Ebastine has no relevant effects on the psychomotor performance. Even with ebastine 20 mg/day skilled performance does not appear to be impaired. Furthermore, ebastine 5-10 and 2.5 mg, appears to be efficient and can be used safely in children 6-11 and 2-5 years of age, respectively. Ebastine appears to be a safe, effective and well-tolerated second-generation antihistamine in the treatment of allergic rhinitis and chronic idiopathic urticaria.     

Clinical-radiological presentation and outcome of surgically treated pulmonary carcinoid tumours: a long-term single institution experience

PURPOSE: To determine the presenting features and the outcome of surgically treated pulmonary carcinoid tumours. METHODS: Retrospective analysis of all consecutive cases with preoperatively suspected or proven pulmonary carcinoid, treated between 1964 and 1994, in order to have full 5-year survival data. RESULTS: Seventy-three patients were retrieved, six had a postoperative histology other than carcinoid. The mean age of the 67 eligible cases was 44 years (range 17-74). There were 59 typical and eight atypical carcinoids. The most frequent presenting symptom was infection, followed by haemoptysis. Sixteen patients were asymptomatic, 15 of these had an abnormal chest X-ray, showing a solitary nodule in 13. Bronchoscopy was abnormal in almost all symptomatic patients. Bronchial biopsy results suggested a malignancy other than carcinoid in seven of eight patients whose postoperative histology was found to be atypical carcinoid. There were 40 lobectomies, 14 bi-lobectomies, nine pneumonectomies, and four limited resections. Ten patients had lymph node involvement (seven typical and three atypical). There was no correlation between the diameter of the primary tumour and the presence of nodal involvement. In particular, three of eight peripheral lesions <30 mm were found to have metastatic lymph nodes. The 5-year survival was 92% (95% in N0 versus 56% in N1-2; 92% in typical versus 67% in atypical). The 10-year survival was 84%. CONCLUSION: The specific diagnosis of atypical carcinoid cannot be reliably made on bronchial biopsies. No relationship was found between tumour size and the presence of lymph node metastases, suggesting that radical excision with detailed lymph node sampling is as important in carcinoids as in other lung cancers. Long-term survival was excellent, nodal status and pathology (typical/atypical) were independent prognostic factors.     

Immunisation against PCV2 structural protein by DNA vaccination of mice

Porcine circovirus type 2 (PCV2) is the causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome (PMWS). The disease affects primarily 5-12-weeks-old pigs which might suggest that infection with PCV2 occurs when the level of maternal antibodies have declined to sub-protective levels around weaning at 3-5-weeks of age. If immunoprophylaxis is to be effective, an immunisation method capable of breaking through maternal immunity must be employed. In this study, we have developed and investigated the potential of a DNA vaccination approach to be one such method. The gene encoding the capsid protein of PCV2 was cloned in a DNA vaccination plasmid and expression of capsid protein was demonstrated in vitro. Mice were gene gun vaccinated three timesand all mice responded serologically by raising antibodies against PCV2. The results suggest, that DNA based vaccination might offer opportunities for vaccination of piglets against PCV2.     

Maternal characteristics and lifestyle factors and the risk of delivering high birth weight infants

OBJECTIVE: To identify factors associated with an increased risk of giving birth to infants weighing more than 4000 g and to study whether changes in these factors over time can explain the increasing proportion of high birth weight infants over the last decade. METHODS: Our analyses included 24,093 pregnancies of nondiabetic women with information on potential risk factors for high birth weight: maternal prepregnancy weight, height, age, parity, smoking habits, alcohol and caffeine intake, marital status, educational level, gestational age, and infant gender. Information was obtained from questionnaires completed during pregnancy and birth registration forms at the Department of Obstetrics and Gynaecology, Aarhus University Hospital, Aarhus, Denmark, from 1990 to 1999. RESULTS: We found a statistically significantly increased risk of giving birth to infants weighing more than 4000 g for women with high prepregnancy weight and height, parity greater than 2, gestational age greater than 42 weeks, and male infant gender and for nonsmokers. Women with a low caffeine intake or 10 or more years of education were also at statistically significantly higher risk. The variation found in birth weight over the past 10-year period was explained by changes in maternal prepregnancy weight, height, smoking habits, educational level, and caffeine intake over the same period. CONCLUSION: Risk factors associated with a higher proportion of high birth weight infants may be clinically significant and have an impact on public health. High birth weight increases the risk of adverse outcomes of delivery as well as the risk of childhood morbidity.     

Endo- and exocytic rate constants for spontaneous and protein kinase C-activated T cell receptor cycling

To determine the rate constants of spontaneous and activated TCR cycling, we examined TCR endo- and exocytosis in the human T cell line Jurkat by three different methods. Using a simple kinetic model for TCR cycling and non-linear regression analyses, we found that the spontaneous endocytic rate constant of the TCR was low (approximately 0.012 min(-1)) whereas the spontaneous exocytic rate constant was similar to that of other cycling receptors (approximately 0.055 min(-1)). Following protein kinase C activation (PKC) the endocytic rate constant was increased tenfold (to approximately 0.128 min(-1)) whereas the exocytic rate constant was unaffected. Thus, the TCR becomes a rapidly cycling receptor with kinetics similar to classical cycling receptors subsequent to PKC activation. This results in a reduction of the half-life of cell surface expressed TCR from approximately 58 to 6 min and allows rapid redistribution of the TCR during T cell activation.