A proGDNF-related peptide BEP increases synaptic excitation in rat hippocampus

The glial cell-derived neurotrophic factor (GDNF) precursor contains several putative sites for prohormone convertase-mediated excision of short peptides. Here, we show that one of the predicted peptides, named BEP (brain excitatory peptide), induces a substantial increase in the synaptic excitability in rat CA1 pyramidal neurons. The excitation is sensitive to N-ethylmaleimide, suggesting involvement of a G-protein-coupled receptor.     

Quantification of angiogenesis by the Chalkley method and its prognostic significance in epithelial ovarian cancer

AimThe aim of the present study was to clarify prognostic role of angiogenesis in epithelial ovarian cancer.MethodsQuantification of angiogenesis was performed by the Chalkley method after immunostaining of 175 epithelial ovarian cancer specimens with an antibody against CD34.ResultsThe Chalkley count was categorised into two groups according to the median value: low <8 or high ⩾8. The low Chalkley count correlated significantly with serous and clear cell histological subtype of the tumour (p < 0.0005), whereas there existed no association with FIGO (International Federation of Gynecology and Obstetrics) stage, histological grade, presence of primary residual tumour, age at diagnosis, or chemotherapy response. In univariate analysis, the high Chalkley count predicted poor overall survival in the subgroup of patients with FIGO stages III–IV tumours (p = 0.007) but not in the entire study cohort. However, in multivariate analysis, the Chalkley count was found to be an independent predictor of death from ovarian cancer in the entire study cohort (p = 0.044, RR = 1.50, 95% CI 1.01–2.21) as well as in the subgroup of FIGO stages III–IV tumours (p = 0.046, RR = 1.58, 95% CI 1.01–2.46) together with the presence of primary residual tumour (p < 0.0005, RR = 5.10, 95% CI 3.02–8.62, and p = 0.002, RR = 4.28, 95% CI 1.34–13.73, respectively).ConclusionsThe Chalkley count seems to be suitable for evaluation of angiogenesis and to have prognostic significance in ovarian cancer.     

Association of serotonin transporter promoter regulatory region polymorphism and cerebral activity to visual presentation of food

Recent functional magnetic resonance imaging (fMRI) studies have revealed links between genetic polymorphisms and cognitive and behavioural processes. Serotonin is a classical neurotransmitter of central nervous system, and it is connected to the control of appetite and satiety. In this study, the relationship between the functional variation in the serotonin transporter gene and the activity in the left posterior cingulate cortex (PCC), a brain area activated by visual food stimuli was explored. Thirty subjects underwent serial fMRI studies and provided DNA for genetic analyses. Subjects homozygous for the long allele exhibited greater left PCC activity in the comparison food > non-food compared with individuals heterozygous or homozygous for the short allele. The association between genotype and activation was linear, the subjects with two copies of the long allele variant having the strongest activation. These results demonstrate the possible genetically driven variation in the response of the left PCC to visual presentation of food in humans.     

Gender-related differences in the management of non-ST-elevation acute coronary syndrome patients

OBJECTIVES: To compare management and outcome of female and male non-ST-elevation acute coronary syndrome (ACS) patients. DESIGN: FINACS Studies are prospective registries of non-ST-elevation ACS patients conducted in 2001, 2003, and 2005 in nine hospitals. RESULTS: The studies enrolled 1,399 patients from which 39% were women. During hospitalisation women were treated less often than men with aspirin (odds ratio [OR]) for women 0.60, 95% confidence interval [CI] 0.41 to 0.88, p=0.03). Women underwent less often in-hospital coronary angiography than men (adjusted OR 0.71, 95% CI 0.55 to 0.93, p=0.01). Also in the subgroup of younger (<75 years) high-risk patients, female sex was independent predictor for not performing in-hospital angiography (OR 0.64, 95% CI 0.42 to 0.97, p=0.04). Age-adjusted mortality at 6 months was similar between men and women. CONCLUSIONS: Compared to men women received less often aspirin. Women were referred less often to in-hospital coronary angiography. Under-use of in-hospital angiography was evident also in patients with high-risk features when guidelines recommend early invasive treatment.     

The A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) associates with low peak bone mass in young healthy men

INTRODUCTION: Polymorphisms in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) contribute to variation in bone mass in the general population. Whether this is due to influence on bone mass acquisition or on bone loss thereafter has not been established. METHODS: We studied the association of LRP5 polymorphisms with peak bone mass in young men. The study included 235 Finnish men, aged 18.3 to 20.6 years. Lifestyle factors and fracture history were recorded. Bone mineral content (BMC), density (BMD) and scan area were measured for the lumbar spine and proximal femur by dual energy X-ray absorptiometry (DXA). Blood and urine were collected for determination of bone turnover markers, serum 25-OHD and PTH. Genomic DNA was extracted from peripheral blood for genetic analysis of LRP5. Ten single nucleotide polymorphisms in LRP5 were analyzed and correlated with bone parameters. RESULTS: Only the A1330V polymorphism of LRP5 significantly associated with bone parameters. In comparison with subjects with the AlaAla genotype (n=215), those with AlaVal genotype (n=20) had lower femoral neck BMC (P=0.029) and BMD (P=0.012), trochanter BMC (P=0.0067) and BMD (P=0.015), and total hip BMC (P=0.0044) and BMD (P=0.0089). Fracture history was similar for the genotypes. CONCLUSION: The polymorphic valine variant at position 1330 of LRP5 was significantly associated with reduced BMC and BMD values in healthy young Finnish men. The results provide evidence for the crucial role of LRP5 in peak bone mass acquisition.     

Breast milk – immunomodulatory signals against allergic diseases

Breastfeeding holds a key position with regard to the increasing burden of allergic diseases in the industrialized countries. Not only does it provide the infant with nutrients for growth and development, it also confers immunological protection during a critical period in life, when the infant's own defense mechanisms are immature. A delicate balance of stimulatory, even inflammatory, maturational signals, together with a myriad of anti-inflammatory compounds, is transferred from mother to infant via breastfeeding. Breastfeeding mothers, however, do not constitute a uniform group. The composition of breast milk shows marked individual variation and so, consequently, does the success of breastfeeding in reducing the risk of disease. Recent clinical studies indicate that the potential of breastfeeding to counteract allergic disease may be promoted by dietary means. While uncoordinated elimination diets result in a risk of general nutritional inadequacy or deficiency of essential single nutrients, a balanced diet following current dietary recommendations, specifically containing fresh fruits and vegetables (antioxidants) and fat of predominantly vegetable origin, may be associated with a lower incidence of atopy in the infant. As early nutrition appears to program the subsequent health of the child, the importance of the maternal dietary composition during breastfeeding should be emphasized. In future, an improved understanding of the mechanisms of this programming may offer specific therapeutic modalities for the prevention of allergic disease.     

Chronic oral nicotine administration affects the circadian rhythm of dopamine and 5-hydroxytryptamine metabolism in the striata of mice

The effect of chronic oral administration of nicotine on the circadian rhythm of striatal dopamine (DA) and 5-hydroxytryptamine (5-HT) was studied in mice. Mice receiving nicotine in their drinking water and control mice drinking tap water were killed at 05:00, 11:00, 15:00 or 21:00 hours on the 50th day of chronic administration. The plasma concentrations of nicotine and cotinine, as well the striatal concentrations of DA, 5-HT and their metabolites 3,4 dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), homovanilic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated. The largest plasma concentrations of nicotine and cotinine were found at 05:00, when they were more than double the concentrations found at the other times studied. This indicates that the mice, typically for nocturnal animals, consumed most of their daily drinking water at night. In the control mice, the striatal DA and 3-MT concentrations showed circadian variation and were lowest at 11:00. The 5-HIAA concentrations also varied, being highest at 11:00. In the nicotine-treated mice the circadian variations in striatal monoamines were altered and more pronounced than in the controls. The concentrations of DA, DOPAC, HVA and 5-HIAA were highest at 11:00 and that of 5-HT at 21:00. The striatal DA, DOPAC, HVA and 5-HIAA concentrations in the nicotine-treated mice were significantly higher at 11:00 and the 5-HT concentrations at 21:00 than in the control mice, and, in contrast to the control mice, in the mice treated with chronic nicotine no circadian rhythm was observed in the 3-MT. No elevation of striatal DA metabolites occurred in the nicotine-treated mice compared with the controls when the plasma nicotine concentration was at its peak at 05:00. This finding suggests development of tolerance to the nicotine-induced changes in striatal DA metabolism. Further, our findings suggest that the chronic administration of nicotine in the drinking water of mice alters the circadian pattern of striatal DA and, to a lesser extent, that of 5-HT, and thus may affect the functions regulated by these transmitters.     

A Qualitative Study of the Difficulties of Smoking Cessation; Health Care Professionals'' and Smokers'' Pints of View

AbstractObjective: To obtain a deeper understanding of smokers' feelings and to establish co-operative networking groups,the opinions about smoking cessation of health careprofessionals and smokers were studied.Design: Focus group discussions were held in order to gainideas and tools to be used in smoking cessation work, inparticular in network groups. Two focus group discussions forhealth care professionals (n = 7) and one focus groupdiscussion for ex-smokers/smokers (n = 3) were held.Results: The study suggests that problems exist in smokingcessation work among health care professionals. The mainissues among the health care professionals were lack ofmotivation and consistency of approach. Informationconcerning the health risk related to smoking no longerreaches people. New ways of health promotion are desired.Smokers feel that lack of positive support and nicotinedependence are the main problems in their attempts to quit.Conclusions: Society and smokers have the same goal:smoking cessation. However, both parties do not seem toagree on ways of achieving this goal. A local network amonghealth care professionals could motivate and give rise to newmethods of smoking cessation counselling. Positive supportand nicotine replacement therapy could significantlyimprove smokers' success rates. Trained personnel havebetter opportunities for meeting smokers and that is whycessation should be part of the core curriculum and basictraining for health care professionals.     

Suicidal ideation among help-seeking adolescents: association with a negative self-image.

Self-image and factors associated with suicidal ideation were studied among adolescents (N=168, age 17.7+/-2.3 years, 72% girls) seeking psychiatric assessment. The Structured Clinical Interview, Beck Depression Inventory and Offer Self-Image Questionnaire were used. Suicidal ideation (SI) was reported by 64% of subjects, of whom 20% received no psychiatric diagnosis and 58% had depressive disorders. SI in boys associated with being bullied at school and talking about one's problems only with friends, and in girls with a negative attitude towards the future and a negative self-image of one's own mental health. Because suicidal ideation frequently occurs without formal psychiatric diagnosis it should be assessed separately. Special attention should be paid to adolescents' negative self-perception.