Liver fat in the metabolic syndrome

BACKGROUND: The liver, once fatty, overproduces components of the metabolic syndrome, such as glucose and lipids. The amount of liver fat in subjects with and without the metabolic syndrome has not been determined. It is unknown which clinically available markers best reflect liver fat content. MEASUREMENTS: Components of the metabolic syndrome as defined by the International Diabetes Federation and liver fat content by proton magnetic resonance spectroscopy were measured in 271 nondiabetic subjects (162 women, 109 men). In addition, other features of insulin resistance (serum insulin, C-peptide), intraabdominal and sc fat by magnetic resonance imaging, and liver enzymes (serum alanine aminotransferase and serum aspartate aminotransferase) were measured. RESULTS: Liver fat was 4-fold higher in subjects with [n = 116; median 8.2% (interquartile range 3.2-18.7%)] than without [n = 155; 2.0% (1.0-5.0%); P < 0.0001] the metabolic syndrome. This increase in liver fat remained significant after adjusting for age, gender, and body mass index. All components of the metabolic syndrome correlated with liver fat content. The best correlate was waist in both women (r = 0.59, P < 0.0001) and men (r = 0.56, P < 0.0001). Liver fat correlated significantly with serum alanine aminotransferase (r = 0.39, P < 0.0001 for women; r = 0.44, P < 0.0001 for men) and aspartate aminotransferase (r = 0.27, P = 0.0005 for women; r = 0.31, P = 0.0012 for men) concentrations. The best correlates of liver fat were fasting serum insulin (r = 0.61; P < 0.0001 for both women and men) and C-peptide (r = 0.62; P < 0.0001 for both women and men). CONCLUSIONS: Liver fat content is significantly increased in subjects with the metabolic syndrome as compared with those without the syndrome, independently of age, gender, and body mass index. Of other markers, serum C-peptide is the strongest correlate of liver fat.     

Early age at onset of bipolar disorder is associated with more severe clinical features but delayed treatment seeking

OBJECTIVE: Our aim was to obtain a comprehensive view of differences between bipolar disorder (BD) patients with onset at early versus adult age in a representative study cohort. METHODS: In the Jorvi Bipolar Study (JoBS), 1,630 psychiatric in- and outpatients were systematically screened for BD using the Mood Disorder Questionnaire (MDQ). A total of 191 bipolar I and II patients with a current DSM-IV episode were interviewed to obtain information about age at onset of mood symptoms, clinical course, treatment, comorbidity, and functional status. The patients were classified as either early onset (<18 years) or adult onset. RESULTS: One-third of subjects with BD (58/191, 30%) had early onset. This was associated with female gender, more lifetime psychotic symptoms, greater overall comorbidity, and a greater length of time from first episode to treatment. CONCLUSIONS: Although BD patients with early age at onset have more severe clinical features and illness course, the delays from first episode to treatment and to correct diagnosis are longer than for those with adult onset disorder. To reduce morbidity rates related to the most severe forms of BD, the recognition and diagnosis of BD during adolescence needs to be improved.     

Serological microarray for detection of HSV-1, HSV-2, VZV, and CMV antibodies

The seroprevalence of human herpesviruses is high and reactivations occur frequently. A microarray was designed and tested for the detection of IgG and IgM antibodies for Puumala hantavirus (PUUV) and IgG antibodies against four herpesviruses. Initially, a microarray platform was set up using an unrelated in-house antigen, PUUV recombinant nucleocapsid protein, to optimize the protocol for the detection of antibodies. Detection of the four herpesviruses was set up in a microarray using the recombinant proteins of herpes simplex virus (HSV) glycoprotein G1 and G2, varicella-zoster virus (VZV) glycoprotein E, and cytomegalovirus (CMV) pp150 phosphoprotein.The results of the PUUV panel were in good agreement with the PUUV IgG immunofluorescent assay and IgM enzyme immunoassay (EIA). Seropositive and negative clinical reference panels were tested for herpesviruses by the serological microarray, and the results were compared to those of individual EIAs used for standard diagnostic purposes.The serologic microarray for HSV, VZV and CMV antibody detection gave good specificities for IgG. However, sensitivities of the assay varied depending on the herpesvirus detected. The serological microarray showed potential for screening purposes. The microarray based analyses were easy to perform, and HSV-1, HSV-2, VZV, and CMV antibodies could be detected on the same microarray.     

The prevalence of alexithymia and its relationship with Youth Self-Report problem scales among Finnish adolescents

This study investigated the relationship between alexithymia, depressive symptoms, and Youth Self-Report (YSR) self-image profiles among 13 to 18-year-old adolescents (n = 7087) attending school in Kuopio, Finland. The final sample consisted of 3936 adolescents (1801 boys, 2135 girls) who completed structured self-rating questionnaires (Toronto Alexithymia Scale [TAS] 20, Beck Depression Inventory [BDI], and YSR) during class periods at school. The overall prevalence of alexithymia was 7.3%. However, girls in all age groups were more frequently alexithymic than boys. Regardless of sex, alexithymic youths reported more depressive symptoms as well as internalizing and externalizing problems than the others. A YSR total score of more than 70 was recorded among 33.4% of alexithymic compared with 3.7% of nonalexithymic adolescents. The TAS-20 correlated significantly with the BDI score, YSR total score, and with internalizing problems. This study revealed alexithymia among adolescents to be associated with various complications such as depressive symptoms, high scores in YSR problem scales, and difficulties in social relationships. Our findings indicate that these adolescents are at high risk of mental disorders and require treatment interventions.     

Drug transporters in the human blood-placental barrier

Studies on the increasing number of transporters found in the placental barrier are gaining momentum, because of their tissue-specific expression, significance in physiology and disease, and the possible utilization of the emerging knowledge in pharmacology. In the placenta, both syncytiotrophoblast and fetal capillary endothelium express transporters. Fetal exposure is determined by the net effect of combination of transporters, their nature and localization in relation to placental cells and their substrate specificity. Although the significance of placental transporters on human fetal drug exposure is almost an unstudied field so far, their potential use to design drugs that do not cross the placenta is already being pursued. It is thus of interest to review the existing knowledge of human placental transporters. Transporters in all groups which take part in drug transport are found in human placenta. Especially, ATP-binding cassette transporters ABCG2/breast cancer resistance protein, ABCB1/P-glycoprotein and ABCC2/MRP2 are all expressed at the apical surface of syncytiotrophoblast facing maternal blood and are putatively important protective proteins both for placental tissue and the fetus, because they are efflux transporters and their substrates include many drugs and also environmental chemicals. Such protective effect has been shown in animals, but these results cannot be directly extrapolated to humans due to interspecies differences in placental structure and function. Experimental models utilizing human placental tissue, especially human placental perfusion, offer valuable possibilities, which have been insufficiently studied so far.     

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.