Central adiposity and hemodynamic functioning at rest and during stress in adolescents

OBJECTIVE: To examine the impact of central adiposity upon hemodynamic functioning at rest and during stress in adolescents. DESIGN: Cross-sectional, correlational study. SUBJECTS: 46 White and 49 Black normotensive adolescents with family histories of essential hypertension. MEASUREMENTS: Systolic and diastolic blood pressure (SBP, DBP), cardiac output and total peripheral resistance responses were assessed at rest, during postural change, video game challenge and forehead cold stimulation. Specific lower and higher waist-to-hip ratio (WHR) tertiles were created for each gender and then integrated for analyses. This resulted in a lower WHR tertile of 11 Whites and 21 Blacks and an upper WHR tertile of 15 Whites and 17 Blacks. RESULTS: No differences in age, gender or ethnicity proportions were found between tertile groups (all P > 0.21). The upper WHR group showed greater body weight, waist and hip circumferences, body mass index (BMI), triceps skinfold and body surface area (all P < 0.001). Controlling for peripheral (that is, triceps skinfold) and overall (that is, BMI) adiposity, the upper WHR group exhibited greater SBP (that is, peak response minus mean pre-stressor level) to all three stressors and greater DBP reactivity to postural change and cold pressor (all P < 0.05). CONCLUSION: Central adiposity appears to adversely influence hemodynamic functioning during adolescence. Underlying mechanisms responsible for these associations require exploration.     

New-onset psychogenic seizures after surgery for epilepsy

BACKGROUND: The emergence of psychogenic seizures after surgery for epilepsy is not well recognized. OBJECTIVES: To identify the frequency of psychogenic seizures in an 11-year surgical experience and to characterize the patients with this complication. METHODS: Ninety-six patients underwent surgery for epilepsy between 1985 and 1996. The surgical database was reviewed and all patients who experienced postoperative psychogenic seizures were identified. Patients were characterized by sex, age, psychopathologic conditions, full-scale IQ, duration of epilepsy, surgical procedure, and operative complications. Patients were compared with the surgical group as a whole for these variables. SETTING: A comprehensive epilepsy center. RESULTS: Five patients were identified: 3 men and 2 women. Mean full-scale IQ was 73 (range, 66-82). Mean age was 29.8 years (range, 22-36 years). Three patients were diagnosed as having psychosis, 1 with borderline personality disorder and 1 with generalized anxiety. Operations included 4 anterior temporal lobectomies and 1 occipital lobectomy. Two patients experienced operative complications. Compared with the surgical cohort, patients had a higher frequency of preoperative psychopathologic conditions, lower mean full-scale IQ, and a greater occurrence of operative complications. CONCLUSIONS: (1) Patients can develop new-onset psychogenic seizures after surgery for epilepsy. (2) Low full-scale IQ, serious preoperative psychopathologic conditions, and major surgical complications may be risk factors. (3) Atypical postoperative seizures should be evaluated with video electroencephalographic monitoring before concluding that they are epileptic.     

Inhibition of NFkappaB activity through maintenance of IkappaBalpha levels contributes to dihydrotestosterone-mediated repression of the interleukin-6 promoter

Androgens repress expression of many genes, yet the mechanism of this activity has remained elusive. The cytokine, interleukin-6, is active in a variety of biological systems, and its expression is repressed by androgens. Accordingly we dissected the mechanism of androgen's ability to inhibit interleukin-6 expression at the molecular level. In a series of co-transfection assays, we found that 5alpha-dihydrotestosterone, through the androgen receptor, repressed activation of the interleukin-6 promoter, in part, by inhibiting NFkappaB activity. It did not appear that 5alpha-dihydrotestosterone inhibited NFkappaB by activating the androgen receptor to compete for the NFkappaB response element as we could not detect androgen receptor binding to the IL-6 promoter by DNase I footprinting assay. However, by electrophoretic mobility shift assay we found that 5alpha-dihydrotestosterone repressed formation of NFkappaB middle dotNFkappaB response element complex formation. In LNCaP prostate carcinoma cells, 5alpha-dihydrotestosterone achieved this effect through maintenance of IkappaBalpha protein levels in the face of phorbol ester, a stimulus that results in IkappaBalpha degradation. Finally, we confirmed that IkappaBalpha inhibits NFkappaB-mediated activation of the interleukin-6 promoter. These data suggest that maintenance of IkappaBalpha levels may represent the first identified mechanism for androgen-mediated repression of a natural androgen-regulated gene.     

Cuticle chirality and body handedness in Caenorhabditis elegans

BACKGROUND AND PURPOSE: Norway has the highest reported incidence of hip fractures in western Europe. Little is known about the epidemiology of falls in Norway where the winter season is long and dark. The objective of this work was to study reported falls and their consequences among elderly Norwegians living at home. METHODS: A cross-sectional design was used for the study. Interviews were performed in the homes of 431 subjects, aged 67-97 years, living at home. Information on falling was gathered through six questions: whether the subject had fallen during the last six months, and if so, how many falls they had, where the last fall occurred, its perceived reason, the activity the subject had been engaged in when the fall occurred, and the resulting injury. RESULTS: In all, 24.1% of subjects reported falling during the last six months, and 9.5% had suffered more than one fall. Falls were most frequently linked to external events (63.1%). Outdoor falls were more frequent (59.0%; 95% CI = 51.2-82.0) than indoor falls. Older subjects were associated with more frequent indoor falls (p < 0.05), but gender was not significant. Fifty-one per cent of subjects had fallen while walking and 53% had suffered an injury from the last fall. In 13.4% of the women and 16.2% of the men, the last fall had resulted in a fracture. CONCLUSIONS: Compared to the results of other studies from industrialized Western countries, a similar crude fall rate, similar frequency and similar type of injury were found. However, in contrast to other studies, no gender difference was observed with regard to falling, place of falling and fracture rate.     

TP63 Is Significantly Upregulated in Diabetic Kidney

The role of tumor protein 63 (TP63) in regulating insulin receptor substrate 1 (IRS-1) and other downstream signal proteins in diabetes has not been characterized. RNAs extracted from kidneys of diabetic mice (db/db) were sequenced to identify genes that are involved in kidney complications. RNA sequence analysis showed more than 4- to 6-fold increases in TP63 expression in the diabetic mice’s kidneys, compared to wild-type mice at age 10 and 12 months old. In addition, the kidneys from diabetic mice showed significant increases in TP63 mRNA and protein expression compared to WT mice. Mouse proximal tubular cells exposed to high glucose (HG) for 48 h showed significant decreases in IRS-1 expression and increases in TP63, compared to cells grown in normal glucose (NG). When TP63 was downregulated by siRNA, significant increases in IRS-1 and activation of AMP-activated protein kinase (AMPK (p-AMPK-Th¹⁷²)) occurred under NG and HG conditions. Moreover, activation of AMPK by pretreating the cells with AICAR resulted in significant downregulation of TP63 and increased IRS-1 expression. Ad-cDNA-mediated over-expression of tuberin resulted in significantly decreased TP63 levels and upregulation of IRS-1 expression. Furthermore, TP63 knockdown resulted in increased glucose uptake, whereas IRS-1 knockdown resulted in a decrease in the glucose uptake. Altogether, animal and cell culture data showed a potential role of TP63 as a new candidate gene involved in regulating IRS-1 that may be used as a new therapeutic target to prevent kidney complications in diabetes.     

On Iron Metabolism and Its Regulation

Iron is a critical metal for several vital biological processes. Most of the body’s iron is bound to hemoglobin in erythrocytes. Iron from senescent red blood cells is recycled by macrophages in the spleen, liver and bone marrow. Dietary iron is taken up by the divalent metal transporter 1 (DMT1) in enterocytes and transported to portal blood via ferroportin (FPN), where it is bound to transferrin and taken up by hepatocytes, macrophages and bone marrow cells via transferrin receptor 1 (TfR1). While most of the physiologically active iron is bound hemoglobin, the major storage of most iron occurs in the liver in a ferritin-bound fashion. In response to an increased iron load, hepatocytes secrete the peptide hormone hepcidin, which binds to and induces internalization and degradation of the iron transporter FPN, thus controlling the amount of iron released from the cells into the blood. This review summarizes the key mechanisms and players involved in cellular and systemic iron regulation.