Relationships among lactate concentration, blood flow and histopathologic profiles in rat C6 glioma

Increased capacity for glycolytic metabolism is a well-known characteristic of neoplastic cells. Because lactic acid is the end product of glycolysis, in vivo MRS measurements of tumor lactate concentration ([lac]t) may provide valuable information about tumor metabolism, which will aid the development of therapies and the clinical diagnosis and treatment of tumors. In the present study, several hemodynamic and histologic parameters were evaluated with respect to their influence on [lac]t. Pronounced differences in [lac]t in two distinct populations of tumors suggested a putative perfusion threshold. Above this threshold, [lac]t was independent of hemodynamic and histologic factors including tumor blood flow (measured using MRS and the method of D2O washout), extent of necrosis and inflammatory cell infiltrate. Thus, for most tumors, [lac]t was not determined by any one single factor such as hypoxia, venous clearance, glucose supply, extent of necrosis or degree of inflammatory cell infiltrate. Rather, [lac]t may be equilibrated, at least in part, by an interplay of forces involving hemodynamics and substrate supply. In general, the data are consistent with the hypothesis that elevated lactate in most tumors is related to the high glycolytic activity of adequately perfused, viable neoplastic cells.     

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.     

Electrodeposited polytyramine as an immobilisation matrix for enzyme biosensors

The application of an electrodeposited polytyramine film as an immobilisation matrix for the construction of enzyme biosensors is described. Glucose oxidase (used as a model enzyme) is covalently attached to free amine groups on the polytyramine film using the coupling reagents 1-ethyl-3(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide. The resultant recognition interface consisted of multilayers of GOx immobilised onto the polymer surface. This method of constructing enzyme biosensors is shown to produce a highly reproducible and stable device. The biosensor showed no loss in electrode response after four months of dry storage and exhibited only minor loss in response after 20 days of repeated use. The resultant biosensor had a linear range of 0.1-28 mM glucose and a detection limit of 0.01 mM.     

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.