Inhibition of human brain tumor cell growth by a receptor-operated Ca2+ channel blocker

SK&F 96365, a reported receptor-operated Ca2+ channel blocker, inhibited the growth of U-373 MG human astrocytoma and SK-N-MC human neuroblastoma cell lines in a dose-dependent manner. Carbachol and serum which act as growth factors for these cells induced a rapid, transient increase of intracellular Ca2+ concentration without a sustained increase. SK&F 96365 also exerted a significant inhibition of carbachol or serum-induced intracellular Ca2+ mobilization. These results suggest that SK&F 96365 is a potent inhibitor of brain tumor cell growth and that its effect may be mediated by the inhibition of agonist-induced intracellular Ca2+ mobilization.     

Acute effects of chundosunbup qi-training on blood concentrations of TSH, calcitonin, PTH and thyroid hormones in elderly subjects

The present study investigated how the systemic treatment of a programmed exercise, ChunDoSunBup (CDSB) Qi-training, affects the secretion of thyroid and parathyroid hormones in elderly subjects (10 male and 5 female). Plasma concentrations of thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), parathyroid hormone (PTH), ionized calcium, and calcitonin were determined. CDSB Qi-training induces a slight increase in TSH. Both T4 and T3 were increased at the mid-time of CDSB Qi-training (p < 0.05). There were significant correlations only between T3 and T4 at mid-training. This shows that increase in the plasma level of T3 was associated with the secretion of T4. The plasma concentrations of calcitonin and PTH were increased at mid-time and post-time of CDSB Qi-training. But ionized calcium was decreased slightly by CDSB Qi-training. These results suggest that Qi-training modulates the secretion of thyroid hormones, calcium metabolism, and parathyroid hormones in the elderly. However, whether the long-term practice of CDSB Qi-training might change bone metabolism and have longitudinal effects on the thyroid hormone of the elderly need further investigation.     

Controlling Legionella in hospital water systems: experience with the superheat-and-flush method and copper-silver ionization

OBJECTIVE: To evaluate the effect of copper-silver ionization on Legionella colonization and nosocomial legionnaires' disease and to compare the efficacy of metal ions versus the superheat-and-flush method of disinfection. DESIGN: Prospective determination over a 36-month period of copper and silver ion concentrations in the recirculating hot-water system, Legionella colonization of the hospital water distribution system, and cases of nosocomial legionnaires' disease. Retrospective comparison of results with the previous 13 years, during which the superheat-and-flush method was used. SETTING: The Pittsburgh Veterans' Affairs Health Care System (University Drive Division) acute-care hospital. INTERVENTION: Three copper-silver ionization systems were installed on the hot-water distribution system in November 1994. RESULTS: The average number of cases of legionnaires' disease per year and the percentage of distal sites positive for Legionella pneumophila for the superheat-and-flush method versus the copper-silver ionization method was six cases with 15% positivity versus two cases with 4% positivity, respectively. The reduction in Legionella colonization after copper-silver ionization was significant (P<.05) compared to the superheat and flush. Mean copper and silver ion concentrations (mg/L) were 0.29 and 0.054 from hot-water tanks, and 0.17 and 0.04 from distal outlets, respectively. CONCLUSIONS: We conclude that a properly maintained and monitored copper-silver ionization system was more effective than the superheat-and-flush method for reducing the recovery of Legionella from the hospital water distribution system.     

Fluid shear stress activation of IkappaB kinase is integrin-dependent

Vascular endothelial cells (ECs), forming a boundary between the circulating blood and the vessel wall, are constantly subjected to fluid shear stress due to blood flow. The aim of this study was to determine the role of the recently identified IkappaB kinases (IKKs) in shear stress activation of NF-kappaB and to elucidate the upstream signaling mechanism that mediates IKK activation. Our results demonstrate that IKKs in ECs are activated by shear stress in a rapid and transient manner. This IKK activation is followed by IkappaB degradation and NF-kappaB translocation into the nucleus. Transfection of plasmids encoding catalytic inactive mutants of IKKs, i.e. hemagglutinin (HA)-IKKalpha(K44M) and HA-IKKbeta(K44A), inhibits shear stress-induced NF-kappaB translocation. In addition, constructs encoding antisense IKKs, i.e. HA-IKKalpha(AS) and HA-IKKbeta(AS), attenuate shear stress induction of a promoter driven by the kappaB enhancer element. Preincubation of the EC monolayer with a monoclonal anti-alphavbeta3 integrin antibody (clone LM609) attenuates shear stress induction of IKK. Inhibition of tyrosine kinases by genistein causes a similar down-regulating effect. These results suggest that the integrin-mediated signaling pathway regulates NF-kappaB through IKKs in ECs in response to shear stress.     

Rat intestinal brush border membrane peptidases. I. Solubilization, purification, and physicochemical properties of two different forms of the enzyme

Two brush border peptidases have been isolated from the particulate fraction of the rat intestinal mucosa and purified to homogeneity as judged by polyacrylamide gel electrophoresis, starch gel electrophoresis, isoelectric focusing, and double immunodiffusion. For convenience, the peptidases have been designated peptidase F (fast) and S (slow) on the basis of their anodic mobilities. The isoelectric point of peptidase F was 4.76 and of peptidase S, 5.10. Both enzymes are glycoproteins. The amino acid compositions of the two peptidases are similar. The same carbohydrates are found in both enzymes, but there are differences in the molar concentrations of individual sugars. Peptidase S has greater concentrations of mannose and galactose and of hexosamines than peptidase F, while sialic acid is slightly greater in peptidase F. Carbohydrate accounted for approximately 19% and 23% of the weight of peptidases F and S, respectively. Estimates of the molecular weights of both enzymes by gel filtration gave values of 280,000. Electrophoresis of the enzymes under denaturing conditions on sodium dodecyl sulfate polyacrylamide gels indicated that each enzyme is a dimer consisting of two subunits of equal molecular weight, 140,000.     

Work in progress. Intraoperative neurosurgical ultrasound: localization of brain tumors in infants and children

Intraoperative real-time ultrasonic sector scanning was performed through the unincised dura mater or the intact brain surface of eight patients (aged six months to 13 years), each of whom had a previously documented mass lesion (four supratentorial, three infratentorial, one intraventricular). In each case, there was a clear definition of the location, configuration, and tissue consistency of the mass. With the exception of a choroid plexus papilloma, all lesions demonstrated both solid and fluid components. The location of a subcortical parietal lobe mass (ependymoma) was apparent only by prior sonography. All neoplastic tissue of one cerebellar astrocytoma that was identified at gross examination was removed, but additional intraoperative scanning following removal of the neoplasm suggested the presence of residual abnormal tissue. This was confirmed during further exploration, and additional gross tumor tissue was excised.     

Reappraisal of eight representative carcinogenic and non-carcinogenic compounds in a new medium-term rat liver bioassay using D-galactosamine

Tuberculosis incidence and mortality rates are rising steeply, reflecting economic hardship and the deterioration of the health infrastructure. The human and technical resources needed to reverse this trend are on hand, but cannot be used effectively without an adequate financial input. The cost of controlling tuberculosis now is modest compared with the cost of allowing it to increase.