Metaphase and anaphase analysis of V79 cells exposed to erionite, UICC chrysotile and UICC crocidolite

The cytogenetic effects of erionite treatment of V79 cells werecompared with those of UICC crocidolite and UICC chrysotiletreatment. A significant reduction in diploid cells with anaccompanying increase in aneuploid and polyploid cells was observedwith all three treatments. In the erionite-treated cultures,an increase in aneuploid was observedy at all dose levels rangingfrom 10 to 100 µg/ml, whereas in the crocidolite- andchrysotile-treated cultures, significant increases in aneuploidywere observed at all dose levels except the low dose, 10 µg/ml.Chromatid aberrations were observed in cultures treated withcrocidolite and chrysotile and were especially pronounced atdose 100 µg/ml of chrysotile. The clastogenic effect oferionite was weaker but statistically significant at dose 100µg/ml. An extrapolation of these cytogenetic changes overdose in number of fibers suggests that erionite was more reactivethan the other two minerals in producing aneuploidy. The numberof fibers required to produce a similar degree of cytogeneticeffects was several orders of magnitude higher for chrysotileand crocidolite than erionite. These results correlate withthe higher tumorigenic potency of erionite. In general, fewercells treated with erionite entered anaphase than those treatedwith the other two minerals. As a result, abnormal anaphasesrepresenting chromosomal mis-segregation were observed onlyin the chrysotile- and crocidolite-treated cultures. To ourknowledge, this is the first report on cytogenetic effects oferionite.     

Ethical Reasoning Among Registered Nurses Experienced in Dementia Care

Abstract. Registered nurses regarded as “experienced and good” in dementia care were interviewed about the feeding of a severely demented patient who showed refusal-like feeding behaviour. Not one of the twenty nurses could see herself using force against her patients. Most interviewees justified their decisions to feed a severely demented patient and answered questions about whether they would change their minds if there were certain circumstances in terms of words that could be interpreted as referring to the ethical principle of beneficence. The nurses stressed the difficulty to understand the meaning of severely demented patients' feeding behaviour and decide when force-feeding occurs. When asked to rank ethical principles of importance for the decision, however, the most common answer was that they would give priority to the ethical principle of autonomy. The nurses did not see the ethical principles as separate entities, that could be applied one by one, but tried to integrate them into a whole. The findings of this study were interpreted as indicating that principled ethics is not an adequate model to describe experienced nurses' ethical reasoning.     

Exposure to allergens of different cattle breeds and their relevance in occupational allergy

Introduction  

Cattle are an important source of allergens in the working area of farmers. Asthma caused by cow allergens is a significant occupational problem. Yet in allergological testing, the results of in vivo and in vitro diagnostic tests are often inconsistent even in cases with clearly cattle-related symptoms.     

Surge Capacity Associated with Restrictions on Nonurgent Hospital Utilization and Expected Admissions during an Influenza Pandemic: Lessons from the Toronto Severe Acute Respiratory Syndrome Outbreak

Background Current influenza pandemic models predict a surge in influenza‐related hospitalizations in affected jurisdictions. One proposed strategy to increase hospital surge capacity is to restrict elective hospitalizations, yet the degree to which this measure would meet the anticipated is unknown. Objectives To compare the reduction in hospitalizations resulting from widespread nonurgent hospital admission restrictions during the Toronto severe acute respiratory syndrome (SARS) outbreak with the expected increase in admissions resulting from an influenza pandemic in Toronto. Methods The authors compared the expected influenza‐related hospitalizations in the first eight weeks of a mild, moderate, or severe pandemic with the actual reduction in the number of hospital admissions in Toronto, Ontario, during the first eight weeks of the SARS‐related restrictions. Results Influenza modeling for Toronto predicts that there will be 4,819, 8,032, or 11,245 influenza‐related admissions in the first eight weeks of a mild, moderate, or severe pandemic, respectively. In the first eight weeks of SARS‐related hospital admission restrictions, there were 3,654 fewer hospitalizations than expected in Toronto, representing a modest 12% decrease in the overall admission rate (a reduction of 1.40 admissions per 1,000 population). Therefore, influenza‐related admissions could exceed the reduction in admissions resulting from restricted hospital utilization by 1,165 to 7,591 patient admissions, depending on pandemic severity, which corresponds to an excess of 0.44 to 2.91 influenza‐related admissions per 1,000 population per eight weeks, and an increase of 4% to 25% in the overall number of admissions, when compared with nonpandemic conditions. Conclusions Pandemic modeling for Toronto suggests that influenza‐related admissions would exceed the reduction in hospitalizations seen during SARS‐related nonurgent hospital admission restrictions, even in a mild pandemic. Sufficient surge capacity in a pandemic will likely require the implementation of other measures, including possibly stricter implementation of hospital utilization restrictions.     

Increased cell death after therapy with an Arg-Gly-Asp-linked somatostatin analog.

Receptor-targeted scintigraphy and radionuclide therapy with radiolabeled somatostatin analogs are successfully applied for somatostatin receptor-positive tumors. The synergistic effects of an apoptosis-inducing factor, for example, the Arg-Gly-Asp (RGD) motif, can increase the radiotherapeutic efficacy of these peptides. Hence, the tumoricidal effects of the hybrid peptide RGD-diethylaminetriaminepentaacetic acid (DTPA)-Tyr3-octreotate (cyclic[c](Arg-Gly-Asp-D-Tyr-Asp)-Lys(DTPA)-D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr), hereafter referred to as RGD-DTPA-octreotate, were evaluated in comparison with those of RGD (c(Arg-Gly-Asp-D-Tyr-Asp)) and Tyr3-octreotate (D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr). METHODS: The therapeutic effects of RGD-111In-DTPA-octreotate, 111In-DTPA-RGD, and 111In-DTPA-Tyr3-octreotate were investigated with various cell lines by use of a colony-forming assay, and caspase-3 activity was also determined. RESULTS: Tumoricidal effects were found with 111In-DTPA-RGD, 111In-DTPA-Tyr3-octreotate, and RGD-111In-DTPA-octreotate, in order from least effective to most effective. Also, the largest increase in caspase-3 levels was found with RGD-111In-DTPA-octreotate. CONCLUSION: RGD-111In-DTPA-octreotate has more pronounced tumoricidal effects than 111In-DTPA-RGD and 111In-DTPA-Tyr3-octreotate, because of increased apoptosis, as indicated by increased caspase-3 activity.     

Divergent expression and localization of aquaporin 5, an exocrine-type water channel,in the submandibular gland of Sprague-Dawley rats

By Western blot analysis, the expression level of aquaporin (AQP) 5 in the submandibular gland (SMG) was found to be different among individual rats of the Sprague-Dawley (SD) strain. Such differences were observed for AQP5 but not for AQP1 and consequently the SD strain was divided into two groups, one expressing a high level of AQP5 and the other a low one. The difference in average intensity of expression between the two groups was more than twofold. Immunohistochemical analysis of the SMG demonstrated that the AQP5 protein was localized in the basal and apical/lateral plasma membrane of acinar cells in rats expressing the high level of AQP5. In the rat expressing the low level, however, this channel protein was localized strongly in the apical/lateral plasma membrane, but only very weakly in the basal membrane of the acinar cells. Such a diverse localization of AQP5 was confirmed by Western blotting as well. Breeding between brother and sister was repeated for two times within high expressers and low expressers to obtain the third generation progenies (F2); the AQP5 level of the SMG in the third generation (F2 rats) from high expressers was significantly higher than the F2 from low expressers. Our present study suggests the existence of genetic variation in the expression of a water channel protein, AQP5, in rats.     

A sensitive isotope modification of the mixed haemadsorption test applicable to the study of prozone effects

Investigations of surface antigens of animal cells require sensitive and quantitative in vitro methods. A modification of the mixed haemadsorption technique (MHT) suitable for such purposes is presented. The indicator cells have been labelled with chromium-51. During studies of experimental conditions, including reproducibility and sensitivity, the technique was used in four model systems including histocompatibility (H-2, HL-A), species, organ and blood group antigens. Isotope labelling of the indicator cells has rendered the test more sensitive and in addition some qualitative properties of antigen—antibody interaction have been studied. The test procedure is simple and fast.     

Influence of Verapamil and Cyclosporin A on bile acid metabolism and transport in rat liver slices.

Verapamil (V) is a specific inhibitor of the P-glycoprotein (mdr1) in the hepatocyte canalicular membrane. Cyclosporin A (CsA) as an essential immunosuppressive drug has potentially cholestatic adverse effects on the liver, but increases the expression of mdr1. In precision-cut liver slices from 34- to 40-day-old male Wistar rats 26 individual free and conjugated bile acids (BAs) as markers of hepatic transport and synthesis function were analysed after 4 h incubation with V (100 microM) or CsA (5 microM) in Krebs-Henseleit buffer. Some slices were loaded with cholic acid (CA 5 microM) or tauro-ursodeoxycholic acid (T-UDCA 5 microM) to investigate the V and CsA effects under conditions of BA supplementation. BAs were determined in tissue and medium by HPLC with postcolumn derivatisation and fluorescence detection. V and CsA, influencing different targets in BA transport, enhanced slice concentrations of T- and glyco- (G-) conjugated CA only when exogenous CA was given additionally. This BA accumulation in tissue is more reflected at decreased medium concentrations of these BAs after V and CsA incubations. Both V and CsA also inhibited CA uptake into the slices. The acidic chenodeoxycholic acid (CDCA) synthesis pathway is disturbed: T- and G-CDCA concentrations are diminished in slices and medium after V and CsA incubations. T-UDCA plus V or CsA enhanced not only its own slice concentration but also the concentration of the trihydroxylated tauro-muricholic acid (T-beta-MCA), reflecting the conversion of the accumulated dihydroxylated T-UDCA into the T-beta-MCA. The similar effects of V and CsA on BA transport and metabolism can be explained by mdr1 mediated disturbances of cellular ATP transport rather than by inhibition of individual BA transporters.