In Uruguay, an ethic of care for the dying

The ethics of care for the terminally ill in Uruguay spring from deeply rooted attitudes which invest the physician with sole power to determine the course of treatment, even to prescribe painkilling drugs and to hasten death actively or passively, without collaboration from the patient's family. The paternal function attributed to the physician has not been questioned by any systematic reflection on biomedical ethics. However, conscientious physicians are interested in these issues and are well informed about the concerns of their foreign colleagues.     

Eudesmanolides from Artemisia santonicum

The reinvestigation of the aerial parts of ARTEMISIA SANTONICUM afforded, in addition to three known eudesmanolides, six new ones, all closely related to taurin. The structures were elucidated by high-field NMR spectroscopy.     

Uptake inhibitors do not change the effect of imidazoline α2-adrenoceptor agonists on transmitter release evoked by single pulse stimulation in mouse vas deferens

Summary The present study was undertaken to compare the presynaptic interaction of neuronal noradrenaline uptake inhibitors with imidazoline and phenylethylamine ₂adrenoceptor agonists under two different conditions: at low and high noradrenaline concentrations in the biophase.Isolated mouse vasa deferentia were stimulated with trains of 7 pulses given at 0.2 Hz and the inhibition by the ₂-adrenoceptor agonists clonidine, -methylnoradrenaline, and UK-14,304 of twitch responses was measured in the absence and in the presence of either cocaine (12 mol/l) or desipramine (40 nmol/l). The effects were determined for the first (equivalent to single pulse stimulation) and the last stimulus of each train. Both uptake inhibitors antagonized the presynaptic inhibitory effects of imidazolines (clonidine and UK-14,304) on the last twitch; the effects on the first twitch remained unchanged. In contrast, the uptake inhibitors potentiated the inhibitory effect of the phenylethylamine (-methylnoradrenaline) on both the first and the last twitches.These results support the view that the concentration of noradrenaline in the biophase plays a decisive role in the inhibition by a₂-adrenoceptor agonists of the electrically evoked release of noradrenaline. Agonists that are not substrates of neuronal uptake (i.e., clonidine, UK-14,304) become less effective when noradrenaline is present in the biophase while substrates of neuronal uptake (i. e., -methylnoradrenaline) do not. The results argue against the hypothesis that uptake inhibitors interact directly with presynaptic ₂-adrenoceptors or act at some link between uptake and receptor sites. Send offprint requests to S. Guimarães at the above address     

Ontogenetic profile of glutamate uptake in brain structures slices from rats: sensitivity to guanosine

The excitotoxicity of the neurotransmitter glutamate has been shown to be connected with many acute and chronic diseases of the CNS. High affinity sodium-dependent glutamate transporters play a key role in maintaining adequate levels of extracellular glutamate. In the present study, we used slices of striatum, hippocampus and cortex from rat brain to describe the in vitro profile of glutamate uptake during development and ageing, and its sensitivity to guanosine. In all structures, glutamate uptake was higher in immature animals. There was a maximum decrease in glutamate uptake in striatum and hippocampus in 15-month-old rats, which later increased, while in cortex there was a significant decrease in rats aged 60 days old. The effect of guanosine seems to be age and structure dependent since the increase in basal glutamate uptake was only seen in slices of cortex from 10-day-old animals.     

The modulation of the Ne-like wave on correct responses foreshadows errors

In reaction time (RT) tasks, event-related potentials (ERPs) reveal a response-locked negative wave when subjects commit errors. This wave, termed "error negativity" (Ne) or "error-related negativity" (ERN), is thought to index response-monitoring processes. With conventional monopolar recordings, this negativity is hardly seen on correct responses, likely overlapped by a large positive wave. Indeed, after Laplacian transformation (a spatial high-pass filter), a small Ne-like wave is unmasked. Recently, it has been shown that the positivity on monopolar recordings was larger for correct responses preceding an error than for correct responses preceding a correct trial. After Laplacian transformation, it appears that this effect is due, at least in part, to a decrease of the Ne-like wave on correct responses preceding an error. This result indicates that, as the Ne on errors, the Ne-like wave on correct responses is sensitive to performance and hence is likely related to response-monitoring processes.     

Epidermal growth factor receptor regulates normal urothelial regeneration

Members of the epidermal growth factor (EGF) family and their receptors are involved in many cellular processes, including proliferation, migration, and differentiation. We have previously reported that these growth factors are expressed and have specific regulatory functions in an organ-like culture model of normal human urothelial cells. Here, we used this model to investigate the involvement of EGF receptor (EGFR) in human urothelial regeneration. Three 4-mm-diameter damaged areas were made in confluent normal human urothelial cell cultures with a biopsy punch. Regeneration was measured, on fixed stained cultures, with an image analyzer, at 4, 24, and 48 hours after injury. Cell proliferation was assessed by 5-bromo-2-deoxyuridine incorporation. To identify EGF family factors potentially involved in the healing process, we studied the effect of these factors on damaged confluent cultures and the level of expression of mRNAs extracted from these cultures. EGFR inhibition of the proliferation and migration of urothelial cells was tested with (1). a specific tyrosine kinase inhibitor (AG1478) and (2). a blocking anti-EGFR antibody (LA22). Exogenously added amphiregulin, EGF, transforming growth factor-alpha and heparin-binding EGF (HB-EGF) stimulated urothelial regeneration. The damaged areas were repaired by regrowth within 48 hours. Both AG1478 and LA22 inhibited the repair (by 50% and 30%, respectively), as well as proliferation and migration. This regeneration was accompanied by increased HB-EGF mRNA expression in cultures of cells from four of six subjects, but no corresponding change in EGFR protein level was observed. These results indicate that the EGFR signaling pathway is involved in urothelial regeneration. Our data support an autocrine role of HB-EGF in this process and suggest that the EGFR pathway is a potential therapeutic target for modulating urothelial cell proliferation.     

Hemocompatibility of medical connectors with biopassive or bioactive surface coatings

Although medical connectors compose very small parts of the extracorporeal circulation (ECC) system they represent a critical localization where early thromboembolic processes can manifest. In the present study we modified an in vitro closed-loop model with fresh human whole blood for the preclinical evaluation of the hemocompatibility of three types of medical connectors: non-coated (control); with silicone-, and heparin-coating. Each single loop consists of five polycarbonate connectors joined together by five pieces of silicone tubes. Thrombin-antithrombin-III, beta-thromboglobulin (beta-TG), PMN-Elastase, terminal complement complex, CD 11b expression, and surface-absorbed fibrinogen were measured. After 1 and 2 h recirculation, platelet loss, release of beta-TG, and adsorption of fibrinogen were significantly higher (p<0.05) within the non-coated connectors compared to the silicone- and heparin-coated groups. Following this experiment, the connectors were filled again with fresh heparinized whole blood from the same donor to evaluate the influence of prior blood contact. Here, the activation of platelets and coagulation was dependent on the duration of the blood preincubation period. Probably, the coated surfaces possess a reduced, or selective adsorption of plasma proteins, which in turn leads to a faster creation of a blood-friendly secondary superficial membrane, and prevents a further denaturation and hence activation of the adsorbed proteins.     

Biological and antigenic variants among Ťahyňa virus strains isolated in Czechoslovakia

Summary Significant differences were observed in plaque size and antigenic relationships studied in plaque reduction neutralization tests and counterimmunoelectrophoresis between TAH virus strains isolated not only in two distant regions but also between strains isolated within one region in Czechoslovakia.Partly presented at the International Symposium: New Aspects in Ecology of Arboviruses, held in Smolenice near Bratislava (Czechoslovakia), June 11–15, 1979.     

Investigations on the biology,epidemiology, pathology and control of<Emphasis Type="Italic"> Tunga penetrans</Emphasis> in Brazil: I. Natural history of tungiasis in man

Tungiasis is an important health problem in poor communities in Brazil and is associated with severe morbidity, particularly in children. The causative agent, the female flea Tunga penetrans, burrows into the skin of its host, where it develops, produces eggs and eventually dies. From the beginning of the penetration to the elimination of the carcass of the ectoparasite by skin repair mechanisms, the whole process takes 4-6 weeks. The present study is based on specimens from 86 patients, for some of whom the exact time of penetration was known. Lesions were photographed, described in detail and biopsied. Biopsies were examined histologically and by means of scanning electron microscopy (SEM). Based on clinical, SEM and histological findings, the "Fortaleza classification" was elaborated. This allows the natural history of tungiasis to be divided into five stages: (1) the penetration phase, (2) the phase of beginning hypertrophy, (3) the white halo phase, (4) the involution phase and (5) residues in the host's skin. Based on morphological and functional criteria, stages 3 and 4 are divided into further substages. The proposed Fortaleza classification can be used for clinical and epidemiological purposes. It allows a more precise diagnosis, enables the assessment of chemotherapeutic approaches and helps to evaluate control measures at the community level.     

ATP-sensitive K+ and Ca2+-activated K+ channels in lamprey ( Petromyzon marinus) red blood cell membrane

The patch-clamp technique was used to demonstrate the presence of ATP-sensitive K(+) channels and Ca(2+)-activated K(+) channels in lamprey ( Petromyzon marinus) red blood cell membrane. Whole-cell experiments indicated that the membrane current under isosmotic (285 mosmol l(-1)) conditions is carried by K(+). In the inside-out configuration an ATP-sensitive K(+) channel (70-80 pS inward, 35-40 pS outward) was present in 35% of patches. Application of ATP to the intracellular side reduced unitary current with half-maximal inhibition in the range 10-100 microM. A block was obtained with 100 microM lidocaine and inhibition was obtained with 0.5 mM barium acetate. A Ca(2+)-activated K(+) channel (25-30 pS inward, 10-15 pS outward) was present in 57% of patches. Inhibition was produced by 10 mM TEA and 500 nM apamin and sensitivity to Ba(2+) was lower than for ATP-sensitive channels. No spontaneous channel activity was recorded in the cell-attached configuration under isotonic conditions. With hypotonic saline 68% of patches showed spontaneous single-channel activity, and, of 75 active patches, 66 cell-attached patches showed channel activity corresponding to Ca(2+)-activated K(+) channels.