The neurotoxicity of sulfur-containing amino acids in energy-deprived rat hippocampal slices

The rat hippocampal slice preparation and its electrophysiology were used to assess the toxicity of two sulfur-containing amino acids, L-cysteate (CA) and L-cysteine (CYS). Both compounds were innocuous under normal conditions but became toxic in energy-deprived (lack of oxygen or glucose) slices. CA and CYS toxicity was apparent as both reduced the number of slices that normally recover their neuronal function (evoked CA1 population spike) after a standardized period of hypoxia or glucose deprivation (GD). The competitive N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate blocked the toxicity of both CA and CYS in hypoxic slices, but it was effective only against CYS toxicity in glucose-deprived slices. The glycine antagonist 7-chlorokynurenate blocked CA and CYS toxicity in hypoxic slices but was unable to block their toxicity in glucose-deprived tissue. Perfusing slices with medium containing a high magnesium concentration blocked the toxicity of CA in both hypoxic and glucose-deprived slices, a treatment that was ineffective against CYS toxicity under either condition. Calcium depletion from the perfusion medium completely blocked the damaging effect of both amino acids in hypoxic slices, but it only partially blocked the toxicity of CA and did not block that of CYS in glucose-deprived slices. These results suggest that CA and CYS activate different NMDA receptor subsets and other glutamate receptor subtypes. Moreover, the results indicate a possible difference between the mechanism that lead to hypoxic neuronal damage and the one that lead to hypoglycemic neuronal damage.     

Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of marrow engraftment in a canine model

Primary graft rejection after marrow transplantation occurs more frequently in patients receiving HLA-haploidentical compared with HLA-identical sibling transplants. Both human and experimental animal data suggest that the cells responsible for this phenomenon are either host natural killer (NK) cells, T cells, or both. To investigate the mechanisms of graft rejection, we have developed a canine model of marrow transplantation, which uses DLA-nonidentical unrelated donors in the absence of postgrafting immunosuppression. In this model most animals rejected their marrow grafts after a preparative regimen of 9.2 Gy total body irradiation (TBI). However, engraftment of DLA-nonidentical marrow can be facilitated when the recipients are pretreated with monoclonal antibody (MoAb) S5, which recognizes CD44. In this report, we extended these observations by first cloning the canine CD44 and, next, mapping the epitope recognized by S5, which was located in a region conserved among human and canine CD44 and was distinct from the hyaluronan binding domain. However, in vitro binding of S5 caused a conformational change in CD44, which allowed increased hyaluronan binding. Then, we reexamined the in vivo model of marrow transplantation and compared results with MoAb S5 to those with two other anti-CD44 MoAbs, IM7 and S3. Only MoAb S5 significantly increased the engraftment rate of DLA-nonidentical unrelated marrow, whereas the two other anti-CD44 MoAbs were ineffective. The enhanced in vivo effect was not related to differences in the MoAbs' avidities, since both S5 and IM7 had equivalent binding to CD44, but most likely related to the specific epitope that S5 recognizes. Thus, this study shows that the effect of the anti-CD44 MoAb S5 in facilitating engraftment is epitope specific and if one is to use an anti-CD44 to facilitate engraftment of marrow in humans, one cannot assume that any anti-CD44 would work.     

The percutaneous endoscopic treatment of staghorn nephrolithiasis

Hyperferremia is shown to affect antioxidant system of the body, oxidation-reduction reactions in the cells seen as shifts in lymphocyte chemiluminescence. Dynamic changes in lymphocyte chemiluminescence reflect the level of hyperferremia.     

The meaning and impact of empathic relationships in hospice nursing

This naturalistic field study was designed to explore the patient's perspective of the nature, meaning, and impact of empathic relationships with hospice nurses. The findings are part of a larger study, focused on the meaning and impact of empathic relationships that develop between hospice nurses and their patients. Data were generated through in-depth interviews with 14 terminally ill adults receiving home-based hospice care. According to the hospice patient, an empathic relationship developed through a process of reciprocal sharing and revealing of personhood within a context of caring and acceptance. The experience of an empathic relationship meant being acknowledged as an individual, a person of value. The outcome of the empathic relationships between hospice nurses and their patients was the improvement and maintenance of patients' physical and emotional well-being. Understanding the patient's perspective is critical for effective nursing interventions and meaningful outcomes. Future research needs to explore empathic relationships between the nurse and family caregivers in various settings.     

Alpha blockaders--first or second line antihypertensive agents?

Alpha-receptor blockers reduce blood pressure by blocking of the alpha 1-receptors in the smooth muscle cells in the arteriolar walls. The heart pump function is not disturbed. Most studies have shown that the alpha-receptor blockers induce a reduction in plasma-triglycerides and an increase in the ratio between HDL- and LDL-cholesterol. They do not interfere with the metabolism of electrolytes, glucose or uric acid and have no negative effect on pulmonary function. Although long-term use does not induce a permanent increase in heart rate, some patients respond to initial therapy with faster heart rate and palpitations. The alpha-receptor blockers should not be used in patients with coronary heart disease if the patient is not on chronic beta-blockade. When these precautions are followed, the alpha-blockers can be used as first-line treatment--just like ACE-inhibitors and calcium-antagonists.