Activity of oxidation-reduction enzymes in endotheliocytes of the intestinal hemomicrocirculatory bed under normal conditions and in portal hypertension

An original quantitative examination of oxidation-reduction enzymes activity in endotheliocytes of hemomicroclrculatory vessels of jejunum and rectum submucosal base in normal state and in portal hypertension was performed by the authors. Comparative analysis of the activity of the enzymes studied revealed different metabolic processes intensity in these organs, dependent on current hemodynamic conditions. Cytochemical changes in hemomicrocirculatory bed are consistent with structural reorganizations that arise in the wall of vessels studied, consist of several phases and may be used as an assessment criterion for defining the portal hypertension stage.     

The binding of receptor-recognized alpha2-macroglobulin to the low density lipoprotein receptor-related protein and the alpha2M signaling receptor is decoupled by oxidation

Receptor-recognized forms of alpha2-macroglobulin (alpha2M*) bind to two classes of cellular receptors, a high affinity site comprising approximately 1500 sites/cell and a lower affinity site comprising about 60,000 sites/cell. The latter class has been identified as the so-called low density lipoprotein receptor-related protein (LRP). Ligation of receptors distinct from LRP activates cell signaling pathways. Strong circumstantial evidence suggests that the high affinity binding sites are responsible for cell signaling induced by alpha2M*. Using sodium hypochlorite, a powerful oxidant produced by the H2O2-myeloperoxidase-Cl- system, we now demonstrate that binding to the high affinity sites correlates directly with activation of the signaling cascade. Oxidation of alpha2M* using 200 microM hypochlorite completely abolishes its binding to LRP without affecting its ability to activate the macrophage signaling cascade. Scatchard analysis shows binding to a single class of high affinity sites (Kd - 71 +/- 12 pM). Surprisingly, oxidation of native alpha2-macroglobulin (alpha2M) with 125 microM hypochlorite results in the exposure of its receptor-binding site to LRP, but the ligand is unable to induce cell signaling. Scatchard analysis shows binding to a single class of lower affinity sites (Kd - 0.7 +/- 0.15 nM). Oxidation of a cloned and expressed carboxyl-terminal 20-kDa fragment of alpha2M (RBF), which is capable of binding to both LRP and the signaling receptor, results in no significant change in its binding Kd, supporting our earlier finding that the oxidation-sensitive site is predominantly outside of RBF. Attempts to understand the mechanism responsible for the selective exposure of LRP-binding sites in oxidized native alpha2M suggest that partial protein unfolding may be the most likely mechanism. These studies provide strong evidence that the high affinity sites (Kd - 71 pM) are the alpha2M* signaling receptor.     

Effect of CYP2D1 inhibition on the behavioural effects of d-amphetamine

In rats, amphetamine (AMP) conversion to 4-OH-AMP is metabolized by CYP2D1, the rat equivalent of the human enzyme CYP2D6. To determine the impact of impaired AMP metabolism on its behavioural effects, AMP-induced hyperactivity, AMP discrimination and AMP self-administration were examined in male Wistar rats with or without pretreatment with the CYP2D1 inhibitors quinine and budipine. In vivo, quinine (20 mg/kg) and budipine (10 mg/kg) increased the plasma area under the curve of AMP 4-fold and 3.6-fold respectively, and decreased the plasma levels of 4-OH-AMP, 3-fold and 8.6-fold, confirming that the doses used suppressed CYP2D1 activity. Both inhibitors prolonged AMP-induced hyperactivity (0.3 mg/kg) and prolonged the duration of AMP-appropriate responding for periods of up to 90 min post-AMP administration in a drug discrimination procedure. In rats given a preload dose of AMP (0.8 mg/kg) 3 h prior to the self-administration test session, CYP2D1 inhibition resulted in fewer AMP infusions being taken compared with rats receiving the AMP preload dose alone. These studies indicate that AMP is responsible for the behavioural effects seen in rats and that a rat phenocopy model of the human CYP2D6 deficiency state can be produced by CYP2D1 inhibitors.     

Effects of hydrogen sulfide containing gas condensate on the hepatic microsomal monooxygenase system]

Chronic action of different xenobiotics which form a part of condensed hydrogen sulphide-containing gas causes substantial changes in the activity of xenobiotic metabolic enzymes, which is suggestive of the damaged hepatic microsomal monooxygenase system. As the rate of biotransformation becomes higher, there are increases in the activity of microsomal monooxygenases and in the generation of active oxygen forms and hydrogen peroxide, by impairing antiradical and antiperoxide mechanisms. The experimentally used concentration of substances as constituents of condensed gas corresponds to the maximum acceptable air concentration of in the working area of gas-refining plants, but the functional features of the body's detoxifying system--the hepatic monooxygenase system should be taken into account while developing preventive measures of occupational diseases.     

Sex differences in olfactory identification and Wisconsin Card Sorting performance in schizophrenia: relationship to attention and verbal ability

We investigated the hypothesis that different prefrontal brain systems (i.e., dorsal vs. ventral) and sex contribute differentially to cognitive deficit in schizophrenia. Performance was assessed among clinically stable, chronic schizophrenic outpatients and matched normal control subjects on olfactory identification [on the University of Pennsylvania Smell Identification Test (UPSIT)] and on executive functions [using the Wisconsin Card Sorting Test (WCST)]. Patients were impaired on both tests compared to controls, and male schizophrenics were impaired on the WCST compared to female schizophrenics. The pattern of results suggests that gender differences on the UPSIT are mildly accentuated in schizophrenia. The data support our previous study indicating that UPSIT performance is largely independent of the executive or attentional deficits typically associated with schizophrenia, with the exception of verbal ability. Further research with larger samples is required to test the hypothesis that there is a severely impaired subgroup of male patients with diffuse prefrontal dysfunctions.     

Undergraduate nursing students' perceptions of their clinical learning environment

The clinical learning environment (CLE) is an interactive network of forces influencing student learning outcomes in the clinical setting. This study used mixed methods to identify factors characterizing students' perceptions of the CLE. The sample consisted of 229 undergraduate students in the second or third year of their biophysical nursing strand. The five subscales of the Clinical Learning Environment Scale, 'staff-student relationships', 'nurse manager commitment', 'patient relationships', 'student satisfaction' and 'hierarchy and ritual', were supported by qualitative data obtained from student interviews. Interpersonal relationships between the participants in the CLE were crucial to the development of a positive learning environment. Student satisfaction with the CLE was both a result of, and influential in creating, a positive learning environment. Nurse educators, clinical venues, and all others participating in the undergraduate nursing students' clinical education, must collaborate in order to create a CLE which promotes the development of well-educated registered nurses capable of providing safe, cost-effective patient care.