Endothelium-dependent effect of perindopril and enalaprilat in rat thoracic aorta

AIM: To study the effect of the angiotensin-converting enzyme (ACE) inhibitors perindopril (Per) and enalaprilat (Ena) on the reactivity of the endothelium in normal rats. METHODS: Male rats were treated intragastrically with Per (2 mg.kg-1.d-1) or placebo (n = 18) for 6 wk. Aorta was isolated for experiment. Another set of isolated aortic rings with and without endothelium were incubated with Ena (0.1 mumol.L-1) for 30 min. Responses to acetylcholine, serotonin, phenylephrine, sodium nitroprusside (SN), and nitroglycerin (Nit) were observed. RESULTS: Endothelium-dependent relaxation to acetylcholine was augmented in aortic rings from rats treated with Per in comparison with control. The IC50 value (95% confidence limits) decreased from 3.8 (0.56-26.1) mumol.L-1 (control group) to 0.98 (0.28-3.41) mumol.L-1 (Per-treated group). The maximal relaxation was augmented from 62 +/- 9% to 78 +/- 10% (P < 0.01). However, the responses to the endothelium-independent vasodilators, SN and Nit, were similar. Serotonin- and phenylephrine-induced contractions were decreased, which were influenced by basal release of endothelium-derived relaxing factor (EDRF). EC50 values was 6.1 (2.6-14.4) nmol.L-1 vs 8.3 (3.6-18.8) nmol.L-1 in comparison with control group and Per-treated group. The maximal contraction was decreased from 2.42 +/- 0.29 g (control group) to 1.96 +/- 0.25 g (treated group) (P < 0.01). Similar results were found in incubation with Ena. CONCLUSION: Ena and Per enhanced the basic release of EDRF from vascular endothelium.     

Using two factor structures of the Mental Adjustment to Cancer (MAC) scale for assessing adaptation to breast cancer

The validity and reliability of two factor structures of the Mental Adjustment to Cancer (MAC) scale for assessing coping style was assessed by examining the relationship between the subscales, psychological distress, and quality of life (QOL) among Stage II and Stage IV breast cancer patients in four phases. First, MANOVAs assessed differences in coping, distress, and QOL across disease stages. Second, for each MAC factor structure, canonical correlation analyses assessed the relationship between coping styles, distress, and QOL, for each disease-stage group separately. Third, structural equation modeling (SEM) assessed the relationship among coping styles, distress, and QOL for all participants. Finally, the internal consistency of both MAC factor structures was assessed using Chronbach's alpha. The results were as follows: (1) significant differences across disease stages were found for coping styles using either the Watson or the Schwartz MAC subscales, but there were no differences in levels of distress or QOL; (2) for both MAC factor structures, coping style was found to be highly related to emotional distress and QOL, however, the strengths of the correlations between individual coping styles and distress/QOL indicators varied across disease stages; (3) SEM indicated that coping style was significantly related to distress and QOL when stage of disease was not considered, and that coping style and indicators of distress/QOL are separate, but highly correlated factors, as opposed to a single latent construct; and, (4) the Watson MAC subscales showed slightly better internal consistency than the Schwartz MAC subscales. Taken together, these findings highlight: (i) the validity of both MAC factor structures for clinical and research use with American breast cancer patients; (ii) the role of coping style as a mediator between disease stage and psychological distress and QOL; and, (iii) the need for refinement of certain Watson and Schwartz subscales.     

Defaults in stereoscopic and kinetic depth perception

This study presents three findings concerning the mechanisms of depth perception. First, the shape of the three-dimensional percept evoked by two-frame motion is defined solely by the rotation component around an axis in the frontoparallel plane; the visual system assigns a default value to this rotation component to arrive at a unique solution. Second, when the visual axes of two eyes are almost parallel, the visual system uses a default vergence value to reconstruct stereoscopic depth. Third, the default vergence and default rotation angles are highly correlated across subjects. This correlation implies that the two modalities share a common scaling default at an internal level.     

Multifrequency tympanometry in chinchillas

Multifrequency tympanometry (MFT), using probe frequencies ranging from 226-2,000 Hz, was performed on normal chinchillas to obtain normative data against which to compare results from animals with middle ear pathology. A series of validating experiments was conducted to determine the effects of anatomical alterations of the middle ear on MFT. These included artificially extending the ear canal, opening the bulla, injecting saline into the middle ear, and disrupting the ossicular chain. The results indicate that MFT characteristics of chinchilla ears are qualitatively similar to those observed in normal humans and patients with middle ear disease, and MFT provides information that is not available from the 226-Hz tympanogram.     

Rolandic type cerebral palsy in children as a pattern of hypoxic-ischemic injury in the full-term neonate

Magnetic resonance images (MRIs) of the brains of 11 patients aged from 1 week to 12 years with a distinctive type of cerebral palsy were selected based on distribution of cerebral lesions, which were restricted to bilateral perirolandic cortical and subcortical regions, including frequent symmetric involvement of basal ganglia and ventrolateral nucleus of thalami. Retrospectively, the perinatal history and clinical features were reviewed to correlate clinical data with this distinctive pattern of brain injury. Clinically affected neonates had an encephalopathy associated with a severe perinatal asphyxial event. Older children with cerebral palsy survived a similar perinatal course and demonstrated spastic quadriparesis with bulbar or pseudobulbar involvement, lack of verbal speech and variable delays in cognitive development. The distribution of hypoxic-ischemic lesions involving bilateral perirolandic regions, basal ganglia, and thalami, appears to correlate with increased metabolic areas of primary myelination in full-term neonates, but not with arterial border zones nor a single cerebral artery distribution. Myelination is a critical process in maturing brain associated with marked increase in tissue respiration and thus greater susceptibility to oxygen deprivation. It is believed that the extent of hypoxic-ischemic brain injury is determined principally by brain maturity and regional metabolic rates at time of insult and this correlates with active myelination in full-term neonates. This study confirms previous data from neuropathologic literature and recent reports of neuroimaging studies of asphyxiated neonates. In addition, retrospective analysis of the clinical data enables recognition of a type of cerebral palsy that might be the hallmark of hypoxic-ischemic injury in term neonates.     

Exploring structure-activity relationships around the phosphomannose isomerase inhibitor AF14049 via combinatorial synthesis

Phosphomannose Isomerase (PMI) has been shown by genetic methods to be an essential enzyme in fungal cell wall biosynthesis. The PMI inhibitor AF14049 was discovered as an unanticipated side product from high-throughput library screening against the enzyme from C, albicans. Solid-phase synthetic methods were developed and a series of libraries and discrete analogs synthesized to explore SAR around AF14049.     

Transforming the cell surface through proteolysis

Protein shedding, or the proteolytic cleavage of a protein from the surface of a cell, is emerging as an important mechanism in the regulation of cellular activity but it is poorly understood. Growing evidence suggesting that protein shedding and protein function are closely linked may lead to new strategies for the treatment of a wide range of diseases.