Reperfusion Adjunctive Therapy: Platelet Active Agents

Changes in a coronary artery thrombus resulting from platelet activation may affect the speed of thrombolysis and the frequency of reocdusion after thrombolytic therapy. In studies performed in canine models, we have found that selected thromboxane and serotonin receptor antagonists given in combination markedly enhance the thrombolytic effect of tissue plasminogen activator, probably by preventing further platelet activation and their incorporation into a thrombus during thrombolytic therapy. The combination of a thromboxane and serotonin receptor antagonist given with heparin and tissue plasminogen activator is effective in delaying or preventing reocdusion after discontinuation of tissue plasminogen activation in experimental canine models in whom coronary artery thrombosis has been induced by an indwelling copper coil.     

Side reactions in solid phase synthesis of histidine-containing peptides

The flow-polyamide synthesis of a histidine-containing sequence (Ac-YDNVLDHLTGR) produced two major impurities which were isolated through Sample Displacement Chromatography and characterized by Fast Atom Bombardment-mass analysis. The impurities correspond to the sequence Ac-YDNVLDH, and to a peptide with the Asp residue cyclized to a succinimide. The latter side-reaction took place during the acetylation procedure, and demands attention where capping procedures are planned in the synthesis of Asp-His sequences.     

Modification of the Dissolution Behaviour of a Water-insoluble Drug,Naftazone, for Zero-order Release Matrix Preparation*

Abstract— The preparation of hydrophilic matrix tablets able to release naftazone, a water-insoluble drug, into an aqueous medium at a constant rate (zero-order dissolution) is described. Enhancement of dissolution rate of the drug was achieved using cross-linked carmellose sodium, β-cyclodextrin or hydroxypropyl-β-cyclodextrin. Hypromellose was used as a water-gelling polymer. Tablets could be prepared that released naftazone at a constant rate over 16 h.     

IMMUNOHISTOCHEMICAL STUDY ON THE PATTERN OF 50 KD CYTOKERATIN IN PSORIASIS

Three biopsies of normal skin and 15 biopsies collected from patients with psoriasis vulgaris were analyzed for the expression of the 50 kd cytokeratin using direct immunofluorescence and ABC technique before and after local treatment with anthralin 0.1% in a petrolatum base, with 0.05% betamethasone dipropionate cream, and finally, after PUVA treatment. Antiserum against the 50 kd anti-cytokeratin reacted with tissue sections of normal skin, staining cells in the basal layer, while the psoriatic skin sections before the various treatments showed a staining concerning the whole thickness of the epidermis. After the various therapies, the 50 kd cytokeratin immunoreactivity was observed only in the basal layer of those psoriatic skin sections that showed complete clinical clearing, while it was observed in the whole thickness of psoriatic patches that did not clear. These data suggest that the normalization of the 50 kd cytokeratin expression pattern can be considered as a marker of clinical remission of psoriasis.     

Neurotensin-like immunoreactivity in the brain of the chicken, Gallus domesticus

The distribution of neurons containing neurotensin in the central nervous system of the chicken was studied immunohistochemically. The majority of the neurotensin-immunoreactive (-ir) cell bodies were located in the hypothalamus. Extensive groups of labelled perikarya were found in the hypothalamic periventricular nucleus and in the magnocellular periventricular nucleus. In addition, ir-perikarya were scattered throughout the lateral hypothalamic area and in the ventromedial hypothalamic nucleus. The only extrahypothalamic site of ir-perikarya was in the region immediately under the lateral forebrain bundle. Immunoreactive fibres were detected in the hippocampus, the parahippocampal area, the hypothalamus, the region of the tractus corticohabenular and corticoseptal tracts, the median eminence, the region above the posterior commissure and in the intercollicular nucleus. The distribution pattern of the neurotensin-ir neurons suggests that neurotensin-like peptides are involved in the hypophysiotropic functions.     

Continuous epidural block for pain control in bladder exstrophy: report of a case and description of technique

We describe in a neonate an unusual epidural technique for pain control after the surgical correction of bladder exstrophy.     

EFFECTS OF ALLOPURINOL ON STRIATAL DOPAMINE, ASCORBATE AND URIC ACID DURING AN ACUTE MORPHINE CHALLENGE: EX VIVO AND IN VIVO STUDIES

In the present studyin vivoandex vivoexperiments were combined to evaluate the effects of allopurinol on the neurochemical changes induced by an acute morphine challenge (2 mg kg⁻¹, s.c.). In samples from rat striatum, levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), ascorbate (AA), dehydroascorbate (DHAA), hypoxanthine, xanthine and uric acid (UA) were measured. Brain microdialysis experiments were carried out in freely moving rats. Striatal dialysate levels were assayed for DA, DOPAC+HVA, AA and UA using liquid chromatography followed by electrochemical detection. Morphine administration increased the striatal levels of DA metabolites, UA and DHAA and the extracellular concentrations of DA, DOPAC+HVA, UA and AA. Allopurinol (50 mg kg⁻¹by gavage), an inhibitor of xanthine oxidase which catalyses oxidation of xanthine to UA, decreased basal UA and AA concentrations and the morphine-induced increase in DA metabolites and AA oxidation. Since oxidation of DA and xanthines generates reactive oxygen species (ROS) and AA and UA are the main cellular antioxidants, these findings suggest that: (a) single morphine administration increases DA and xanthine oxidative metabolism with a consequent increase in ROS production, which may account for changes in concentrations of extracellular AA and tissue DHAA; (b) allopurinol decreases morphine-induced DA and xanthine oxidation; (c) UA and AA may act in concert to regulate levels of ROS in the brain.     

Rate-Responsive Pacing: Biosensor Reliability and Physiological Sensitivity

Various sensor systems that indicate the hypermetabolic state have been used to provide input signals for controlling rate responsive pacing systems. The sensitivity of an indicator may be related directly or indirectly to metabolic requirements. Metabolic, respiratory, and cardiac dynamics during exercise have been described. Direct measurement of oxygen consumption provides the best index of work rate and exercise capacity. In pacemaker-dependent patients, heart rate is not an independent variable. During exercise, changes in pacing rate and hemodynamics do not show the specificity of a rate-responsive system, but are the result of a combination of sensor response and electronic or signal processing. Following the general patterns of change in various measurable parameters during exercise with progressively increasing work rates, the hypermetabolic indicators have been categorized into five groups according to the accuracy of their relationship to oxygen consumption. The indicators that are used or proposed as sensors for the regulation of rate-responsive systems are described. Sensor sensitivity, specificity, reliability, and physiologic sensitivity are defined and discussed with the single rate-responsive system in clinical or experimental use.     

Liver transplantation in man: morphometric analysis of the parenchymal alterations following cold ischaemia and warm ischaemia/reperfusion

Ischaemia and reperfusion phases represent critical events during liver transplantation. The purpose of this study was to describe morphological alterations of both vascular and parenchymal compartments after ischaemia and reperfusion and to evaluate the possible relationship between morphometric parameters and biochemical/clinical data. Three needle biopsies were drawn from 20 patients who underwent orthotopic liver transplantation. The first biopsy was taken before flushing with preservation solution, and the second and the third to evaluate respectively the effects of cold ischaemia and of warm ischaemia/reperfusion. Biopsies were examined by an image analyser and morphometric parameters related to the liver parenchyma were evaluated. At the second biopsy we observed a decrease of the endothelium volume fraction while the same parameter referred to the sinusoidal lumen achieved a peak value. The hepatocytes showed a lower surface parenchymal/vascular sides ratio. This parameter was reversed at the end of the reperfusion phase; furthermore the third biopsy revealed endothelial swelling and a decreased volume fraction of the sinusoidal lumen. The results quantify the damage to the sinusoidal bed which, as already known, is one of the main targets of cold ischaemia; warm ischaemia and reperfusion accentuate endothelial damage. The end of transplantation is characterised by damage chiefly to parenchymal cells. Hepatocytes show a rearrangement of their surface sides, probably related to the alterations of the sinusoidal bed. In addition, the fluctuations of morphometric parameters during ischaemia/reperfusion correlate positively with biochemical data and clinical course of the patients.