Alpha 1-adrenergic receptors in the brain: characterization in astrocytic glial cultures and comparison with neuronal cultures.

Binding of [125I]HEAT to membranes prepared from primary cultures of astrocytic glial cells was time-dependent and 70-85% specific. Various adrenergic agonists and antagonists competed for [125I]HEAT binding according to the potencies of prazosin greater than, yohimbine greater than or equal to, clonidine, norepinephrine (NE), and propranolol. Scatchard analysis showed the Bmax of 209 fmol/mg protein and a Kd of 184 pM for [125I]HEAT binding by astrocytic glial membranes. Pretreatment of astrocytes with NE resulted in a dose-dependent downregulation of [125I]HEAT binding sites with a maximal response observed after 8 h at 100 microM NE. Removal of NE from cultures after pretreatment resulted in a time- and protein synthesis-dependent recovery of binding sites to control levels within 120 h. Incubation of astrocytic glial cultures with NE stimulated phosphoinositide (PI) hydrolysis in a time- and dose-dependent manner with a maximal stimulation of 2-fold observed in 60 min by 100 microM NE. Clonidine expressed differential effects on alpha 1-adrenergic receptors of the neuronal and astrocytic glial cultures. Pretreatment with 10 microM clonidine caused a 40% decrease in the Bmax of [125I]HEAT binding without influencing the Kd value in neuronal cultures. This downregulatory effect of clonidine was associated with a reduction in the ability of NE to stimulate PI hydrolysis in clonidine pretreated cells. In contrast to neuronal cultures, clonidine neither downregulated [125I]HEAT binding sites nor stimulated PI hydrolysis in glial cultures.

On the pathogenesis and therapy of dementia of the Alzheimer type: some neuropathological, biochemical, genetic and pharmacotherapeutic considerations.

The extensive literature on dementia of Alzheimer type (DAT) testifies to the enormous progress achieved in the clinical and biochemical delineation of this disease. Newly developed laboratory and imaging techniques are also being applied to the diagnosis of DAT. Nevertheless, unequivoval diagnosis still relies primarily on morphological data from biopsy or autopsy. An overview is presented of major morphological changes occurring at different levels of organization in the central nervous system (CNS) in DAT. Currently formulated etiopathogenic hypotheses of DAT are reviewed and discussed in the context of morphological alterations. Some of the recombinant DNA methods, that are currently available for gene analysis, are described. Some approaches for studying Alzheimer specific genes using the above methods have been suggested. Finally, a critical overview of the current pharmacotherapeutic armamentarium used in DAT and senile dementia is presented. The efficacy, side effects, and the main mechanisms of action of the two categories of drug therapy -supposed etiopathogenic and symptomatic- are presented.

Isolation and purification of rat liver morphine UDP-glucuronosyltransferase.

A UDP-glucuronosyltransferase (UDPGT) isoenzyme capable of morphine glucuronidation has been purified to apparent homogeneity and partially characterized from hepatic microsomes of female Wistar rats which have low 3 alpha-hydroxysteroid UDPGT. A rapid and sensitive assay was developed to quantify morphine glucuronide formation using 14C-UDP-glucuronic acid and reverse phase C-18 minicolumns whereby radioactive glucuronides were differentially eluted from 14C-UDP-glucuronic acid. Trisacryl-DEAE and chromatofocusing chromatographic procedures were employed to separate and purify morphine UDPGT in the presence of exogenous phosphatidylcholine. The addition of phospholipid was necessary to stabilize UDPGT activities throughout the purification procedures. Morphine UDPGT was isolated to apparent homogeneity and displayed a pl of 7.9 upon chromatofocusing. A monomeric molecular weight of 56,000 was obtained. The purified enzyme reacted with morphine but not with 4-hydroxybiphenyl, p-nitrophenol, testosterone, androsterone, estrone, bilirubin, 4-aminobiphenyl, or alpha-naphthylamine. The MgCl2 requirement for maximal expression of morphine glucuronidation was higher for the purified enzyme than for solubilized and intact microsomes. Codeine competitively inhibits morphine glucuronidation with an apparent Ki of 1.1 mM with the purified morphine UDPGT. 4-Hydroxybiphenyl UDPGT was separated from morphine UDPGT using a chromatofocusing procedure for Emulgen 911-solubilized microsomes. An apparent pl value of 5.5 was obtained for this protein. Based on this work we conclude that morphine and 4-hydroxybiphenyl can react with separate UDPGT isoforms.

Leptomeningeal cysts after spot freezing: transmission and scanning electron microscopic observations.

The sequential development of the early phases of leptomeningeal cyst formation was studied in an experimental model. Light, transmission and scanning electron microscopic data were compared with those from human arachnoid cysts. Common features observed were: the participation of leptomeningeal cells in the structure of the cysts with exclusion of dural components; the absence of internal traversing trabeculae; the hyperplasia of leptomeningeal cells, particularly in the dome of the cysts. Other features of the experimental cysts were: the splitting of the pio-arachnoid membrane; the scarcity of collagen at the early stages; the presence of areas of mineralization at more advanced stages; the presence of remodeling parenchymal changes at the underlying nervous tissue.

[Brain aging. Ultrastructural study of changes in man and laboratory animals]. / Envejecimiento cerebral. Estudio ultraestructural de algunas alteraciones en el hombre y en el animal de laboratorio.

The authors present a study on ultrastructural changes observed in aged human and animal brain. These changes are analyzed and compared with those described in classic optic microscopy and with those observed in experimental models of the same lesions.

[Pathology of cerebral edema. I. Concept, etiopathogenesis and classification]. / Patología del edema cerebral. I. Concepto, etiopatogenia y clasificación.

Taking into account its complex pathogenesis, we stress the inadequacy of considering brain edema as a single clinical or pathological entity. Vasogenic, cytotoxic and hydrocephalic varieties are considered. Some clinical conditions underlied by the common morphologic feature of "status spongiosus" are discussed. The methods of investigation of brain edema are presented as well as problems concerning its diffusion and resolution.

[Pathology of cerebral edema. II. Experimental models and modifying agents]. / Patología del edema cerebral. II. Modelos experimentales y agentes modificadores.

Current experimental models of brain edema are described and evaluated for their contribution to the knowledge of basic processes involved in its production as well their contribution to the understanding of different clinical forms. The participation of each main pathogenic mechanism in a given experimental model is analyzed and proves to vary with each particular model and site studied. The importance of various experimental models in the evaluation of different therapeutic procedures directed to control the genesis and evolution of brain edema is stressed.

Metallic deposition in specimens presenting cavities using the sputter coater.

Local charging effects in small biological cavities during SEM observation are apparent, even after sputter coating. Using an experimental model, the thickness of metallic coating at the bottom of cylindrical cavities has been measured and found to be less than 50% the thickness on the surface, depending on the relation of diameter to depth of the cylinder.

Solitary abscess in rat brain: light and electron microscopy observations.

The authors describe the histological and ultrastructural features of a well demarcated single abscess. Histopathological features are consistent with those observed in experimental models and human material. In addition this study allowed the ultrastructural definition of some of the capsule components as meningothelial-like structures and myofibroblasts. Their possible role in the evolution of the lesion is discussed.

[Ultrastructural semiology of lesions of striated muscle]. / Semiologia ultraestructural de las lesiones del músculo estriado.

Basic changes of the striated muscle fiber are described after the electron microscopy study of 200 surgical muscle biopsies from the Montevideo Neurological Institute. The inventory of these changes--true ultrastructural "signs" of muscle derangement--is presented according to the involved organelle. The value of these data is considerably enhanced by a systematic approach to the study of a muscle biopsy that should begin with the in situ examination of the muscle territory before the excision of the tissue. A throroughful histopathological study and a careful screening of semithin sections previous to the selection of areas for E.M. are also of paramount importance. The description of individual fiber lesions and that of the topography of the lesions should be accompanied by the study of vessels. nerves and muscle spindles. We stress that most of the ultrastructural findings are nonspecific. They will however acquire diagnostic value and greater interest when grouped and related to the clinical data and to the results of other diagnostic methods, besides morphology.