Prevention of renovascular and cardiac pathophysiological changes in hypertension by angiotensin II type 1 receptor antisense gene therapy

Hypertension produces pathophysiological changes that are often responsible for the mortality associated with the disease. However, it is unclear whether normalizing blood pressure (BP) with conventional therapy is effective in reversing the pathophysiological damage. The duration and initiation of treatment, site of administration, and agent used all appear to influence the reversal of the pathophysiological alterations associated with hypertension. We have previously established that retrovirally mediated delivery of angiotensin II type 1 receptor antisense (AT₁R-AS) attenuates the development of high BP in the spontaneously hypertensive (SH) rat model of human essential hypertension. Our objective was to determine whether this attenuation of high BP is associated with prevention of other pathophysiological changes induced by the hypertensive state. Intracardiac delivery of AT₁R-AS in neonates prevented the development of hypertension in SH rats for at least 120 days. Contractile experiments demonstrated an impaired endothelium-dependent vascular relaxation (acetylcholine) and an enhanced contractile response to vasoactive agents (phenylephrine and KCl) in the SH rat renal vasculature. In addition, the voltage-dependent K⁺ current density, which is believed to contribute to smooth muscle resting membrane potential and basal tone, was decreased in renal resistance artery cells of the SH rat. AT₁R-AS treatment prevented each of these renal vascular alterations. Finally, AT₁R-AS delivery prevented the pathological alterations observed in the SH rat myocardium, including left ventricular hypertrophy, multifocal fibrosis, and perivascular fibrosis. These observations demonstrate that viral-mediated delivery of AT₁R-AS attenuates the development of hypertension on a long term basis, and this is associated with prevention of pathophysiological changes in SH rats.     

Effect of Policosanol on Foam-cell Formation in Carrageenan-induced Granulomas in Rats

Policosanol is a new cholesterol-lowering drug isolated and purified from sugar-cane wax. which prevents the development of lipofundin-induced lesions and foam-cell formation in New Zealand rabbits and Wistar rats. This study was conducted to examine the effects of policosanol on foam-cell formation in carrageenan-induced granulomas in rats. Eighteen Wistar rats were randomly distributed in three experimental groups which received orally for 20 days Tween 20 H₂O as vehicle (control group) or policosanol at 2.5 or 25 mg kg^?1. At the 11th day. lipofundin was injected intrapcritoneally for 8 days to induce formation of foam cells in the granuloma. At day 13, carrageenan was injected subcutaneously for granuloma induction and seven days later animals were killed. A significant reduction of the foam-cell formation in granulomas of policosanol-treated rats was observed. It is concluded that policosanol prevents the development of foam cells in carrageenan-induced granulomas (extravascular medium) in rats.     

The psychiatric management of the globus syndrome

Controversy surrounding the term "globus hystericus" points up the historical dichotomy between organic disease and conversion disorder that has hampered the understanding of this syndrome. Regardless of its sometimes incapacitating nature, there is little information in the literature regarding the treatment of globus when an organic cause cannot be established. Regarding the syndrome as psychosomatic in nature, rather than merely hysterical, we suggest the need for an integrated treatment approach. A case study is utilized to illustrate a model for psychiatric management of the globus syndrome. In this model, pharmacologic and psychotherapeutic interventions are integrated into a comprehensive, biopsychosocial treatment plan. Each aspect of the model is reviewed and discussed.     

A quantitative analysis of the distribution of Purkinje cell axonal collaterals in different zones of the cat's cerebellum: an intracellular HRP study

Summary Purkinje cells in zones a and b of the vermis and zone c in the intermediate cortex of the anterior lobe were intracellularly injected with horseradish peroxidase and the distribution patterns of the varicosities present on their axonal collaterals were quantified and compared at the light microscopic level. The data derived from this study reveal that each individual axonal arbor had a unique pattern of distribution. However, certain principles of distribution could be applied to the collaterals regardless of the cortical location of the parent cell, including the following: 1) the total number of varicosities derived from the axonal collaterals of individual Purkinje cells is relatively uniform; 2) the collateral plexi have a greater extent in the sagittal plane as compared to the transverse plane; 3) the majority of varicosities remain within 200–300 m of the parent cell in both the sagittal and transverse planes; 4) there is a heterogenous distribution of varicosities within the area traversed by the axonal branches; and 5) the majority of varicosities are located within the Purkinje cell layer. Although there were similarities in the pattern of distribution for collaterals, there were also variations which distinguished the plexi in the three zones. The collaterals of zone a cells tended to be the most confined in both the sagittal and transverse planes. In contrast, several cells in zone b and c had branches that extended for relatively long distances in the sagittal plane. In zone b the collaterals have an asymmetric distribution around the cell of origin in the transverse plane. In zones a and c there is a tendency for a more symmetric pattern of distribution in this plane. The similarities in the number and laminar distribution of varicosities, as well as the predominantly sagittal orientation of the collaterals in all zones of the cerebellar cortex suggest that the collaterals subserve a common function throughout the cerebellar cortex. However, variations indicate that there may be subtle differences in the way recurrent collaterals process information in the cerebellar cortex that may be related to the functional heterogeneity or the location of the targets of the collaterals in the three zones analyzed.     

Directed establishment of rat brain cell lines with the phenotypic characteristics of type 1 astrocytes.

Interest in obtaining cell lines for use in studies on the development and biochemistry of the central nervous system has motivated efforts to establish cells from primary brain cultures by the use of oncogene-transfer techniques. In previous reports, cell lines derived from astrocytes in this way have had immature or abnormal phenotypes. We have explored the possibility of specifically "targeting" expression of exogenous oncogenes to differentiated astrocytes by using the promoter of the gene encoding glial fibrillary acidic protein, which is expressed almost exclusively in such cells. We report here that cell lines displaying the phenotypic characteristics of type 1 astrocytes can be established reproducibly in this manner. Given the heterogeneity of primary cultures, the availability of clonal cell lines displaying characteristics of type 1 astrocytes should greatly facilitate our understanding of the biology of these cells.     

HLA and Kaposi''s sarcoma in Sardinia

Twelve Sardinian patients affected by histologically defined classic Kaposi's sarcoma (KS) were HLA-A, B, C and DR typed. Compared to 220 age and ethnically matched healthy controls, KS patients showed a significant increase in HLA-DR5 (66.6 vs 23.1%, P less than 0.001) and a considerable decrease in HLA-DR3 (8.3 vs 53.6%, P = 0.0055). No definite association was observed for other HLA antigens. These results confirm the existence of an HLA associated genetic control of KS susceptibility and support the hypothesis that HLA-DR5 plays the role of a predisposition marker while HLA-DR3 bears a genetic resistance to the disease.     

Bicycle helmet ventilation and comfort angle dependence

Five modern bicycle helmets were studied to elucidate some of the variations in ventilation performance, using both a heated manikin headform and human subjects (n=7). Wind speed and head angle were varied to test their influence on the measured steady-state heat exchange (cooling power) in the skull section of the headform. The cooling power transmitted by the helmets varied from about 60% to over 90% of that of the nude headform, illustrating the range of present manufacturer designs. Angling the head forward by 30° was found to provide better cooling power to the skull (up to 25%) for three of the helmets and almost equal cooling power in the remaining two cases. Comparisons of skull ventilation at these angles with human subjects strongly supported the headform results.