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Rabbits given 1 ppm of vanadate in drinking water for twelve months showed (a) increased plasma levels of catecholamines (b) reduction of the arterial concentration of nitric oxide (c) lower activity of urine kallikrein and higher activities of urine kininases I and II and enkephalinase (d) reduced cardiac inotropism and augmented total peripheral resistance, with unchanged blood pressure levels (e) accumulation of the metal in the aorta and cardiac ventricles. Monoaminooxidase and glucose-6-phosphate dehydrogenase activities were increased by vanadate in both kidney and liver and that of NADH-diaphorase in the kidney, in which NADPH-diaphorase activity was reduced. Some of the above results were also obtained in rats given 10 and 40 ppm of vanadate in drinking water for six-seven months; these animals showed arterial hypertension and reduced activity of Na, K-ATPase in the kidney. Vanadium appears to act on the cardiovascular function through selective neurohumoral, autacoidal and transductional mechanisms only in part depending on the species.

The effects of 1 microgram/mL of vanadium, given for 12 mo as sodium metavanadate in drinking water, on cardiovascular and biochemical indices of male rabbits were investigated. At the end of the exposure period, vanadium was more accumulated in bones and kidneys than in spleen and liver; the cardiac ventricles and the aorta contained similar amounts of this element. Blood pressure and heart rate were unchanged in the vanadate-exposed animals since the observed decrease of both cardiac inotropism and stroke volume was counteracted by an increase of peripheral vascular resistance, with reduction of arterial blood flow. The arterial levels of sodium, potassium and aldosterone were unmodified by vanadate which, however, strongly raised those of noradrenaline, adrenaline, L-DOPA, and dopamine. Vanadate caused a marked increase of the activity of monoamine oxidase in renal tubules and liver (probably in relation to the increased plasma catecholamine levels) and a reduction of that of glucose-6-phosphate dehydrogenase in the kidney. There was also evidence that vanadium reduces synthesis and/or release of nitric oxide, the endothelium-derived vasodilating factor, likely through a reduced formation from bradykinin. It was concluded that vanadium may represent an environmental factor of altered cardiovascular homeostasis.

Interleukin-1, a soluble polypeptide, plays an important role in inflammatory reactions by increasing prostaglandin E2 (PGE2) generation. Human recombinant IL-1 receptor antagonist (hrIL-1ra) is a natural inhibitor of IL-1 which blocks its activity in several inflammatory states. In these studies we found that hrIL-1ra (250 mg/ml) inhibits the generation of PGE2, as measured by RIA method, in minced mouse granuloma tissue (700 mg) treated overnight with LPS (10-1000 ng/ml) or hrIL-1 beta (0.1-10 ng/ml). In addition, we show that hrIL-1ra (250 ng/ml) strongly inhibited IL-1 alpha and IL-1 beta, as measured by ELISA method, in the minced granuloma tissue treated overnight with LPS 1 micrograms/ml or IL-1 beta (10 ng/ml). The granuloma tissue induced in mice by a dorsal subcutaneous injection (0.2 ml) of a saturated solution (1:40 dilution) of KMnO4 crystals, presented an alkaline phosphatase activity which was not inhibited by two intraperitoneal administrations of hrIL-1ra 20 micrograms/200 ml bolus injections (given at the same time as KMnO4 injection and one 24 h later). These results show for the first time that hrIL-1ra blocks PGE2, IL-1 alpha and IL-1 beta but not alkaline phosphatase activity, which is a marker in growing bone and in calcific and inflamed tissue.

Male weanling Wistar rats received 200 micrograms/ml of mercury (Hg), as HgCl2, in drinking water for 180 days. At the end of the treatment, systemic arterial blood pressure was augmented, cardiac inotropism was reduced, and heart rate was unchanged. Light and electron microscopical studies of the kidney showed a mesangial proliferative glomerulonephritis in about 80% of the glomeruli. Tubular cells showed reduction of the acid phosphatase activity, which was related to functional abnormalities of the lysosomes. In the 24 hour urine samples of the Hg exposed rats, there was slight reduction of kallikrein activity, but evident proteinuria was not present in all samples. Plasma renin activity was reduced, that of angiotensin I-converting enzyme was augmented, and plasma aldosterone concentrations were unchanged. Mercury was accumulated mostly in the kidney of the Hg treated animals; and the content of Hg in the heart was higher than in the brain. These data show that chronic exposure to Hg acts on the kidney with complex mechanisms of toxicity; these contribute to modify systemic haemodynamics.

Glutathione transferase (GST) activity in the cytosolic fractions of renal cortex tumour was found to be significantly lower (215 +/- 156 mU/mg) than that present in the corresponding non-tumour (466 +/- 278 mU/mg) tissues. Using the immunoblotting technique, glutathione transferase isoenzymes expression in both tumour and non-tumour kidney was investigated. Alpha and pi class glutathione transferases were the most abundant enzymes in non-tumour kidney and were expressed by all samples investigated. Immunofluorescence analysis indicated that the pi class enzymes are localized mainly in the distal convoluted tubules, whereas alpha class enzymes are localized in the proximal tubules. In the tumour moiety the alpha class GST appears to be absent or expressed at low level as compared with non-tumour samples. On the contrary, no significant differences in the expression of pi class GST were found in tumour as compared with non-tumour tissues. Mu class GST protein was detected in 12 of 26 samples tested. When present, mu class GST constitutes a few per cent of total GST protein. Immunofluorescence studies indicate that mu class GSTs are localized within the distal convoluted tubules. According to the electrophoretic mobility at least two different mu GST subunits (26.5 and 27.5 kd) were found. In one sample only the faster mu class GST subunit was present, two samples expressed both types of GST subunits, whereas nine samples expressed only the slower GST subunit. With the exception of one sample, a reduction of mu class GST expression was seen in tumour as compared with non-tumour tissues. The decrease of activity seen in the cytosolic fraction of tumour kidney must be ascribed mainly to a reduction or to a lack of expression of alpha class GST and to a lesser extent of mu class GST.

The effect to paraquat in normobaric conditions and hyperbaric conditions with either a normal or low (10%) oxygen percentage was investigated in rats. Results showed that hyperbaric conditions increased the toxic effect of paraquat on the lung. By contrast, in hypoxic-hyperbaric conditions, the toxic effect of paraquat was decreased either clinically or macro-/microscopically, and lung injury was reduced.

In this study we report the effect of Vit. E, as an immunostimulating factor, on the induction of Experimental Allergic Encephalomyelitis in Lewis rat. The animals were inoculated intracutaneously in the plantar areas with emulsion of isologous spinal cord suspensed in Incomplete Freund's Adjuvant (IFI) and Vit. E. Histologic examination revealed the basic lesion of a perivenous cuff of mononuclear cells and small areas of demyelinated axons. The clinical signes are graded in order to the time of induction. It is possible an action of "adjuvanticity" of Vit. E on the various cells involved in the immune response by cell transformation and moltiplication.

We report the cytogenetic data of two patients with erythroleukemia showing the chromosome Ph'. In one case the chromosome Ph', as revealed with the GTG band technique was the result of a translocation involving the chromosomes 19 and 22. The aim of this work is to provide more contribution to the knowledge of the origin of the Ph' and to give data in the field of this disease for which few cytogenetic data are available after the introduction of the banding techniques.

One case of Chronic Granulocytic Leukemia is reported, in which the patient showed, during a blastic crisis, an aneupolid cariotype 45, XX, t (9; 22) (q34; q11), -16. This paper emphasizes the rare involvement of the chromosome 16 in Leukemias, and stresses the high frequency of the alterations of the chromosome group E in the course of blastic crisis.

Negatively charged phosphatidylserine vesicles increase RNA polymerase activity of isolated rat liver nuclei, whereas inhibition is obtained with sphingomyelin, phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol vesicles. The effect of phosphatidylserine on template activity is dose-dependent and similar to that reported for acidic polymers like heparin. These data indicate that the nature of the polar head is mainly responsible for the different effects and suggest that the phospholipids may be involved in mediating gene expression.

By using affinity chromatography and isoelectric focusing techniques, several forms of glutathione transferase (GSTs) were resolved from human testis obtained from patients operated on for malignant diseases. Large interindividual variations in the expression of different isoenzymes resulted in the samples investigated. Five out of six samples analysed expressed GST-4.4 that resulted in being structurally and immunologically identical to GST-pi (class Pi). All the cationic GSTs of human testis, except for GST-8.36, GST-9.1 and GST-10.1, are homodimers of 24,500 Mr subunit and cross reacted with antisera raised against class Alpha GST. Some of the forms isolated (GST-3.8, GST-8.36, GST-9.1 and GST-10.1) can not apparently be related to any of GSTs so far characterized in other human tissues. Upon SDS/polyacrylamide gel electrophoresis, GST-8.36 and GST-9.1 appeared to be heterodimers of 24,500 and 26,500 Mr subunits and were found only in the testis seminoma suggesting that they might be tumour specific isoenzymes. GST-3.8 appeared to be formed by heterodimers of 23,000 and 26,500 Mr subunits whereas, GST-10.1 was found to be dimers of 22,000 and 24,500 Mr subunits. In addition, the results of immunohistochemical studies with antisera raised against both class Pi and Alpha GSTs are reported.

In this we report cytogenetic data concerning two patients with Acute Lymphoblastic Leukemia (ALL), submitted to bone marrow transplantation. In one of two patients the chimere was present while in the other case it was absent, since the donor and the acceptor were of the same sex. However even in the latter case, the cytogenetic analysis was useful and led to the identification of endomitosis and endoreduplication phenomena, which are signs for an unlucky prognosis.

The alterations induced in the lymphoid and epitelial cells of the Bursa of Fabricius in chicks exposed at different doses of gamma rays mainly occur during the interfase. The extent of these alterations appears reduced in comparison with that observed in the chick thymus treated in the same way.

A cooperative study between clinical and cytogenetic steps in 44 patients with Ph'+ CGL is reported in order to verific the usefulness of the cytogenetic screening for the diagnosis and the right classification of the patients. The study of the clinical steps is carried out on the basis of the parameters suggested by Tura and coll.; in the one of the cytogenetic steps Sandberg classification modified by the Authors is adopted. In 40 cases the comparison shows a marrow correspondence between clinical and cytogenetic steps. In fact the overage survival in the classical true steps of the disease is almost the sance in the 1st and 2nd step. In the 3rd step the survival is strongly reduced meaning that the more chromosome alterations are observed the more survival is reduced.

One case of a patient with Chronic Granulocytic Leukemia showing a double Ph' together with trisomy 17 during blastic crisis is reported. The Ph' chromosome resulting from a standard translocation of the chromosomes 9 and 22 was present in all the 16 mitoses observed, while the trisomy 17 was found in 15. This case is an additional contribution which demonstrates the presence of the alterations of the chromosome group E during the blastic crisis.