In ischaemia-reperfusion syndromes lipid peroxidation appears an important factor contributing to tissue damage. The 21-aminosteroids (lazaroids) exhibit beneficial effects in various pathological conditions, especially in post-traumatic lesions of the central nervous system, where a peroxidative injury seems to be involved. The aim of our study was to ascertain if one of these compounds, U-74389G, plays a significant role in protecting heart muscle from ischaemia-reperfusion damage. Rat hearts used for heterotopic transplantation represented the experimental model in this investigation. Animals (Wistar rats weighing 200-250 g) were divided into five groups: controls, untreated and treated donors, untreated and treated recipients. Donors were anaesthetized and heparinized, and the heart was excised through a bilateral thoracotomy, arrested with St Thomas solution and stored in cold saline for 2 hours. For the recipient preparation, a modified Ono's technique was used, and heart reimplantation was performed with a termino-lateral aorto-aortic anasthomosis and a termino-lateral pulmonary-cava anasthomosis. After the anasthomoses were completed hearts were reperfused for 30 min; then hearts were excised and specimens were taken for biochemical and morphological studies. These were conducted on three groups of hearts: (A) hearts reimplanted and reperfused without treatment of the donor or of the recipient animal; (B) hearts subjected to the same procedure but in the presence of U-74389G treatment of donors and recipient rats; (C) control hearts rapidly excised from normal, non-operated animals. Electron microscopy studies showed, in hearts transplanted without treatment, the typical morphological aspects of lipoperoxidative injury: swollen mitochondria with disrupted cristae, damaged endothelial cells with the nucleous bulging into the lumen and a discontinued endothelial lining with diffuse oedema among the fibers. Lazaroid treatment attenuated most of these damages in hearts of group B. As for the biochemical findings, the hearts transplanted in the presence of U-74389G treatment had significantly higher ATP and creatine phosphate levels (P < 0.01) and lower malondialdehyde concentrations (P < 0.05) with respect to the hearts transplanted without treatment. Furthermore, serum creatine kinase activity was lower in treated than in untreated recipient animals (P < 0.05). Taken together, all these results indicate that U-74389G treatment is effective in protecting cardiac muscle from structural and functional ischaemia-reperfusion injuries, at least from those arising during a heart transplantation procedure.

Adenosine Triphosphate↗

PubMedDate not supplied

Changes in enzyme levels in human skeletal muscle during obstructive arteriopathy of the lower limbs.

Some enzymatic activities have been assayed in the gastrocnemius muscle of patients with obstructive arteriopathy of the lower limbs. The specific activities of all the examined glycolytic enzymes, of malate dehydrogenase and of glycerol-3-phosphate dehydrogenase are significantly decreased while the specific activities of two lysosomal enzymes, beta-glucuronidase and cathepsin A, are significantly higher than in the controls. Therefore it may be inferred that the metabolic capacity of glycolysis and of Krebs cycle are lowered. On the other hand the increased specific activity of lysosomal enzymes suggests the hypothesis that the above mentioned modifications and the morphologic alterations of the muscle and of the small blood vessels might be ascribed, at least partly, to a release of lysosomal hydrolases in active form.

Adult↗

PubMedDate not supplied

[Lysosomal lesions during a course of acute experimental muscular ischemia. Protective effect of a polypetitide proteinase inhibitor].

Three groups of rabbits were used: a) with acute ischaemia in a rear limb; b) with acute ischaemia in a rear limb and treated with i.v. 100,000 KIU of a proteinase-inhibitor polypeptide extracted from ox lung; c) normal controls. Acute ischaemia was obtained by ligature of the ipsilateral common iliac, external iliac, inferior epigastric and femoral arteries. Soluble and total activity of 3 lysosomal enzymes (cathepsin, acid phosphatase and N-acetyl-glucosaminidase) were determined in gastrocnemius muscle from all 3 groups. The mean ratio between bound and soluble activity for all 3 enzymes in normal gastrocnemius muscle was higher than in ischaemic muscle, but not significantly different from that in ischemic muscle of animals treated with the polypeptide. Furthermore, this ratio in ischemic muscle was significantly lower than that of ischemic muscle of the rabbits treated with the polypeptide. These data suggest that the polypeptide offers protection against lysosomal lesion in the course of experimental ischaemia of the skeletal muscle.

Acetylglucosaminidase↗

PubMedDate not supplied

Reactive oxygen species and antioxidant status in essential arterial hypertension during therapy with dihydropyridine calcium channel antagonists.

PURPOSE: To evaluate reactive oxygen species and antioxidant status in essential arterial hypertension during therapy with dihydropiridine calcium channel antagonists. PATIENTS AND METHODS: Fifteen patients, affected by essential arterial hypertension, were examined. They received once a day oral dihydropyridine calcium antagonists for 10 weeks: five patients received felodipine (5 mg), five amlodipine (10 mg) and five lercanidipine (10 mg). The levels of end products of lipid peroxidation, free radicals and hydroperoxides and total antioxidant capacity were determined in the plasma of all subjects before and during treatment. Values are expressed as mean +/- S.E. Systolic blood pressure decreased from 171 +/- 4 to 135 +/- 6 mmHg (p < 0.01) and diastolic blood pressure decreased from 99 +/- 5 to 82 +/- 3 mmHg (p < 0.01). Hydroperoxides and free radicals decreased from 321.3 +/- 8.96 to 247.9 +/- 8.69 units (p < 0.01) and the end products of lipid peroxidation decreased from 11.0 +/- 1.93 to 6.74 +/- 1.41 nmol/ml (p < 0.01). Total antioxidant capacity increased from 0.74 +/- 0.03 to 1.05 +/- 0.05 mmol/l (p < 0.01). RESULTS: Imbalance in the pro-oxidant-antioxidant equilibrium shifts in favour of antioxydant namely oxidative stress decreases. The calcium channel antagonists decrease peripheral arterial resistances and therefore decrease or abolish relative ischaemia, moreover decrease arterial pressure and therefore normalize parietal stress on endothelial cells. As a conseguence they act on two hypothesized mechanisms of oxidative stress in hypertension. CONCLUSIONS: Dihydropyridine calcium antagonists used in this trial seem useful in hypertension because they decrease oxidative stress, and normalize of pressure values.

Adult↗

PubMedDate not supplied

Horse muscle acylphosphatase: a more rapid purification procedure and crystallization.

A crystalline acyl phosphatase has been obtained from horse muscle. The enzyme purified by a modified procedure which allowed to obtain a larger yield with respect to a method previously developped in this laboratory, was homogeneous by disc electrophoresis on polyacrylamide gel. Crystals of this enzymatic protein have been obtained by the addition of ammonium sulphate to around 52% saturation.

Acid Anhydride Hydrolases↗