The importance of the Holter ECG monitoring of patients in the acute period of an ischemic stroke

10 guinea pigs of group 1 were injected subcutaneously kanamycin (400 mg/kg). The other 10 guinea pigs of group 2 received human ceruloplasmin as an intraperitoneal injection of 10% solution (0.25 ml of the protein preparation per 100 g body weight) 30 min before kanamycin administration. 7 days after the treatment the cochlease were isolated and examined electron microscopically. The Corti's organ was stained with alcyan blue and lanthanum hydroxide. In animals of group 1 there was mitochondrial vacuolization, enlargement of the cisterns of the endoplasmic network, Golgi apparatus, sub-superficial network; glycocalix layer on the surface of the receptor epithelium was unbroken but uneven, in the sensor cells of the Corti's organ of the group 2 animals only few mitochondria were vacuolized. A great number of ribosomes and mitochondrial contacts with membraneous cell structures were indicative of active protein synthesis and energetic processes. Glycocalix was less damaged. This was indicative of an otoprotective effect of ceruloplasmin which diminished kanamycin ototoxicity.     

Effect of tamoxifen feeding on metabolic activation of tamoxifen by the liver of the rhesus monkey: does liver accumulation of inhibitory metabolites protect from tamoxifen-dependent genotoxicity and cancer?

Tamoxifen induces hepatocellular carcinomas in rats and is converted by rat hepatic cytochrome P450 enzymes into reactive metabolites capable of forming adducts with nucleic acids, proteins and chromosomal aberrations. In rats tamoxifen has also been shown to induce liver cytochrome P450 enzymes, to stimulate its own metabolism leading to greater covalent binding and to induce a higher degree of unscheduled DNA synthesis. This suggests that, at least in the rat, a sensitive species, tamoxifen may contribute significantly to its genotoxic and carcinogenic potential, by assisting its own metabolic activation. We have now investigated the effect of feeding tamoxifen to male and female Rhesus monkeys. A marked induction of the hepatic cytochrome(s) P450 is found in the monkey but, in spite of this, the in vitro metabolism of 7-ethoxyresorufin by microsomes from treated animals is markedly inhibited and so is the dealkylation of two other 7-alkoxyresorufin substrates. Evidence is presented for the accumulation in the liver of monkeys treated with tamoxifen of a powerful inhibitor of drug metabolism, and the inhibitor is identified as a metabolite of tamoxifen, its N,N-didesmethyl derivative. The level of 32P-postlabelled DNA adducts was considerably higher in rats given tamoxifen than in similarly treated monkeys. Also, whereas rats responded to tamoxifen treatment with a marked increase in covalent binding to microsomal protein, in the monkeys, where accumulation of the inhibitory metabolite in the microsomal fraction was also seen, covalent binding was not greater with microsomes from treated animals than in the corresponding controls. N,N-Didesmethyl-tamoxifen, added in vitro to human and rat microsomes, reduced significantly the extent of covalent binding, suggesting that the accumulation of the metabolite observed in the liver of primates may discourage the cytochrome P450-dependent conversion of tamoxifen into reactive derivatives and in this way protect against the formation of adducts. This mechanism may also contribute to protecting the primate against tamoxifen- induced liver cancer.     

Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast carcinomas: clinico-pathological correlations

The purpose of this study was to investigate the association among matrix metalloproteinases (gelatinases A and B, stromelysin-3 (ST3) and matrilysin) mRNAs expressed in primary breast carcinomas and standard prognostic parameters and clinical outcome. mRNA levels were determined by Northern analysis in samples of 81 breast cancer patients (median follow-up, 40 months) and 27 samples of uninvolved adjacent breast tissue. Proteases were expressed by the majority of the tumors and normal breast tissues examined. ST3, gelatinase A and matrilysin mRNAs were more often expressed at high levels in carcinomatous than in normal breast tissues. Differences in the distribution of gelatinase B mRNA were not found. However, paired normal tissues generally produced weaker signals when compared to matched tumor samples. Univariate analysis showed no significant association of gelatinase A and matrilysin mRNAs with the classical prognostic markers (age, menopausal status, stage, size, nodal status, vascular infiltrate, necrosis, steroid receptors, metastasis and survival). Overexpression of ST3 was more frequently found in tumors of post-menopausal women (P < 0.022). Elevated expression of gel B mRNA was associated with the presence of vascular infiltrate (P < 0.026), necrosis (P < 0.039), PR negative tumors (P < 0.014) and inversely correlated to the number of survivors (P < 0.021). Multivariate analysis including 68 patients for whom all information was available indicated that neither stromelysin correlated significantly with pathological, clinical or biochemical features. High levels of gelatinase A and B mRNAs were inversely associated with the number of survivors. Our findings suggest that measurements of gelatinase A and B mRNAs expression in breast carcinoma may help to identify patients with an aggressive form of the disease.     

Purification and characterization of aminopeptidase P from Lactococcus lactis subsp. cremoris

BACKGROUND: Neutrophils, platelets, and cytokines are thought to play a pivotal role in the pathogenesis of endotoxin-induced lung injury which resembles features of acute respiratory distress syndrome (ARDS). For initiation of this pathological process, neutrophils and platelets are activated and adhere to pulmonary endothelium. Nitric oxide (NO) inhibits adhesion and activation of these cells and decreases the cytokine level in bronchoalveolar lavage (BAL) fluid obtained from patients with ARDS. Limited data are available on the effect of NO treatment before and after endotoxin on the development and advance of ARDS. The aim of the current study was to determine whether NO inhalation prevents acute lung injury. METHODS: Thirty-two male anaesthetized rabbits were randomly assigned to receive one of four treatments (n = 8 each); Group S-N received saline with nitrogen (N2), Group S-NO received saline infusion with NO (20 p.p.m.) inhalation, Group E-N received an infusion of Escherichia coli endotoxin 100 micrograms/ kg over 60 min with inhalation of N2, and Group E-NO received endotoxin with NO (20 p.p.m.) inhalation. The lungs of the rabbits were ventilated with 40% oxygen until 6 h after the start of endotoxin or saline administration. Haemodynamics and PaO2 were recorded during the ventilation period. After observation, the lung wet-to dry-(W/D) weight ratio, lung mechanics, and cell fraction, activated complements, cytokines, arachidonic acid metabolites, and albumin concentrations in the BAL fluid were measured and analysed. Light microscopic findings were compared among the four groups. RESULTS: Pulmonary hypertension and deterioration of oxygenation by endotoxin were less pronounced in rabbits receiving NO. The lung compliance after endotoxin was similar in Groups E-NO and E-N. The W/D weight ratio and neutrophils and albumin concentrations in the BAL fluid increased in Groups E-NO and E-N. The BAL fluid concentrations of interleukin-8, thromboxane A2, and prostacyclin were similar in the two endotoxin-treated groups. Endotoxin caused extensive morphologic lung damage regardless of NO inhalation. CONCLUSIONS: The increase in pulmonary arterial pressure and deterioration of oxygenation were less in endotoxin-exposed rabbits receiving NO inhalation compared with those receiving N2. Accumulation of neutrophils and platelets in the lung, morphological lung damage, and the release of cytokines and prostanoids were observed in the E-NO group. However, we are unable to extrapolate these results directly to the human clinical setting because of the short observation period, the use of only one dose of NO, and the species difference.     

The stimulation of the creatine kinase activity of tissue cultures with high-energy laser radiation

Effects of copper laser stimulating doses on biochemical parameters of competent chicken embryo myoblast and neuroblast cultures were studied. It was shown that in both systems biostimulation was characterized by an increase of water-extractable protein level and a considerable rise of total and specific creatine kinase activity. The authors believe that cases of protein drop during myoblast culture exposure to chemical agents described in literature were caused by these agents overdosage and that this drop may be considered as a manifestation of a peculiar biochemical shock induced by overdosage. They suggest to follow up the time course of water-extractable protein levels in the cultures to differentiate between trophic and injurious loading.     

The use of Cordanum in combination with Corinfar-Retard for the treatment of ectopic arrhythmias in the sick sinus syndrome in patients with ischemic heart disease

38 patients with ischemic heart disease (IHD) and sick sinus syndrome (SSS) received combined therapy with nifedipine (Corinfar-Retard) and talinolol (Cordanum). The former drug had a positive chronotropic effect on the heart, the latter's chronotropic effect was slightly negative. All the patients had sinus bradycardia and ectopic arrhythmia which needed therapeutic correction: supraventricular and ventricular extrasystoles, fibrillation paroxysms or/and atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia. Cordanum was given in a dose 50 mg twice a day, Corinfar-Retard 20 mg twice a day for 16 days. 30 patients responded to the treatment. In addition to good subjective response, episodes of extrasystoles, paroxysms, flutter and fibrillation occurred much less frequently. Side effects resulted in the treatment discontinuation in 3 patients.     

Antimicrobial properties of pectins and their effects on antibiotics

The influence of food fibres and plant proteins on microorganisms, bacteriophages, antibiotics and penicillinase was studied in vitro. It was shown that pectin was the only agent that had a bactericidal effect on the most widely distributed pathogenic and opportunistic microorganisms and did not influence indigenic microflora. High concentrations of pectin (> 2 per cent) had an inactivating effect on therapeutic bacteriophages. There was also a decrease in the antimicrobial activity of penicillins. The other agents tested i.e. wheat bran, soya isolate and soybean flour had no influence on microorganisms, bacteriophages and antibiotics. No sorption activity of the food fibres and plant proteins with respect to microorganisms and antibiotics or their effect on penicillinase was observed.