Assessment of the adrenergic effects of orphenadrine in rat vas deferens.

The peripheral adrenergic effects of orphenadrine, an antiparkinsonian drug, have been evaluated in the rat vas deferens to investigate whether these properties are the same as those of other phencyclidine ligands. In the low micromolar range, orphenadrine enhanced electrically-evoked and exogenous noradrenaline contractile responses in the epididymal portion of rat vas deferens. It also induced spontaneous activity that was inhibited by prazosin (1 microM) but not by atropine (20 nM). It inhibited accumulation of [3H]noradrenaline in rat vas deferens (IC50 = 14.2+/-2.3 microM). Orphenadrine competitively inhibited [3H]nisoxetine binding in rat vas deferens membranes (Ki = 1.05+/-0.20 microM). It can be concluded that orphenadrine, at low micromolar concentrations, interacts with the noradrenaline reuptake system inhibiting its functionality and thus potentiating the effect of noradrenaline.     

Phyllanthus orbicularis aqueous extract: cytotoxic, genotoxic, and antimutagenic effects in the CHO cell line

The present work evaluates the cytotoxic, genotoxic, and antimutagenic effects of Phyllanthus orbicularis (plant of genus Phyllantus) aqueous extract in Chinese hamster ovary (CHO) cells. P. orbicularis aqueous extracts are used in Cuban traditional medicine for their antiviral activity against Hepatitis B virus and A and B flu virus. The cytotoxicity of the extract was tested by means of colony-forming ability and growth-inhibition assays as well as by measuring the mitotic index. Apoptosis induction and cell-cycle kinetics were analyzed by cytofluorimetric methods. Chromosome aberration assays were performed to study the genotoxic and antimutagenic activity of the extract. Results show that doses of up to 100 microg/ml of the extract did not induce any cytotoxic effects. Cell survival and mitotic index decreased significantly at doses higher than 100 microg/ml as a function of dose as well as of treatment time. Moreover, continuous treatments of up to 18 h induced the appearance of a significant number of apoptotic cells. Following a 3-h exposure to a dose of 750 microg/ml, cells accumulated significantly in G(2)-M phase and remained blocked in G(1-) and G(2)-M phases after several posttreatments in fresh growth medium. The aqueous extract alone did not induce chromosome aberrations but, in combined treatment with H(2)O(2), significantly reduced H(2)O(2)-induced chromosome aberrations. Flow cytometric analysis of DCFH intracellular oxidation showed that the extract decreased the oxidizing power of H(2)O(2.) This ability could possibly explain the extract's antigenotoxic activity. Absence of cytotoxicity at the lower tested doses and the antimutagenic properties of the extract stimulate the interest in studying possible new pharmaceutical uses of P. orbicularis.     

Inhibition of endotoxin-induced interleukin 8 release by teicoplanin in human whole blood

Antibiotic-induced endotoxin (lipopolysaccharide; LPS) release may precipitate septic shock. In the present study the effect of teicoplanin, which has been reported to neutralize LPS in experimental models, on LPS neutralization was investigated in human whole blood samples. Levels of interleukin 8, a proinflammatory cytokine which was stimulated bySalmonella minnesota R595 LPS (12.6 µg/ml), were monitored over time. Interleukin 8 concentrations increased over time up to 24 h. When LPS was preincubated with teicoplanin (antibiotic: LPS ratio 20:1, w/w), interleukin 8 concentrations were found significantly (p<0.05) reduced at 4, 8 and 24 h after LPS challange. Interleukin 1 (at 4, 8 and 24 h) and tumor necrosis factor (at 8 and 24 h) levels were also significantly decreased by teicoplanin. In this experiment model, a teicoplanin: LPS ratio 100-fold less than the ratio achievable in plasma of septic shock patients was able to reduce interleukin 8, which has been correlated with the severity of septic disease.     

Time course of plasma levels and electrophysiologic effects of propranolol in man

We studied the time course of three electrophysiologic effects of propranolol after intravenous and oral administration and their relationship with plasma levels within the same subjects. Ten patients who had undergone cardiac catheterization for diagnostic purposes received 0.1 mg/kg of propranolol intravenously. Blood was drawn at intervals for 12 hr and heart rate and the effective refractory periods of the atrium (ERPA) and the atrioventricular node (ERPAVN) were determined at the same time. Eight patients continued treatment with propranolol by the oral route for up to 4 days (40 mg every 12 hr). Blood was sampled after each morning dose. Plasma concentrations of propranolol were measured by gas chromatography. Maximal lengthening of ERPA after propranolol (15.1% i.v. and 9.4% oral) was much less marked than that of ERPAVN (23.2% i.v. and 19.4% oral). Heart rate decreased 23.5% (i.v.) and 13.1% (oral). Effects were seen much sooner after intravenous (5-8 min) than after oral administration (86-146 min), but they lasted about twice as long after oral as after intravenous treatment.     

Intracranial arachnoid cysts in myotonic dystrophy

Summary Clinically apparent brain dysfunction is common in myotonic dystrophy. In a sample of fourteen adult patients with the definite form of this disease, brain magnetic resonance imaging detected frequent white matter abnormalities and ventriculomegaly. In addition, two patients exhibited an intracranial arachnoid cyst, a condition of neurosurgical interest that could be related to the generalized dysmaturational process present in this disease. Patients with myotonic dystrophy deserve a careful screening for brain involvement. Further MRI studies should ascertain the actual prevalence of brain anomalies in myotonic dystrophy and define the role of this procedure in the workup of this disease.     

Sonographic patterns of Caroli's disease: report of 5 new cases.

We have reviewed 5 cases of Caroli's disease, studied from 1982 to 1987, in order to define the validity of its sonographic signs. The "intraluminal portal vein" sign, found in all the cases, is emphasized. This sign may be easily identified and it is never encountered in other diseases. Recessive polycystic kidney disease was present in 3 cases, and congenital hepatic fibrosis was demonstrated in the 2 cases studied by liver biopsy.     

Temporal relationship between the decrease in arterial pressure and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis

It has been proposed that the initial event of sodium retention in cirrhosis is a peripheral arteriolar vasodilation causing underfilling of the arterial vascular compartment and stimulation of the renin-aldosterone and sympathetic nervous systems. To test this hypothesis, systolic blood pressure, sodium balance and urinary excretion of sodium and aldosterone were sequentially measured in 13 conscious spontaneously hypertensive rats submitted to a cirrhosis induction program with carbon tetrachloride and phenobarbital and in 14 control hypertensive animals. No significant differences were found between control and cirrhotic rats in any of the measured parameters during the first 7 wk of the study. The eighth week sodium retention developed in cirrhotic rats as indicated by a positive sodium balance and a marked decrease of sodium excretion. At the same time a significant reduction in systolic blood pressure and a great increase in urinary excretion of aldosterone were detected. These changes were more marked the ninth week of the study. In cirrhotic rats there was a highly significant direct correlation between systolic blood pressure and urinary sodium excretion. Postmortem examination showed a histological picture of cirrhosis in all animals given carbon tetrachloride and ascites in six of them. These results indicate that the onset of hyperaldosteronism and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis is chronologically related to a significant decrease in arterial pressure, thus supporting the "peripheral arterial vasodilation hypothesis" of ascites.     

Factor V Leiden and G20210A prothrombin mutation and the risk of subclavian vein thrombosis in patients with breast cancer and a central venous catheter.

BACKGROUND: To analyze the influence of the prothrombotic gene mutation factor V G1691A (factor V Leiden) and prothrombin G20210A on the risk of a first episode of catheter-related deep venous thrombosis (DVT) in a group of patients with breast cancer treated with chemotherapy. PATIENTS AND METHODS: Between January 1999 and February 2001, the occurrence of a first symptomatic DVT was investigated in a cohort of 300 consecutive patients with locally advanced or metastatic breast cancer treated at a single institution with fluorouracil-based chemotherapy, administered continuously through a totally implanted access port. A nested case-control study included 25 women (cases) with catheter-related DVT and 50 controls without DVT matched with cases for age, identical chemotherapy, stage of disease and prognostic features. The G1691A factor V and G20210A prothrombin mutation genotypes were analyzed. RESULTS: Five cases [20%; 95% confidence interval (CI) 9% to 39%)] and two controls (4%; 95% CI 1% to 14%) were heterozygous carriers of G1691A factor V (P = 0.04). The age-adjusted odds ratio for catheter-related DVT was 6.1 (95% CI 1.1-34.3). Only one patient (case) had the G20210A prothrombin gene mutation. Time from start of chemotherapy infusion to DVT was not significantly different between patients with (median 31 days) and without (median 43 days) G1691A factor V mutation (P = 0.6). CONCLUSIONS: Factor V Leiden carriers with locally advanced or metastatic breast cancer have an increased risk of developing catheter-related DVT during chemotherapy.     

Trends in childhood cancer incidence and mortality in Catalonia, Spain, 1975-1998.

Childhood cancer mortality has sharply declined in most economically developed countries over the last years, whereas no substantial changes in the incidence have been observed. In Catalonia (Spain), childhood cancer mortality showed a considerable decline until 1992, but incidence trends have not been analysed in this population. To assess both recent incidence and mortality trends in this population, we analysed childhood (0-14 years) cancer data from the population-based Tarragona Cancer Registry and from the Mortality Registry of Catalonia (Spain) from 1980 to 1998. All cancer mortality decreased by -2.6% annually in boys (95% confidence interval, 95% CI -3.7, -1.6) and -3.7% in girls (95% CI -4.9, -2.5). Mortality due to leukaemia decreased annually -3.0% in boys (95% CI -4.7, -1.4) and -4.4% in girls (95% CI -6.3, -2.4). Mortality for brain tumours showed a reduction of -3.2% in boys (95% CI -5.5, -0.9) and of -4.4% in girls (95% CI -6.3, -2.4). No significant trend in incidence rates, either in boys or in girls, was observed (annual per cent of change for all cancers -0.5%, 95% CI -3.5, 2.7, in boys and 1.7%, 95% CI -1.9, 5.5, in girls). These results suggest an improvement in both childhood cancer diagnosis and treatment, which may explain current higher childhood cancer survival rates.