Molecular biology in prostate cancer

Summary Genes involved in cancer generation are usually tumor suppressors and oncogenes. Progressive genetic alterations in these genes are involved in the mechanisms of tumorigenesis. In prostate cancer, additionally several chromosomal loci that should harbor mutated genes have been proposed. Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment. Besides, gene therapy has been suggested to be suitable for prostate cancer treatment. This approach includesex vivo corrective therapy, suicide, and antisense therapy.     

Distribution and function of cholinergic receptors in the sheep detrusor muscle

The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes.     

Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures

Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.     

Skeletal muscle characteristics of sprint cyclists and nonathletes

Muscle fiber distribution and muscle enzyme activity (m. vastus lat.) were investigated in 10 elite sprint cyclists and 12 nonathletes. The ratio of fast to slow muscle fibers was 2:3 in cyclists and 3:2 in nonathletes. The mean diameter of each muscle fiber type was significantly higher in the athletes. The mean enzyme activity values in mu kat X g-1 w.w. for cyclists and nonathletes, respectively, were as follows: triosephosphate dehydrogenase (TPDH), 6.2 and 3.78; lactate dehydrogenase (LDH), 4.4 and 4.59; citrate synthase (CS), 0.154 and 0.13; hydroxyacyl-CoA dehydrogenase (HAD), 0.041 and 0.07. The mean difference between groups in TPDH and in (TPDH + LDH)/(CS + HAD) ratio were statistically significant. Maximum voluntary isometric strength (knee extension) was about 17% greater in cyclists than the mean value for Czechoslovakian men of the same age. A strong positive correlation (r = 0.72) between the percent of fast glycolytic fibers (type II B) and isometric strength was observed in the cyclists. Furthermore, mean weight-compensated maximal oxygen consumption (VO2 max, ml X kg-1 X min-1) for all subjects (n = 22) was significantly related to percent of slow oxidative fibers (type I) (r = 0.75) and to the mean diameter of type II B (r = 0.58), fast oxidative-glycolytic fibers (type II A) (r = 0.68) and type I fibers (r = 0.59).     

Erythrocyte deformability in acute and chronic kidney failure patients

The authors presented some data on the platelet deforming ability in patients with acute and chronic renal failure treated with hemodialysis. Platelet deformity was studied by means of a proposed method of the filtration of platelet suspension through glass filtering funnels with a porous plate (GOST 9775-69). The deterioration of platelet deformity in patients with uremia and its direct correlation with a degree of nitremia were established. It was assumed that the deterioration of platelet deformity resulted in premature cell destruction and anemia development. Platelet deformity can be used as a test to characterize platelet function in patients with renal failure. The problem of the appropriateness of trental therapy was discussed.     

Carcinogenicity of zeolite-phillipsite

Phillipsite dust was intrapleurally administered to random-bred rats by 20 mg in 0.5 ml of saline three times with an interval of a month. Higher incidence of hemoblastoses has been experimentally found in exposed animals compared to the control ones. One rat developed pleural mesothelioma, two rats lung adenocarcinoma. It was concluded that phillipsite has weak carcinogenic activity.     

Relationship between oxidative stress and essential hypertension.

This study investigated the association of blood pressure with blood oxidative stress-related parameters in normotensive and hypertensive subjects. A cross-sectional design was applied to 31 hypertensive patients and 35 healthy normotensive subjects. All subjects were men between the ages of 35 and 60 years. Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking and current use of any medication. All patients underwent 24-h ambulatory blood pressure monitoring and sampling of blood and urine. Antioxidant enzymes activity, reduced/oxidized glutathione ratio (GSH/GSSG), and lipid peroxidation (malondialdehyde) were determined in erythrocytes. Parameters measured in the plasma of test subjects were plasma antioxidant status, lipid peroxidation (8-isoprostane), plasma vitamin C and E, and the blood pressure modulators renin, aldosterone, endothelin-1 and homocysteine. Daytime systolic and diastolic blood pressures of hypertensives were negatively correlated with plasma antioxidant capacity (r=-0.46, p<0.009 and r=-0.48, p<0.007), plasma vitamin C levels (r=-0.53, p<0.003 and r=-0.44, p<0.02), erythrocyte activity of antioxidant enzymes, and erythrocyte GSH/GSSG ratio, with hypertensives showing higher levels of oxidative stress. Blood pressures showed a positive correlation with both plasma and urine 8-isoprostane. Neither plasma vitamin E nor the assessed blood pressure modulator levels showed significant differences between the groups or correlation with blood pressures. These findings demonstrate a strong association between blood pressure and some oxidative stress-related parameters and suggest a possible role of oxidative stress in the pathophysiology of essential hypertension.