Inhibition of proliferation on some neoplastic cell lines-act of carvedilol and captopril

The present work examines the effects of beta and alpha1-adrenoceptor antagonist carvedilol, and angiotensin converting enzyme (ACE) inhibitor captopril, on in vitro growth of tumor cell lines derived from breast tumor (MDA-MB-361), melanoma (Fem-x), cervix adenocarcinoma (HeLa) and human myelogenous leukemia (K562). Carvedilol or captopril were applied on malignant cells at 0.1, 1, 5, 10 and 50 micromol. Cell survival was determined 48 hrs after drugs action by MTT. On all cell lines tested, carvedilol was a very potent inhibitor of cell proliferation. The order of sensitivity of various human cell lines to carvedilol's antiproliferative action was: myelogenous leukemia K562 (IC50 = 22.66 +/- 2.14 micromol), > cervix carcinoma HeLa (IC50 = 30.56 +/- 5.16 micromol), > melanoma Fem-x (IC50 = 32.17 +/- 5.75 micromol), > breast tumor MDA-MB-361 (IC50 = 35.04 +/- 2.95 micromol). In contrast, captopril, used in doses from 0.1-50 micromol, was ineffective (IC50 > 50 micromol) to the same cell lines. It is important to note that captopril in concentrations > 1 micromol led to a statistically significant increase in the percent of survived melanoma Fem-x cells (p < 0.05). Understanding the action of these established and clinically accepted agents could provide a basis for design of improved therapeutic regimens in the treatment of cancer diseases.     

NG-nitro-L-arginine methyl ester potentiates the effect of aminophylline on the isolated rat hemidiaphragm

The effects of different concentrations of N(G)-nitro-L-arginine methyl ester (L-NAME) (0.3, 1, 3, and 10 mM), a non-selective inhibitor of NOS, on the effect of aminophylline on the isometric contraction of the isolated rat hemidiaphragm were investigated. The muscle contractions were induced by direct subtetanic electrical stimulation. Aminophylline (0.36 - 3.60 mM) produced a typical concentration-dependent increase in both parameters of the isometric contraction: tension developed (Td) and the maximum rate of rise of tension (dT/dt max). The second series of additions of aminophylline produced a more pronounced effect. L-NAME (0.3, 1, 3, and 10 mM, 30 min of incubation without stimulation) itself did not change Td and dT/dt max. However, L-NAME (1, 3, and 10 mM) produced a statistically significant potentiation of the effect of aminophylline on Td and dT/dt max.     

Triple pelvic osteotomy in the treatment of Legg-Calve-Perthes disease

This article presents the results of Legg-Calve-Perthes (LCP) disease treatment using triple pelvic osteotomy. Thirty patients were analysed. The conditions for inclusion in the study were complete medical documentation and follow-up until the disease was resolved. Postoperatively, no patients were immobilised. Rehabilitation was initiated early in all patients, and full weight bearing was allowed after ten weeks. With this method, an increase of the CE angle of 17.43 ± 4.020° was achieved. Containment was increased from an initial 6.67% to 53.33% of patients at the final check-up. Similar improvement was achieved by using Herring classification of the damage; preoperatively most hips belonged to group C, and postoperatively to group A. Postoperatively, functional results were also considerably improved. The authors recommend triple pelvic osteotomy as the method of choice in the treatment of severe cases of LCP disease.     

Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients.

BACKGROUND: Overproduction of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) may be an important factor in the pathogenesis of amyotrophic lateral sclerosis (ALS). Owing to their ability to permeate through biological membranes, excess NO and H(2)O(2) may be present in the media surrounding motor neurones. Anti-oxidative defence enzymes (ADEs) in erythrocytes are capable of detoxifying reactive oxygen species (produced endogenously or exogenously), but may also be structurally modified and inactivated by reactive oxygen and nitrogen species. Both balanced and coordinated ADE activities are of utmost importance for their correct physiological function. METHODS: We determined activity of the following ADEs: copper-zinc superoxide dismutase (CuZn SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in erythrocytes from sporadic ALS patients [SALS (-/+)], familial ALS patients with the Leu144Phe mutation in the SOD1 gene [FALS (+/+)], asymptomatic carriers with the Leu144Phe mutation in the SOD1 gene (+/-), and control subjects (-/-). We also examined the in vitro effect of diethyldithiocarbamate (DDC) on CuZn SOD activity in erythrocytes from FALS patients, SALS patients and control subjects. RESULTS: The influence of the Leu144Phe mutation and/or disease was apparent for ADE activities measured in all three patient groups. The SOD1 gene mutation decreased CuZn SOD and GSH-Px activity (two-way ANOVA, significant mutation effect). We noted that the disease also contributed to decreased CuZn SOD activity in SALS patients in comparison with the control group (two-way ANOVA, mutation and disease effect). The disease also influenced CAT and GR activity. CAT activity was decreased in both SALS and FALS patients. In all three patient groups, GR activity was higher than in the control group. Finally, DDC inhibited CuZn SOD activity in erythrocytes from control subjects, FALS (Leu144Phe) patients and SALS patients; however, its effect was more pronounced and significant in FALS patients. CONCLUSIONS: Changes in erythrocyte ADE activities suggest that oxidative stress, involved in the motor neurone pathogenesis of SALS and FALS, also has systemic effects. Differences in ADE systems between the study groups revealed the presence of different types of oxidative pressure, indicating the potential additional benefit of individually designed anti-oxidant cocktail therapies.     

Abnormal fatty acid distribution of the serum phospholipids of patients with non-Hodgkin lymphoma

The data about the fatty acid (FA) status of non-Hodgkin lymphoma (NHL) patients are poor. Therefore, the aim of this study was to investigate the FA profile of serum phospholipids in NHL patients related to the aggressiveness and clinical stage of NHL. We analyzed the FA profile of serum phospholipids in 47 newly diagnosed, untreated NHL patients and in 29 healthy subjects. Significantly higher (p?<?0.001) levels of palmitic (16:0), oleic (18:1 n-9) and arachidonic acids (20:4 n-6), saturated and monounsaturated FA were found in NHL patients, while linoleic acid (18:2 n-6) and the levels of total polyunsaturated FA (PUFA), n-3 PUFA, eicosapentaenoic (20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) were significantly reduced (p?<?0.01). The level of oleic acid in patients with indolent NHL was significantly lower (p?<?0.05) than in more aggressive types of disease. Contents of palmitoleic acid, docosatetraenoic (22:4 n-6), and PUFA was lower in very aggressive NHL. According to clinical stage (CS), patients with CS I had significantly higher SFA and lower n-6 FA than other three groups, and group with CS IV showed significantly decreased DHA and n-3 PUFA. Our results showed an abnormal FA profile in serum phospholipids in NHL patients.     

Route-dependent effects of cadmium/cadmium and magnesium acute treatment on parameters of oxidative stress in rat liver

The study was designed to evaluate and compare the effects of single oral (or) and intraperitoneal (i.p.) cadmium (Cd) administration on parameters of oxidative stress in liver of rats. Furthermore, investigation on protective effects of magnesium (Mg) or and i.p. pretreatment on the same parameters was performed. Wistar rats were administrated oral dose of Cd (30 mg Cd/kg b.w.)/Cd+Mg (30 mg Cd/kg b.w., 50 mg Mg/kg b.w.) or i.p. dose of Cd (1.5 mg Cd/kg b.w.)/Cd+Mg (1.5 mg Cd/kg b.w., 3 mg Mg/kg b.w.) and sacrificed after 24 h. In liver homogenates superoxide anion, malondialdehyde, non-protein sulfhydryl groups, total sulfhydryl groups content, and superoxide dismutase activity were determined. Cadmium intoxication caused the increase of superoxide anion and malondialdehyde levels and had negative effect on investigated parameters of antioxidant defense system, except on total sulfhydryl groups. The negative effect was more emphasized after i.p. Cd administration. Oral Mg pretreatment induced more pronounced positive effect than Mg given intraperitoneally that can be attributed, at least partly, to Cd and Mg interactions on the level of GIT. On the basis of the obtained results it can be concluded that both Cd and Cd+Mg effects on parameters of oxidative stress in rats liver are route-dependent.     

Controlled release of lipase from Candida rugosa loaded into hydrogels of N-isopropylacrylamide and itaconic acid

The series of poly(N-isopropylacrylamide-co-itaconic acid) hydrogels, with lipase from Candida rugosa as a model protein, were synthesized by free radical copolymerization. The composition of hydrogels was varied by monomers ratio, crosslinking agent concentration and amounts of lipase, which was loaded by in situ polymerization. All samples were characterized regarding morphology. The investigation of hydrogel swelling properties revealed their pH and temperature sensitive character. Protein loading efficiency, release profiles and the specific activity yield of the released lipase were also investigated as a function of hydrogel composition, protein content and pH, at the physiological temperature of 37°C. Copolymers of N-isopropylacrylamide and itaconic acid presented high lipase loading efficiency. Another very important feature of these copolymers was that the protein release kinetic strongly depended on the pH value of the medium. The diffusion exponents values around 1 denoted that these hydrogel compositions could be adjusted to follow near zero-order kinetics. Namely, hydrogel formulations released low amounts of lipase at pH 2.20, but much higher released protein quantities were observed at pH 6.80 enabling these copolymers to be attractive candidates as site specific protein oral drug delivery systems.     

Henna tattoo contact dermatitis — a report of four cases and brief review of the selected literature

Temporary henna tattoos have recently become increasingly popular, especially among teenagers. Combining henna with other colouring agents such as para-phenylenediamine (PPD) may increase its potential for contact sensitization, cross-reaction to related compounds, as well as life-long allergy. Several cases of contact dermatitis from temporary tattoos with black henna have been reported in the literature. We present our experiences with 4 pediatric cases of allergic contact dermatitis induced by henna tattooing and give a brief review of the literature. The agent responsible for contact allergy was proven to be PPD in 3 patients, and in one patch testing revealed positive reactions to PPD and benzocaine, as well as to wool alcohols, nickel sulphate and potassium dichromate, to previously used hair dye—all being of clinical relevance.     

Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk

Glutathione peroxidase 1 (GPX1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides. Some epidemiological studies have correlated low GPX activity or particular GPX1 polymorphisms with enhanced risk of cancer, although these correlations have not been consistently observed in all populations. Therefore, we conducted the present study to evaluate the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Macedonian population. The GPX1 Pro198Leu genotype was determined in 82 prostate cancer cases and 123 control individuals. We found an overall protective effect of the variant Leu allele of the GPX1 polymorphism on the prostate cancer risk. Heterozygous carriers of the variant Leu allele had a significantly lower risk of prostate cancer compared with homozygous wild-type individuals (OR, 0.38; 95% CI, 0.20–0.75; P = 0.004). Erythrocyte GPX activity was analyzed in 73 cases and 91 controls. The erythrocyte GPX activity in the cancer group was lower than in the healthy controls. Additionally, we compared the erythrocyte GPX activity in the control group of 90 subjects and found no significant differences by genotype. These findings suggest that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism and that the combination of genetic factors involved in oxidative response with environmental carcinogens may play an important role in prostate carcinogenesis.