Effects of melatonin on oxidative stress parameters and pathohistological changes in rat skeletal muscle tissue following carbon tetrachloride application

Animal models demonstrating skeletal muscle (SM) disorders are rarely investigated, although these disorders accompany liver disorders and can occur during prolonged exercise/training. In cases of SM disorders exogenous antioxidants, such as melatonin, could help by generally improving tissues antioxidant capacities. We aimed to analyze the potential of melatonin in preventing biochemical and structural changes in rat biceps muscle (BM) occurring after an acute exposure to carbon tetrachloride (CCl₄). Biceps muscles obtained from male Wistar rats belonging to different experimental groups were biochemically (determination of tissue MDA, total antioxidant capacity, GSH, CAT, SOD and GPx activities) and pathologically analyzed. Also, serum levels of potassium, LHD and CK were analyzed in all experimental animals. The obtained results were statically compared with those from vehicle-treated control group. The applied melatonin prevented potassium and intracellular enzyme leakage (CK and LDH) that was induced by CCl₄, as well as an increase in tissue MDA. From a panel of determined oxidative stress parameters melatonin was able to statistically significantly prevent changes in total antioxidative capacity and in CAT, SOD and GPx activities induced by CCl₄. Microscopic analysis of BM from the animals exposed to CCl₄ revealed significant muscle fiber disorganization and massive inflammatory cell infiltration. All these changes were significantly ameliorated in the group that received melatonin prior to CCl₄. Changes in serum and tissue biochemical parameters accompanied the observed pathological changes, which demonstrated a significant influence of melatonin in preventing skeletal muscle damage induced by CCl₄.     

Clinical significance of autoantibodies induced by infliximab treatment: two-year follow-up after infliximab discontinuation

Infliximab is anti-TNFα monoclonal antibody, which is widely used in the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. Anti-TNFα treatment can induce the occurrence of autoantibodies but in the majority of treated patients, they have no clinical significance although several cases of drug induced lupus have been described. In our cohort of refractory RA patients treated with infliximab for one year, we found a very high number of patients who developed antinuclear autoantibodies (16 of 24 (66.6%) at the time of infliximab discontinuation) and anti-ds-DNA autoantibodies (12 of 24 (50%) at the time of infliximab discontinuation). However, in most of these patients they had no clinical significance. One patient developed clinical and laboratory signs of systemic lupus erythematosus (SLE), which over time became overt as SLE-RA overlapping unmasked by infliximab.     

Influence of nano and bulk copper on agile frog development

Ecotoxicology - Nanotechnology, as one of the fastest-growing industries, offers many benefits in various fields. However, properties that contribute to its positive effects, in other context, can...     

Rare zoonosis (hemotrophic mycoplasma infection) in a newly diagnosed systemic lupus erythematosus patient followed by a Nocardia asteroides pneumonia

Systemic lupus erythematosus (SLE) is per se a disease characterized by suppressed immune response and thus susceptibility to various opportunistic infections. We describe the case of a 21-yearold woman who developed a rare zoonosis - hemotrophic mycoplasma infection in the initial stage of SLE, complicated with Nocardia asteroides pneumonia afterwards. Nocardia infection coincided with initiation of glucocorticoids and cyclophosphamide therapy for SLE. After the treatment she recovered completely. To our knowledge the only case of human hemoplasmosis (then referred to as eperythrozoonosis) in medical literature was the one described by a group of Croatian authors 22 years ago. No cases of a hemotrophic mycoplasma infection in a SLE patient have been published up to now.     

Neutrophil Elastase Gene Polymorphisms: Modulators of Response to Therapy in Childhood Bronchiectasis?

Background

The aim of this study was to investigate polymorphisms in the promoter region of the neutrophil elastase (ELANE) gene as potential modulators of the therapeutic response in children with idiopathic bronchiectasis.

Methods

The study included 48 children between 5 and 17 years old who were diagnosed with idiopathic bronchiectasis based on high-resolution computed tomography of the thorax. In all patients therapy included administration of antibiotics, anti-inflammatory drugs, expectorants, and postural drainage. Response to therapy was evaluated by the change in FeNO levels before and after administration of therapy. The ELANE promoter region polymorphisms were analyzed by PCR-direct DNA sequencing.

Results

According to the predicted activity of ELANE genotypes, subjects were divided into two groups: low/intermediate activity (n = 18) and high activity (n = 30). Subjects in the group with high-activity genotype had higher initial FeNO levels and this difference was statistically significant (t = 2.906; p = 0.006). The difference between FeNO levels before and after therapy was also statistically significantly higher in children with high-activity genotype (t = 3.329; p = 0.002). Statistically significant correlation was observed between the change in FeNO levels and ELANE genotypes (r = 0.350; p = 0.015).

Conclusion

Children with high-activity genotype had higher initial FeNO levels and showed better response to therapy than children with low/intermediate-activity genotypes.     

Novel substituted benzothiophene and thienothiophene carboxanilides and quinolones: synthesis, photochemical synthesis, DNA-binding properties, antitumor evaluation and 3D-derived QSAR analysis

A series of new N,N-dimethylaminopropyl- and 2-imidazolinyl-substituted derivatives of benzo[b]thienyl- and thieno[2,3-b]thienylcarboxanilides and benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones were prepared. Quinolones were prepared by the reaction of photochemical dehydrohalogenation of corresponding anilides. Carboxanilides and quinolones were tested for the antiproliferative activity. 2-Imidazolinyl-substituted derivatives showed very prominent activity. By use of the experimentally obtained antitumor measurements, 3D-derived QSAR analysis was performed for the set of compounds. Highly predictive 3D-derived QSAR models were obtained, and molecular properties that have the highest impact on antitumor activity were identified. Carboxanilides 6a-c and quinolones 9a-c and 11a were evaluated for DNA binding propensities and topoisomerases I and II inhibition as part of their mechanism of action assessment. The evaluated differences in the mode of action nicely correlate with the results of the 3D-QSAR analysis. Taken together, the results indicate which modifications of the compounds from the series should further improve their anticancer properties.     

Preliminary observations of intraperitoneal carboplatin pharmacokinetics during a phase I study of the Northern California Oncology Group

Summary The pharmacokinetic behavior of carboplatin administered by the i.p. route at a dose of 200 mg/m² was studied during five courses of therapy in four patients with ovarian cancer. A regional pharmacologic advantage was noted with carboplatin administered by this route, with (1) peak peritoneal fluid concentrations 18-fold those in plasma, and (2) area under the curve (AUC) for the peritoneum showing a 18-fold and 6-fold increase over plasma AUC at 4 and 24 h, respectively. The mean residence time of total platinum in the peritoneum was 4.7 h. Approximately 10% and 40% of plasma platinum was protein bound at 4 and 24 h after treatment, respectively, whereas peritoneal fluid platinum showed minimal protein binding. Peak plasma platinum levels were comparable to those recorded in previous studies with i.v. doses of carboplatin. Peritoneal clearance of carboplatin in these four patients appeared to be less than that previously reported for cisplatin. Further studies are in progress with higher doses of i.p. carboplatin.Supported in part by the Louis R. Lurie Foundation, the Randy Lynn Baruh Research Foundation, and grants CA21744, CA19408, CA25827, and CA25862 from the National Institutes of Health, Department of Health and Human Services     

[3H]haloperidol labels brain dopamine receptors after its injection into the internal carotid artery of the rat

Pulse injection of [³H]haloperidol (0.1 μCi; 0.003 μg) into the internal carotid artery of the rat specifically labelled dopamine receptors in striatum and olfactory tubercle, as indicated by the kinetics of, and the effects of neuroleptic drugs on, the ligand disposition. The described method may prove useful for labelling brain receptors with ligands which readily cross the blood-brain barrier but which do not selectively mark their receptors if injected systemically.