Teat tablet with sodium ibuprofen: the effect of sorbitol on therapeutic agent pharmaceutical availability and on physicochemical parameters of a drug form

Dosing pediatric drugs available on pharmaceutical markets of analgesic, antifebrile and anti-inflammatory activity to children up to 3 years of age is not precise and frequently causes problems. The aim of the study was to work out a pediatric teat form of a drug with sodium ibuprofen and to determine the effect of sorbitol content on pharmaceutical availability of the therapeutic agent. Three variants of tablets containing 50 mg of sodium ibuprofen differing in the percentage content of sorbitol (from 37% - batch I to 79% - batch III) were produced. Quality tests of the produced forms of drugs (PPVI) were performed and the tests of therapeutic agent pharmaceutical availability by spatula method and by a method with a teat. Tablets of all batches had a smooth surface and same shape. The content of the therapeutic agent was within the limit of 95-105% of the declared value. The highest value of Q coefficient in the release test by pharmacopeal method and the shortest disintegration time (12 minutes) were obtained for tablets with 79% content of sorbitol. In conclusion, teat tablets with sodium ibuprofen of the highest sorbitol content (79%) demonstrated the expected physicochemical parameters and high pharmaceutical availability.     

Subacute toxicity of polychlorinated naphthalenes and their effect on cytochrome P-450

The aim of the study was to investigate the subacute toxicity of a polychlorinated naphthalene (PCN) mixture and its effect on cytochrome P-450 levels in rats. The animals were administered PCNs intragastrically in repeated daily doses of 1, 10, and 100 mg/kg. The animals were dissected after 7, 14, or 21 doses. Doses of 10 and 100 mg/kg induced a significant decrease in the body weight at all time points of the experiment compared with the control group. The exposure to PCNs increased both the level of total cytochrome P-450 and the activity of CYP 1A at the same time points. In the groups of rats given PCNs in doses of 10 and 100 mg/kg, an evident dose- and time-dependent increase in malondialdehyde (MDA) level was observed throughout the experiment. The correlation between the increased MDA and decreased glutathione (GSH) levels in the liver was also observed.     

p38alpha MAP kinase as a sensor of reactive oxygen species in tumorigenesis

p38alpha is a stress-activated protein kinase that negatively regulates malignant transformation induced by oncogenic H-Ras, although the mechanisms involved are not fully understood. Here, we show that p38alpha is not a general inhibitor of oncogenic signaling, but that it specifically modulates transformation induced by oncogenes that produce reactive oxygen species (ROS). This inhibitory effect is due to the ROS-induced activation of p38alpha early in the process of transformation, which induces apoptosis and prevents the accumulation of ROS and their carcinogenic effects. Accordingly, highly tumorigenic cancer cell lines have developed a mechanism to uncouple p38alpha activation from ROS production. Our results indicate that oxidative stress sensing plays a key role in the inhibition of tumor initiation by p38alpha.     

Y-STR variation among Slavs: evidence for the Slavic homeland in the middle Dnieper basin

A set of 18 Y-chromosomal microsatellite loci was analysed in 568 males from Poland, Slovakia and three regions of Belarus. The results were compared to data available for 2,937 Y chromosome samples from 20 other Slavic populations. Lack of relationship between linguistic, geographic and historical relations between Slavic populations and Y-short tandem repeat (STR) haplotype distribution was observed. Two genetically distant groups of Slavic populations were revealed: one encompassing all Western-Slavic, Eastern-Slavic, and two Southern-Slavic populations, and one encompassing all remaining Southern Slavs. An analysis of molecular variance (AMOVA) based on Y-chromosomal STRs showed that the variation observed between the two population groups was 4.3%, and was higher than the level of genetic variance among populations within the groups (1.2%). Homogeneity of northern Slavic paternal lineages in Europe was shown to stretch from the Alps to the upper Volga and involve ethnicities speaking completely different branches of Slavic languages. The central position of the population of Ukraine in the network of insignificant AMOVA comparisons, and the lack of traces of significant contribution of ancient tribes inhabiting present-day Poland to the gene pool of Eastern and Southern Slavs, support hypothesis placing the earliest known homeland of Slavs in the middle Dnieper basin.     

Interaction Between Val158Met Catechol‐O‐Methyltransferase Polymorphism and Social Cognitive Functioning in Schizophrenia: Pilot Study

The Val158Met catechol‐O‐methyltransferase (COMT) functional polymorphism may influence social cognitive functioning in patients with schizophrenia. Aspects of social cognition were evaluated with the Facial Expression Recognition Test, the Voice Emotion Recognition Test, and the Reading the Mind in the Eyes Test. The Short Recognition Memory Test for Faces was used as a control measure. The Schedule for the Assessment of Negative Symptoms, Schedule for the Assessment of Positive Symptoms, and Beck Depression Inventory were used to rate of patient symptoms. There were 100 patients with the following genotypes: Val/Val (21), Met/Met (30), and Val/Met (49). The genotype distribution of polymorphism of Val158Met COMT did not differ between the patient and control groups. Schizophrenia carriers of the Val/Val genotype performed worse in social cognitive measures, in comparison with the other groups. No statistically significant correlations were recorded between age at schizophrenia onset and polymorphism of Val158Met COMT. There was an influence of genotype in the control group: the Met homozygotes performing better. Schizophrenia patients homozygous for the Val allele showed significant disadvantages over patients homozygous or heterozygous for the Met allele in social cognitive processes. The COMT genotype may not, however, contribute to the age of onset of schizophrenia.     

Prognostic role of non-sustained ventricular tachycardia in a large cohort of patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The identification of patients with idiopathic dilated cardiomyopathy (IDC) at higher risk of sudden death (SD) is still an unsolved issue, and the role of non-sustained ventricular tachycardia (NSVT) uncertain. METHODS: The effect of NSVT on total mortality, SD and life-threatening arrhythmias was evaluated in 554 patients with IDC on optimal medical treatment and at long-term follow-up (81 +/- 58 months). RESULTS: At diagnosis, 240 patients (43%) had NSVT at Holter monitoring and 314 (57%) did not. During follow-up, 189 patients (5/100 patients-year) died or underwent heart transplantation; SD occurred in 53 patients (1.4/100 patients-year); SD + non-fatal ventricular arrhythmias occurred in 75 patients (2/100 patients-year). Patients with and without NSVT at diagnosis had the same 5-year transplant-free survival rate (76 vs 76%, p = NS) and a similar incidence of SD (10 vs 7%, p = NS). The length and rate of NSVT did not show any significant relationship with the outcome. Only heart failure symptoms (NYHA class III-IV) (hazard ratio [HR] 1.9, p = 0.015) and severe left ventricular impairment (left ventricular ejection fraction < or = 0.30 and left ventricular end-diastolic diameter > or = 70 mm) (HR 2.7, p < 0.0001) were independently associated with higher SD risk. At multivariate analysis the presence of frequent NSVT episodes (> or = 3 runs/day) was associated with an increased risk of total mortality (HR 1.68, p = 0.041) and of major ventricular arrhythmias (HR 2.11, p = 0.037), but only in the subgroup of patients with severe left ventricular impairment. CONCLUSIONS: Patients with advanced heart failure symptoms, severe left ventricular dysfunction and dilation had a higher risk of SD independently of NSVT. The finding of more frequent NSVT was associated with an increased risk of all-cause mortality and of major ventricular arrhythmias in patients with severe left ventricular impairment.