Stakišaitis, Donatas

The aim of the study was to assess the effect of vitamin D-binding protein (DBP) polymorphism on coronary artery disease (CAD). DBP phenotypes were identified in the groups: control (), men suffering from CAD (), and long-lived individuals (). Isoelectric focusing of DBP phenotypes in serum was performed on polyacrylamide gel. Distribution of DBP phenotypes in the study groups was found to be in Hardy-Weinberg equilibrium. Gc1s-1s phenotype and Gc1s allele frequency in CAD groups were significantly higher than in control, and Gc1s allele frequency was found significantly more often in CAD compared with long-lived group (). The Gc2 allele frequency in control was higher as compared with Gc2 frequency in CAD group (). The Gc2-2 phenotype was more frequent in long-lived survivors than in the CAD group (). It was found that the Gc1s allele significantly increased the risk of CAD with the odds ratio (OR) equal to 1.45 () and showed Gc2 to be related with a decreased risk of CAD (OR = 0.69; ). Authors review the role of DBP in resistance to atherosclerosis and cancer as the main longevity determinants.

Alpha 1-antitrypsin deficiency is a genetic risk factor for manifestation of COPD and chronic liver diseases. There is an ongoing worldwide discussion concerning the role of serpins (serine protease inhibitors) in tumor genesis. Protease inhibitors such as alpha 1-antitrypsin have generally been considered to counteract tumor progression and metastasis because of their ability to inhibit proteases. In this case report we analyze relationship between inherited alpha-1 antitrypsin deficiency and chondrosarcoma. A 47-year-old woman was admitted to the hospital with relapse signs of humerus chondrosarcoma. The patient also had a history of COPD. After chest X-ray and CT, alpha 1-antitrypsin deficiency was suspected. Severe alpha-1 antitrypsin deficiency (PiZZ homozygous genotype) was confirmed. Alpha 1-antitrypsin deficiency might have facilitated the development of chondrosarcoma. Because of a small incidence rate of such diseases, we presume that there is a slight chance for such rare disorders to manifest concurrently in the same patient.

In the study, the possible effect of sodium valproate (NaVP) on urethane-induced lung tumors in mice has been evaluated. BALB/c mice (n = 120; 4–6 weeks old, both sexes) were used in the following groups: 1) urethane-treated, 2) urethane–NaVP-treated, 3) only NaVP-treated, 4) control. In the same groups, castrated male mice (n = 48) were investigated. Urethane was given by intraperitoneal injections 10 mg/mouse, twice a week, the total dose 50 mg/mouse. In NaVP-treated mice, the 0.4 % NaVP aqueous solution was offered to mice ad libitum. The duration of the experiment was 6 months. The number of tumors per mouse in urethane– NaVP-treated males was significantly higher than in those treated with urethane only (13.82 ± 1.12 vs 6.77 ± 0.43, p < 0.0001). No significant difference in the number of tumors per mouse was revealed while comparing the female urethane- and urethane–NaVP-treated groups (6.50 ± 0.79 vs 8.15 ± 0.55, p = 0.105). No difference in the number of tumors per mouse was found in urethane–NaVP-treated castrated males as compared with urethane-treated castrated males. However, in the urethane–NaVP-treated castrated males the number of tumors per mouse was significantly lower than in analogous non-castrated males (7.8 ± 1.67 vs 13.82 ± 1.12, p < 0.01). NaVP combined with urethane potentiates urethane tumorigenicity in BALB/c non-castrated but not in female and castrated male mice. These data indicate an important role of testosterone in the urethane-NaVP induced lung tumorigenesis.

Sodium-dependent Cl−/HCO3− exchanger acts as a chloride (Cl−) efflux in lymphocytes. Its functional characterization had been described when Cl− efflux was measured upon substituting extracellular sodium (Na+) by N-methyl-D-glucamine (NMDG). For Na+ and Cl− substitution, we have used D-mannitol or NMDG. Thymocytes of male Wistar rats aged 7–9 weeks were used and intracellular Cl− was measured by spectrofluorimetry using MQAE dye in bicarbonate buffers. Chloride efflux was measured in a Cl−-free buffer (Cl− substituted with isethionate acid), in Na+ and Cl−-free buffer with D-mannitol or with NMDG. The data have shown that Cl− efflux is mediated in the absence of Na+ in a solution containing D-mannitol and is inhibited by H2DIDS. Mathematical modelling has shown that Cl− efflux mathematical model parameters (relative membrane permeability, relative rate of exchanger transition, exchanger efficacy) were the same in control and in the medium in which Na+ had been substituted by D-mannitol. The net Cl– efflux was completely blocked in the NMDG buffer. The same blockage of Cl− efflux was caused by H2DIDS. The study results allow concluding that Na+ is not required for Cl− efflux via Cl−/HCO3− exchanger. NMDG in buffers cannot be used for substituting Na+ because NMDG inhibits the exchanger.

Aim of this research was to investigate the functioning of chloride/bicarbonate exchanger in thymic lymphocytes in view of better understanding the mechanisms involved in chloride fluxes. Materials and methods: Experiments were performed using a suspension of freshly isolated thymocytes representing a homogeneous population of thymic lymphocytes. Thymic lymphocytes were isolated from Wistar male rats’ gl. thymus, 6 – 7 weeks of age. The cells were incubated with the MQAE chloride dye. Cl– concentration in the cytoplasm of lymphocytes was measured spectrophotometrically. A model of exchanger activation has been suggested based on the analysis of experimental data. Results and conclusion: It has been shown that: (a) involvement and activity of chloride transport mechanisms depend on where chloride concentration is made zero: in the medium or cytoplasm; (b) under certain experimental conditions, the activity of the exchanger proceeds in two steps: switching on and off; (c) in the absence of HCO3–, the relative rates of the exchanger transitions decline considerably, its efficacy remaining the same. Chloride/bicarbonate exchanger merits further research under conditions closer to physiological.

Physicians are obliged to provide treatment that is consistent with their commitment to avoid or minimize harm (nonmaleficence) and their commitment to do good (beneficence). Therefore, if patient’s desires were contradictory to the primary aim of medicine, the doctor’s calling would require him/her to thoroughly analyze the cause of the disease and provide an adequate as well as ethical treatment rather than obediently follow patient’s requests. Yet, chemical and surgical sex reassignment is one of the areas where some physicians surrender to the desire of their patients instead of finding out what their real condition is and trying to manage it in a way the essence of medicine would require. The objective of this article was to provide specific pharmacovigilance search details for the evaluation of the current situation and the scientific background of the treatment of gender dysphoria and to analyze its conformity with one of the two main ethical principles of medicine – nonmaleficence. Literature retrieval was accessed through Medline (1979–2011) using the terms “gender dysphoria,” “replacement hormonal therapy,” and “pharmacovigilance.” The article concludes that hormonal and surgical interventions have not proven to be medically justified and could be harmful, not treating the cause, but resulting in irreversible disability. Thus, these interventions contradict the principle of nonmaleficence and goals of basic therapeutics and pharmacovigilance. They are not based on clinical trials and are lacking a thorough follow-up assessment.

Conclusion: The understanding of the hypothesized NaVP mechanism may lead to the recognition of Cl– as an important mediator in tumor development and as a novel therapeutic target for cancer.

Aim and methods. Hypomagnesemia is a frequent adverse effect of chemotherapy in cancer patients. Its gender-dependent peculiarities are unknown. The aim of the current work was to define peculiarities of urinary magnesium (Mg) excretion in healthy adolescents; to elucidate gender-related differences in Mg urinary excretion; to determine a correlation between urinary Mg excretion and arterial blood pressure (BP) in healthy adolescents. Mg was examined in diurnal and nocturnal urine of adolescent boys (n = 27) and girls (n = 42) aged 13 - 17 years. Urinary Mg (both during day and night) was monitored 24-h concomitantly with BP (hourly) in 44 adolescents (22 girls and 22 boys). Additionally, of the same girls 15 were examined during different phases of their menstrual cycle (follicular, ovulation and luteal). Results. 24-h urinary Mg excretion was significantly higher in boys than in girls (2.66 +/- 0.9 mmol vs. 2.1 +/- 0.9 mmol; p < 0.05). Nocturnal systolic BP was significantl y higher (p < 0.05) in boys than in girls in all phases of their menstrual cycle. Diurnal systolic BP in boys was significantly higher than in girls during the follicular phase. It revealed a significant positive correlation between Mg excretion and BP in boys at night (p < 0.05). Girls exhibited a significant inverse correlation between Mg nocturnal excretion and BP (p < 0.05) during the luteal phase of their menstrual cycle, as well as a significant negative correlation between diurnal Mg excretion and BP (p < 0.05) during the ovulation phase. Urine Mg was negatively related to height in girls (p < 0.05). Conclusion. Mg urinary excretion is related to gender, height, circadian rhythm, and blood pressure. The further preclinical and clinical studies of gender-related risks of hypomagnesemia under chemotherapeutic treatment could contribute to improving the efficacy of anticancer treatment.

Daugelis vaistų vaikams naudojami neatlikus klinikinių vaistinių preparatų tyrimų, o tai reiškia, jog gamintojai, o kartu ir gydytojai, skirdami vaisto dozes pagal vaiko amžių ir svorį, neturi reikalingų veiksmingumo bei saugumo duomenų, nežino, kokia tokio gydymo nepageidaujamo poveikio tikimybė. Vaisto skyrimo būdai ir vartojamo vaisto formos vaikams turi būti moksliškai pagrįsti, nes kitaip yra galimybė gydyti nepakankama vaisto doze ar vaistas gali būti perdozuotas. Straipsnio tikslas - apžvelgti istorines susiklosčiusios vaikų gydymo vaistais padėties prielaidas bei apibendrinti teisinį pediatrinių klinikinių vaistinių preparatų tyrimų reglamentavimą, kuriuo siekiama užtikrinti, jog vaikai būtų gydomi saugiais ir veiksmingais vaistais Jungtinės Amerikos Valstijose ir Europos Sąjungoje. Straipsnyje tai pat pateikiama ir Lietuvos Respublikos teisės aktų, kurie reglamentuoja vaikų klinikinių tyrimų atlikimą, apžvalga.