Franciszek Rogowski

Study of the mechanisms of aldosterone prothrombotic effect in rats.

Introduction: We investigated the role of primary haemostasis, fibrinolysis, nitric oxide (NO) and oxidative stress as well as mineralocorticoid receptors (MR) in acute aldosterone prothrombotic action. Materials and methods: Venous thrombosis was induced by stasis in Wistar rats. Aldosterone (ALDO; 10, 30, 100 µg/kg/h) was infused for 1 h. Eplerenone (EPL; 100 mg/kg, p.o.), a selective MR antagonist, was administered before ALDO infusion. Bleeding time (BT) and platelet adhesion to collagen were evaluated. The expression of nitric oxide synthase (NOS), NADPH oxidase, superoxide dismutase (SOD) and plasminogen activator inhibitor (PAI-1) was measured. NO, malonyl dialdehyde (MDA) and hydrogen peroxide (H2O2) plasma levels were assayed. Results: Significant enhancement of venous thrombosis was observed after ALDO infusion. ALDO shortened BT and increased platelet adhesion. Marked increases were observed in PAI-1, NADPH oxidase and SOD mRNA levels. MDA and H2O2 levels were augmented in ALDO-treated groups, and NOS expression and NO level were decreased. EPL reduced ALDO effects on thrombus formation, primary haemostasis, PAI-1 expression and MDA level. Conclusion: Short-term ALDO infusion enhances experimental venous thrombosis in the mechanism involving primary haemostasis, fibrinolysis, NO and oxidative stress-dependent pathways. The MR antagonist only partially diminished the ALDO effects, suggesting the involvement of additional mechanisms.

TNF family molecules in the serum of patients with B-cell chronic lymphocytic leukemia (B-CLL)

Tumor necrosis factor (TNF) superfamily, involving membrane receptors and ligands are important for the growth and survival of leukemic B cells. In the present study levels of TNF-alpha, sTNFRp55, sTNFRp75 and sCD40 and sCD40L in the serum of patients with B-CLL before and after treatment were measured. In sera of patients before treatment increased concentrations of sCD40 and decreased concentrations of sCD40L were shown. Increased concentrations of TNF-alpha and sTNFRp75 and lack of changes in sTNFRp55 concentrations were also found. Results obtained suggest that the relationships between examined soluble form of TNF family proteins may influence the development of B-cell chronic lymphocytic leukemia. The used therapy with 2CdA and CMC led to a favorable effect for host through changes in the relations between sCD40 and sCD40L. It was also found that sCD40 and sCD40L serum concentrations, which are dependent on the clinical stage and used therapy, are more sensitive tumor markers than TNF-alpha and its soluble receptor in patients with B-CLL treated with 2CdA and CMC.

Iodine isotope (131I) therapy for toxic nodular goitre: treatment efficacy parameters

BACKGROUND When planning radioactive iodine therapy, it frequently happens, both in Poland and world-wide, that inadequate attention is paid to such easily measurable parameter sas: 1) the serum concentration of thyrotropin (TSH) before administering radioiodine, which is a key factor for extranodular(non-autonomous) iodine uptake of the thyroid gland, 2) thyroid gland iodine uptake, and 3) the effective half-life of 131I (Teff.). The aim of the study is to evaluate the impact of the above factors on the efficacy of 131I treatment in hyperthyroid patients. METHODS The material consisted of 4140 patients: 2190 with autonomous toxic nodules (ATN) and 1950 with toxic multinodular goitres (TMG). The patients were prepared for treatment in such a way that the concentration of TSH did not exceed 0.1 mU/land Teff.< 5 days. The therapeutic activity of 131I was calculated using Marinellis formula. The selection of absorbed dose value was determined by the degree of suppression of extranodulart issue. Monitoring was performed every eight weeks. RESULTS At one year after 131I administration showed that a euthyroid status was achieved in 94%, hypothyroidism was seen observed in 3%, while persistence or recurrence of hyperthyroidism in 3% of ATN patients and, respectively, 89%, 4% and 7% of TMG patients. CONCLUSIONS Patients with toxic nodular goitre who are to be treated with radioiodine should have the lowest possible serum concentration of TSH. The suppression of extranodular determines the optimal value of absorbed dose for Marinellis formula.

Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter

BACKGROUND Radioiodine therapy (RIT) in patients with large nontoxic multinodular goiter (MNG) recently becomes more common method in comparison to surgery (especially in elderly patients and with contraindications because of severe chronic diseases other systems). Repeatedly low thyroid radioactive iodine uptake (RAIU) decreases effectiveness of RIT or makes it impossible. The recombinant human thyrotropin can increase RAIU and improve the results of RIT. THE AIM OF THE STUDY was to assess the influence of a single very low dose (0.03 mg) of rhTSH on RAIU and thyroid function in euthyroid (MNG-EU) and subclinical hyperthyroid (MNG-SC) patients with a large multinodular goiter. MATERIAL AND METHODS 40 patients (14 male, 26 female, age 57-80 yr) with large non-toxic MNG over 80 grams and with baseline RAIU < 40% were included into the double-blind randomized study and divided into two groups: rhTSH-group and control group. First group received the single intramuscular injection of 0.03 mg rhTSH and the second received placebo. The RAIU were measured 24 and 48 hours after the rhTSH and then all the patients were administered therapeutic doses of I-131. TSH and free thyroxine levels were measured at 1st and 2nd day after the injection of rhTSH and later, at 4 and 8 weeks after the RIT. RESULTS The mean RAIU increased significantly from 30.44 ± 7.4% to 77.22 ± 8.7% (p < 0.001). There were no statistically significant differences in RAIU between euthyroid (MNG-EU) and subclinically hyperthyroid (MNG-SC) patients. The peak of serum TSH was noticed 24 hours after rhTSH injection and in MNG-EU patients it has remained within normal range, similarly as fT4. In the MNG-SC group the administration of rhTSH resulted in a significant increase in the TSH values after 24 hours, whose mean level slightly exceeded the upper limit of the normal range with normalization at 48 hours. 8 weeks after the RIT, the TSH and fT4 levels did not exceed the normal range and did not differ in a statistically significant way. CONCLUSIONS Even the single very low dose of rhTSH increases the values of RAIU in significant way, in euthyroid and subclinically hyperthyroid patients. The administration of rhTSH is well-tolerated. Neoadjuvant administration of a low dose (0.03 mg) of rhTSH before I-131 seems to be an optimal method of management which may increase the effectiveness of RIT and decrease the exposure of the patients to absorbed doses of ionizing radiation.