A randomized clinical trial for the assessment of the efficacy and safety of guluronic acid (G2013) in patients with rheumatoid arthritis.

Objective: To evaluate the safety, efficacy and tolerability of guluronic acid (G2013) in order to treat the rheumatoid arthritis patients who had inadequate response to conventional drugs. Methods: A randomized, 12-week clinical trial with two treatment arms: guluronic acid (G2013) and conventional treatment was performed. The diagnosed RA patients according to the ACR/European League against Rheumatism 2010 classification criteria, with an active disease at baseline that had inadequate response to conventional therapy were considered for the study. G2013 was administered orally twice a day with capsules of 500 mg during a period of 12 weeks and the patients were followed up for the safety and efficacy. Results: Our data showed that, the mean changes in the G2013 and control groups were -7.54 and -2.5 for tender joint count; -7.59 and -3.59 for swollen joint count; -30 and -0.9 for physician global assessment; -23.18 and -1.81 for patient global assessment; -14.45 and -1.45 for erythrocyte sedimentation rate, respectively. Improvements seen with G2013 were significantly greater than those with conventional drugs. In total, in 15.3% of G2013-treated patients and 69.2% of conventional-treated patients adverse events (AEs) occurred in this study. Conclusion: These data from routine rheumatology clinical practice highlight the effectivenessof G2013 in combination with conventional therapy with more desirable safety profile compared to the conventional-treated patients. Therefore, G2013 therapy could be an appropriate choice in order to manage the RA disease. (Clinical trial identifier: IRCT2016092813739N5).

[Use of local hemostyptic drugs in liver resections]. / Vyuzití lokálních hemostyptik pri jaterních resekcích.

INTRODUCTION: Bleeding during and following liver resection continues to be an object of surgeon's attention and a potential source of significant morbidity. Topical hemostatic agents are used during surgical intervention when conventional methods are not sufficient because of the site of surgery or degree of bleeding. A variety of agents with different effects is now available. AIM: To verify the efficacy and safety of cellulose based local hemostat during liver resections. METHODS: In 67 cases of liver resection the surface was covered by Traumacel TAF net which was left in place. RESULTS AND CONCLUSION: There were no postoperative bleeding in this group of patients. No other serious complication has been observed. Traumacel is a safe and effective local hemostat during liver resections.

Angiogenesis and cardioprotection after TNFalpha-inducer-Tolpa Peat Preparation treatment in rat's hearts after experimental myocardial infarction in vivo.

The aim of the presented work was to evaluate whether short subcutaneous (s.c.) administration of TNFalpha-inducer-Tolpa Peat Preparation (TPP or TPP batch 0210) modulates the process of ischemic remodeling and spontaneous angiogenesis after experimental myocardial infarction (MI) in rats in vivo. The results obtained using three complementary and correlative methods: histological studies, Proliferating Cell Nuclear Antigen (PCNA) reaction and Lymphocytes Induced Angiogenesis (LIA) test showed a clear pro-angiogenic and cardioprotective effect of TPP administration after experimental MI. TPP batch 0210 should be considered as an angiogenesis stimulating factor and consecutively as a cardioprotective preventing development of ischemic cardiomyopathy after MI in rats. It might possibly be used as an adjunct to conventional therapy of coronary artery disease, including late phase after myocardial infarction or ischemic cardiomyopathy.

The influence of long-term administration of Tolpa Peat Preparation on immune reactivity in mice. III. The effect on primary humoral response to sheep erythrocytes.

Tolpa Peat Preparation (TPP) was administered to mice in daily doses of 1, 10 and 50 mg.kg-1 for 3, 5, 7, 9 or 12 consecutive weeks. After each of the above mentioned periods the primary response to sheep erythrocytes (SRBC) was examined by determination of the percentage of splenocytes forming E rosettes, the number of splenocytes producing anti-SRBC haemolysins of 19S and 7S type, and the level of serum haemagglutinins to SRBC (19S + 7S and 7S types). The effect of enhanced humoral response by TPP was observed in mice immunized with SRBC. This effect depended, first of all on TPP does but also on the duration of time TPP administration. The stimulating effect on the humoral response occurred after the daily dose of 1 mg.kg-1 during 12 weeks. On the other hand, the daily doses of 10 or 50 times higher enhanced the humoral response only during the first 5-7 weeks of TPP administration. Longer administration of TPP in these doses caused disappearance of this effect or reduction of the response to SRBC.

The effect of Tolpa Peat Preparation on the phagocytic and metabolic activity of neutrophils in normothermic rabbits and with pyrogen-induced fever.

The studies on normothermic rabbits show that intravenous administration of Tolpa Peat Preparation (TPP) at a dose of 5 mg/kg for 3 or 6 consecutive days increases the percentage of phagocytizing cells and the number of bacteria phagocytized by a single neutrophil. The stimulated phagocytic activity of neutrophils coincides with increased nitroblue tetrazolium (NBT) reduction. In contrast, a single administration of TPP to rabbits with fever induced by E.coli lipopolysaccharide (LPS) has a modulating effect on the metabolic activity of neutrophils, depending on TPP dose. TPP administered at a dose of 0.5 mg/kg potentiates the stimulating effect of pyrogen on the percent of NBT-positive neutrophils. A tenfold increase of TPP dose (5 mg/kg) reduces the stimulating effect of LPS and a hundredfold increase (50 mg/kg) leads to total inhibition of LPS-induced changes.

The influence of long-term administration of Tolpa Peat Preparation on immune reactivity in mice. I. Morphological changes in the thymus.

In experiment I BALB/c 200 mice were given in drinking water the TPP (Tolpa Peat Preparation) in daily doses of 1, 10 and 50 mg/kg over the period of 3, 5, 7, 9 and 12 weeks. In experiment II before the administration of TPP (as in experiment I) mice were immunized with a single dose i.p. administration of 0.2 cm3 of a 10% suspension of sheep erythrocytes (SRBC), i.e. 4 x 10(8) cells. Histopathological and ultrastructural studies have shown that TPP in all three doses causes morphological changes characteristic of thymus activity stimulation. However, the doses of 10 and 50 mg/kg administered longer than 7 weeks caused retrograde changes that did not occur after administration of 1 mg/kg of TPP. Morphological changes in the thymus of immunized and non-immunized mice simultaneously receiving TPP were similar.

The influence of long-term administration of Tolpa Peat Preparation on immune reactivity in mice. II. The effect of intermittent TPP administration on the morphological picture of lymphatic organs.

The studies were conducted on 200 Balb/c mice (inbred strain), aged 8 weeks. The mice were administered Tolpa Peat Preparation (TPP) in drinking water (10 or 50 mg/kg/day) for seven weeks (experiment I). Two lobes of the thymus, the spleen and the axillary and mesenteric lymph nodes of mice were taken for histological examinations after 3, 5 and 7 weeks of continuous TPP treatment and also 12 and 16 weeks from the beginning of the treatment. In experiment II, TPP was administered daily at the same doses for 3 weeks, and intermittently for 9 consecutive weeks; a week interval followed each seven-day cycle. The lymphatic organs of mice were taken for histological examinations after 3, 5, 7, 9 and 12 weeks of TPP treatment. It was found that daily administration of TPP (as described above) to mice for 7 weeks (10 mg/kg) induced a marked stimulation of the lymphatic organs (in the first weeks of TPP treatment) and resulted in retrograde changes (depletion of thymocytes and lymphocytes) in the lymphatic structures when TPP administration was prolonged (4-7 weeks). The morphological changes due to TPP administered at the dose of 50 mg/kg were less pronounced in the organs examined. The retrograde changes in the lymphatic structures disappeared 9 weeks after TPP treatment had been stopped. Similarly, the changes showing stimulation of the lymphatic organs were maintained throughout the entire period of 9 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of hepatic lipogenesis by pectin and galacturonic acid orally-fed at the separate timing from digestion-absorption of nutrients in rat.

This study was conducted to know the possibility that pectin-induced alterations in lipid metabolism of animals might be partly ascribed to galacturonic acid produced by the degradation of ingested pectin in the digestive tract. After a 4-week meal feeding twice a day, fasted rats were fed glucose and fructose and 3 h later orally administered 213 mg of pectin (from apple) or galacturonic acid per kg of body weight, or fed water alone. Significant changes in serum and liver lipids were observed 30 min and 1 h after the administration of pectin and galacturonic acid but not 5 h after the administration. Pectin and galacturonic acid showed contradictory effects on serum lipids, adipose tissue lipoprotein lipase activity and triacylglycerol (TG) production and removal rates. However, the elevation of total lipid and TG levels in liver with the sugar feeding was significantly inhibited by the administration of either pectin or galacturonic acid. These results support our hypothesis that galacturonic acid produced by the degradation of ingested pectin in the digestive tract may be partly responsible for the pectin-induced changes in lipid metabolism. This was discussed in relation to another possible regulation of lipid metabolism by short-chain fatty acids which are produced by the intestinal fermentation of pectin and galacturonic acid.