Analysis of treatment efficacy and safety with leflunomide according to patients’ age and rheumatoid arthritis duration

Celem artykułu jest ocena skuteczności i bezpieczeństwa terapii leflunomidem w zależności od wieku chorych oraz czasu trwania reumatoidalnego zapalenia stawów (RZS). Bezpieczeństwo terapii leflunomidem przeanalizowano w grupie 261 pacjentów, porównując liczbę działań niepożądanych będących przyczyną przerwania terapii oraz liczbę działań niepożądanych leku niebędących przyczyną odstawienia leku, w zależności od wieku chorych, a także czasu trwania reumatoidalnego zapalenia stawów. W trakcie 6-miesięcznej obserwacji leczenie przerwało 27 pacjentów. Skuteczność terapii leflunomidem analizowano w grupie pozostałych 234 pacjentów na podstawie różnicy wartości wskaźnika DAS 28, ocenianego przed rozpoczęciem leczenia i po sześciu miesiącach terapii w zależności od wieku pacjentów. Wyniki potwierdziły skuteczność terapii leflunomidem we wszystkich grupach wiekowych chorych. Nie stwierdzono statystycznie istotnych różnic w skuteczności terapii w zależności od wieku pacjentów. Działania niepożądane leflunomidu wystąpiły u 47 chorych (18,8%), a u 23 (8,8%) były przyczyną przerwania terapii. Nie stwierdzono różnic statystycznie istotnych w występowaniu działań niepożądanych w zależności od wieku pacjentów oraz czasu trwania choroby podstawowej.Aim of the study: Evaluation of safety and therapeutic effectiveness of leflunomide according to age of the patients and duration of rheumatoid arthritis. Methods: Leflunomide therapy safety was analyzed in a group of 261 patients based on number of adverse effects responsible for treatment interruption and according to adverse effects number that allowed for continuing therapy. During six-month observation 27 patients interrupted therapy and in the group of remaining 234 persons leflunomide therapy efficacy was evaluated according to DAS-28 score. Results: Efficacy of leflunomide therapy was confirmed in every group according to patients age and no significant differences were observed between groups of patients with different age. Adverse leflunomide effects occurred in 47 (18.8%) patients and were the cause of therapy interruption in 23 (8.8%) cases. No significant differences in adverse leflunomide effects were observed to depend on patients age or rheumatoid arthritis period. Conclusions: (1) Patients’ age and period of rheumatoid arthritis do not influence leflunomide therapy safety. (2) Efficacy of leflunomide was confirmed in each group of patients. (3) Patients’ age does not influence leflunomide therapy outcome

Effect of haloxyfop and cerulenin on de novo biosynthesis of lipids in roots of wheat and maize

The study examines the effects of haloxyfop (herbicide) and cerulenin (antibiotic) on de novo biosynthesis of fatty acids and complex lipids in roots of two sensitive species: wheat and maize. Seedlings were grown in hydroponic cultures with addition of [1-14C]acetate (control) and [1-14C]acetate together with one of the tested substances. Neither haloxyfop nor cerulenin prevented the uptake of [1-14C]acetate by the roots of tested species. In contrast, a strong inhibition of de novo biosynthesis of fatty acids was observed after a 4-h treatment. This phenomenon, however, tended to disappear with treatment time. After a 24-h incubation, the amount of radioactivity in de novo biosynthesized fatty acids in 1-cm-long root tips was up to three times higher than in the untreated control. In the "rest of roots", restoration of fatty acid biosynthesis capacity was less pronounced. Besides the effect on fatty acid biosynthesis, both tested inhibitors strongly suppressed the de novo biosynthesis of non-fatty acid-containing lipids. Analyses of radioactivity in individual lipid classes showed that after a 4-h treatment with haloxyfop or cerulenin the biosynthesis of most of the lipid classes was inhibited, although not to the same extent. After a 24-h treatment, an inhibition of de novo biosynthesis of some of the lipids was still observable, whereas the biosynthesis of others, especially phosphatidylethanolamine and phosphatidic acid, was strongly up-regulated. Contrary to the mainstream view that inhibition of fatty acid biosynthesis is the cause of haloxyfop and cerulenin phytotoxicity, the obtained results suggest multidirectional effects of both inhibitors

Detailed characterization of the substrate specificity of mouse wax synthase

Wax synthases are membrane-associated enzymes catalysing the esterification reaction between fatty acyl-CoA and a long chain fatty alcohol. In living organisms, wax esters function as storage materials or provide protection against harmful environmental influences. In industry, they are used as ingredients for the production of lubricants, pharmaceuticals, and cosmetics. Currently the biological sources of wax esters are limited to jojoba oil. In order to establish a large-scale production of desired wax esters in transgenic high-yielding oilseed plants, enzymes involved in wax esters synthesis from different biological resources should be characterized in detail taking into consideration their substrate specificity. Therefore, this study aims at determining the substrate specificity of one of such enzymes -; the mouse wax synthase. The gene encoding this enzyme was expressed heterologously in Saccharomyces cerevisiae. In the in vitro assays (using microsomal fraction from transgenic yeast), we evaluated the preferences of mouse wax synthase towards a set of combinations of 11 acyl-CoAs with 17 fatty alcohols. The highest activity was observed for 14:0-CoA, 12:0-CoA, and 16:0-CoA in combination with medium chain alcohols (up to 5.2, 3.4, and 3.3 nmol wax esters/min/mg microsomal protein, respectively). Unsaturated alcohols longer than 18°C were better utilized by the enzyme in comparison to the saturated ones. Combinations of all tested alcohols with 20:0-CoA, 22:1-CoA, or Ric-CoA were poorly utilized by the enzyme, and conjugated acyl-CoAs were not utilized at all. Apart from the wax synthase activity, mouse wax synthase also exhibited a very low acyl-CoA:diacylglycerol acyltransferase activity. However, it displayed neither acyl-CoA:monoacylglycerol acyltransferase, nor acyl-CoA:sterol acyltransferase activity

Biosynthesis and Transfer of α-Elostearic Acid In Vivo in <i>Momordica charantia</i> L. Developing Seeds and In Vitro in Microsomal Fractions of These Seeds

The research concerned the efficiency of biosynthesis and transfer to triacylglycerols (TAG) of α-eleostearic acid (αESA). The experiments were carried out on developing seeds of Momordica charantia L. and on microsomal fractions obtained from these seeds. The seeds from in vivo conditions were collected 20, 23, 26 and 33 days after pollination (DAP) and used for lipid extraction and further analyses. Microsomal fractions were prepared from seeds at 26 DAP. The most intensive lipid accumulation occurred between 20 and 26 DAP, but continued up to 33 DAP. The most abundant lipid fraction was TAG; up to 98% of total acyl lipids at 33 DAP. The synthesised in vivo αESA was very efficiently transferred to TAG and constituted about 60% of its total fatty acids in 33 DAP. The content of αESA in polar lipids (containing, among others, phosphatidylcholine—the place of αESA biosynthesis) was very low. The biosynthesis of αESA in vitro (assays with microsomal fractions and [14C]-labelled substrates) in the presence of NADPH was fairly intensive (about 60% of the corresponding intensity in vivo) when linolenic acid was used as a substrate. Contrary to the in vivo condition, most of the synthesised in vitro αESA remained in phosphatidylcholine