Effects of glycosaminoglycan polysulphate in the treatment of chondrocalcinosis.

The effect of intra-articular injections of glycosaminoglycan polysulphate (Arteparon) on pain, joint mobility, inflammatory reactions, cartilage calcification and the urinary excretion of inorganic pyrophosphate was studied in 12 patients with chondrocalcinosis. All cases were bilateral and the less affected homologous joint served as an untreated control. The patients were followed over a one-year period. The glycosaminoglycan polysulphate treatment brought about a significant reduction of pain (p less than 0.01) and improvement of joint mobility (p less than 0.001). This effect continued for the whole one-year follow-up period, but could not be seen in the control joints. After the treatment period of 2-7 weeks there was a marked decrease in cartilage calcification paralleled with an increase in the excretion of inorganic pyrophosphate.

Effect of sample handling on alkaloid and mineral content of aqueous extracts of greater celandine (Chelidonium majus L.).

The authors examined the extraction of alkaloids from the greater celandine (Chelidonium majus L.) by different methods (traditional pressing and tea making, microwave and supercritical fluid extraction). The extractants were water and propylene glycol. For comparison of the extraction methods, the yield was evaluated according to total alkaloid content measured by spectroscopy. The highest alkaloid yield was obtained by microwave extraction and by making tea. Distribution of the components was studied by thin-layer chromatography and densitometry. The concentration and the ratio of alkaloid components in extracts are significantly different depending on the extraction method. The solution obtained by supercritical fluid extraction contains coptisine and chelidonine, while berberine could be obtained by microwave extraction only. Extracts with high coptisine content were obtained by supercritical fluid extraction, followed by pressing and microwave extraction. Mineral element content of the drug and extracts was also determined by inductively coupled plasma atomic emission spectrometry. Element content (Na, Ca, Fe) was found to be highest in microwave extracts.

[Serum keratan sulfate studies and their significance in the evaluation of cartilage degradation in degenerative and inflammatory joint diseases]. / Szérum keratán szulfát vizsgálatok és jelentöségük a porcdegradáció megítélésében degeneratív és gyulladásos ízületi betegségekben.

Fragments of high density cartilage proteoglycan (aggrecan) are released during either the normal or pathological turnover of cartilage proteoglycans, which fragments diffuse into the synovial fluids and then appear in the serum. The keratan sulphate (KS; a glycosaminoglycan side chain of aggrecan) is resistant to enzymatic degradation, it has a relatively low clearance and has a "standard" serum level indicating the actual level of cartilage (proteoglycan) breakdown. Using anti-KS monoclonal antibody in ELISA (enzyme-linked immunosorbent assay), we measured serum KS levels in patients with different joint diseases. The highest KS content (595 ng/ml) was measured in the sera of patients with articular chondrocalcinosis (calcium pyrophosphate crystal deposition disease/pseudogout). Slightly lower KS levels were determined in osteoarthrosis (OA; 578 ng/ml) and much less in rheumatoid arthritis (RA; 421 ng/ml). All these patient groups (either with degenerative or inflammatory joint diseases) expressed slightly higher KS levels compared to control blood donors (295 ng/ml). However, there were remarkable variations between these diseased groups, i. e., KS levels in patients with RA were significantly lower than in patients with OA (p < 0.001) and this difference was more pronounced in rheumatoid patients with I-II Steinbrocker stage (370 ng/ml) or in those treated with non-steroid anti-inflammatory drugs (NSAIDs) (382 ng/ml). Keratan sulphate levels in RA patients chronically treated with corticosteroid (460 ng/ml) or auro-thiomalat (473 ng/ml) indicate that these drugs may influence the cartilage metabolism more effectively than the NSAIDs.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pathogenesis of Sudeck's syndrom and a new possibility for its treatment (author's transl)]. / A Sudeck-szindróma patogenetikája és új kezelési lehetösége.

Authors describe the microcircular haemodynamics of Sudeck's syndrom together with the characteristic vitious circle of pain, rigidity, oedema and osteoporosis. Based on theoretical considerations and own results the infusion of dextran (Rheomacrodex 10%) as a pathogenetic base therapy is recommended. For increasing efficiency according to their experiences early treatment is suggested.

[Effect of arteparon on the formation of calcium phosphate and calcium pyrophosphate crystals--comparative experimental study]. / Wirkung von Arteparon auf die Bildung von Calciumphosphat- und Calciumpyrophosphatkristallen--Vergleichende experimentelle Untersuchung.

The influence of Arteparon on crystal formation in vitro has been examined in calcium orthophosphate and in calcium pyrophosphate mixtures. Similar factors may be operative in the cartilage calcification processes, and thus in chondrocalcinosis. Authors have ascertained that Arteparon - like chondroitin sulphate - inhibits crystal separation. The optimal concentration for this inhibition lies in the range of the proteoglycan content of normal cartilage. Where there are physiological phosphate-pyrophosphate ratios and a low magnesium concentration, it is certain that Arteparon has an inhibiting effect. Apart from the spatial structure of the substance, the importance of negative charge density for the inhibition of separation of calcium phosphate and pyrophosphate crystals is thought to contribute to this effect of Arteparon.

The effect of proteoglycans of cartilage and over-sulphated polysaccharides on the development of calcium-hydroxy-apatite (CHA) crystal formation in vitro.

A coulometric model system is described which facilitates the quantitative study of the kinetics of transformation of amorphous calcium phosphate (ACP) into calcium-hydroxy-apatite (CHA) crystals. Proteoglycans of high molecular weight and over-sulphated polysaccharides (Arteparon, dextran sulphate) delayed CHA crystal formation. The results have enabled us to characterize the structure activity relationship of inhibitors of CHA formation, and to postulate a general structural requirement for molecules with inhibitory effect. As working mechanism, binding of calcium ions by sulphate groups of polyanions was supposed, which might reversibly impair "the critical nuclei formation", and/or further deposition of calcium ions in the CHA crystals. The clinical, therapeutical significance of the determination of the threshold concentration of different compounds is discussed.

Dose-dependent effect of folic acid on the prevention of orofacial clefts.

OBJECTIVE: In 1982, Tolarova(4) found a reduction in the recurrence rate of isolated cleft lip (CL) with or without cleft palate (CP; CL +/- CP) after periconceptional supplementation with a multivitamin including a very high dose (10 mg) of folic acid. The Hungarian randomized, double-blind, controlled trial of periconceptional supplementation with a multivitamin including a physiologic dose (.8 mg) of folic acid did not show any preventive effect on the first occurrence of isolated CL +/- CP and CP. However, the general evaluation of congenital abnormalities in the Hungarian Case-Control Surveillance of Congenital Abnormalities indicated, among others, a reduction of isolated CL +/- CP and CP after the use of high doses of folic acid in the critical period for the development of these congenital abnormalities in the 12-year dataset between 1980 and 1991. We hypothesized that the prevention of orofacial clefts by folic acid has a dose-dependent effect, and this hypothesis was tested in 2 recent Hungarian datasets. DESIGN: In a prospective cohort study, the occurrence of isolated CL +/- CP and CP was studied in the newborn infants born to mothers with or without periconceptional folic acid-containing (.8 mg) multivitamin supplementation. Supplemented women with confirmed pregnancy were recruited from the participants of the periconceptional service. Unsupplemented women were invited to take part in the study after the first visit between the 8th and 12th week of gestation in the antenatal care. Supplemented and unsupplemented women were matched based on age, socioeconomic status, and residence. In contrast, the occurrence of high-dose (in general daily 6 mg) folic acid supplementation was evaluated in the case-control pairs of CL +/- CP and CP, particularly during the critical period of these 2 types of orofacial clefts in the 17 years dataset of the Case-Control Surveillance of Congenital Abnormalities, between 1980 and 1996. Cases were selected from the population-based Hungarian Congenital Abnormality Registry, whereas population controls without congenital abnormality were ascertained from the national birth registry. Two population controls were matched to every case according to sex, week of birth, and district of parental residence. The drug uses, including pregnancy supplements as folic acid, were evaluated based on retrospective self-reported maternal questionnaire and prospective medically documented data of antenatal care logbook. RESULTS: In the prospective cohort study, of 3019 informative offspring (termination of pregnancies in the second and third trimesters because of fetal defect, stillborn fetuses, and liveborn infants) in the supplemented group, 3 had CL +/- CP and 1 was affected with CP, whereas of 3432 informative offspring in the unsupplemented group, 2 had CL +/- CP and 1 had CP. The lack of preventive effect was in agreement with the result of the previous Hungarian randomized double-blind controlled trial; thus, these 2 datasets were combined. The preventive effect of a folic acid containing multivitamin used in the periconceptional period for the first occurrence of isolated CL +/- CP and CP was estimated by the Mantel-Haenszel test. Of 5488 supplemented women, 6 had CL +/- CP, and of 5821 unsupplemented women, 4 had CL +/- CP. Of 5489 supplemented women, 1 had CP, and of 5823 unsupplemented pregnant women, 3 had CP. The Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996, included 38 151 population controls (1.8% of the Hungarian births) and 22 865 cases with congenital abnormalities. Within the latter group, 1368 had isolated CL +/- CP, and 596 had CP. A significantly more frequent use of high-dose folic acid (in general daily 6 mg) supplementation was found in controls than in cases of 1246 case-control pairs of CL +/- CP group and of 537 case-control pairs of CP group, respectively. (ABSTRACT TRUNCATED)