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Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease specific to pregnancy. The cardinal symptom of pruritus and a concomitant elevated level of bile acids in the serum and/or alanine aminotransferase (ALT) are suggestive for the diagnosis. Overall, the maternal prognosis is good. The fetal outcome depends on the bile acid level. ICP is associated with increased risks for adverse perinatal outcomes, including preterm delivery, meconium-stained amniotic fluid, and stillbirth. Acute fetal asphyxia and not chronic uteroplacental dysfunction leads to stillbirth. Therefore, predictive fetal monitoring is not possible. While medication with ursodeoxycholic acid (UDCA) improves pruritus, it has not been shown to affect fetal outcome. The indication for induction of labour depends on bile acid levels and gestational age. There is a high risk of recurrence in subsequent pregnancies.Zusammenfassung Die Schwangerschaftscholestase (Intrahepatic Cholestasis of Pregnancy, ICP) ist die haufigste schwangerschaftsspezifische Lebererkrankung. Das Leitsymptom Juckreiz und eine begleitende Konzentrationserhohung von Gallensauren im Serum und/oder der Alanin-Aminotransferase (ALT) sind richtungsweisend fur die Diagnosestellung. Insgesamt ist die mutterliche Prognose gut. Das fetale Outcome ist abhangig von der Gallensaurenkonzentration. Die ICP ist sowohl mit einer Fruhgeburt als auch mit dem intrauterinem Fruchttod (IUFT) assoziiert. Ursachlich ist eine akute fetale Asphyxie und nicht eine chronische uteroplazentare Dysfunktion. Daher ist ein pradiktives Monitoring, z.B. durch CTG oder Ultraschall nicht moglich. Eine medikamentose Therapie mit Ursodeoxycholsaure (UDCA) bessert den Juckreiz - beeinflusst jedoch das fetale Outcome nicht nachweislich. Eine Entbindungsindikation ergibt sich in Abhangigkeit der Gallensaurenkonzentration und des Gestationsalters. In Folgeschwangerschaften besteht ein hohes Wiederholungsrisiko.

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease specific to pregnancy. The cardinal symptom of pruritus and a concomitant elevated level of bile acids in the serum and/or alanine aminotransferase (ALT) are suggestive for the diagnosis. Overall, the maternal prognosis is good. The fetal outcome depends on the bile acid level. ICP is associated with increased risks for adverse perinatal outcomes, including preterm delivery, meconium-stained amniotic fluid, and stillbirth. Acute fetal asphyxia and not chronic uteroplacental dysfunction leads to stillbirth. Therefore, predictive fetal monitoring is not possible. While medication with ursodeoxycholic acid (UDCA) improves pruritus, it has not been shown to affect fetal outcome. The indication for induction of labour depends on bile acid levels and gestational age. There is a high risk of recurrence in subsequent pregnancies.Zusammenfassung Die Schwangerschaftscholestase (Intrahepatic Cholestasis of Pregnancy, ICP) ist die haufigste schwangerschaftsspezifische Lebererkrankung. Das Leitsymptom Juckreiz und eine begleitende Konzentrationserhohung von Gallensauren im Serum und/oder der Alanin-Aminotransferase (ALT) sind richtungsweisend fur die Diagnosestellung. Insgesamt ist die mutterliche Prognose gut. Das fetale Outcome ist abhangig von der Gallensaurenkonzentration. Die ICP ist sowohl mit einer Fruhgeburt als auch mit dem intrauterinem Fruchttod (IUFT) assoziiert. Ursachlich ist eine akute fetale Asphyxie und nicht eine chronische uteroplazentare Dysfunktion. Daher ist ein pradiktives Monitoring, z.B. durch CTG oder Ultraschall nicht moglich. Eine medikamentose Therapie mit Ursodeoxycholsaure (UDCA) bessert den Juckreiz - beeinflusst jedoch das fetale Outcome nicht nachweislich. Eine Entbindungsindikation ergibt sich in Abhangigkeit der Gallensaurenkonzentration und des Gestationsalters. In Folgeschwangerschaften besteht ein hohes Wiederholungsrisiko.

Intrahepatic cholestasis of pregnancy (ICP) is the most frequent pregnancy-specific liver disease. It is characterized by pruritus and an accompanying elevation of serum bile acid concentrations and/or alanine aminotransferase (ALT), which are the key parameters in the diagnosis. Despite good maternal prognosis, elevated bile acid concentration in maternal blood is an influencing factor to advers fetal outcome. The ICP is associated with increased rates of preterm birth, neonatal unit admission and stillbirth. This is the result of acute fetal asphyxia as opposed to a chronic uteroplacental insufficiency. Reliable monitoring or predictive tools (e.g. cardiotocography (CTG) or ultrasound) that help to prevent advers events are yet to be explored. Medicinal treatment with ursodeoxycholic acid (UDCA) does not demonstrably reduce adverse perinatal outcomes but does improve pruritus and liver function test results. Bile acid concentrations and gestational age should be used as indications to determine delivery. There is a high risk of recurrence in subsequent pregnancies.

Intrahepatic cholestasis of pregnancy (ICP) is the most frequent pregnancy-specific liver disease. It is characterized by pruritus and an accompanying elevation of serum bile acid concentrations and/or alanine aminotransferase (ALT), which are the key parameters in the diagnosis. Despite good maternal prognosis, elevated bile acid concentration in maternal blood is an influencing factor to advers fetal outcome. The ICP is associated with increased rates of preterm birth, neonatal unit admission and stillbirth. This is the result of acute fetal asphyxia as opposed to a chronic uteroplacental insufficiency. Reliable monitoring or predictive tools (e.g. cardiotocography (CTG) or ultrasound) that help to prevent advers events are yet to be explored. Medicinal treatment with ursodeoxycholic acid (UDCA) does not demonstrably reduce adverse perinatal outcomes but does improve pruritus and liver function test results. Bile acid concentrations and gestational age should be used as indications to determine delivery. There is a high risk of recurrence in subsequent pregnancies.

The aim of this meta-analysis based on the literature was to gather all evidence of randomized clinical trials to assess the efficacy of adenosylmethionine (SAM) and oxaceprol in the treatment of osteoarthritis. Findings in MEDLINE and EMBASE were added to publications catalogued by the AkdA and a reference search. The meta-analysis was based mostly on pain scores but also on pain and function scores. We used the fixed effects and the random effects model.A superiority of SAM vs placebo ( n=468) could not be shown; the 95% CI of standardized difference of pain scores was (-0.89, 0.12). The comparison of SAM vs NSAIDs with seven studies ( n=850) did not show a difference: (-0.59, 0.19). This cannot be seen as proof for equivalence. A post-hoc analysis of SAM vs ibuprofen gave nearly a positive result for SAM: (-0.43, 0.02). No adequate placebo-controlled RCT was found. There was no significance for a difference between oxaceprol and NSAIDs using the four trials found (two diclofenac and two ibuprofen); the 95% CI of standardized difference of pain and function scores was (-0.19, 0.27). Since only a few trials with heterogeneous results were found which mostly have a low quality of the studies and/or publications, the results must be interpreted very carefully. The meta-analysis does not give enough evidence for the efficacy of SAM and oxaceprol for treating the symptoms of osteoarthritis, but it might be that there is a comparable effect to other NSAIDs.

This report deals with a prospective study of 21 patients with finger osteoarthritis treated over a period of three months with either Ademetionin (therapy group: 14/21) or without (control group: 7/21). MR-Imaging was carried out before and after treatment using spin-echo and 3D-Flash sequences. Morphological parameters and signal intensity changes of the hyaline cartilage were evaluated. The increase of the cartilage signal intensity was significant in the therapy group, this can be interpreted as an structural improvement. Also a decrease of the cartilage signal intensity with age was found. The morphological parameters showed no significant changes in the therapy and control groups.

The basic therapeutic principle in alcoholic liver diseases in general and in alcoholic hepatitis in particular is the consequent withdrawal of alcohol intake. Basic therapy of more complicated causes includes well balanced nutrition and symptomatic treatment according to the known principles of hepatology and intensive care medicine. Infusions with glucose-glucagon-insulin, or the administration of silymarin, and in individual cases of glucocorticoids seems to be justified as additional treatment. The therapy with S-adenosyl-L-methionine is promising, but clear evidence of the therapeutic effect has to be supplied by clinical studies. Liver transplantation should be taken into consideration in prognostically infaust cases.

After a brief summary of the pathophysiology and natural history of different cholestatic disorders novel forms of treatment are considered. Treatment of different syndromes with ursodeoxycholic acid is considered in some depth. While the substance has clearly proven its efficacy in the symptomatic treatment, its influence on hard parameters such as survival and transplantation requirements remains to be documented. S-adenoylmethionine has shown to be efficaceous in some but not all studies on pruritus of pregnancy. The substance holds promise in other cholestatic disorders as well, but clearly more studies are needed before its therapeutic potential can be appreciated. Finally, nowadays orthotopic liver transplantation should be considered early in patients with progressive cholestatic liver disorders.

A standardized pharmacological model of biochemically induced osteoarthritis in the knee joint of laboratory animals was used for the study of a possible antidegenerative effect of ademetionine (S-adenosyl-methionine, active substance of Gumbaral) in-vivo. Four days after the initial induction of osteoarthritis by 2 intraarticular injections of 0.6 mg sodium iodoacetate into the left knee joint of adult hens, the therapy started with once-weekly intraarticular doses of 0.5 mg, 1.0 mg and 2.0 mg ademetionine over a period of 14 weeks. Quantitative monitoring of the intensity and progression of osteoarthritis was performed every 2 weeks by joint space measurements, topographic-radiological evaluations, and by a macroscopic post-mortem assessment of the joint cartilage and bone. These objective analytical parameters clearly demonstrated that weekly intraarticular doses of 1.0 mg ademetionine significantly reduced the intensity of degenerative processes compared to the placebo (saline) treated joints. The antidegenerative effect of doses of 0.5 mg or 2.0 mg ademetionine were less pronounced and of no statistical significance. Our findings indicate an interesting therapeutic potency of ademetionine in experimental osteoarthritis and confirm the positive clinical observations as well as in-vitro results with this new drug by other researchers.

The report deals with a double-blind study of nine patients treated over a period of three months with either ademetionin (five patients) or with a placebo (four patients). Prior to treatment, and after three months, clinical and biochemical studies were carried out as well as radiological examinations and MRT. The latter had been standardised previously in order to obtain a cartilage signal which could be quantified. Of the five patients treated with ademetionin, none were improved clinically, two were worse and three were unchanged, but on MRT, three were improved, one was worse and one was unchanged. Amongst the placebo patients, the clinical results were: three improved, none worse and one unchanged, with similar findings on MRT. MRT appears to be useful for complementing the information for treatment planning with chondroprotective drugs.

Experience in therapy with sulindac and S-adenosyl-L-methionine (SAMe) is reported. Sulindac is an indene derivative which is particularly indicated in degenerative skeletal diseases and is essentially free from the well-known side-effects of traditional analgesics. The results of therapy were good in 75%. SAMe is the most important methyl group donor and is consequently responsible for the methylation (inactivation) of histamine, upon which its antiphlogistic action is based. SAMe is also particularly involved in the transfer of sulfate groups in the body. Sulfur compounds are esentially involved in the synthesis of cartilage. The short-term trials with SAMe were altogether more favorable than the longterm trials, yet there was a longterm effect in about half the cases.

In the yeasts C. albicans, C. tropicalis, and C. stellatoidea but not in C. krusei, R.rubra, and S. cerevisiae enzyme activity was found by which--as by the catechol-O-methyltransferase (EC 2.1.1.6) found in the liver--the O-methylation of epinephrine to metanephrine and paranephrine, of 3,4-dihydroxybenzoic acid to 4-hydroxy-3-methoxybenzoic acid and 3-hydroxy-4-methoxybenzoic acid, and of 6,7-dihydroxycoumarin to 7-hydroxy-6-methoxycoumarin and 6-hydroxy-7-methoxycoumarin is catalysed. When the substrates 3,4-dihydroxybenzoic acid, or 6,7-dihydroxycoumarin or epinephrine were incubated in the presence of S-adenosyl-L-[methyl-14C]methionine and S-adenosylmethionine hydrogensulfate with a 100 000 X g supernatant of C. albicans, C. tropicalis or C. stellatoidea the corresponding O-methylethers were detected in the extracts of the incubation medium by thin-layer chromatography. Final identification of the isomeric radioactive O-methylethers obtained from 3,4-dihydroxybenzoic acid and 6,7-dihydroxycoumarin was performed after thin-layer chromatographic separation by the reversed isotope dilution technique. The radioactive m- and p-O-methyl derivatives from epinephrine were separated by thin-layer chromatography and then cleaved with periodate to the corresponding aldehydes which were also identified mainly by the reversed isotope dilution technique.

A method for the determination of catechol-methyltransferase activity is described, based on the measurement of fluorometric intensity of 7-hydroxy-6-methoxycoumarin (scopoletin), enzymatically produced by dihydroxycoumarin in the presence of the methyl donor S-adenosylmethionine.