Stimulation of corticosterone secretion by the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat

The selective 5-HT1A receptor agonist 8-OH-DPAT increased serum corticosterone concentration in rats in a dose-dependent manner. The synthetic corticoid dexamethasone lowered the serum corticosterone level and abolished its rise induced by 8-OH-DPAT. The corticosterone response to 8-OH-DPAT was also antagonized by spiperone, (+/-)- and (-)-pindolol and (+/-)-propranolol, all of which have been shown to have a high affinity for 5-HT1A receptors, though in most cases no complete blockade was found. A partial antagonism of the response was also observed after flumazenil, a benzodiazepine antagonist. On the other hand, the 5-HT1B receptor antagonist 21009, the 5-HT2 receptor antagonists ketanserin and pirenperone, the 5-HT3 receptor antagonist ICS 205-930, the alpha 2-adrenoceptor antagonists yohimbine and idazoxan, the beta-adrenoceptor blocker with no affinity to 5-HT1 receptors, atenolol, the dopaminergic antagonist pimozide, the histamine receptor blocker chloropyramine and the opiate receptor antagonist naloxone did not affect the hormonal response to 8-OH-DPAT. The 8-OH-DPAT-induced corticosterone secretion was not affected either in rats pretreated with p-chlorophenylalanine (PCPA, an inhibitor of tryptophan hydroxylase) or p-chloroamphetamine (PCA, a drug-inducing lesion of serotonergic nerve terminals). It is concluded that 8-OH-DPAT-induced increase in serum corticosterone concentration results from its action at a site different than the adrenal cortex and is mediated by postsynaptic 5-HT1A receptors, whereas other subtypes (5-HT1B, 5-HT2, 5-HT3) of 5-HT receptors do not participate in this response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microbial transformation of azacarbazoles. VI. Conversion of 6-hydroxy- and 6-amino-alpha-carbolines with copper oxidases

alpha-Carboline substituted at C-6 with hydroxy-group is oxidized by human ceruloplasmin and fungal laccase into reactive intermediate which dimerizes, while 6-amino-alpha-carboline subjected to action of both enzymes yields the polymeric products. To prepare sufficient quantities of compounds needed for structure elucidation studies, laccase, immobilised in polyacrylamide gel was employed as a convenient reagent. The resulting products are suggested to be metabolities of 6-hydroxy- and 6-amino-alpha-carbolines formed in vivo.     

Antioxidative and anti-inflammatory effects of repaglinide in plasma of diabetic animals.

Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense, is considered to be an important pathogenic factor in diabetes mellitus and its complications. In diabetic state, ROS might also be implicated in promoting a state of systemic inflammation. Recently, it was demonstrated that antioxidant therapy could be used to stop the initiation and propagation of this inflammatory response. Repaglinide is a new oral antidiabetic agent with a possible antioxidant activity. Therefore, in the present study, a possible therapeutic value of repaglinide in ameliorating the oxidative and inflammatory processes was tested in diabetic animals. In the study, the levels of total antioxidant status (TAS), ascorbic acid (AA), protein carbonyl groups (PCG) and interleukin-6 (IL-6) were determined in plasma of diabetic rabbits after 4 and 8 weeks of repaglinide treatment (1mg daily). Ex vivo analysis revealed that there were significant differences in these markers between hyperglycemic and control animals (P<0.05). Some of these parameters were ameliorated by repaglinide treatment. In diabetic rabbits treated with repaglinide, protein oxidation was diminished by 17.8% after 8 weeks of experiment. The level of AA in plasma of diabetic treated animals was higher than in non-treated diabetic groups (by 9.4 and 22.6% after 4 and 8 weeks, respectively). In diabetic treated animals, the TAS level was also significantly increased (by 23.6 and 16.7%). However, in diabetic rabbits, repaglinide did not affect the concentration of IL-6.     

"Taurolin-Gel" and Taurolin-Trockengel" in treatment of osseous tissue inflammation]

The activity and principles of administration of Taurolin have been presented. That drug was used in 15 patients with chronic osteitis. Healing by first intention was obtained in 10 patients, necrosis of the skin occurred in 3 patients, recurrence of inflammation was found in one patient in whom accessory sequestroctomy was performed in the last case of osteitis and arteriosclerosis healing was obtained by second intention. The clinical observation of 15 patients has revealed: a) irritating influence of Taurolin on the soft tissue, b) increased phase of secretion of exudate since the 5 day after surgery, c) bactericidal influence of the drug. Sterilization of the focus occurred at 2 to 3 weeks after surgery. The use of Taurolin requires experience, complete abiding by the principles of use of this drug and equipment with a set of Charrier's drains. The authors are carrying on further observation of the use of Taurolin in the treatment of osteitis.     

Polymyositis-dermatomyositis:25 years of follow-up of 50 patients disease course, treatment, prognostic factors

Therapeutic results were analysed in 50 patients, including 17 with polymyositis (PM) and 30 with dermatomyositis (DM). All patients were treated with prednisone (Encorton, Polfa) and 47% of patients with PM and 73% with DM required combined treatment with prednisone and cytostatic agents, mostly with cyclophosphamide (Endoxan G.D.R.). Long-term treatment monitored with the clinical status led to remissions persisting after treatment discontinuation in 17.6% of PM patients and 24.2% of DM patients. In 64.7% of PM patients and 57.6% of DM patients regression of the clinical signs of the disease was achieved but these patients required further treatment. No information was obtained on 5 cases. Four DM patients died. The cumulative 17-year survival rate of PM patients was 100%, and that of DM patients was 78.8% . In 45 follow-up cases, the mortality was 8.9%. Side effects of the combined treatment included most frequently mucosal candidiasis (22.2%), transient leucopenia (14.8%) and recurrent respiratory tract infections (11.1%). In 5 cases liver biopsy was done and histological examination disclosed moderate fatty, glycogen and vacuolar degeneration of the hepatocytes. The statistical analysis of prognostic factors such as the diagnosis of PM or DM, sex, age at disease onset, disease duration till diagnosis establishing and beginning of treatment, fever, dysphagia, circulatory and respiratory changes, leucocytosis nad ESR at the beginning of the disease showed that sex (female), older age at disease onset and respiratory system changes may be accepted as poor prognosis factors.