Synergism between long-acting bromocryptine microcapsules and cyclosporine A in the prevention of various autoimmune diseases in rats

Pre-treatment of male Sprague-Dawley rats with long-acting bromocryptine microcapsules (CBLA) significantly inhibited the arthritic response to Freund's complete adjuvant and reduced weight loss, thymolysis, splenomegaly and leukocytosis. In the prevention of adjuvant arthritis (AA), the combination of CBLA plus sub-optimal doses of cyclosporine A (CsA) was more efficient than either of the drugs alone. Sub-optimal doses of CsA were 0.1 and 1.0 mg/kg/day s.c. for 5 days. Furthermore, CBLA alone did not decrease the incidence of experimental allergic uveitis (EAU) in the male Lewis rats. Low-dose CsA reduced the incidence of uveitis by 50%, and with the addition of CBLA, 100% of rats were protected. Low-dose CsA was 2 mg/kg/day i.m. for 14 days. Long-term treatment of male Sprague-Dawley rats with CBLA alone reduced the incidence and severity of spontaneous autoimmune periateritis nodosa (PN) in a dose-dependent manner; CsA was less potent than CBLA, and only additive effects were obtained. Finally, for the prevention of spontaneous autoimmune insulin-dependent diabetes (DM), the administration of CBLA did not improve the effect of a low-dose CsA in male BB rats. Nevertheless, a delay in onset of DM could be achieved. A sequential therapy using CsA plus CBLA clearly showed beneficial effects. The dose of CsA was 10 mg/kg p.o. 6 days/week for 21 weeks. Compared with Sprague-Dawley or Lewis male rats, BB male rats showed only weak prolactin suppression after the same doses of CBLA. It is suggested that the use of CBLA may be particularly beneficial in autoimmune disorders. The effectiveness of the combination therapy CBLA plus CsA, however, was dependent on the model considered. Various factors could play a role: (1) the different ways of administering CsA (s.c. in AA, i.m. in EAU and PN, oral in DM); (2) strain-dependency in the capacity of CBLA to suppress Prl secretion; and(3) at least in the BB rats, the transient increase of CsA bioavailibility which was possibly induced by CBLA.     

Tissue specificity of testosterone fixation: demonstrated by ultrastructural immunocytochemistry after cryoultramicrotomy]

Testosterone can be detected by immunocytochemistry on ultrathin slices obtained by cryoultramicrotomy. Testosterone detected by this method is likely bound on a binding site having a high affinity. In order to study the tissue specificity of this binding, testosterone was tested in Rat pituitary gland, liver and adrenal glands. Immunoreactive testosterone was detected in the gonadotropic cells of the pituitary gland, in the hepatocytes. Testosterone was not detected by immunocytochemistry in the pituitary cells other than the gonadotropic cells and in the cells of the medulla of adrenal glands. These data testify in favour of tissue specificity of the testosterone binding.     

Lithium lowers renal,cardiac and splenic ornithine decarboxylase activity in mice

Summary A single i.p. injection of lithium chloride (5–7.5 moles/g b.wt) in mice caused a 70–80% decrease in renal, cardiac and splenic ornithine decarboxylase (ODC) activity within 1 h, whereas pulmonary ODC activity was unaffected. Lithium chloride did not have any effect on ODC activity in vitro when added to homogenates of the tissues studied. We suggest that the effect of lithium on ODC activity is not direct, but mediated via e.g. hormonal or nervous influence.This study was supported by grants from the Swedish Medical Research Council (04X-02212, 14X-00028), and the Faculty of Medicine, University of Lund (Sweden).     

Effects of constant light exposure and blindness on the oxidative metabolism of selected brain areas in male rats

Summary Male rats were housed in continous illumination or blinded when 21 day-old and killed 69 days later. The continuous illumination exposure increased the weights of testes and sex accessory organs and reduced the pineal gland weight. Blindness decreased weights of testes, sex accessory organs and anterior pituitary. The oxygen consumption rate of the hypothalamus was higher in the blinded animals than in the controls and lower in the continuously illuminated rats. No one of such groups showed significant changes in the oxygen consumption by either the amygdata or the hippocampus.     

Effects of probenecid on plasma/tissue distribution of14C-benzylpenicillin in rats

Summary Probenecid (50 mg·kg^–1) was found to induce an increase of the plasma concentration of¹⁴C-benzylpenicillin with a decrease of the concentration in liver and kidney. Accumulation in corresponding tissue slices was reduced by probenecid. Therefore, the well known increase of penicillin in plasma after probenecid seems to be not only due to an inhibition of renal excretion but also to a reduced tissue uptake in liver and kidney.     

Dipeptidyl aminopeptidase in neonatal rat brain regions

Summary Changes in the activity of dipeptidyl aminopeptidase in rat pituitary gland and various brain regions were examined at 3, 5 and 20 weeks of age. The enzyme activity per g tissue wet weight in pituitary gland was the highest of all tissues studied. Subcellular distribution of the activity was also studied. The highest enzyme activity was found in a crude mitochondrial fraction including synaptosomes.     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4°C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4°C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.This work was supported by a grant from the National Aeronautics and Space Administration (NSG 2183 and NAG 2-411), a grant from the National Institutes of Health (NIH RR 0811) and a grant from the Division of Research Resources (NIH grant RR 03020).     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat.

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4 degrees C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4 degrees C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.     

Aldolase C is localized in neuroendocrine cells

To elucidate the localization of the subunit C of aldolase (aldolase C) in peripheral neuroendocrine cells, we made an immunohistochemical study with monospecific antibodies against human aldolase C. Aldolase C was found to be localized in various types of neuroendocrine cells; in the pituitary gland, thyroid, pancreas, adrenal gland, bronchus, and gastrointestinal tract.     

Aldolase C is localized in neuroendocrine cells

Summary To elucidate the localization of the subunit C of aldolase (aldolase C) in peripheral neuroendocrine cells, we made an immunohistochemical study with monospecific antibodies against human aldolase C. Aldolase C was found to be localized in various types of neuroendocrine cells; in the pituitary gland, thyroid, pancreas, adrenal gland, bronchus, and gastrointestinal tract.     

Thyroid hormones and cathepsin D activity in the rat liver,kidney and brain

Summary The effect of thyroidectomy and subsequent treatment with tri-iodothyronine (T₃), as well as that of thyrotoxicosis, was examined on cathepsin D activity in the rat liver, kidney and brain. Thyrotoxicosis resulted in a generalized increase in the enzyme activity in the 3 tissues; the effect of other thyroidal states was diverse and tissue-specific.     

Influence of ethanol on thyroxine accumulation in the hypothalamus,pituitary gland and cerebrospinal fluid in the newborn rabbit

Summary The effect of ethanol on thyroxine (T₄) accumulation in the hypothalamus (H), pituitary gland (P) and cerebrospinal fluid (CSF) has been investigated in 1–15-day-old rabbits. It has been found that H or CSF serum ratios decreased with age by about 2 in the course of 13 postnatal days. Stable T₄ resulted in an increase of¹²⁵I-T₄ in H, P and CSF. Ethanol per se caused an increase in transfer and accumulation of radiothyroxine or made the changes after loading animals with carrier T₄ more pronounced.     

The effect of ascorbic acid on cadmium accumulation in guinea pig tissues.

Accumulation of cadmium in organs of guinea pigs after subchronic oral cadmium treatment (1 mg Cd/animal/24 h) was in the following order: kidneys > liver > heart > testes > brain. The preventive effects of high doses of ascorbic acid (AA) against cadmium deposition were more pronounced in the testes, heart and brain, and in the kidney only after short-term cadmium treatment. Ascorbic acid had no protective effect on cadmium accumulation in the liver.     

The effect of ascorbic acid on cadmium accumulation in guinea pig tissues

Accumulation of cadmium in organs of guinea pigs after subchronic oral cadmium treatment (1 mg Cd/animal/24 h) was in the following order: kidneys > liver > heart > testes > brain. The preventive effects of high doses of ascorbic acid (AA) against cadmium deposition were more pronounced in the testes, heart and brain, and in the kidney only after short-term cadmium treatment. Ascorbic acid had no protective effect on cadmium accumulation in the liver.     

Immunochemical identity of dipeptidyl aminopeptidase IV from pig serum, liver, submaxillary gland and kidney.

The enzymes which were extracted by autodigestion from the microsomal fractions of the pig kidney, liver and submaxillary gland and from the serum showed an immunochemical identity by a double immunodiffusion test. But the kidney enzyme had a different pI-value from the pI-values of the enzymes of other organs.     

Über die Entwicklung des Fremdkörpergranuloms in verschiedenen Organsystemen

Summary The weight has been measured of the granuloma produced after implantation of the same foreign body in the kidneys, the testes, the liver and the subcutaneous tissue of male rats. It was found that granulomae in the testes and liver are nearly twice as heavy as in the kidney or in the subcutaneous tissue. Enhancement or inhibition of this reaction by treating the animals with cortexone shows organ-dependent effects on granuloma formation.     

Distribution of polyamine oxidase activity in rat tissues and subcellular fractions

The activity of polyamine oxidase (PAO) in rat tissues, and its subcellular distribution, were assayed using a simple polarographic method. The highest PAO activity was measured in the liver and the lowest in the skeletal muscle. In liver, kidney and uterus the highest specific PAO activity was found in the light mitochondrial fraction. PAO was not found in the microsomal fraction except in the kidney.     

Distribution of polyamine oxidase activity in rat tissues and subcellular fractions.

The activity of polyamine oxidase (PAO) in rat tissues, and its subcellular distribution, were assayed using a simple polarographic method. The highest PAO activity was measured in the liver and the lowest in the skeletal muscle. In liver, kidney and uterus the highest specific PAO activity was found in the light mitochondrial fraction. PAO was not found in the microsomal fraction except in the kidney.     

Adrenal corticosteroidogenesis after removal of ventral prostate gland

Summary Removal of the ventral prostate gland in adult male rats causes an increase in adrenal weight, and stimulation of adrenal ⁵-3-hydroxysteroid dehydrogenase activity along with elevation of serum levels of corticosterone and prolactin.     

Amylase released from the parotid gland by pilocarpine elevates the enzyme activity in the submandibular and sublingual glands of rats

Stimulation by pilocarpine led to a marked increase in amylase activity in the submandibular and sublingual glands and serum, and resulted in a considerable depletion of the enzyme in the parotid gland and pancreas of rats. Parotidectomy reduced these pilocarpine effects. It is concluded that amylase released by pilocarpine from the parotid gland but not from the pancreas elevated the enzyme activity in the submandibular and sublingual glands.