Biomedical subjects
Publications and source records attributed to J Rungby.
Two histochemical methods, Timm's sulphide silver method and the selenium method reveal the presence of two pools of metal ions in the Paneth cells. Ultrastructurally one pool is located in the secretion granules, the other in the cytoplasm.
The localization of gold in normal, stimulated and activated mouse peritoneal cells exposed in vivo to sodium aurothiomalate was examined by a new histochemical technique based on physical development. Activated macrophages from mice infected with herpes simplex virus type II showed the greatest amount of gold localized within lysosomes. Mast cells contained gold in their granules. Polymorphonuclear leucocytes and lymphocytes, on the other hand, were devoid of gold. Pinocytosis is discussed as the mechanism by which gold is taken up into the cells.
Silver accumulations in the anterior pituitary of argyric rats were demonstrated using a histochemical method that visualizes minute traces of the metal. Silver was localized intra- and extracellularly throughout the anterior pituitary. Intracellular deposits were found within the lysosomes of somatotrophs and gonadotrophs. Extracellularly, the grains were located in basal laminae of portal veins and sinusoidal capillaries and in the membrane separating the anterior pituitary and part intermedia. The amount of deposited silver was dependent upon the dose of silver administered. Increasing the dose of silver lactate from 10 to 30 mg resulted in increased deposition, whereas a further increase to 60 mg did not alter the amount of silver deposited.
The functional implications of the presence of silver in the central nervous system are unknown. Since silver is present in the environment and since systemic silver poisoning leads to intraneuronal accumulations of the metal we have evaluated the possible effects of silver on the open field behaviour of mice. Argyric mice have been compared with controls in three experiments, one including long term administration of 0.015% silver nitrate in the drinking water and two in which the reactions of male and female mice to shock doses of silver lactate have been studied. In all experiments the silver treated mice were hypoactive. We suggest that this hypoactivity is due to an influence of silver upon the functional status of the CNS.
Exogenous silver in brain and spinal cord sections from rats treated with Protargol, silver lactate or silver nitrate was visualized by physical development. The silver penetrated the blood-brain barrier and accumulated in neurones and glia. The distribution of silver in the CNS was heterogeneous. Even with low doses and short survival periods, silver was found to accumulate in large motoneurones in the brain stem and spinal cord and neurones in the cerebellar nuclei. Silver was only found in di- and telencephalic structures after extensive exposure. Silver distribution following oral silver lactate and silver nitrate treatment differed in that silver nitrate resulted in a relatively high content of silver in glia whereas deposition occurred preferentially in neurones following silver lactate treatment. Electron-microscopical studies showed that silver was located intracellularly in the lysosomes and extracellularly in basement membranes and elastic fibres of the vessels.
Using a photochemical method silver was demonstrated in the brains of 1-, 14-, and 45-day-old rats which had been exposed to silver on gestational days 18 and 19. In the brain tissue of new-born rats, silver was found in the lysosomes of neurons and astroglia. Minor changes in the anatomic distribution of silver were observed between days 1 and 45. The pattern seen at day 45 was identical to that observed in silver-exposed adults. At day 1, the choroid plexus and meninges were heavily loaded with silver both intra- and extracellularly. In particular, macrophage-like cells of the meningeal spaces contained large amounts of silver. In these structures, the silver had virtually disappeared by day 45. Silver was always seen in basement membranes of the cerebral vessels.
Accumulations of silver and mercury can be visualized in tissue sections by a technique called autometallography or physical development. In order to make a histological differentiation between mercury and silver in tissue exposed to both metals, it is necessary to remove one of the metals while leaving the other untouched. The present paper describes a technique by which silver accumulations in histological sections can be removed by potassium cyanide, yet leaving mercury accumulations intact to be developed autometallographically.
The histochemical silver amplification technique autometallography (AMG), was used to trace bismuth in the testis of Wistar rats injected intraperitoneally with bismuth subnitrate. In the seminiferous tubules, bismuth was located in lysosomes of Sertoli cells closely associated with heads of spermatids in the late stages of the spermatogenesis, i.e. shortly before the release of Step 19 spermatids in Stage XIII. No bismuth-specific AMG silver grains were detected in the spermatogenic cell line. However, tails of free sperm cells located in the tubular lumen showed autometallographic grains in close contact to the nine outer microtubule doublets in the axonema. Leydig cells concentrated huge amounts of AMG-bismuth in their lysosomes. Furthermore, parallel exposure to selenium significantly increased the amount of histochemically traceable bismuth in the rat testis.
Bismuth, a component of many gastrointestinal medications, is a heavy metal little studied as regards nervous system uptake. We were interested to see if low doses of intragastric bismuth entered the nervous system, and if dietary selenium influenced the amount of bismuth detected. Mice were given 40 to 1200 mg/kg of bismuth subnitrate (BSN), bismuth subsalicylate (BSS), colloidal bismuth subcitrate (CBS), or ranitidine bismuth citrate (RBC) intragastrically. Mice on low- or high-selenium diets were given 4 to 32 mg/kg of bismuth from RBC. One week later, sections of nervous tissue were stained with autometallography to detect bismuth grains (Bi(AMG)). Bismuth was found in neurons with axons outside of the nervous system, in particular motor neurons, and in cells outside the blood-brain barrier. The lowest bismuth dose which resulted in Bi(AMG) in motor neurons was 696 mg/kg from BSN, 57 mg/kg from BSS, 29 mg/kg from CBS, and 26 mg/kg from RBC. No bismuth was seen in motor neurons of mice on the low-selenium diet. Intragastric doses of bismuth therefore enter mouse motor neurons, and the amount detectable varies with dietary selenium.
Old sulphonylureas have been linked with adverse cardiovascular effects; however, data on the clinical implications are sparse. We examined the association between use of sulphonylureas and other antidiabetic drugs and the risk and case fatality rate (CFR) of myocardial infarction (MI) in a population-based case-control and follow-up study, respectively. A total of 6738 cases of first-time MI and 67,374 age- and gender-matched population controls were identified from the Hospital Discharge Registry and the Civil Registration System of North Jutland County, Denmark, in the period 1994 through 2002. Prescriptions for antidiabetic drugs before the index date were retrieved from a prescription database. We estimated odds ratios (ORs) of MI (case-control study) and 30-day CFR (follow-up study) associated with antidiabetic drug use adjusted for possible confounding factors and using nondiabetic subjects as the reference group. The risk of MI appeared higher among users of old sulphonylureas (adjusted OR, 2.07; 95% confidence interval (CI), 1.81-2.37) than among users of new sulphonylureas (adjusted OR, 1.36; 95% CI, 1.01-1.84). The adjusted ORs among users of nonsulphonylurea oral antidiabetic drugs, insulin, and patients with diabetes not receiving pharmacotherapy were 1.38 (95% CI, 0.90-2.11), 2.56 (95% CI, 2.16-3.03), and 3.51 (95% CI, 2.92-4.22), respectively. The overall 30-day CFR was 24.6%, but varied between 9.5% and 37.0% among the different categories. New sulphonylureas may be associated with a lower risk of MI than old sulphonylureas. Furthermore, the 30-day CFR may vary according to type of antidiabetic drug. These differences indicate the need for further examination of the cardiovascular safety of antidiabetic drugs.
Long-term treatment of survivors of an acute myocardial infarction with angiotensin-converting enzyme inhibitors has a beneficial impact on their long-term outcome. We tested the hypothesis that captopril could reductively cleave the lipoprotein(a) molecule and in addition act as a scavenger of oxygen free radicals. In a double-blind trial, 20 patients were randomized to receive either captopril 50 mg daily or corresponding placebo. patients were followed for a period of 30 days. Blood samples were drawn prior to randomization and after 30 days of treatment. Plasma concentrations of lipoprotein(a) and malondialdehyde were evaluated. Captopril treatment produced a significant reduction in plasma content of lipoprotein(a) ( < 0.05) and at day 30 the plasma content of lipoprotein(a) was also significantly lower than that in the placebo group (p < 0.05). furthermore, on day 30 plasma concentrations of malondialdehyde, an indicator of oxidative damage, were significantly lower in the captopril group when compared to baseline values and corresponding placebo group values (p < 0.05). The observed effect of captopril treatment on lipoprotein(a) and malondialdehyde might be ascribed to the sulfhydryl group in the captopril molecule.