The effect of Gaboon viper venom on iron exchange in the rat

Plasma iron turnover (PIT) has been measured by means of 59Fe in rats treated with the haemorrhagic venom of the Gaboon viper (Bitis gabonica). Venom was administered on 3 occasions over a period of 9 days and after this time PIT had fallen from 1045 micrograms/kg/day in normal animals to 449 micrograms/kg/day in envenomated animals. Plasma iron half-life was markedly increased from 64.8 min to 417.6 min and this change was associated with a reduced uptake of 59Fe by the liver. However, marrow and spleen uptake of 59Fe was normal, as were the red-cell indices, MCH, MCV and MCHC. There was a slight reduction in total red-cell numbers and haemoglobin concentration as a result of the mild internal haemorrhage induced by the venom. It is concluded that Gaboon viper venom produces a marked disturbance of iron handling by the liver without an associated change in erythropoiesis. The mild haemorrhage was insufficient to produce a microcytic hypochromic anaemia. The results of the study provide further confirmation of the belief that standard ferrokinetic measurements give only limited information on erythropoietic status.     

The effect of partial pancreatectomy on on the electrocardiogram in dogs

Summary Excision of a part of the pancreas and ligation of its ducts causes on the 6–10th postoperative day a marked diminution and disappearance of the vagus tone, provoked chiefly by the disturbed activity of the corresponding reflex centers. There is also a reduction of the range of frequencies causing the parasympathetic effects to shorten, and in some cases disappearance of the vagus cardiac arrest, as well as weakening of the negative chronotropic and dromotropic effect of the parasympathetic innervation. In the animals operated there is a shortenining of the P-Q interval, prolongation of the QRST complex, and a partial splitting of the R wave.(Presented by Active Member AMN SSSR A. V. Lebedinskii) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 54, No. 11, pp. 46–50, November, 1962     

The effect of anti-lipolytic agents on isoprenaline-induced myocardial necrosis in the rat.

The effect of inhibiting isoprenaline-induced lipolysis on the degree of damage produced in the rat myocardium by this amine has been investigated by pre-dosing rats with the anti-lipolytic agent 5-fluoro-nicotinic acid. The degree of myocardial necrosis produced in animals given isoprenaline alone and those pre-dosed with the anti-lipolytic agent was measured by the use of an automated flying spot microscope to show absence of formazan from dead muscle fibres in sections treated to demonstrate succinic dehydrogenase. The use of the anti-lipolitic considerably reduced the degree of myocardial damage produced by a standard dose of isoprenaline bitartrate. This was associated with an inhibition of the post-isoprenaline rise in plasma free fatty acid levels. The results are discussed in relation to the possible protective roles of the lowering of plasma free fatty acid levels and inhibition of the adenyl cyclase system at the plasma membrane of the myocardial cell produced directly by the anti-lipolytic.     

The effect of Gaboon viper venom on iron exchange in the rat.

Plasma iron turnover (PIT) has been measured by means of 59Fe in rats treated with the haemorrhagic venom of the Gaboon viper (Bitis gabonica). Venom was administered on 3 occasions over a period of 9 days and after this time PIT had fallen from 1045 micrograms/kg/day in normal animals to 449 micrograms/kg/day in envenomated animals. Plasma iron half-life was markedly increased from 64.8 min to 417.6 min and this change was associated with a reduced uptake of 59Fe by the liver. However, marrow and spleen uptake of 59Fe was normal, as were the red-cell indices, MCH, MCV and MCHC. There was a slight reduction in total red-cell numbers and haemoglobin concentration as a result of the mild internal haemorrhage induced by the venom. It is concluded that Gaboon viper venom produces a marked disturbance of iron handling by the liver without an associated change in erythropoiesis. The mild haemorrhage was insufficient to produce a microcytic hypochromic anaemia. The results of the study provide further confirmation of the belief that standard ferrokinetic measurements give only limited information on erythropoietic status.     

The effect of iron deficiency on skeletal muscle metabolism of the rat

Using ³¹P magnetic resonance spectroscopy we compared skeletal muscle bioenergetics in Wistar rats made chronically anaemic by being fed a diet deficient in iron for 6 weeks with chronically iron deficient animals given a normal diet as well as 5 mg iron dextran at 2 or 7 days before experimentation. Spectra of the gastrocnemius muscle were taken at rest and during stimulation of the sciatic nerve at 2 Hz for 10 min. Relative concentrations of intracellular phosphate (Pi), phosphocreatine (PCr) and ATP were determined. Iron deficiency increased PCr breakdown and production of acid in stimulated skeletal muscle. Recovery of PCr and Pi concentrations after exercise was slow. These metabolic changes are consistent with either a reduction in supply of oxygen to the muscle cell or altered oxidative phosphorylation by the mitochondria. The latter may be mediated by defective function of iron-containing proteins crucial in oxidative phosphorylation and this is suggested both by the observation that treatment with iron, sufficient to correct the anaemia, does not completely reverse the metabolic changes and that there is a different time course for such metabolic improvements and the observed increase in haemoglobin concentration.     

The role of bicarbonate and other buffers on isotonic fluid absorption in the proximal convolution of the rat kidney

Summary The fluid reabsorption from the proximal convolution of the rat kidney was measured with the Gertz shrinking droplet technique. Simultaneously, the peritubular capillaries were perfused with artificial solutions. In some experimental series, fluid from the shrinking droplet was withdrawn and analysed for Cl^–, Na⁺, and osmolality so that the transtubular transport of Na⁺, Cl^–, and HCO ₃ ^– could be calculated. Capillary perfusate in some experiments was also withdrawn and its pH was measured. The following results were obtained: 1. With increasing concentration of HCO ₃ ^– in the capillary perfusate, the transtubular water, sodium, chloride, and bicarbonate reabsorption increased. 2. The sulfonamide buffers sulfamerazine and glycodiazine (Redul^®), which easily penetrate the tubular wall, could, in equimolar concentrations, substitute totally for the bicarbonate buffer in promoting isotonic fluid absorption. 3. Butyrate, propionate, and acetate were also effective; pyruvate, lactate, and paraaminohippurate, however, were not. 4. The effect of HCO ₃ ^– and glycodiazine on isotonic absorption was shown to depend exclusively on the concentration of the buffer anion and not on the concentration of undissociated acid or pH. From these data it is suggested that for proximal isotonic absorption of water, sodium, and chloride, the reabsorption of buffer anions via H⁺ secretion and nonionic diffusion may be essential. The H⁺ secretion or the buffer anion absorption across the luminal cell wall may secondarily influence the active Na⁺ transporting mechanism located at the basal cell site either by a luminal H⁺–Na⁺ exchange mechanism or by a lyotropic effect which would increase the Na⁺ permeability of the luminal cell site. Thereby more Na⁺ would be delivered to the Na⁺ pumping site and the rate of Na⁺ pumping would be augmented.     

The effect of amino acids on the intestinal absorption of immunoglobulins in the neonatal rat

An in vitro preparation of 10-day-old rat intestine was used to examine the absorption of a number of amino acids and immunoglobulins. Evidence was obtained for the active absorption of alanine, leucine, methionine, histidine and lysine, but not for aspartic acid. A selective absorption of the homologous molecule was found in experiments where ¹³¹I-labelled rat and bovine IgG were presented to the ileum in 10-minute incubations. The greater uptake of rat IgG was unrelated to the relative rates of catabolism of the two molecules.

Although the uptake of rat IgG was unaffected by 100 mM concentrations of neutral and acidic amino acids, the basic amino acids arginine and lysine significantly stimulated uptake.

     

The effect of immunosuppressive agents on lymphocyte subsets in rat peripheral blood

A method for monitoring circulating lymphocytes subsets in the rat on an automated flow cytometer with monoclonal antibodies was used to ascertain in vivo effects of various doses of immunosuppressive agents. The agents tested were anti-lymphocyte serum (ALS), azathioprine (AZA), cyclophosphamide (CTX), cyclosporin A (CsA) and methylprednisolone (MP). Each immunosuppressive agent varied in its capacity to induce changes in T cell subsets and B cell numbers. The rapidity of onset of action of the agents varied considerably; with ALS and MP maximal effects were seen within hours whilst the effects with CsA, cyclophosphamide (CTX) and azathioprine (AZA) took several days to develop. ALS had marked anti-T cell activity but did not selectively affect the T cell subsets. AZA and CTX both exerted their major effect upon the B cell (OX4+) subpopulation. CsA administration was associated with the appearance of many circulating lymphocytes which expressed the pan-T marker (W3/13) but neither of the T cell subset markers (W3/25, OX8). With CsA there was no significant alteration in the W3/25:OX8 ratio, although a persistent decrease in the number of all T lymphocytes was observed after administration of this drug at a dose of 45 mg/kg had ceased. MP was the only drug which had a marked selective effect on a T cell subset. The numbers of circulating Class II major histocompatibility complex (MHC) reactive lymphocytes (W3/25+) were significantly more depressed than the Class I MHC reactive subset (OX8+). This effect persisted for up to 31 days after the single injection of a depot preparation of this drug, and was found to be associated with prolonged survival of precultured endocrine xenografts.     

The effect of cAMP on electrogenic Na(+) absorption in the rat distal colon

Cyclic AMP is a ubiquitous second messenger produced in cells in response to extracellular stimulants. The aim of this study was to examine its role in the regulation of amiloride-sensitive electrogenic Na(+) absorption in the rat distal colon by measuring the short-circuit current (I(sc)) and (22)Na(+) fluxes in a chamber-mounted mucosal sheet. Forskolin stimulated the amiloride-inhibitable I(sc) and amiloride-inhibitable (22)Na(+) absorption. 8Br-cAMP also stimulated the amiloride-inhibitable I(sc). Furthermore, isoproterenol, acting via beta-adrenergic activation, stimulated the amiloride-inhibitable I(sc). The isoproterenol-induced increase in the amiloride-sensitive I(sc) was largely suppressed by H89, a protein kinase A inhibitor. In conclusion, cAMP can upregulate amiloride-sensitive electrogenic Na(+) absorption in the rat distal colon.