Facilitated uptake of zinc into human erythrocytes. Relevance to the treatment of sickle-cell anaemia

The ability of a number of heterocyclic metal chelators to deliver zinc into red cells, to release the liganded zinc to haemoglobin and thereby cause a left shift in the oxygen dissociation curve of intact red cells has been investigated. Incubation of neutrally charged zinc-pyrone and zinc-pyridin-2-one complexes with red cells led to the rapid accumulation of zinc within cells, whereas unliganded zinc in the form of zinc acetate, zinc chloride or zinc sulphate accumulated only slowly. The rate at which zinc was delivered to red cells by pyrone and pyridin-2-one ligands increased with increasing lipid solubility of the ligands. The uptake of zinc into both normal adult and sickle red cells was associated with a dose-dependent increase in the oxygen affinity of haemoglobin. The degree of left shift in the oxygen dissociation curve following the incubation of red cells with zinc-pyrone and -pyridin-2-one complexes suggests that these complexes may find application as agents to increase the oxygen affinity of haemoglobin in sickle cell disease and thereby decrease the probability of intravascular sickling at low tissue oxygen tensions. Ethylmaltol appears to be a particularly useful agent due to its known low toxicity.     

Diets rich in n-9, n-6 and n-3 fatty acids differentially affect the generation of inositol phosphates and of thromboxane by stimulated platelets, in the rabbit

We have studied the effects of semi-synthetic diets rich in either n-9 (olive oil, OO) or n-6 (corn oil, CO), or n-3 (fish oil, FO, as MaxEPA) fatty acids on the levels of major PUFA in platelet lipids, on the generation of inositol phosphates by [3H]inositol labelled platelets after stimulation with thrombin and of thromboxane B2 (TxB2) by platelet rich plasma (PRP) after stimulation with collagen. The predicted elevations of oleic (OA), linoleic (LA) and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were observed in platelet lipids of each animal group, but in the MaxEPA fed group accumulation of EPA was associated with depletion of linoleic acid (LA) rather than of arachidonic acid (AA). Basal levels of inositol-tris-phosphate (IP3) in platelets were lowest in the OO group and highest in the CO group, whereas the increment after thrombin stimulation (1 unit/ml NIH) was maximal in the OO group and minimal in the FO group. Instead, when generation of TxB2 by stimulated platelets was evaluated, no appreciable difference among the various groups could be detected, in accordance with the limited modifications of platelet AA content induced by the diets. The overall data indicate that dietary fatty acids modulate the pathway of inositol phosphate generation in rabbit platelets, independently of modifications of TxB2 production.     

Corneal endothelial cell loss following trephination

The amount of endothelial cell loss that occurs to the donor cornea during the trephination process was evaluated in 40 porcine eyes. A vital staining technique (alizarin red S and acid violet 19) was used to quantify the extent of endothelial damage and removal. Two types of corneal punches (Weck and H&I0 were used for trephination. The average amount of endothelial loss from the peripheral cornea was 7.9%, accounting for only a 3% loss of endothelial cells over the total surface area of the corneal button. a comparison of the Weck and H&I corneal punches showed no significant difference (P greater than 0.1) by Student's test for both endothelial cell damage and removal.     

Increased (L+)-lactic acid production in lysozyme-inactivated suspensions of human dental plaque

The effect of lysozyme-inactivation on L(+)-lactic acid (LA) production in dental plaque suspensions was evaluated. From 10 children 24-h plaque was collected and lysozyme activity inhibited by addition of goat antiserum to human lysozyme. Acid production was stimulated by addition of glucose. The results showed significantly increased LA levels (50-150%) in lysozyme-inactivated plaque suspensions from 8 of the subjects compared to untreated controls. The increase in acid production activity was not related to plaque lysozyme levels. The findings indicate that the presence of lysozyme may be limiting on acid production in the early dental plaque.     

Regulation of guinea pig ileal electrolyte transport by M3-muscarinic acetylcholine receptors in vitro

To determine the muscarinic receptor subtype mediating guinea pig ileal mucosal electrolyte secretion, we compared the potencies (Kb) of selective M1 (pirenzepine) (PZ), M2 (AF-DX 116, methoctramine), and M3 [4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), hexahydrosiladifenidol (HHSiD)] antagonists as inhibitors of carbachol-induced reductions in guinea pig atrial heart rate and ileal longitudinal muscle contractions, responses mediated by M2 and M3 receptors, respectively. Pretreatment with all five muscarinic antagonists shifted the carbachol concentration-response curve to the right, in a manner suggesting competitive antagonism. The following affinity profiles (Kb, nM) were obtained for: 1) ileal mucosa: 4-DAMP (2.7) greater than HHSiD (23.0) greater than PZ (110) greater than or equal to methoctramine (395) greater than AF-DX 116 (784); 2) atrial heart rate: 4-DAMP (9.5) congruent to methoctramine (11) greater than AF-DX 116 (63) greater than HHSiD (222) greater than PZ (256); and 3) ileal longitudinal muscle: 4-DAMP (3.1) greater than HHSiD (21) greater than PZ (143) greater than methoctramine (388) greater than or equal to AF-DX 116 (482). The selectivity profiles of these antagonists suggest that muscarinic receptors in the ileal mucosa more closely resemble those in the ileal muscle (M3) than those in atrial muscle (M2). Moreover, M1-muscarinic receptors appear to be relatively unimportant in mediating the effects of carbachol on short circuit current (ISC). Carbachol-induced increases in ISC were also unaffected by pretreatment with 0.5 microM tetrodotoxin, suggesting that electrolyte transport in the guinea pig ileal mucosa may be mediated, in part, by postsynaptic M3-muscarinic receptors on the enterocytes.     

Mycenon, a new metabolite from a Mycena species TA 87202 (basidiomycetes) as an inhibitor of isocitrate lyase

Mycenon (C11H5Cl3O3), a new inhibitor of isocitrate lyase (EC 4.1.3.1) was isolated from the culture broth of a basidiomycete, Mycena sp. Mycenon is a novel chlorinated benzoquinone derivative which is also active against bacteria and fungi. Malate synthase (EC 4.1.3.2) the second key enzyme of the glyoxylate cycle was not affected by mycenon. Isocitrate lyase preparations from plants, bacteria and fungi were sensitive. The following Ki-values for mycenon have been determined: Ricinus communis, 5.2 microM; Acinetobacter calcoaceticus, 11 microM; Neurospora crassa, 7.4 microM. The structure of mycenon has been determined by a single crystal X-ray analysis.     

Levodopa up-regulates platelet alpha 2-adrenoceptors

Treatment of dogs for 21 days with oral levodopa (100 mg b.i.d.) plus benserazide (25 mg b.i.d.) induced a significant increase in the number of platelet alpha 2-adrenoceptors labelled by [3H] yohimbine with no change in Kd. The rise was maximal at the end of the treatment and remained significant during the month following the cessation of treatment. Plasma catecholamine levels did not vary. Competition experiments showed a low affinity of both dopamine and levodopa for platelet alpha 2-adrenoceptors. These results suggest that levodopa treatment regulates alpha 2-adrenoceptor number in dog platelets.     

Alcoholism in patients with sexual disorders

The authors screened for alcoholism 145 consecutive patients who presented with sexual dysfunction or disorders. Using the Michigan Alcoholic Screening Test (MAST), 29% of the patients scored in the probable alcoholic range. Probable alcoholics were more likely to present without a partner and claimed higher sex drive than nonalcoholic patients. Probable alcoholic males reported less joy and vigor than probable alcoholic females, while the reverse held for the nonalcoholic groups. Blind to the MAST results, the staff made six alcohol-related diagnoses and referred one patient for alcohol treatment. The authors discussed the importance of training faculty and resident staff in the relationship of alcohol abuse associated with psychosexual dysfunctions.     

Comparison of two analytical procedures for the determination of free urinary catecholamines under the demands of shiftwork experiments

Summary A typical shiftwork experiment was chosen to prove the validity of an automated procedure for the analysis of free noradrenaline and adrenaline in urine. The method consists of a column switching technique with an adsorption/elution clean-up and a reversed phase high performance liquid chromatography followed by chemical reaction detection based on the trihydroxyindole method. The analysis of variance was performed using a second data set obtained by a semi-automated procedure for which the accuracy had already been confirmed. The analysis of covariance showed that for field studies, as well as for laboratory experiments in which the variances contributed by the experiments themselves are greater than 10% rel., the data sets of the two methods provide the same information.Dedicated to Prof. H. Hartkamp, University of Wuppertal, on the occasion of his 60th birthday     

Risk of non-Hodgkin's lymphoma among men occupationally exposed to organic solvents

An occupational history of exposure to organic solvents, defined as daily occupational exposure for at least one year, was more common among 167 men with newly diagnosed non-Hodgkin's lymphoma than among 130 healthy referents from the general population (38 versus 14%). Categorization in five-year age groups gave 3.3 as a Mantel-Haenszel estimate of the odds ratio (95% CI 1.9-5.8). The odds ratio was 6.5 (95% CI 3.2-13.3) for localized supradiaphragmatic tumors and 2.3 (95% CI 1.3-4.3) for other lymphoma presentations. In a logistic model including age and organic solvent, phenoxy acid, and chlorophenol exposure, it could be shown that solvent exposure was an independent risk factor and that no important interaction occurred between the risk factors. With increasing duration of exposure there was a significantly increased risk of lymphoma, a finding implying a dose-response relationship. There was no significant difference in tumor histology between the exposed and unexposed patients. These findings support the concept that occupational exposure to organic solvents is a risk factor for non-Hodgkin's lymphoma. The results also confirm a strong association between such exposure and an initial supradiaphragmatic location of the lymphomas.