STUDIES OF SERUM ELECTROLYTES: IV. The Chloride and Nitrogen Balances, and Weight Changes in Pneumonia.
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Biomedical subjects
Publications and source records attributed to F W Sunderman.
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Recent clinical and experimental studies suggest that zinc deficiency may play an important role in the pathogenesis of (1) acrodermatitis enteropathica, and in certain cases of (2) hypogonadal dwarfism, (3) congenital malformations, (4) hypogeusia and hyposmia, (5) nyctalopia and (6) impaired wound healing. Distrubances of zinc metabolism also occur in a broad spectrum of other clinical disorders. The pathophysiological factors which are responsible for hypozincemia include: (1) nutritional deficiency and/or intestinal malabsorption of zinc; (2) hyperzincuria secondary to aminoaciduria; (3) hormonal effects (cortisol, growth hormone, estrogens); (4) hypoalbuminemia; and (5) effects of leukocytic endogenous mediator. The clinical diagnosis of zinc deficiency in patients with specific neurological, dermatological and musculoskeletal disorders is complicated by the complex interactions of these pathophysiological factors and by the need for more dependable laboratory indices of zinc deprivation.
An automated micromethod is described for measurement of serum ceruloplasmin by assay of its p-phenylenediamine oxidase activity using the Abbott bichoromatic analyzer. Ten mul of serum are mixed with 250 mul of p-phenylenediamine (PPD) substrate (9.2 mmole per liter) in acetate buffer (0.1 mole per liter, pH 5.45). Spectrophotometric measurements of the rate of formation of the purple oxidation porduct of PPD are performed after a 10 min delay for thermal equilibration at 37 degrees and for avoidance of the lag-phase of the enzymatic reaction. The coefficients of variation of replicate analyses of normal serum by this technique are 1.1 percent (within-the-run) and 3.3 percent (day-to-day). Measurements of ceruloplasmin concentrations in serums from 75 patients by this automated method provided close correlation with measurements by a manual reference procedure (correlation coefficient=0.973). The mean concentration of ceruloplasmin in serums from 64 healthy men was 29 mg per dl (central 95th percentile limits=22 to 40 mg per dl).
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An improved method for analysis of serum iron is described which is simple, rapid, precise and convenient for routine use in clinical laboratories. Serum proteins are precipitated with trichloroacetic acid-hydrochloric acid solution, with simultaneous release of Fe(III) from transferrin. Fe(III) is reduced to Fe(II) by sodium ascorbate, and Fe(II) is reacted with ferrozine to form a lavender complex, which is measured by spectrophotometry at 562 nm. Measurements of iron in 183 serum samples by this method were compared with measurements by a "direct" spectrophotometric method without without deproteinization, as previously described. Close agreement was obtained in 171 of these 183 pairs of analyses (93.5 percent). Discrepancies (greater than 12 mug per dl) were noted in the remaining 12 serums, which were attributed to interference in direct spectrophotometric analyses of iron, owing to (1) hemolysis, (2) lipemia, (3) jaundice, (4) protracted storage or (5) repeated freezing and thawing of the serums.
Electrothermal atomic absorption spectrometry has five major advantages for measurements of trace metals in biological materials, in comparison to measurements by conventional flame atomic absorption analysis: (1) Trace metal contamination is minimized by avoidance of preliminary chemical extractions and additions of reagents; (2) Sample volumes are small (1 to 50 mu1). The entire sample is vaporized in electrothermal atomization, whereas in most flame nebulization systems only a small fraction of the sample enters the flame; (3) Atoms are released in higher concentrations. In electrothermal atomization, the atom cloud is released into a relatively small volume of gas. In contrast, in flame atomization, the atom cloud is diluted by the high flow rate of gases and by expansion of gases during combustion; (4) Molecular recombination of atoms is retarded by the atmosphere of inert gas which restricts chemical reactions (e.g., oxidation). In contrast, in flame atomization, oxidation occurs very rapidly; and (5) By programmed increments in temperature, electrothermal atomization permits organic constituents to be pyrolyzed prior to vaporization and atomization of metals. Despite these advantages, electrothermal atomic absorption is particularly subject to interferences and sources of imprecision which necessitate critical evaluations in the prospective analyst's laboratory before an electrothermal method can be confidently employed for diagnostic measurements of a specific trace metal in body fluids.
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The embryotoxicity and teratogenicity of cadmium chloride (CdCl2) were tested by the FETAX (Frog Embryo Teratogenesis Assay: Xenopus) procedure in the South African frog, Xenopus laevis. In five assays, groups of Xenopus embryos were grown in media that contained CdCl2 at concentrations ranging from 0.75 to 56 mumol per L; control groups were incubated in the same medium without added CdCl2. The exposures to CdCl2 were begun at the blastula stage (five hours post-fertilization) and were terminated 96 hours later (101 hours post-fertilization). The embryos were counted, fixed in formalin, and examined by microscopy to score malformations and measure head-to-tail lengths. In control groups, greater than or equal to 95 percent of the embryos survived at 101 hours post-fertilization, and the incidence of malformations was less than or equal to 7 percent. In Cd(2+)-exposed groups, there was concentration-dependent mortality, and the embryos showed a concentration-related pattern of malformations, including gut malrotation, ocular anomalies, bent notochord, misshapen dorsal fin, facial dysplasia, cardiac deformities, and dermal blisters. Other abnormalities, not categorized as malformations, included stunted growth and hypopigmentation. The minimum concentration of CdCl2 that inhibited growth (MCIG) was 18 mumol per L. The median embryolethal concentration (LC50) of CdCl2 was 32 (SE +/- 4) mumol per L; the median teratogenic concentration (EC50) was 3.7 (SE +/- 1) mumol per L; the teratogenic index (TI = LC50/EC50) was 8.6. This study demonstrates that CdCl2 is teratogenic for Xenopus laevis and provides a standardized experimental model for studies of the molecular mechanisms of cadmium teratogenesis.
The therapeutic history of sodium diethyldithiocarbamate (dithiocarb) is briefly reviewed. Dithiocarb was discovered serendipitously in our laboratory 35 years ago for the specific treatment of nickel carbonyl poisoning. Since that time, the therapeutic efficacy of dithiocarb has been reported for many disorders, including: nickel, cadmium, thallium, copper, and mercury poisonings, experimental nickel carcinogenesis, protection against radiation damage to bone marrow, treatment of candidiasis in experimental animals, hepatolenticular degeneration (Wilson's disease), systemic lupus erythematosis, and human immunodeficiency virus infection (HIV). It has been used as an antagonist to cisplatin and cyclophosphamide toxicities, and as an antidote to hepatotoxicity induced by chloroform, carbon tetrachloride, and halothane. Most recently, it has been observed that the progression of HIV-1 infection is inhibited by dithiocarb administered intravenously or orally to patients with acquired immunodeficiency syndrome (AIDS). Attention is directed to the interactions of divalent cations to viral infections and to metal chelators (e.g., dithiocarb) as potential antiviral agents.
Male Fischer-344 rats (10 to 12 rats per group) were given 14 i.m. injection of nickel sulfate (NiSO4) over a period of 26 days in order to delineate the two-year survival, body weight curves, hematocrit responses, and histopathological reactions, including carcinogenesis. Group A (vehicle controls) received the NaCl vehicle; Groups B, C, and D received NiSO4 solution at dosages of 63, 83, or 125 mumol per kg, respectively. Rats in Group D all died during the period from 4 to 32 days after the first injection; survival of rats in Groups B and C did not differ significantly from the controls (Group A). No differences were found at any time between the mean body weights or blood hematocrits of the NiSO4-treated groups vs. the controls. In Group D, histopathological lesions of the lung, liver, thymus, and spleen were consistently observed; these lesions were most severe in rats that died during the period from 22 to 32 days after the first injection. The lungs showed proliferation of alveolar lining cells, thickening of the alveolar wall, and proteinaceous alveolar exudate. The livers showed microvesicular steatosis, and necrotic hepatocytes were scattered throughout the lobules. Degeneration of lymphocytes, with pyknosis and karyorrhexis, was observed in the thymic cortex and the white pulp of the spleen. At necropsy, no significant differences were found between the NiSO4-treated rats of Groups B and C and the controls (Group A). No sarcomas or other neoplasms occurred near the injection sites in NiSO4-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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