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Biomedical subjects

R F Labbé

Publications and source records attributed to R F Labbé.

At least 19 recordsLinked to original sources
PubMed1999

Zinc protoporphyrin: A metabolite with a mission.

Zinc protoporphyrin (ZnPP) is a normal metabolite that is formed in trace amounts during heme biosynthesis. The final reaction in the biosynthetic pathway of heme is the chelation of iron with protoporphyrin. During periods of iron insufficiency or impaired iron utilization, zinc becomes an alternative metal substrate for ferrochelatase, leading to increased ZnPP formation. Evidence suggests that this metal substitution is one of the first biochemical responses to iron depletion, causing increased ZnPP to appear in circulating erythrocytes. Because this zinc-for-iron substitution occurs predominantly within the bone marrow, the ZnPP/heme ratio in erythrocytes reflects iron status in the bone marrow. In addition, ZnPP may regulate heme catabolism through competitive inhibition of heme oxygenase, the rate-limiting enzyme in the heme degradation pathway that produces bilirubin and carbon monoxide. Physiological roles, especially relating to carbon monoxide and possibly nitric oxide production, have been suggested for ZnPP. Clinically, ZnPP quantification is valuable as a sensitive and specific tool for evaluating iron nutrition and metabolism. Diagnostic determinations are applicable in a variety of clinical settings, including pediatrics, obstetrics, and blood banking. ZnPP analytical methodologies for clinical studies are discussed. In addition to diagnostic tests and metabolic studies, ZnPP has a potential therapeutic application in controlling bilirubin formation in neonates as a preventive measure for hyperbilirubinemia. Biochemical research techniques, both in vivo and in vitro, are described for further studies into the role of ZnPP in metabolism and physiology.

Anemia, Iron-Deficiency↗
PubMed1994

Multicenter evaluation of automated immunoturbidimetric assays for measurement of apolipoproteins A-I and B in serum and plasma.

Results of a multicenter evaluation of automated assays for measurement of apolipoproteins (apo) A-I and B with the Paramax analytical system are reported. Apo A-I and apo B response surface models were used to optimize concentrations of critical assay variables. Overall imprecision for apo A-I controls at concentrations of 1.01-1.61 g/L was 3.7-6.6%; overall imprecision for apo B controls at 1.00-1.61 g/L was 2.8-6.9%. There was no interference in apo A-I measurements. Albumin concentrations > 59 g/L resulted in a negative interference, and collection in sodium heparin caused a positive interference in apo B results. Apo A-I and apo B assays demonstrated acceptable agreement with comparative methods, although the Paramax apo B assays had a negative bias with respect to comparison methods. In 116 healthy individuals, serum apo A-I ranged from 0.97 to 2.05 g/L and serum apo B ranged from 0.51 to 1.32 g/L.

Apolipoprotein A-I↗
PubMed1993

Nutrition in the clinical laboratory.

Nutrition is a developing facet of patient care that can be enhanced by appropriate laboratory support. The importance of the laboratory is underscored by the growing interest and appreciation for marginal malnutrition that can only be diagnosed by biochemical means. Clinical laboratories have the opportunity to provide leadership in advancing nutrition to the forefront of medical care. The overall quality and cost-effectiveness of medical care can be improved through the development of reliable tests to detect malnutrition, abandonment of tests of little value, emphasizing those tests of merit, and persuading clinicians of the benefits of measuring nutritional analytes. Nutrition test panels are an effective way of assuring appropriate and comprehensive laboratory support of nutritional care.

Chemistry, Clinical↗
PubMed1992

Laboratory monitoring of nutritional status in burn patients.

Most nutrition laboratory testing relies on serum concentrations of ingested nutrients, their coenzymes, proteins, or lipids. Alternatively, functional tests measure a specific physiological process or biochemical reaction. We compared these two approaches to nutritional assessment in intensive-care burn patients, in whom the serum concentrations of transthyretin (prealbumin), albumin, transferrin, carotene, retinol, ascorbic acid, copper, cholesterol, iron, and calcium were all below established reference ranges. In contrast, serum triglyceride concentrations were often above the reference range. Functional tests for thiamin, riboflavin, pyridoxine, and iron (by zinc protoporphyrin/heme ratio) in these patients all showed normal values. Dietary intake, weight trends, and nitrogen balances all indicated that these patients' estimated caloric and protein needs had been met. These findings suggest that static measurements of serum concentrations may be unreliable indicators of nutritional status in burn patients.

Adolescent↗
PubMed1990

Chemiluminescent measurement of total urinary nitrogen for accurate calculation of nitrogen balance.

This instrumental method for total urinary nitrogen (TUN) is based on the principle of gas-phase chemiluminescence. Results correlate well with measurements of TUN by the Kjeldahl method, which has long provided the means to calculate nitrogen balances for nutritional management. In recent years, because of speed and convenience of measurement, determination of urinary urea nitrogen (UUN) has been substituted for Kjeldahl TUN. However, in patients requiring aggressive nutritional support, the UUN may not be a valid indicator of total nitrogen excretion. We compared nitrogen balances calculated for patients, using both UUN and chemiluminescence TUN data. For both normal and hospitalized populations, nitrogen balance calculated from UUN data exceeded that calculated from TUN data. We show that use of UUN data in calculating nitrogen balance may result in an incorrect assessment of many patients as being in positive nitrogen balance. TUN determined by chemiluminescence evidently provides a simple means of calculating nitrogen balance more nearly accurately.

False Positive Reactions↗
PubMed1987

Zinc protoporphyrin. Past, present, and future.

The course of zinc protoporphyrin research has progressed at an increasingly rapid pace on several fronts. A variety of biochemical and clinical evidence viewed in toto now suggests that ferrochelatase catalyzes zinc protoporphyrin formation in states of relative iron-deficient erythropoiesis and in lead-inhibited iron metabolism. Furthermore, a redefinition of the relationship of zinc protoporphyrin to certain other parameters of iron status has been made based upon changes during the earliest states of iron depletion. These clinical studies show that the zinc protoporphyrin level and the ferritin level vary in concert but that changes in the percent transferrin saturation and in the hematocrit results are less consistent. Thus zinc protoporphyrin and ferritin are closely linked metabolically such that iron-deficient erythropoiesis becomes an initial manifestation of iron depletion. The measurement and expression of results as mumoles zinc protoporphyrin/mole heme have improved the quality of results, partly by the elimination of the assumed hematocrit designed into existing instruments. Other refinements in hematofluorometry technology have permitted exploration of the potentially extensive applications of zinc protoporphyrin measurements for lead surveillance and diagnosis, blood banking, pediatrics, obstetrics, sports medicine, and other clinical situations where a very sensitive, cost-effective indication of iron status is required.

Erythrocytes↗
PubMed1987

Interpreting results of coulometry and immunoprecipitation in diagnosing iron disorders.

Concentration of iron in plasma, total iron-binding capacity (TIBC), and transferrin saturation are often determined by standard spectrophotometric methods, but iron concentration may be quantified by immunoprecipitation or, electrochemically, by controlled-potential coulometry. Because these iron assays do not all measure the same form(s) of iron, we studied subjects in various states of iron nutriture: normal adults, iron-deficient patients, thalassemia patients with unsaturated transferrin or oversaturated transferrin, and patients with idiopathic hemochromatosis. The spectrophotometric and coulometric methods detected essentially all non-heme iron in plasma; results correlated well but showed a negative bias toward the coulometric method. Results by an immunoprecipitation procedure, which measures only transferrin-bound iron, correlated well with those obtained coulometrically but were slightly higher than the latter. The characteristics of the various methods for iron must be understood by the clinical laboratory if diagnosis of iron disorders is to be accurate.

Electrochemistry↗
PubMed1987

Plasma iron and transferrin iron-binding capacity evaluated by colorimetric and immunoprecipitation methods.

We evaluated plasma iron (PI) and total iron-binding capacity (TIBC) or transferrin in normal individuals and in patients with iron imbalance. The standard colorimetric measurements of PI and TIBC and the standard isotope-dilution measurement of TIBC were compared with an immunoprecipitation method and also with immunoelectrophoresis of transferrin. PI concentrations as measured by the standard and immunoprecipitation methods agreed closely for all individuals except those with saturated transferrin, where nontransferrin iron increased the results in the standard assay. This excess iron in saturated plasma may be derived from either free iron or iron-bearing ferritin. There were also differences in TIBC between the two methods. Iron-deficient sera gave higher values for transferrin when measured by immunoelectrophoresis. Unsaturated iron-binding capacity was increased in the isotope-dilution method in some iron-saturated plasma, compounding errors when added to erroneously high PI values to compute TIBC. Perhaps some exchange of iron occurred between added iron and transferrin iron in the isotope-dilution method. These measurements confirm the accuracy of the standard colorimetric method of measuring PI and TIBC except in iron-saturated plasma. However, the greater specificity of a polyclonal immunoprecipitation method of measuring PI and TIBC makes it particularly useful in differentiating transferrin-bound iron from nontransferrin iron.

Colorimetry↗
PubMed1983

Hyperglycemia-induced intracellular depletion of ascorbic acid in human mononuclear leukocytes.

It has recently been reported that glucose and its analogues inhibit in vitro ascorbic acid transport across the cell membrane of polymorphonuclear leukocytes and fibroblasts. We have studied the effect of in vivo hyperglycemia on the intracellular ascorbic acid level of mononuclear leukocytes in normal and diabetic human subjects. Administration of an intravenous glucose load resulted in a prompt decrease of mononuclear leukocyte ascorbic acid level in the normal subjects. The rate of its decline correlated closely with the rate of change of plasma glucose. Among the NIDDM subjects in the fasting state, the plasma glucose was high and the leukocyte ascorbic acid level was low when compared with that of the normal subjects. The decrease in the leukocyte ascorbic acid level during disposition of the i.v. glucose load was not statistically significant in the diabetics. The hyperglycemia-induced intracellular depletion of ascorbic acid could be clinically important and requires further evaluation.

Adult↗
PubMed1983

Liquid-chromatographic profiles of urinary porphyrins.

Information on changes in the urinary excretion pattern of porphyrins can be especially useful in the diagnosis of disorders of porphyrin metabolism. Most clinical laboratory procedures are designed for assay of uroporphyrin and coproporphyrin only, and in many cases even these are not cleanly separated. Hence, we developed a "high-performance" liquid-chromatographic procedure to separate and quantify all five urinary porphyrins--that is, those with four through eight carboxyl groups. Before chromatography, the porphyrins are isolated from other urinary components by two simple, rapid pretreatment steps, then injected into the chromatograph in nonesterified form. They are separated and eluted with a step gradient of methanol/phosphate buffer, pH 3.0, in which the methanol content is first 650, then 850 mL/L. As little as 1 ng of eluted porphyrins can be measured fluorometrically. Analytical recovery of coproporphyrin is virtually 100% and of uroporphyrin 75-80%. CVs are about 10% for coproporphyrin at 70 micrograms/L and 20-40% for uroporphyrin at 8 micrograms/L.

Chromatography, High Pressure Liquid↗
PubMed1982

Ascorbic acid in lymphocytes: cell preparation and liquid-chromatographic assay.

Measurements of ascorbic acid concentration in leukocytes by "high-performance" liquid chromatography (HPLC) provides better nutritional assessment, leading to better management, particularly of presymptomatic and critically ill patients. This procedure includes a simple, reproducible cell-separation technique that requires no more than 2 mL of whole blood. Cell populations are separable with greater than 95% purity and greater than 99% viability. Ascorbic acid is assayed by HPLC. The vitamin can be reproducibly quantified in concentrations as low as 0.1 microgram/mL of cell extract. The chromatographic procedure is very rapid, analysis being completed within 15 min after specimen preparation. The assay is suitable also for urine and protein-free filtrates of plasma and of other biological materials. Reference intervals for plasma, mononuclear leukocytes, and polymorphonuclear leukocytes were established. A preliminary clinical evaluation revealed that hospital patients were at a greater risk of ascorbic acid deficiency than expected.

Ascorbic Acid↗
PubMed1979

Erythrocyte protoporphyrin/heme ratio in the assessment of iron status.

The protoporphyrinemia of iron deficiency is well recognized. Clinically, information on the protoporphyrin/heme molar ratio in whole blood offers certain advantages over protoporphyrin measurement alone. A procedure for determining this ratio is reported. Protoporphyrin is extracted, solubilized, and measured fluorometrically. Heme (as hemin chloride) is precipitated with the blood proteins, the precipitate is dissolved in an alkaline/pyridine solvent, and the resulting bispyridine ferriprotoporphyrin is measured spectrophotometrically. The molar ratio of these two metabolites correlates well with values for plasma ferritin, plasma iron, transferrin saturation, hemoglobin, and hematocrit. In some cases the ratio increases detectably while the other variables, especially hematocrit and hemoglobin, remain normal. Evidently it is a more sensitive index to iron status. For healthy men and women, the mean ratio is 16.0 (SD, 5.3). The mean + 3 SD, or a ratio of 32, is distinctly abnormal, as shown by a confirmatory test. We validated the test by surveying routine blood specimens obtained from several population groups.

Anemia, Hypochromic↗
PubMed1978

Modified erythrocyte uroporphyrinogen I synthase assay, and its clinical interpretation.

Assay of erythrocyte uroporphyrinogen I synthase is an accepted diagnostic test for acute intermittent porphyria, particularly in those individuals who are asymptomatic or in whom the disease is not biochemically manifested by excretion of excess porphyrin precursor. The assay described is based upon a coupled-enzyme procedure in which added delta-aminolevulinic acid and its dehydratase present in erythrocytes are used to generate porphobilinogen as substrate for uroporphyrinogen synthase. Zinc and dithiothreitol are added with preincubation to give maximum activity and reproducibility. These agents also prevent inhibition by lead. Healthy young women had a mean activity of 40 nmol of porphyrin formed per milliliter of erythrocytes per hour, men and activity of 38 nmol/ml/h. Preparation of control specimens is described. This assay gave within-day CVs ranging from 1.9 to 2.8%. Precautions in interpretation of results are discussed.

Adult↗