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Biomedical subjects

M De Broe

Publications and source records attributed to M De Broe.

At least 19 recordsLinked to original sources
PubMed2006

Bisphosphonates prevent experimental vascular calcification: Treat the bone to cure the vessels?

Bisphosphonates are inhibitors of bone resorption that are widely used to treat osteoporosis. Price and colleagues demonstrate that ibandronate suppressed the development of uremia-related vascular calcification in rats. These findings extend the link between bone remodeling and vascular calcification to the context of chronic renal failure, opening perspectives toward novel therapeutic strategies.

Animals↗
PubMed1998

Adverse effects of chronic low level lead exposure on kidney function--a risk group study in children.

BACKGROUND: Children have been considered a risk group for lead (Pb) toxicity, mainly because of neurophysiological or neuro-cognitive deficits following Pb exposure. Blood Pb levels (b-Pb) of 100 microg/l currently have been defined as the lowest adverse effect level. The aim of this study was to compare, with the help of urinary markers, the kidney function of children with b-Pb just above this threshold with that of unexposed children, to assess from a nephrological point of view whether the current threshold is justified and whether children really are a particularly vulnerable risk group in terms of Pb-induced kidney damage. METHODS: In a cross-sectional study, 112 children, either from unexposed areas (controls, n=50) or Pb-contaminated areas (n=62), the latter partly with a known history of elevated b-Pb, were examined. Twenty nine urinary or serum markers mostly related to the function or integrity of specific nephron segments were determined (e.g. filtered plasma proteins, tubular enzymes, tubular antigens, eicosanoids). RESULTS: b-Pb were 39+/-13 microg/l in controls and 133+/-62 microg/l in exposed children. The main findings were increased excretion rates of prostaglandins and thromboxane B2, epidermal growth factor, beta2-microglobulin and Clara cell protein in the exposed children. A relationship between b-Pb and the prevalence of values above the upper reference limits was observed. CONCLUSIONS: With the help of urinary markers, nephron segment-specific effects of chronic low-level Pb exposure could be detected in children. The pattern of effects on glomerular, proximal and distal tubular and interstitial markers was similar to that previously observed in adults. The changes, however, occur at lower b-Pb levels than in adults. The current threshold appears to be justified also from a nephrological point of view, and children can indeed be considered a special risk group.

Biomarkers↗
PubMed1998

Lead absorption and renal dysfunction in a South African battery factory.

OBJECTIVES: To test the association between inorganic lead (Pb) exposure, blood pressure, and renal function in South African battery factory workers, with both conventional and newer measures of renal function and integrity. METHODS: Renal function measures included serum creatinine, urea, and urate (n = 382). Urinary markers (n = 199) included urinary N-acetyl-beta-D-glucosaminidase (NAG), retinol binding protein, intestinal alkaline phosphatase, tissue non-specific alkaline phosphatase, Tamm-Horsfall glycoprotein, epidermal growth factor, and microalbuminuria. RESULTS: Mean current blood Pb was 53.5 micrograms/dl (range 23 to 110), median zinc protoporphyrin 10.9 micrograms/g haemoglobin (range 1.9 to 104), and mean exposure duration 11.6 years (range 0.5 to 44.5). Mean historical blood Pb, available on 246 workers, was 57.3 micrograms/dl (range 14 to 96.3). After adjustment for age, weight and height, positive exposure response relations were found between current blood Pb, historical blood Pb, zinc protoporphyrin (ZPP), and serum creatinine and urate. Blood pressure was not associated with Pb exposure. Among the urinary markers, only NAG showed a positive association with current and historical blood Pb. CONCLUSION: An exposure-response relation between Pb and renal dysfunction across the range from < 40 to > 70 micrograms/dl blood Pb was found in this workforce, with conventional measures of short and long term Pb exposure and of renal function. This could not be explained by an effect on blood pressure, which was not associated with Pb exposure. The findings probably reflect a higher cumulative renal burden of Pb absorption in this workforce in comparison with those in recent negative studies. The results also confirm the need for strategies to reduce Pb exposure among industrial workers in South Africa.

Acetylglucosaminidase↗
PubMed1996

Biochemical activity, pharmacokinetics and tolerability of tepoxalin, a cyclooxygenase/5-lipoxygenase inhibitor, in man.

Tepoxalin, a novel inhibitor of cyclooxygenase (CO) and 5-lipoxygenase (5-LO), was investigated for biochemical activity and pharmacokinetics in two studies. Study I was a 4-period, double-blind, randomized, single rising dose using 2 alternating panels (A, B) with interspersed placebo design (A: 25, 100, 400 mg, B: 50, 200, 800 mg p.o.). Study II was a 3-panel, randomized, placebo-controlled, double-blind, multiple dose study (A: 100 mg, B: 200 mg, C: 400 mg). In both studies, CO inhibition was assessed by generation of serum thromboxane (TxB2), 5-LO activity by LTB4 production ex vivo in Caionophore-stimulated blood. Plasma drug concentrations were assayed by HPLC for tepoxalin and its identified acid metabolite. It was found in both studies that at all dose levels the TxB2 generation was markedly suppressed (> 95% 2 h postdose). In study I, at 2 h postdose, % inhibition of LTB4 biosynthesis was marginal for the 3 lower doses but significant at 200 (14%), 400 (25%) and 800 mg (43%). In study II, the only significant inhibition occurred at the 400 mg dose at 6 h postdose on day 1 (17%) and on day 8 at 4, 6 and 8 h postdose (32, 42 and 32% respectively). In both studies and at all doses, plasma concentrations of tepoxalin varied widely between subjects. Linearity between plasma concentrations and dose could not be ascertained, and correlation between drug plasma levels and effect on LTB4 synthesis was poor. Single doses up to 800 mg and multiple doses up to 400 mg of tepoxalin were generally well tolerated.

Adult↗
PubMed1994

Nephron target sites in chronic exposure to lead.

With established urinary markers of kidney integrity the early renal effects of lead have previously been considered to be mainly tubular or tubulointerstitial. In a cross-sectional study on 81 male lead-exposed workers and 45 age-matched controls (median blood lead concentrations 2.03 and 0.34 mumol/l respectively) not only well-established but also new urinary markers of renal integrity preferentially or exclusively located along the different nephron segments were analysed. Markers related to the glomerulus were 6-keto-prostaglandin 1 alpha, thromboxane B2, mainly produced in the glomerulus, and the extracellular matrix protein fibronectin. Markers of the proximal tubule were the brush-border antigens BBA, BB50, and HF5 and the intestinal alkaline phosphatase. Prostaglandin E2 and F2 alpha, preferentially synthesized in the collecting duct and medullary interstitial cells, served as markers of these more distal nephron segments. In contrast to previous studies on the early phase of lead nephrotoxicity, not only tubular but also glomerular involvement could be shown in the study presented here by increases in the median values of 6-keto-prostaglandin 1 alpha and decreases in fibronectin. The proximal tubular markers intestinal alkaline phosphatase and BBA confirmed that this particular segment of the nephron is affected by lead. Effects on the collecting tubule or medullary interstitial cells could also be observed. It is concluded that lead affects both the glomerulus and the tubular apparatus and that combinations of new and established markers could be valuable for a better definition and early detection of lead nephropathy.

Adult↗
PubMed1987

Applications of laser microprobe mass analysis in medicine.

An instrument for laser microprobe mass analysis (LAMMA) has been available for applied research for several years. The value of this sensitive microanalytical technique has been demonstrated in various fields of science, including medicine and biology. The LAMMA instrument comprises two laser systems. The first is a weak continuous pilot laser that can be aimed at a region of interest of the sample, e.g., a histological microtome section, using a light microscope. The second is a powerful pulsed laser that can evaporate the selected area. The generated ions are then analyzed in a time-of-flight mass spectrometer. The advantages of LAMMA present new perspectives in biomedical research. Elements can be located and analyzed down to the parts per million-level with a 1 micron spatial resolution. Speciation and/or fingerprinting of (in)organic molecules may be obtained. However, the technique is destructive, the quality of the light-microscopic view is poor, and quantification is still under investigation. In this review, the analytical characteristics of LAMMA are evaluated, including instrumental features, detection sensitivity, ionization parameters, molecular speciation, and quantification. Applications of LAMMA in medicine are reviewed, covering the microanalysis of a wide range of physiological and toxic constituents (alkali metals, calcium, aluminum, titanium, fluorine and iodine, heavy metals, transition elements, and molecular compounds).

Humans↗
PubMed1983

Use of monoclonal antibodies to detect human placental alkaline phosphatase.

Convenient, sensitive, and specific solid-phase immunoassays involving monoclonal antibody are described for the determination of human placental alkaline phosphatase (hPLAP). An endogenous enzyme immunoassay combined the specificity of the immunological and the enzymatic reactions. Alternatively, a solid-phase "sandwich" radioimmunoassay involving immobilized polyclonal rabbit anti-hPLAP in combination with iodinated monoclonal antibody provided some additional advantages. Both tests can be used to detect hPLAP from various sources, e.g., in human sera during pregnancy or as a tumor marker. The radioimmunoassay detected an increase in hPLAP at nine weeks of gestation. We discuss the use of monoclonal antibodies for the differentiation of different alkaline phosphatase isoenzyme types by electrophoresis on starch gel.

Alkaline Phosphatase↗
PubMed1977

Serum binding of quinidine in experimental acute renal failure.

Quinidine serum binding is increased in some patients with acute renal failure, but in animals with renal failure conflicting results were published. Therefore, serum binding of quinidine, papaverine and phenylbutazone was studied by equilibrium dialysis in rabbits and rats with acute renal failure induced either by injection of uranyl nitrate or ligation of the ureters. From the results it appears that, in animals, quinidine binding changes are different according to the model used for induction of the renal failure, regardless of the species studied. After ligation of the ureters, lipoprotein concentration increases, but the meaning of this increase for increased serum quinidine binding is not clear.

Acute Kidney Injury↗