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Biomedical subjects

R Lauwerys

Publications and source records attributed to R Lauwerys.

At least 37 records · Page 2Linked to original sources
PubMed1995

Time-integrated blood lead concentration is a valid surrogate for estimating the cumulative lead dose assessed by tibial lead measurement.

The concentration of lead in tibia (Pb-T) was measured in vivo by a 109Cd K-shell X-ray fluorescence technique in 123 workers from a primary lead smelter (age: mean, 45 years; range, 30-61; duration of employment: mean, 20 years; range, 7-45). Their cumulative blood lead index (CBLI) was also calculated on the basis of the blood lead (Pb-B) records available from the company's medical files. Geometric mean for Pb-T was 49 micrograms Pb/g bone mineral (range, 15-167). The company's health surveillance programs, implemented since 1945, resulted in Pb-B values which rarely exceeded 70 micrograms Pb/dl whole blood. Pb-B at the time of Pb-T measurement averaged 31 micrograms Pb/dl (range, 6-62) and the geometric mean for CBLI amounted to 803 micrograms Pb/dl x year (range, 220-2130). Despite various assumptions and uncertainties inherent in the assessment of the cumulative lead dose through Pb-T measurement or CBLI calculation, the relation between both variables in the present lead smelter populations is very strong (rpearson = 0.80, P < 0.0001; age explained at the most 9.5% of the variance). The slope of the regression equation of log Pb-T vs log CBLI showed that a doubling of CBLI also corresponds to doubling of Pb-T. It may be concluded that a sound calculation of CBLI represents a valid surrogate for estimating the life time integrated dose of lead as assessed by the measurement of cortical bone lead (e.g., in tibia).

Adult↗
PubMed1995

The delayed lung responses to single and repeated intratracheal administration of pure cobalt and hard metal powder in the rat.

Epidemiological and clinical studies suggest that inhalation of cobalt metal dust (Co) mixed with tungsten carbide particles (WC), but not of cobalt dust alone, may cause interstitial pulmonary lesions (hard metal disease). In previous experimental studies in the rat, we have demonstrated the greater acute pulmonary toxicity of a WC-Co mixture compared to Co or WC alone. The present study was undertaken to compare in the same animal model the delayed lung response after intratracheal administration of Co or WC-Co particles (cobalt particle 6.3 wt%). The responses were also compared with those obtained after treatment with arsenic trioxide and crystalline silica used a reference materials producing an acute toxic insult and a progressive fibrogenic response, respectively. Cellular (total and differential counts) and biochemical parameters (LDH, N-acetyl-beta-D-glucosaminidase, total protein, albumin, fibronectin, and hyaluronic acid) were measured in bronchoalveolar lavage fluid following single and repeated intratracheal instillations. The results indicate that the delayed lung response observed after WC-Co is different from that after cobalt metal alone. A single intratracheal dose of WC-Co (1, 5, or 10 mg/100 g body wt) induced an acute alveolitis which persisted for at least 1 month. Four months after a single instillation of WC-Co, no clear histological lung fibrosis could however be evidenced, indicating a reversibility of the lesions. The effects of cobalt (0.06, 0.3, or 0.6 mg/100 g body wt) or tungsten carbide alone (1, 5, 10 mg/ 100 g body wt) were very modest, if any. Following repeated intratracheal instillations (four administrations at 1-month interval), increased lung hydroxyproline content and histopathological evidence of interstitial fibrosis were observed after WC-Co (4 x 1 mg/100 g body wt), but not after administration of each component separately, i.e., Co (4 x 0.06 mg/100 g body wt) or WC (4 x 1 mg/100 g body wt). The mechanism of the fibrotic reaction induced by WC-Co seems different from the progressive inflammatory reaction induced by crystalline silica. We suggest that it might result from a scarring reaction elicited by repeated acute insults as observed after repeated administration of arsenic trioxide.

Acetylglucosaminidase↗
PubMed1995

The role of vitamin E in the susceptibility of rat lung and liver microsomes to iron-stimulated peroxidation.

The production of thiobarbituric acid-reactive substances (TBA-RS) and ethane, two markers of the lipid peroxidation process, was evaluated in rat lung and liver microsomal membranes incubated in the presence of either ferrous ions or a mixture of ferric ions and ascorbate. Microsomal fractions isolated from lung tissue were more resistant than those isolated from the liver. Compared to Fe2+, the association of Fe3+/ascorbate seemed to be totally ineffective in stimulating peroxidation of lung microsomes. The fatty acid profile of lung and liver microsomal membranes could not be responsible for their different susceptibility to free radical degradation. The microsomal fraction isolated from lung showed a higher vitamin E concentration than the liver. The importance of vitamin E in protecting lung membranes was assessed by using lung and liver isolated from vitamin E-deficient and vitamin E-supplemented rats. For both lung and liver microsomal fractions an inverse relationship between vitamin E concentrations and the extent of lipid peroxidation was observed. However, although the vitamin E concentrations in lung and liver microsomes isolated from rats submitted to a vitamin E-deficient diet were not different, lung microsomes still exhibited a lower production of TBA-RS and ethane than liver. In addition to vitamin E, other factors must be involved to explain the resistance of lung microsomes to lipid peroxidation.

Animals↗
PubMed1995

Lung toxicity of hard metal particles and production of interleukin-1, tumor necrosis factor-alpha, fibronectin, and cystatin-c by lung phagocytes.

Hard metal alloys (WC-Co) are made of a mixture of cobalt (Co; 6%) and tungsten carbide (WC; 94%) particles. Chronic inhalation of hard metal dust can lead to the development of a fibrosing alveolitis, the pathogenesis of which is still undefined. The present investigation was undertaken to assess the effect of Co, WC, and WC-Co particles on the release by lung phagocytes of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), fibronectin, and cystatin-c. The responses were compared with those induced by two other lung toxicants, i.e., crystalline silica (DQ12) and arsenic trioxide (As2O3). IL-1 and TNF-alpha activities produced in the presence and absence of LPS stimulation were measured with the aid of bioassays while fibronectin and cystatin-c were determined by latex immunoassays. In vitro, maximal noncytotoxic doses of As2O3, Co, WC, or WC-Co did not significantly affect the production of these mediators by rat alveolar macrophages. In contrast, DQ12 enhanced the production of TNF-alpha (with and without LPS stimulation) and IL-1 (after LPS stimulation) and decreased cystatin-c release (in the absence of LPS). Following a single intratracheal instillation of the different test preparations in the rat, the response of the lung phagocytes obtained by bronchoalveolar lavage (BAL) 24 hr later was examined. We were unable to detect any consistent effect of Co (0.06 mg/100 g body wt), WC (1 mg/100 g body wt), or WC-Co treatment (1 mg/100 g body wt) on the production of the above mediators. In contrast, after LPS stimulation, As2O3 (0.5 mg/100 g body wt) and DQ12 (1 mg/100 g body wt) stimulated the production of TNF-alpha and IL-1. In the absence of LPS, As2O3 stimulated fibronectin and cystatin-c production and DQ12 stimulated cystatin-c release. Since the dose of WC-Co used in vivo (1 mg/100 g body wt) caused pronounced lung inflammation (increased LDH, protein, and albumin levels in BAL fluid), we conclude that the acute lung toxicity of WC-Co particles is not mediated through enhanced production of the examined mediators by lung phagocytes.

Alloys↗
PubMed1995

Effect of the benzene metabolite, hydroquinone, on interleukin-1 secretion by human monocytes in vitro.

Decreased interleukin-1 (IL-1) production by mononuclear phagocytes has been shown to contribute to benzene myelotoxicity in animals. The study presented here was designed to examine the relevance of this mechanism in humans. Fresh human blood monocytes were exposed to 0.001-10 microM hydroquinone (HQ) and assessed for their ability to release IL-1 alpha and IL-1 beta in response to a stimulation with endotoxin. Both cytokines were measured by specific ELISA. Exposure of human monocytes to micromolar concentrations of HQ for 2 hr resulted in a dose-dependent reduction of IL-1 secretion. For both IL-1 alpha and IL-1 beta, the decreases were statistically significant at concentrations of 5 microM and above. HQ also inhibited RNA and protein synthesis in a dose-dependent manner, with 50% inhibitory concentrations of 21 +/- 11 and 10 +/- 9 microM, respectively. Furthermore, monocytes treated with 5 microM HQ also displayed a reduced total protein content when compared with control cells. These data suggest that the reduction of IL-1 production caused by HQ results from a global impairment of monocyte essential functions such as transcription or translation. Taken as a whole, our results support a mechanism whereby HQ may contribute to the myelotoxicity of benzene in humans by inhibiting the production by mononuclear phagocytes of cytokines involved in the regulation of hematopoiesis.

Benzene↗
PubMed1995

Low-molecular-weight proteins as markers of organ toxicity with special reference to Clara cell protein.

Low-molecular-weight (M(r) between 5 and 40 kDa) proteins present several features related to their small size making them potentially interesting biomarkers of toxicity. They are readily exchangeable and might serve as peripheral indicators of toxic events in relatively inaccessible target organs. They have a short half-life in plasma and may thus respond to both acute and chronic toxic effects. Their catabolism takes place in the proximal tubule which is the segment of nephron which is the most vulnerable to toxic injury. Low-M(r) proteins have been used hitherto in toxicology mainly in relation to their renal handling, i.e. as markers of proximal tubule dysfunction or of glomerular filtration rate, e.g. beta 2-microglobulin (beta 2-m), alpha 1-microglobulin (alpha 1-m) and retinol-binding protein (RBP). The potential of low-M(r) proteins as biomarkers of toxicity might go beyond the field of nephrotoxicity, as suggested by our investigations on a new low-M(r) protein called protein 1 or Clara cell protein (CC16). CC16 is a 16-kDa protein synthesised by non-ciliated cells of the tracheobronchial epithelium, among which the Clara cells which, because of their high xenobiotic-metabolizing activity, are particularly vulnerable to a number of air pollutants. CC16 secreted in the respiratory tract diffuses passively by transsudation into the serum where it may mirror changes occurring in the lung. Recent studies on subjects exposed to lung toxicants (e.g. tobacco smoke and silica) suggest that CC16 in serum or bronchoalveolar lavage fluid is a sensitive marker of bronchial tree injury. CC16 is handled by the kidney as other low-M(r) proteins and may also be used to detect proximal tubule dysfunction. In this respect too, CC16 shows a unique sensitivity and can detect very subtle defects in proximal tubular dysfunction that remain undetected when screening is based on the assay of classical urinary low-M(r) proteins (i.e. beta 2-m, alpha 1-m or RBP).

Biomarkers↗
PubMed1995

Physicochemical mechanism of the interaction between cobalt metal and carbide particles to generate toxic activated oxygen species.

Hard metal alloys (or cemented carbides) are made of a mixture of tungsten carbide particles (WC, more than 80%) cemented in cobalt metal powder (Co, 5-10%). The inhalation of hard metal particles may cause an interstitial pulmonary disease, the mechanism of which involves an interaction between Co and WC particles. Some epidemiological data also suggest that hard metal dust can induce lung cancer in workers. In a macrophage culture model, butylated hydroxytoluene (1 mM) protected from the cytotoxicity of hard metal particles, suggesting a possible involvement of lipid peroxidation in the toxicity of these powders. In a biochemical system, a mixture of Co and WC particles, but not Co or WC alone, stimulated the production of thiobarbituric acid-reactive substances from arachidonic acid. Using a spin trapping system applied to aqueous particulate suspensions and electrochemical techniques, we present experimental evidence that the association of Co and carbide particles represents a specific toxic entity producing large amounts of activated oxygen species. The mechanism of this interaction proceeds through the oxidation of cobalt metal catalyzed at the surface of carbide particles and resulting in the reduction of dissolved oxygen. This physicochemical property of hard metal particles provides a new basis for interpreting their inflammatory action and their possible carcinogenic effect on the lung.

Animals↗
PubMed1995

Low molecular weight proteinuria in Chinese herbs nephropathy.

Urinary excretion of five low molecular weight proteins (LMWP) [beta 2-microglobulin (beta 2m), cystatin C (cyst C), Clara cell protein (CC16), retinol-binding protein (RBP) and alpha 1-microglobulin (alpha 1m)], albumin and N-acetyl-beta-D-glucosaminidase (NAG) were quantified in 16 patients who followed a weight reduction program which included Chinese herbs, which have been incriminated in the genesis of Chinese herbs nephropathy (CHN). An additional group of four patients transplanted for CHN were investigated. Urinary data were obtained for comparison purpose in five groups of proteinuric patients: two groups with normal serum creatinine (SCr) and glomerular albuminura [12 patients with diabetes mellitus and microalbuminuria (DN), 10 patients with primary nephrotic syndrome (NS)]; two groups with normal SCr and toxic nephropathy [6 patients with analgesic (AN), 9 patients with cadmium nephropathy (CdN)]; and one group of seven patients with glomerular diseases and increased SCr (GN). Patients were classified according to serum level S beta 2m to take into account the possibility of overflow proteinuria at S beta 2m > or = 5 mg/liter. Three patients (CHN0) with a S beta 2m < 5 mg/liter, had a normal urinary protein pattern including NAG and a normal S beta 2m. Eight patients (CHN1) with a S beta 2m < 5 mg/liter had various abnormalities of their urinary protein pattern. In four of them (CHN1a) only beta 2m, RBP and CC16 were increased while total proteinuria and SCr were normal. In the other four (CHN1b and c) albumin, cyst C, alpha 1m and NAG were also elevated, while total proteinuria and SCr were moderately raised. Five patients (CHN2) with a S beta 2m > or = 5 mg/liter had a markedly increased excretion of all LMWP, albumin and NAG (CHN1 vs. CHN2, P < 0.05) as well as a further increase in total proteinuria and SCr. The urinary LMWP/albumin concentration ratio was strikingly higher in CHN patients than in patients with glomerular albuminuria (CHN1 vs. DN and NS, P < 0.01) or moderate renal failure with elevated S beta 2m level (CHN2 vs. GN, P < 0.01), confirming the existence of a tubular proteinuria independent of glomerular albuminuria or overflow proteinuria. A similar proteinuria pattern was present in the two toxic nephropathies (CdN and AN). This pattern was no longer recognizable after transplantation. In conclusion, CHN exhibits various profiles of tubular proteinuria which are the hallmarks of the disease. This pattern is still detectable in patients with renal failure and/or glomerular albuminuria. It is identical to that observed in cadmium and analgesic nephropathies. It does not recur after transplantation. Its most sensitive and reliable marker is a raised urinary level of CC16 or RBP.

Adult↗
PubMed1995

Factors influencing serum levels and peritoneal clearances of low molecular weight proteins in continuous ambulatory peritoneal dialysis.

To identify the factors influencing the serum concentrations and the peritoneal clearances of low molecular weight proteins (LMWP), fourteen patients on continuous ambulatory peritoneal dialysis (CAPD) for 1 to 57 (mean 9.4) months were examined. LMWP [Beta 2-microglobulin (Beta 2m, molecular wt 11.8 kD), cystatin C (cyst C, molecular wt 13.2 kD), Clara cell protein (CC16, molecular wt 15.8 kD), retinol-binding protein (RBP, molecular wt 21 kD) and alpha 1-microglobulin (Alpha 1m, molecular wt 33 kD)] and high molecular weight proteins (HMWP) [albumin (Alb, molecular wt 66 kD), immunoglobulins (IgG, molecular wt 170 kD and IgM, molecular wt 600 kD) and alpha 2-macroglobulin (Alpha 2m, molecular wt 718 kD)] were determined by latex immunoassay in the serum and dialysate collected during the peritoneal equilibration test (PET) with 2.27% dextrose (N = 14), and in dialysate from 56 standard exchanges, performed the day preceding PET, with 1.36% (N = 21), 2.27% (N = 23) and 3.86% (N = 12) dextrose. Determinants of serum concentrations and transperitoneal clearances of the proteins were traced by stepwise regression analysis using as possible contributors age, sex, residual diuresis, duration of the therapy (for serum concentrations), molecular radius of the protein and peritoneal membrane characteristics (for peritoneal clearances). LMWP serum concentrations were markedly increased whereas serum concentrations of HMWP were within the normal range. Residual diuresis, age and duration of dialysis emerged as significant determinants of serum concentration of some proteins, whereas transperitoneal clearance was dependent mainly on the size of the protein and, only for HMWP, on the dwell time. Residual diuresis was inversely related to the serum concentrations of four LMWP. Age was negatively correlated to the serum concentrations of beta 2m, CC16 and RBP. RBP and Alb were the only proteins whose serum concentration significantly decreased with time on CAPD. The relationship between peritoneal clearance and M(r) shows two slopes suggesting the existence of two populations of pores in the peritoneal capillary wall: small pores of about 20 to 25 A radius and large pores exceeding 100 A radius. A long dialysis cycle is associated with significant loss of HMWP only. Daily peritoneal protein losses, in mg (mean +/- SD), were as follows: Beta 2m 43.4 +/- 4.5; cyst C 9.6 +/- 1.8; CC16 1.8 +/- 0.3; RBP 58.9 +/- 11.1; Alpha 1m 149.5 +/- 15.7; Alb 6570 +/- 530; IgG 750 +/- 111; IgM 46.4 +/- 14.9; and alpha 2m 67.0 +/- 12.7. In conclusion, LMWP concentrations in the serum of patients on CAPD were markedly increased and influenced mainly by patient-related factors (residual diuresis and age). Serum albumin and RBP declined with the duration of dialysis. Peritoneal protein loss was determined by the size of the protein and, for large proteins, by the dwell time. The peritoneum behaves as a membrane with at least two populations of pores.

Adult↗
PubMed1995

Effect of oxygen concentration on production of ethane and thiobarbituric acid-reactive substances by peroxidizing lung and liver homogenates and formation of ethanol by peroxidizing docosahexaenoic acid preparations under hyperoxic conditions.

The oxygen dependence of ethane formation was investigated in rat lung and liver homogenates, incubated in sealed flasks, in which the peroxidation was stimulated by the addition of ferrous ions. For both tissues, the production of ethane was maximal under a 20% oxygenated gas phase, while hyperoxic conditions led to a decreased ethane in the gas phase. The formation of thiobarbituric acid-reactive substances (TBA-RS), another marker of the lipid peroxidation process, in the homogenates of lung and liver was strongly stimulated at 100% compared to 20% oxygen. Experiments were also carried out on iron-stimulated peroxidation of pure docosahexaenoic acid preparations, which under air led to a large production of ethane. As for tissue homogenates, the TBA-RS content was increased in the presence of 100% oxygen. Those conditions, however, did not induce an increase in ethane production but led to the formation of ethanol. Therefore, the quenching of ethyl radical by molecular oxygen seems to be a very attractive hypothesis to explain the lack of increased ethane production in favor of ethanol when iron-induced lipid peroxidation was stimulated by oxygen.

Animals↗
PubMed1995

Association between NAG-B and cadmium in urine with no evidence of a threshold.

OBJECTIVES: To explore the significance of the increase in urinary excretion of the lysosomal enzyme beta-N-acetylglucosaminidase (NAG) at low exposures to cadmium (Cd) that is frequently found in the absence of any other sign of renal dysfunction. METHODS: The activity was measured of the two main isoenzymes of NAG (NAG-A secreted by exocytosis and NAG-B released with cell membranes) in the urine of 49 male workers employed in a Cd smelter and of 20 age matched controls. RESULTS: An increased urinary excretion of low molecular weight proteins was noted only in subjects who excreted > 10 micrograms Cd/g creatinine. The urinary activity of NAG-B showed a dose related increase that was already significant in the group excreting 0.5-2 micrograms Cd/g creatinine. In multiple regression analysis the NAG-B activity correlated with the excretion of Cd but not with that of lead or mercury. The NAG-A activity was by contrast unaffected by exposure to Cd but correlated with the urinary excretion of lead and copper. CONCLUSIONS: As NAG-B is considered to be the lesional form of NAG, the existence of a specific association between this enzyme and urinary Cd excretion with no detectable threshold suggests that this metal produces cellular alterations at exposures commonly found in the general population.

Acetylglucosaminidase↗
PubMed1995

Subclinical signs of kidney dysfunction following short exposure to silica in the absence of silicosis.

Signs of kidney dysfunction detectable in urinary protein excretion were searched for in a group of 86 silica-exposed workers who were compared to 86 control subjects matched for age, smoking status and body mass index. No worker had any clinical, spirometric or radiographic sign of silicosis, and exposure duration averaged 15.2 months (range: 11-20). An increase in the urinary excretion of albumin, transferrin, retinol-binding protein and N-acetyl-beta-D-glucosaminidase was found in the exposed group, and the prevalences of pathological values were also elevated in this group. By contrast, both groups had similar serum levels of creatinine and beta 2-microglobulin. These results strongly suggest that occupational exposure to silica may lead to subclinical renal effects after less than 2 years and in the absence of silicosis.

Adult↗
PubMed1995

Clara cell protein (CC-16) induces a phospholipase A2-mediated inhibition of fibroblast migration in vitro.

Clara cell protein (CC-16, also designated CC-10) is synthesized by the bronchiolar epithelium and has been suggested as an inhibitor of phospholipase A2 (PLA2) activity. Therefore, CC-16 is a candidate for controlling inflammatory events in the lung. Because CC-16 amounts and function may be altered in fibrosing lung diseases in which bronchiolar injury has been reported, it was measured in alveolar fluids and sera. Secretory PLA2 activity in alveolar fluids and the influence of CC-16 on platelet-derived growth factor-induced human fibroblast chemotaxis and cytosolic PLA2 activity were also explored. CC-16 content was decreased in alveolar fluids from idiopathic pulmonary fibrosis (IPF: 1.3 +/- 0.1 mg/L) and bleomycin lung (1.1 +/- 0.2 versus 2.1 +/- 0.2 mg/L in controls, p < 0.05), whereas there was a three- to ninefold increase in secretory PLA2 activity (p < 0.05 versus controls). CC-16 inhibited fibroblast chemotaxis in a dose-dependent manner (90% inhibition at 30 micrograms/ml CC-16). This inhibition was reversed by reducing CC-16. CC-16 was also able to lower fibroblastic cytosolic PLA2 activity by 50% in vitro. In summary, CC-16 is able to inhibit fibroblast chemotaxis in vitro by mechanisms that may be related to a blockage of cytosolic PLA2 activity. It can be postulated that CC-16 deficiency may contribute to fibroblast burden activity in fibrosing lung diseases.

Adult↗
PubMed1995

Preliminary in vitro investigation into the use of alkaline elution assay for the biomonitoring of humans exposed to genotoxic agents.

1. This in vitro study was undertaken as a preliminary approach before assessing whether the alkaline elution assay can be applied to peripheral blood lymphocytes (PBL) for the monitoring of humans exposed to genotoxic agents such as polycyclic aromatic hydrocarbons (PAH). We have compared in vitro, with the aid of the alkaline elution assay, the formation and the repair of DNA single-strand breaks (ssb) induced by different genotoxic agents [gamma-irradiation, ethyl methanesulfonate (EMS), benzo pyrene diol epoxide (BPDE)] on quiescent and PHA-stimulated human lymphocytes and on a fibroblast cell line. 2. Gamma-irradiation (4 Gy) induced an equivalent amount of DNA ssb in the three cell types. On the other hand, after treatment with EMS (10 mM) and BPDE (50 microM), a higher production of DNA ssb was observed in replicating cells (PHA-stimulated lymphocytes and fibroblasts) when compared with quiescent lymphocytes. 3. After gamma-irradiation, all cell types repaired more than 65% of ssb within 1 h. After treatment with EMS, we noted a deficient DNA repair capacity in quiescent lymphocytes in comparison with replicating cells. In all cell types treated with BPDE, more breaks were observed after a 2 h repair period than immediately after treatment, demonstrating the involvement of a slow repair mechanism after BPDE treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1995

Potential role of Clara cell protein, an endogenous phospholipase A2 inhibitor, in acute lung injury.

It is now recognized that epithelial cells lining airways and alveoli are capable of releasing various mediators, which have the potential to modulate local inflammatory reactions. The amount of the 16 kDa Clara cell protein (CC16), an inhibitor of phospholipase A2 activity produced by pulmonary epithelial cells, was measured by means of a sensitive immunoassay in the unconcentrated bronchoalveolar lavage fluid (BALF) of 13 control subjects, and in patients with acute lung injury (14 with the full-blown adult respiratory distress syndrome (ARDS); 21 after standard cardiopulmonary bypass surgery, a known risk factor for ARDS). The level of CC16 was compared with other markers of inflammation with a wide range of molecular weights: albumin (nephelometry); total protein (spectrophotometry); beta 2-microglobulin (latex immunoassay); cystatin C (latex immunoassay); alpha 1-antitrypsin (immunoradiometry), and lipocortin-1 (enzyme-linked immunosorbent assay (ELISA)). The Clara cell protein (CC16) was detectable in all BALF, and significantly higher levels of this protein were observed in BALF from patients with acute lung injury. Changes in BALF Clara cell protein levels differed from those of alpha 2-macroglobulin and the natural phospholipase inhibitor lipocortin-1. Alpha 2-macroglobulin levels were not significantly enhanced in patients at risk for ARDS, but were increased in patients with ARDS; whereas, lipocortin 1 levels were not elevated in either group. Pretreatment of patients at risk for ARDS with high dose methylprednisolone did not alter the amount of Clara cell protein recovered in BALF. The mean CC16 level in BALF from patients with ARDS who died was significantly lower than from those who survived. The data presented in this study suggest that pulmonary epithelial cells secrete a natural anti-inflammatory protein during acute lung injury, which might have a protective and immunosuppressive role.

Adult↗
PubMed1995

Fatal encephalopathy after otoneurosurgery procedure with an aluminum-containing biomaterial.

Refractory status epilepticus was observed in two patients who underwent vestibular neurectomy. We investigated the relationship with the use of an aluminum containing bone cement during the procedure. Two patients developed focal and thereafter generalized seizures in the late postoperative period of vestibular neurectomy (respectively after 42 and 35 days). A cement (1 g aluminum-calcium fluorosilicate) was used during the procedure to bridge bone defects. Both patients presented cerebrospinal fluid fistula. Investigations excluded common etiologies, in particular infections, and a toxic origin was suspected. Aluminum concentration was determined repeatedly in serum urine, cerebrospinal fluid and retroauricular fistula. The highest aluminum values were respectively in case 1 and 2, 112 and 63 micrograms/L for the cerebrospinal fluid, 495 and 1440 micrograms/L for the fistula, 4.4 and 4.4 micrograms/L in serum. Desferrioxamine was used as chelating agent and aluminum elimination was analyzed in the urine. Status epilepticus became refractory to intensive care therapy. The patients never recovered normal consciousness. Case 1 died 143 days after the procedure and case 2 at 80 days from brain failure. Brain post-mortem examination was obtained in Case 2. Brain aluminum concentration was 2.5 micrograms/g (wet weight) (0.85 micrograms/g in a control non exposed cadaver). The cement (0.2 g) was incubated in vitro (16 h-37 degrees C) with the cerebrospinal fluid of a control patient (cerebrospinal fluid aluminum 8 micrograms/L): aluminum concentration reached 2750 micrograms/L. A close contact between an aluminum containing cement and the cerebrospinal fluid may have resulted in encephalopathy and fatal status epilepticus in these two patients.

Adult↗
PubMed1994

Health risks associated with cobalt exposure--an overview.

Cobalt is an essential oligoelement which enters in the composition of vitamin B12. For the general population, food and beverages represent the main source of cobalt exposure. Traces of cobalt are also present in cement and various household products. In industry, the potential for exposure to cobalt is particularly important during the production of cobalt powder, the production, processing and use of hard metals, the polishing of diamonds with cobalt containing disks and the processing of cobalt alloys. Except in the production of cobalt powders, these activities involve exposure not only to cobalt but also to other substances such as tungsten carbide, iron and diamond which may modulate the biological reactivity of cobalt. Cobalt salts are used for the preparation of enamels and pigments. Cobalt is mainly absorbed from the pulmonary and the gastrointestinal tracts. Absorption through the skin can occur but is low. Concomitant exposure to tungsten carbide increases the pulmonary absorption rate of cobalt metal. Cobalt is not a cumulative toxin and is mainly excreted in urine and to a lesser extent via faeces. Cobalt in blood and urine mainly reflects recent exposure. In the past, outbreaks of cardiomyopathy occurred among heavy consumers of cobalt fortified beer. It is likely that poor nutrition and ethanol had played a synergistic role. Toxic manifestations, however, have mainly been reported following inhalation of cobalt containing dusts in industry. The two main target organs are the skin and the respiratory tract. Cobalt itself may cause allergic dermatitis, rhinitis and asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Cobalt↗