Biological effect monitoring of occupational exposure to 1,3-dichloropropene: effects on liver and renal function and on glutathione conjugation.

A prospective study was performed in the Dutch flower bulb culture to investigate the possible effects of subchronic exposure to the soil fumigant 1,3-dichloropropene (DCP) on liver and kidney function and on glutathione conjugation capacity in blood. Urine spot samples and venous blood samples from 14 workers applying DCP (applicators) were taken at the start of the season in July, and after the season in October. The parameters of liver function measured were: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, and total bilirubin (conjugated and unconjugated). Total bilirubin was significantly decreased from 9.5 before to 7.0 mumol/l after the season. In combination with an increase in serum gamma-glutamyltranspeptidase activity from 12.5 to 19.5 U/l this indicates moderate hepatic enzyme induction. To study renal function, creatinine and beta 2-microglobulin in serum, and beta 2-microglobulin, albumin, alanine aminopeptidase, beta-galactosidase, and retinol binding protein in urine were measured. The glomerular function parameters albumin in urine and creatinine in serum changed significantly during the season: albumin concentration increased from 5.2 to 7.6 mg/l, whereas creatinine concentration [corrected] decreased from 93.0 to 87.5 mumol/l. The tubular function parameter retinol binding protein also increased in concentration from 20.0 to 26.9 micrograms/l. Therefore, a subclinical nephrotoxic effect of subchronic exposure to DCP cannot be excluded. Effects on glutathione conjugation capacity were studied by measuring erythrocyte glutathione S-transferase activity and blood glutathione concentrations. The activity of glutathione S-transferase in erythrocytes was significantly decreased from 4.7 before to 3.3 U/g haemoglobin after the season. The same was true for the blood glutathione concentrations, which decreased from 0.93 to 0.82 mM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood lead concentration, renal function, and blood pressure in London civil servants.

Blood lead concentration was measured in 398 male and 133 female London civil servants not subject to industrial exposure to heavy metals. The relation between blood lead and serum creatinine concentrations and blood pressure were examined. Blood lead concentration ranged from 0.20 to 1.70 mumol/l with a geometric mean concentrations of 0.58 mumol/l in men and 0.46 mumol/l in women (p less than 0.001). In women blood lead concentration increased with age (r = +0.27; p = 0.002). In the two sexes blood lead concentration was positively correlated with the number of cigarettes smoked a day (men r = +0.17 and women r = +0.22; p less than or equal to 0.01), with the reported number of alcoholic beverages consumed a day (men r = +0.34 and women r = 0.23; p less than 0.01), and with serum gamma-glutamyltranspeptidase (men r = +0.23 and women r = +0.14; for men p less than 0.01). Blood lead concentration was not correlated with body weight, body mass index, and employment grade. In men 14% of the variance of blood lead concentration was explained by the significant and independent contributions of smoking and alcohol intake and in women 16% by age, smoking, and alcohol consumption. In men serum creatinine concentration tended to rise by 0.6 mumol/l (95% confidence interval from -0.2 to +1.36 mumol/l) for each 25% increment in blood lead concentration. In men and women the correlations between blood lead concentration and systolic and diastolic blood did not approach statistical significance. In conclusion, in subjects not exposed to heavy metals at work gender, age, smoking, and alcohol intake are determinants of blood lead concentration. At a low level of exposure, lead accumulation may slightly impair renal function, whereas blood pressure does not seem to be importantly influenced. Alternatively, a slight impairment of renal function may give rise to an increase in blood lead concentration.     

Blood lead concentration, renal function, and blood pressure in London civil servants

Blood lead concentration was measured in 398 male and 133 female London civil servants not subject to industrial exposure to heavy metals. The relation between blood lead and serum creatinine concentrations and blood pressure were examined. Blood lead concentration ranged from 0.20 to 1.70 mumol/l with a geometric mean concentrations of 0.58 mumol/l in men and 0.46 mumol/l in women (p less than 0.001). In women blood lead concentration increased with age (r = +0.27; p = 0.002). In the two sexes blood lead concentration was positively correlated with the number of cigarettes smoked a day (men r = +0.17 and women r = +0.22; p less than or equal to 0.01), with the reported number of alcoholic beverages consumed a day (men r = +0.34 and women r = 0.23; p less than 0.01), and with serum gamma-glutamyltranspeptidase (men r = +0.23 and women r = +0.14; for men p less than 0.01). Blood lead concentration was not correlated with body weight, body mass index, and employment grade. In men 14% of the variance of blood lead concentration was explained by the significant and independent contributions of smoking and alcohol intake and in women 16% by age, smoking, and alcohol consumption. In men serum creatinine concentration tended to rise by 0.6 mumol/l (95% confidence interval from -0.2 to +1.36 mumol/l) for each 25% increment in blood lead concentration. In men and women the correlations between blood lead concentration and systolic and diastolic blood did not approach statistical significance. In conclusion, in subjects not exposed to heavy metals at work gender, age, smoking, and alcohol intake are determinants of blood lead concentration. At a low level of exposure, lead accumulation may slightly impair renal function, whereas blood pressure does not seem to be importantly influenced. Alternatively, a slight impairment of renal function may give rise to an increase in blood lead concentration.     

Effects of exposure to low concentrations of chlorinated hydrocarbons on the kidney and liver of industrial workers.

An assessment has been made of biochemical alterations in renal and hepatic functions of 73 male operators employed for an average of 8.2 years (range 0.5-23 years) in a chemical plant producing chlorinated hydrocarbons. Exposure to allyl chloride (AC), 1,3-dichloropropene (DCP), epichlorohydrin (ECH), and hexachlorocyclopentadiene (HEX) has regularly been determined by personal air monitoring since 1980. Although exposures to DCP and ECH were well below currently accepted maximum allowable concentrations (MACs), relatively high exposures to AC and HEX, occasionally exceeding the MAC, have been measured. The results of the kidney and liver function tests were compared with those of a control group comprising 35 men employed at the materials division and not occupationally exposed to chemicals. Biochemical alterations of liver function were assessed by determination in serum of alanine and aspartate aminotransferases (ALAT, ASAT), alkaline phosphatase (AP), total bilirubin (BIL), gamma-glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), and total bile acids (SBA). No differences between the exposed group and the control group were found. Nor were differences found in biochemical tests for renal tubular damage (urinary alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) and renal tubular function (urinary retinol binding protein (RBP). Total urinary protein and albumin excretion were measured to assess the integrity of the glomerulus. Urinary total protein did not differ between the groups, but urinary albumin, although within normal limits in both groups, was significantly higher (p < 0.02) in the exposed group. This difference in urinary albumin could not simply be explained by exposure to chlorinated hydrocarbons because albumin concentrations did not correlate with the duration of employment. It is concluded that long term exposure to concentrations of AC, DCP, ECH, or HEX below or near the current limit threshold value does not lead to clinically significant effects on kidney and liver.     

Reduced antioxidant capacity in paediatric patients with homozygous sickle cell disease

The sickled erythrocyte has been shown to be susceptible to lipid peroxidation and a role has been suggested for antioxidants in this process. The present study was undertaken in 22 children, aged 5-18 years with homozygous sickle cell disease (SS) and 9 HbAA controls (AA) of similar age. All the SS patients were in steady state ie, not in crisis or any acute illness at the time of the study. Levels of plasma tocopherol, retinol, carotenes and ascorbic acid (antioxidant vitamins of major nutritional importance) were measured. Plasma tocopherol carotenes and retinol were measured by HPLC after extraction into heptane. Total ascorbic acid (in trichloroacetic acid extracts of plasma) was measured colorimetrically following reaction with 2,4-dinitrophenylhydrazine. Riboflavin status was measured by the glutathione reductase activation test. Levels of all the measured antioxidants except ascorbate were reduced in SS patients compared with control children but only plasma alpha-tocopherol concentration was significantly different between the patients and controls. The median tocopherol level in SS patients (11.32 mumol/l) was significantly lower (P less than 0.02 Mann-Whitney) than that in control children (18.02 mumol/l) when measured directly or when calculated from tocopherol: cholesterol ratio, 4.55 mumol/mmol in SS patients and 7.50 mumol/mmol in control children. The median concentration of total plasma carotenes of SS patients (5.67 mumol/l) was lower than that of control children (12.14 mumol/l). Similarly, plasma beta-carotene concentration of SS patients was lower than that of control children but the difference in each case was not significant. Despite this, the vitamin A status (plasma retinol concentration) of SS patients was poorer than that of control children.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low plasma selenium as a risk factor for cancer death in middle-aged men

In a population study, 10,000 men (aged 46-48 years) were invited to a health screening program. At follow-up, which was up to eight years later, 61 subjects had died from cancer; from 35 of these subjects, plasma samples were available that were obtained at the initial screening. These samples, together with samples from two living controls for each case, were analyzed for selenium, retinol, cholesterol, triglyceride, and a number of plasma proteins. Plasma selenium was significantly lower (p less than 0.05) in cases than in controls (means: 1.06 vs. 1.12 mumol/l). The proportion of cases increased significantly from the highest to the lowest quintile of plasma selenium, and the relative risk for cancer death was 3.8 times higher in the lowest quintile compared with the highest. Mean plasma retinol was similar in cases (2.53 mumol/l) and controls (2.56 mumol/l). Cases and controls also had similar values for plasma cholesterol, triglyceride, uric acid, apolipoprotein B, orosomucoid, prealbumin, retinol-binding protein, and beta 2-microglobulin. Apolipoprotein AI in plasma was lower among cases (p less than 0.025). Cases smoked significantly more than controls did (p less than 0.05). Data indicate that low plasma selenium was a risk factor for cancer death in middle-aged men who lived in the same area. Further studies are necessary to establish whether differences in selenium intake, selenium metabolism, or other factors related to selenium are responsible for the relations observed. At present, the available data do not justify selenium supplementation programs in the whole population.     

Biologic markers of oxidative stress and nephrotoxicity as studied in biomonitoring of adverse effects of occupational exposure to lead and cadmium

OBJECTIVES: In this work, we studied impregnation levels of workers occupationally exposed to lead (Pb) and cadmium (Cd), usefulness of early urinary markers of nephrotoxicity, and occurrence of oxidative stress as the underlying mechanism involved in Pb- or Cd-induced adverse effects. Thirty-five men were recruited from a nonferrous metal smelter. Pb and Cd in blood (B-Pb, B-Cd) and urine (U-Pb, U-Cd) were measured. Relations between oxidative stress markers (malondialdehyde, superoxide dismutase, glutathione peroxidase, selenium, glutathione reductase, glutathione status, 8-hydroxy-2'-deoxyguanosine) and exposure levels, on the one hand, and early urinary markers (alpha-1-microprotein, beta-2-microglobulin, retinol binding protein, alpha and pi-glutathione S-transferases) and exposure levels, on the other hand, were evaluated. RESULTS: Mean exposure levels were moderate (B-Pb = 395.71 microg Pb/L; U-Pb = 95.19 microg Pb/g creatinine; B-Cd = 5.83 microg Cd/L; U-Cd = 4.67 microg Cd/g creatinine). Changes in malondialdehyde, glutathione status, 8-hydroxy-2'-deoxyguanosine, and alpha-glutathione S-transferases were closely correlated with exposure levels and did not depend on tobacco consumption. We showed that these workers showed moderate Pb and Cd exposure levels. CONCLUSIONS: Taken together, the data suggests the use of alpha-glutathione S-transferases excretion in urine as a hallmark of early changes in the proximal tubular integrity that could later lead to clinical disease if exposure is not reduced.     

Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity

Transferrin and protein 1, a sex linked alpha 2-microprotein, were assayed in urine from 58 workers exposed to cadmium (Cd) in a non-ferrous smelter and from 58 age matched referents. These two new markers of nephrotoxicity were compared with urinary beta 2-microglobulin (beta 2-m), retinol binding protein (RBP), albumin, and beta-N-acetyl-glucosaminidase (NAG). The response of protein 1 to Cd tubulotoxicity was similar to that of beta 2-m, RBP, and NAG. In Cd workers, protein 1 had a correlation with urinary Cd (r = 0.56) similar to beta 2-m (r = 0.48), RBP (r = 0.58), and NAG (r = 0.49). Values of these three low molecular weight proteins and of NAG were increased only in workers with urinary Cd higher than 10 micrograms/g creatinine. Urinary transferrin and albumin were similarly affected by exposure to Cd. Their response, however, was clearly more sensitive than that of low molecular weight proteins. Prevalences of positive values of these two high molecular weight proteins were not only higher but also tended to rise at lower concentrations of Cd in urine or blood. This finding suggests that in some subjects subtle defects in glomerular barrier function may precede the onset of proximal tubular impairment after chronic exposure to Cd. It remains to be assessed whether these subjects are more at risk of developing renal insufficiency.     

Renal and immunological effects of occupational exposure to inorganic mercury.

Seven parameters of renal dysfunction (urinary excretion of albumin, orosomucoid, beta 2-microglobulin, N-acetyl-beta-glucosaminidase (NAG), and copper; serum creatinine concentration, and relative clearance of beta 2-microglobulin) were examined in a group of chloralkali workers exposed to mercury vapour (n = 89) and in an unexposed control group (n = 75). Serum concentrations of immunoglobulins (IgA, IgG, IgM) and auto-antibodies towards glomeruli and other tissues were also determined. The parameters examined were compared between the two groups and related to different exposure parameters. In the chloralkali group median blood mercury concentration (B-Hg) was 55 nmol/l, serum mercury (S-Hg) 45 nmol/l, and urine mercury concentration (U-Hg) 14.3 nmol/mmol creatinine (25.4 micrograms/g creatinine). Corresponding concentrations for the control group were 15 nmol/l, 4 nmol/l, and 1.1 nmol/mmol creatinine (1.9 micrograms/g creatinine) respectively. None of the parameters of renal dysfunction differed significantly between the two groups, but there was a tendency to increased excretion of NAG in the exposed group compared with the controls. Also, a statistically significant relation existed between U-Hg and U-NAG (p less than 0.001). Serum immunoglobulin concentrations did not differ between the groups, and serum titres of autoantibodies (including antiglomerular basement membrane and antilaminin antibodies) were low in both groups. Thus the results gave no evidence of glomerular damage or of a tubular reabsorption defect at the current relatively low exposures. The findings still indicate slight, dose related tubular cell damage in the mercury exposed group. There were no signs of a mercury induced effect on the immune system.     

Renal and immunological effects of occupational exposure to inorganic mercury.

Seven parameters of renal dysfunction (urinary excretion of albumin, orosomucoid, beta 2-microglobulin, N-acetyl-beta-glucosaminidase (NAG), and copper; serum creatinine concentration, and relative clearance of beta 2-microglobulin) were examined in a group of chloralkali workers exposed to mercury vapour (n = 89) and in an unexposed control group (n = 75). Serum concentrations of immunoglobulins (IgA, IgG, IgM) and auto-antibodies towards glomeruli and other tissues were also determined. The parameters examined were compared between the two groups and related to different exposure parameters. In the chloralkali group median blood mercury concentration (B-Hg) was 55 nmol/l, serum mercury (S-Hg) 45 nmol/l, and urine mercury concentration (U-Hg) 14.3 nmol/mmol creatinine (25.4 micrograms/g creatinine). Corresponding concentrations for the control group were 15 nmol/l, 4 nmol/l, and 1.1 nmol/mmol creatinine (1.9 micrograms/g creatinine) respectively. None of the parameters of renal dysfunction differed significantly between the two groups, but there was a tendency to increased excretion of NAG in the exposed group compared with the controls. Also, a statistically significant relation existed between U-Hg and U-NAG (p less than 0.001). Serum immunoglobulin concentrations did not differ between the groups, and serum titres of autoantibodies (including antiglomerular basement membrane and antilaminin antibodies) were low in both groups. Thus the results gave no evidence of glomerular damage or of a tubular reabsorption defect at the current relatively low exposures. The findings still indicate slight, dose related tubular cell damage in the mercury exposed group. There were no signs of a mercury induced effect on the immune system.     

Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity.

Transferrin and protein 1, a sex linked alpha 2-microprotein, were assayed in urine from 58 workers exposed to cadmium (Cd) in a non-ferrous smelter and from 58 age matched referents. These two new markers of nephrotoxicity were compared with urinary beta 2-microglobulin (beta 2-m), retinol binding protein (RBP), albumin, and beta-N-acetyl-glucosaminidase (NAG). The response of protein 1 to Cd tubulotoxicity was similar to that of beta 2-m, RBP, and NAG. In Cd workers, protein 1 had a correlation with urinary Cd (r = 0.56) similar to beta 2-m (r = 0.48), RBP (r = 0.58), and NAG (r = 0.49). Values of these three low molecular weight proteins and of NAG were increased only in workers with urinary Cd higher than 10 micrograms/g creatinine. Urinary transferrin and albumin were similarly affected by exposure to Cd. Their response, however, was clearly more sensitive than that of low molecular weight proteins. Prevalences of positive values of these two high molecular weight proteins were not only higher but also tended to rise at lower concentrations of Cd in urine or blood. This finding suggests that in some subjects subtle defects in glomerular barrier function may precede the onset of proximal tubular impairment after chronic exposure to Cd. It remains to be assessed whether these subjects are more at risk of developing renal insufficiency.     

Intestinal uptake of retinol: enhancement by bovine milk beta-lactoglobulin

The effect of bovine milk beta-lactoglobulin (BLG) on intestinal uptake of retinol was examined in suckling rats with the everted sac technique. Uptake of 0.06 mumol retinol/L bound to BLG (BLG-retinol) was significantly (p less than 0.01) higher than that of 0.06 mumol free retinol/L both in the jejunum and the ileum. The enhancing effect of BLG on retinol uptake was specific because equimolar concentrations of bovine serum albumin and lactoferrin had no effect on retinol uptake. However, serum retinol-binding protein (RBP), which shares structural and conformational similarities with BLG, also enhanced retinol uptake. BLG, BLG-retinol, and RBP-retinol all inhibited the uptake of retinol from BLG-[3H]retinol in a concentration-dependent manner. Uptake of retinol from BLG-retinol was saturable (apparent Km = 5.6 mumol/L, Vmax = 22.7 nmol.g-1.5 min-1), not affected by metabolic inhibitors, and partially temperature dependent (Q10 = 2.77). BLG also significantly (p less than 0.01) enhanced retinol uptake in the intestine of adult rats. These results demonstrate that BLG specifically enhances intestinal uptake of retinol and suggest the possibility of a receptor for BLG-like proteins at the brush border membrane of the enterocyte.     

From gene to disease; unconjugated hyperbilirubinemia: Gilbert's syndrome and Crigler-Najjar types I and II

Gilbert's syndrome consists of a mild unconjugated hyperbilirubinemia occurring in the absence of liver disease or haemolysis. Total plasma bilirubin can be as high as 80 mumol/l and mild intermittent jaundice does occur. The inheritance pattern is probably autosomal recessive. It has been estimated that some 10-15% of the Western population suffers from Gilbert's syndrome. Bilirubin-uridinediphosphate-glucuronosyltransferase (UGT1A1) is the only enzyme involved in the conjugation of bilirubin. In patients with Gilbert's syndrome, hepatic glucuronidation by UGT1A1 is reduced to about 30% of normal. In Western populations a variant TATAA element in the upstream promotor region of the UGT1A1 gene is firmly associated with the disease. Crigler-Najjar types I and II are autosomal recessive disorders associated with near (type II) or complete absence (type I) of UGT1A1 enzyme activity. There is a persistent unconjugated hyperbilirubinemia (range 300-850 mumol/l) with the plasma concentrations being higher in type I than in type II. Genetic mutations in exon 1-5 cause both Crigler-Najjar type I and type II.     

The relationships between anthropometric measurements,serum vitamin A and E concentrations and lipid profiles in overweight and obese subjects

The weight, height, body mass index (BMI), waist/hip ratio, serum retinol and alpha-tocopherol and lipid profiles of 16 overweight (BMI > or = 25.0 kg/m2) Thai males and 56 overweight females, compared with 14 males and 58 females in a control group (BMI 18.5-24.9 kg/m2), were investigated. Subjects for the study were those persons who turned up regularly for physical check-up at the Outpatient Department, General Practice Section of Rajvithi Hospital, Bangkok. The study was conducted between December 2000-March 2001. Higher levels of cholesterol, LDL-C, LDL-C/HDL-C ratio were found in the overweight compared with the control subjects. Statistically significant higher triglyceride levels were found in the overweight compared with the control subjects. The median serum retinol concentration in overweight subjects was 2.80 mumol/L (range 0.53-4.62 mumol/L) compared with 2.97 mumol/L (range 1.21-4.12 mumol/L) in control subjects (p = 0.0736). The median serum alpha-tocopherol concentration in overweight subjects was 17.30 mumol/L (range 6.29-28.65 mumol/L) compared with 18.75 mumol/L (range 5.30-30.28 mumol/L) in control subjects (P < 0.05). The median values of retinol and alpha-tocopherol serum concentrations in the overweight and obese males were lower than those of the overweight and obese females. A total of 6.3% (1 out of 16) and 12.5% (2 out of 16) of the overweight/obese males had decreased retinol and alpha-tocopherol levels, while the overweight/obese females had decreased retinol and alpha-tocopherol level of 1.8% (1 out of 56) and 10.7% (6 out of 56), respectively. A total of 12.5% and 39.3% of the overweight/obese males and females had cholesterol concentrations of > or = 6.48 mmol/l. However, the prevalence of low HDL-C (HDL-C < or = 0.91 mmol/l) was found to be 50% in the overweight and obese males and 10.7% in the overweight and obese females. Statistically significant associations were found between age, cholesterol, LDL-C, and serum alpha-tocopherol in the overweight and obese male and female subjects. A negative correlation was found between weight, BMI, AC, MAMC, hip circumference and serum retinol in both the overweight and obese subjects. A negative correlation was found between weight, BMI, MAMC, waist, hip circumferences and serum alpha-tocopherol in both the overweight and obese subjects.     

Changes in thiamin, riboflavin, niacin, beta-carotene, vitamins, C, A, D and E status of French Elderly Subjects during the first year of institutionalization

Vitamin status was assessed in 26 recently institutionalized elderly subjects by combining dietary and biochemical measurements of thiamin, riboflavin, niacin, beta-carotene, vitamins C, A, D and E at admission (P1), and 1.5 (P2), 3.0 (P3), 4.5 (P4), 6.0 (P5), 12 (P6) months later. At admission, except for vitamin A, mean vitamin intakes were lower than the 1992 French Recommended Dietary Allowance. Thiamin, vitamins C, A and E status seemed nearly satisfactory as less than one-fourth of the population sample had blood values lower than the cut-off point for thiamin (erythrocyte thiamin pyrophosphate < 0.17 mumol/l), vitamin A (serum retinol < 1.05 mumol/l), vitamin C (serum vitamin C < 11.3 mumol/l) and vitamin E (serum alpha-tocopherol < 9.3 mumol/l) or higher than the cut-off point for thiamin (erythrocyte transketolase activity coefficient > 1.19). Almost half of the subjects for riboflavin, and almost all non supplemented subjects for vitamin D were in risk of vitamin deficiency (46% had an erythrocyte glutathione reductase activity coefficient > 1.19 and 72% had a plasma 25(OH)D3 < 25 nmol/l). During the study, vitamins status remained unchanged for riboflavin, niacin, vitamins A, D and E, improved for vitamin C (P = 0.004) or impaired for thiamin (P = 0.008). Thus, institutionalization seemed to have no effect on riboflavin, niacin, vitamins A, D and E status and a slight effect on thiamin and vitamin C status.     

Glucose-based versus fat-based total parenteral nutrition (TPN): effects on hepatic function in septic patients complicated with cholestatic jaundice

A prospective study of two types of total parenteral nutrition (TPN) was carried out in 34 patients suffering from sepsis and complicated liver dysfunction. Group 1 (18 patients) received non-protein energy as glucose plus fat emulsion in a caloric ratio of 19:1, while group 2 (16 patients) received the same energy intake but with a ratio of 1:1. Group 1 exhibited higher levels of bilirubin and alkaline phosphatase with values of 93.5 +/- 25.5 mumol/l and 160 +/- 30 IU/l respectively compared to Group 2, in which the corresponding values were 81.6 +/- 32.3 mumol/l and 120 +/- 10 IU/l (p < 0.05). On the other hand, group 1 had lower levels of serum albumin and serum transferrin with values 25 +/- 1.3 g/l and 40 +/- 20% of normal, compared to group 2 in whom the corresponding values were 28 +/- 8 g/l and 48 +/- 30% of normal (p < 0.05). There were no differences between the two groups, in the absolute number of T-lymphocytes and in transaminase levels. In sepsis complicated by liver dysfunction a 50:50 glucose: fat regimen caused less disturbance of liver function than one consisting almost entirely of glucose.     

Renal function and hyperfiltration capacity in lead smelter workers with high bone lead.

OBJECTIVE--The study was undertaken to assess whether the changes in urinary excretion of eicosanoids (a decrease of 6-keto-PGF1 alpha and PGF2 and an increase of thromboxane) previously found in lead (Pb) exposed workers may decrease the renal haemodynamic response to an acute oral protein load. METHODS--The renal haemodynamic response was estimated by determining the capacity of the kidney to increase the glomerular filtration rate (in terms of creatinine clearance) after an acute consumption of cooked red meat (400 g). A cross sectional study was carried out in 76 male Pb workers (age range 30 to 60 years) and 68 controls matched for age, sex, socioeconomic state, general environment (residence), and workshift characteristics. RESULTS--The Pb workers had been exposed to lead on average for 18 (range 6-36) years and showed a threefold higher body burden of Pb than the controls as estimated by in vivo measurements of tibial Pb concentration (Pb-T) (geometric mean 66 v 21 micrograms Pb/g bone mineral). The geometric mean concentrations of Pb in blood (Pb-B) and Pb in urine (Pb-U) were also significantly higher in the Pb group (Pb-B: 430 v 141 micrograms Pb/l; Pb-U: 40 v 7.5 micrograms Pb/g creatinine). These conditions of chronic exposure to Pb did not entail any significant changes in the concentration of blood borne and urinary markers of nephrotoxicity, such as urinary low and high molecular weight plasma derived proteins (beta 2-microglobulin, retinol binding protein, albumin, transferrin), urinary activities of N-acetyl-beta-D-glucosaminidase and kallikrein, and serum concentrations of creatinine, beta 2-microglobulin, urea, and uric acid. All participants also had normal baseline creatinine clearances (> 80 ml/min/1.73 m2) amounting on average to 115.5 in the controls v 121.3 ml/min/1.73 m2 in the Pb group. Both control and Pb exposed workers showed a significant increment in creatinine clearance (on average 15%) after oral protein load suggesting that the previously found changes in secretion of urinary eicosanoids apparently has no deleterious effect on renal haemodynamics in the examined Pb workers. CONCLUSIONS--The finding that both baseline and stimulated creatinine clearance rates were not only significantly higher in the Pb workers but also positively correlated with Pb-T, suggests that moderate exposure to Pb may be associated with a slight hyperfiltration state, which has been found to attenuate the age related decline in baseline creatinine clearance by a factor of two. Although the relevance of this effect for the worker's health is unknown, it can be concluded that adverse renal changes are unlikely to occur in most adult male Pb workers when their blood Pb concentration is regularly kept below 700 micrograms Pb/l. One should, however, be cautious in extra-polating this conclusion to the general population because of pre-employment screening of the Pb workers for the absence of renal risk factors.     

Early detection of nephrotoxic effects due to low-dose exposure of cadmium among cigarette smokers

The effects of low-level exposure to cadmium due to cigarette smoking on renal function were judged by the estimation of urinary levels of total proteins, cadmium, alpha-1-microglobulin (alpha1M) and glutathione S-transferase (GST) activity among 50 males (38 smokers and 12 control non-smokers). Elevated urinary cadmium levels [2.408-28.160; 9.31 +/- 7 .1 microg Cd/gm urine creatinine] were observed among the majority of smokers (24 cases, 63.16%) and these levels showed a positive correlation with age and smoking index. Furthermore, urine total proteins [115.18-652.14; 242.89 +/- 121.88 mg protein/gm urine creatinine) were increased suggesting glomerular involvement among 20 cases (52.63%) of smokers. In addition, urinary alpha1M levels (14.645-86.053; 34.05 +/- 16.83 mg alpha1M/gm urine creatinine) and urinary GST activity [0.0-0.008; 0.00015 +/- 0.0002 micromol/min/100 microl/gm urine creatinine] were elevated among 18 (47.37%) and 20 (52.63%) cases of smokers respectively. Since urinary alpha1M and GST originate from renal proximal tubules, the data of the present investigation could reflect early low-level cadmium exposure nephrotoxic effect on both the glomeruli and tubules.     

Reduced concentration of hepatic alpha-tocopherol in patients with alcoholic liver cirrhosis.

The concentration of alpha-tocopherol was measured in liver biopsy specimens obtained from 83 patients with alcoholic and non-alcoholic liver diseases. The mean hepatic vitamin E content (as alpha-tocopherol) was significantly lower in 23 patients with alcoholic cirrhosis (17.6 +/- 12.1 nmol/mg wet weight liver), compared with 12 patients with normal liver histology (39.2 +/- 29.7 nmol/mg, P less than 0.01). The mean serum concentration of alpha-tocopherol was lower in patients with alcoholic cirrhosis (13.9 +/- 7.0 mumol/l) than in individuals with alcoholic fatty liver (21.3 +/- 9.3 mumol/l, P less than 0.01) and patients with normal liver histology (23.4 +/- 11.6 mumol/l, P less than 0.01). A decreased ratio of serum alpha-tocopherol/total serum lipids was also observed in patients with alcoholic cirrhosis, compared with patients with normal liver histology (P less than 0.05). There was a significant correlation between concentrations of alpha-tocopherol in liver and serum (r = 0.43, P less than 0.001). Furthermore, serum alpha-tocopherol correlated with retinol (r = 0.53, P less than 0.001), selenium (r = 0.45, P less than 0.001), and albumin (r = 0.37, P less than 0.001) in serum. We suggest that the reduced content of hepatic alpha-tocopherol observed in some patients may play a role in ethanol-induced lipid peroxidation.     

Coagulation factors V and VIII in relation to severity and outcome in acute alcoholic hepatitis.

The relationship between levels of coagulation Factors V and VIII and disease severity was evaluated in 33 patients with alcoholic liver disease, and related to outcome in the 23 with severe acute alcoholic hepatitis. Factor V levels in acute alcoholic hepatitis were significantly lower than in inactive alcoholic liver disease (median 28% vs 74%), and both results were lower than values in 10 control subjects (median 101%; P less than 0.001 and P less than 0.002, respectively). Plasma Factor VIII concentrations were not significantly higher in alcoholic hepatitis than in inactive alcoholic liver disease, although both results significantly exceeded control values (median 163% and 151% vs 104%; P less than 0.005 and P less than 0.05, respectively). In the 18 in-patients with alcoholic hepatitis who survived, admission factor V (median 32%) was higher, and admission serum bilirubin (65 mumol/l) and discriminant function score (derived from prothrombin time and bilirubin: median 31) were lower than in the four who died and one who received a liver transplant (median 16%, 527 mumol/l and 113; P less than 0.005, P less than 0.005, P less than 0.05, respectively). An admission Factor V level less than 15% correctly predicted outcome in a greater number (87%) of cases than admission discriminant function greater than 100 (83%), bilirubin greater than 300 mumol/l (83%) or prothrombin ratio greater than 1.5 (78%). This predictive accuracy increased to 100% for minimum Factor V less than 15% and was again superior to maximum discriminant function greater than 100 or greater than 300 mumol/l (both 83%) or maximum prothrombin ratio greater than 1.5 (78%).(ABSTRACT TRUNCATED AT 250 WORDS)