The disposition of theophylline in blood in chronic obstructive lung disease

In 42 subjects with chronic obstructive lung disease receiving chronic oral theophylline therapy, the venous whole blood theophylline concentration was closely related to the total plasma theophylline concentrations (r = 0.976, p less than 0.001). The blood/plasma concentration ratio was 0.85 +/- 0.13 and was not related to the haematocrit or the free fraction of theophylline in plasma. The red blood cell theophylline concentration was closely related and numerically similar to the free plasma concentration. This indicates that the free plasma concentration is the most important determinant of red blood cell concentration, and that binding of drug by red blood cells or active uptake into erythrocytes is unlikely to occur. Whole blood concentration can be used to predict plasma theophylline concentration in subjects with obstructive lung disease in situations where preparation of plasma is inconvenient. The therapeutic range for whole blood concentration is approximately 8.5-17 mg/L.     

CSF and plasma levels of nortriptyline and its 10-hydroxy metabolite.

After 3 weeks' nortriptyline (NT) treatment the mean plasma concentration of its 10-hydroxy metabolite (10-OH-NT) (599 +/- 207 nmol l-1) was higher than that of the parent drug (433 +/- 199 nmol l-1) in 25 depressed patients. Also in the cerebrospinal fluid (CSF) the mean level of 10-OH-NT (67 +/- 20 nmol l-1) was higher than that of NT (39 +/- 23 nmol l-1). There was a strong correlation (P less than 0.001) between the CSF and plasma concentration of both NT (r = 0.92) and 10-OH-NT (r = 0.77). The interindividual variation in the CSF/plasma ratio of both compounds was small, compared to the variation in plasma levels. These results show that 10-OH-NT passes the blood-brain barrier as it is present in concentrations higher than those of NT in the CSF. 10-OH-NT has previously been shown to be a potent blocker of noradrenaline uptake and to have much less affinity for muscarinic receptors than NT itself. This active metabolite might therefore be a potential antidepressant with less disturbing anticholinergic side-effects.     

Use of urinary lead concentration in interpretation of the EDTA mobilization test

In young children with plumbism who receive an EDTA mobilization test (EMT), the need exists for a means of interpreting inadequate or incomplete urine collections. We evaluated the ability of urinary lead concentration (UPbC), whole blood lead (PbB) and erythrocyte protoporphyrin (EP) to predict a positive EMT ratio (greater than or equal to 0.05% of EDTA dose excreted as urine lead). The results of 58 satisfactory EMT's in a group of young (aged 1-3.5 yr) lead-poisoned children were reviewed. A strong and significant correlation was found between UPbC and mobilization ratio (r = .63, p less than 0.0001). Weaker but significant correlation was also found between PbB versus mobilization ratio (r = .45, p = 0.0007) and EP versus ratio (r = .48, p = 0.0003). These data were placed into receiver-operator curves (ROC) to determine their optimal use as discriminants between children with positive versus negative mobilization tests. Ideal ROC characteristics (optimal sensitivity and specificity) were found in the use of a UPbC greater than or equal to 1.0 mcg/ml; at this cutoff a sensitivity of .80, specificity of .89 and positive predictive value of .90 were found. ROC's for PbB and EP demonstrated poor discriminating abilities. Our results suggest that in the absence of a satisfactory urine collection, urinary lead concentration serves as an acceptable indirect indicator of mobilization ratio. A urinary lead concentration of greater than or equal to 1.0 micrograms/ml most accurately identifies children who will have a positive mobilization ratio.     

Plasma concentration of topiramate correlates with cerebrospinal fluid concentration

The authors examined the ratio between the plasma and the cerebrospinal fluid (CSF) concentration of topiramate in 14 adults with epilepsy. Simultaneous trough samples of venous blood and CSF were collected and analyzed as total and unbound concentrations. Concomitant levels were also analyzed of lamotrigine (n = 5) and the relevant oxcarbazepine metabolite, 10-hydroxycarbazepine (n = 3). There was a close correlation between the plasma and the CSF concentration for both the total and unbound concentration of topiramate. The median CSF/plasma ratio of total topiramate was 0.85. The free topiramate concentration in plasma was not different from the free topiramate concentration in CSF. The CSF/plasma ratios showed little variation and were independent of the plasma level for both the total and the unbound levels. The unbound fraction of topiramate was 84% in plasma and 97% in CSF. The CSF concentrations of lamotrigine and 10-hydroxycarbazepine were 50% and 61% of the plasma concentrations, respectively. For topiramate, there is a close correlation between the plasma concentration and the CSF concentration. There does not seem to be a saturable carrier mechanism restricting topiramate transport across the blood-brain barrier. The concentration of topiramate in CSF is equal to the unbound proportion of topiramate in plasma, implying that the delivery of topiramate to the brain occurs via transfer from the unbound plasma pool. Plasma is thus a relevant matrix for therapeutic drug monitoring of topiramate.     

Stereoselective efflux of (E)-10-hydroxynortriptyline enantiomers from the cerebrospinal fluid of depressed patients.

In 5 patients treated with nortriptyline or amitriptyline for at least 9 months, the cerebrospinal fluid (CSF)/plasma ratio for 10-hydroxynortriptyline (10-OH-NT) ranged from 0.085 to 0.172, which is similar to the ratio previously measured in patients treated for 3 weeks. In 4 other patients treated with racemic (E)-10-OH-NT, the mean concentration ratio between (-)- and (+)-(E)-10-OH-NT was 3.56 in plasma, 2.39 in plasma ultrafiltrate and 1.42 in CSF (one-way ANOVA; P less than 0.001). The mean free fraction in plasma determined by ultrafiltration for (-)-(E)-10-OH-NT was 28.9 +/- S.D.1.1% and for the (+)-enantiomer 43.7 +/- 0.8% (P less than 0.001) confirming the difference in protein binding shown previously in healthy subjects. There was a correlation between the concentration of 10-OH-NT (sum of enantiomers) in CSF and plasma ultrafiltrate (r = 0.96; n = 7; P less than 0.001). The concentration in CSF was, however, only about 50% of that in the plasma ultrafiltrate and this seems to be due to a stereoselective transport of (E)-10-OH-NT out from the CSF. The secretion from the CSF is more pronounced for the (-)-compared to the (+)-enantiomer, which is consistent with the stereoselectivity of the renal secretion of these compounds.     

A prospective study of cyclosporine concentration in relation to its therapeutic effect and toxicity after renal transplantation.

1. Cyclosporine (CsA) concentrations in plasma and whole blood were monitored prospectively in 66 consecutive kidney transplant recipients for 6 months after transplantation or until graft loss. Immunosuppression was based on treatment with CsA and prednisolone in 27 patients and CsA, azathioprine and prednisolone in 39 patients. 2. Whole blood and plasma samples (separated at 37 degrees C) were collected 10-12 h after CsA dosage twice weekly over the first 3 months and thereafter once weekly. CsA concentrations were measured by high pressure liquid chromatography (h.p.l.c.) in plasma, by specific and non-specific monoclonal radioimmunoassays (r.i.a.) in whole blood, and by polyclonal r.i.a. and polyclonal fluorescence polarization immunoassay (f.p.i.a.) in whole blood and plasma. 3. There were no differences between the treatment schedules regarding graft or patient survival, occurrence of acute rejection, nephrotoxicity or infection. 4. CsA concentrations were significantly lower at the time of acute rejection than one week earlier based on all of the analytical methods used except f.p.i.a. 5. The lowest CsA concentration, recorded during the first month after transplantation, was significantly lower in patients with than in patients without experience of acute rejection episodes when the CsA concentrations were measured by polyclonal r.i.a. in whole blood and plasma and by specific and non-specific monoclonal r.i.a. in whole blood, but not by h.p.l.c. in plasma or polyclonal f.p.i.a. in whole blood or plasma. 6. The highest CsA concentration recorded during the second post-transplantation month, was higher in patients with acute nephrotoxicity than in those without nephrotoxicity when CsA was measured by specific monoclonal r.i.a. in whole blood (471 +/- 409 ng ml-1 vs 327 +/- 150 ng ml-1, P less than 0.05), but not by the other methods. 7. The mean plasma h.p.l.c. concentration of CsA measured by h.p.l.c. during the first month after transplantation was significantly higher in patients who suffered from systemic infection than in patients who did not (116 +/- 70 ng ml-1 vs 82 +/- 52 ng ml-1; P less than 0.05). 8. Thus, significant relationships between CsA concentrations and clinical events were apparent using assay methods specific for CsA as well as using polyclonal r.i.a., but not using polyclonal f.p.i.a. When h.p.l.c. was used, however, plasma drug concentrations were often below the limit of determination. Our results suggest that specific analysis of CsA in whole blood allows the best distinction between patients who respond favourably and less favourably to treatment with CsA.     

SODIUM AND NORADRENALINE IN CEREBROSPINAL FLUID AND BLOOD IN SALT-SENSITIVE AND NON-SALT-SENSITIVE ESSENTIAL HYPERTENSION

1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16-18 g/day) and after 7 days of a low salt intake (1-3 g/day). 2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na+ concentration: 147.7 +/- 0.4 mmol/L vs 145.3 +/- 0.5 mmol/L; P less than 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period. 3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt-sensitive (n = 8) and the non-salt-sensitive (n = 7) subjects, but the changes in plasma NA and PRA were smaller in the salt-sensitive subjects. 4. These results indicate that the sympathetic nervous system is less suppressed in salt-sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system.     

Implication of steady state concentrations of nitrite and nitrate metabolites of nitric oxide in plasma and whole blood in healthy human subjects

1. The aim of the present study was to determine whether the steady state NOx concentration reflects NOx formation in vivo. 2. A NO3- load study was performed after achieving NOx steady state. Chronological changes in NOx concentrations in plasma and whole blood samples from nine healthy subjects were determined by the HPLC-Griess system and NOx concentrations in erythrocytes were estimated as a possible NOx compartment influential in regulating plasma NOx concentrations. 3. Analysis was performed using the first-order one-compartment open model and the NOx formation rate was subsequently calculated. 4. The mean (+/-SEM) steady state NOx concentration of plasma (15.5 +/- 1.6 micromol/L), whole blood (12.8 +/- 1.2 micromol/L) and erythrocytes (11.9 +/- 0.7 micromol/L) did not correlate with the NOx formation rate in the compartments (0.50 +/- 0.05, 0.61 +/- 0.04 and 0.91 +/- 0.17 micromol/kg per h, respectively), whereas a significant correlation was found between the steady state NOx concentration and NOx elimination rate (Kel) in plasma (r=-0.69; P=0.04) and whole blood (r=-0.79; P=0.01). 5. Although there was no direct correlation between steady state NOx concentrations and serum creatinine levels, the correlation between half-life and serum creatinine levels was significant (plasma: r=0.60, P=0.02; whole blood: r=0.49, P=0.04). 6. Plasma NOx concentrations correlated significantly with erythrocyte NOx concentrations (r=0.92, P <0.01; erythrocyte NOx=0.66 x plasma NOx). 7. The results of the present study indicate that NOx does not accumulate excessively into erythrocytes at steady state and during a NO3- load and that the steady state NOx concentration in whole blood and plasma preferentially implies NOx elimination (mainly depending on renal function) rather than NOx formation.     

The associations between serum alpha-1-antitrypsin level and the whole blood contents of trace metals in normal women in reproductive age

The concentration of Alpha-1-Antitrypsin (A-1-AT) in the blood serum was measured by single radial immunodiffusion in 21 healthy women in reproductive age. Simultaneously the whole blood levels of cadmium, lead, copper and zinc were determined by atomic absorption spectrometry. Serum A-1-AT correlated significantly with blood copper (r = 0.55, p less than 0.01). The importance of quantitative relations between "acute phase reactants" in blood serum and the blood trace metals is discussed from the point of view of reproductive medicine.     

Single-dose cyclosporine pharmacokinetics in various biological fluids of patients receiving allogeneic marrow transplantation

The clinical usefulness of cyclosporine is hampered by dose-limiting toxicities to the kidney that are not predicted by drug levels in serum or whole blood. Because of its lipophilic nature, circulating plasma lipoproteins may play a role in drug disposition. This study characterized the pharmacokinetic parameters of a single 2-mg/kg i.v. infusion of cyclosporine in the whole blood, plasma, high-density (HDL), low-density (LDL), and very low-density (VLDL) lipoprotein fractions of nine patients before bone marrow transplantation. The dose- and protein-corrected area under the concentration-time curve in whole blood; plasma; and HDL, LDL, and VLDL compartments were 44.6 +/- 11.3, 19.2 +/- 2.4; 33.6 +/- 12.3, 49.0 +/- 19.9, and 17.5 +/- 9.0 ng h/ml, respectively. The mean half-life of the drug from the VLDL fraction was significantly less than from the other biologic fluids. The systemic clearance rate of cyclosporine was greater in the total plasma or VLDL fractions compared with whole blood and the HDL and LDL fractions. The HDL-cyclosporine clearance inversely correlated with the serum creatinine (r = -0.71; p less than 0.05) and total bilirubin levels (r = -0.76; p less than 0.05). The plasma half-life and volume of distribution directly correlated with fasting HDL cholesterol levels (r = 0.94 and 0.99; p less than 0.01). Correlations between pharmacokinetic parameters and lipid fractions suggest a role of lipids in the distribution of cyclosporine. These data may be useful in the development of guidelines for therapeutic drug monitoring of cyclosporine in the transplantation population.     

Comparison of plasma and saliva concentrations of levetiracetam following administration orally as a tablet and as a solution in healthy adult volunteers

OBJECTIVE: Concentrations in saliva, as an alternative to concentrations in blood, can be advantageous for the monitoring of antiepileptic agents. This study assesses the relationship between saliva and plasma concentrations of levetiracetam after administration orally as a solution and as a tablet. The possibility that saliva concentrations of the drug are altered by contamination in the buccal cavity was also examined. METHODS: 4 healthy male subjects received a single 750 mg oral dose of levetiracetam as a 10% solution and 4 subjects received three 250 mg tablets (750 mg). Levetiracetam concentrations in plasma and saliva were monitored for 24 hours post dose. RESULTS: In subjects receiving the levetiracetam solution, maximum saliva concentrations were observed at the first collection point (15 min) after administration and these were 19-74 times higher than corresponding plasma levels. The mean saliva/plasma ratio rapidly decreased thereafter, becoming stable after 4 hours. In subjects receiving tablets, levetiracetam concentration profiles for saliva paralleled the plasma concentration profiles with a fairly constant saliva/plasma concentration ratio throughout the 24-hour sampling period. A significant linear correlation between levetiracetam saliva and plasma concentrations was demonstrated (Pearson r = 0.88; p < 0.001 for tablet (n = 35) and r = 0.87; p < 0.001 for solution at times > or = 4 hours post-dose (n = 20)). The saliva to plasma concentration ratio was 1.11 (95% confidence interval: 0.99 - 1.22) following tablet intake, and 1.55 (95% CI: 1.34 1.77) following oral solution (> or = 4 hours post dose). CONCLUSIONS: Using saliva to monitor therapeutic exposure to levetiracetam is feasible beginning 15 minutes after tablet intake but beginning 4 hours after intake of an oral solution.     

Human atrial natriuretic peptide in aortic and coronary sinus blood during atrial pacing in patients with ischemic heart disease

This study investigated the plasma concentrations of human atrial natriuretic peptide (hANP) of blood samples obtained from the aorta and coronary sinus (CS) in 19 male patients (mean age of 52.8 +/- 2.1 years) with ischemic heart disease before and during atrial pacing. The plasma concentrations of hANP were measured by radioimmunoassay, and the secretion rate of hANP was calculated on the basis of the CS-aorta difference in plasma hANP concentration and the CS flow rate recorded at blood sampling. Before atrial pacing, aortic plasma hANP concentration showed a significant positive correlation with mean pulmonary capillary wedge pressure (r = 0.67, p less than 0.002) or mean pulmonary artery pressure (r = 0.71, p less than 0.001), and a significant negative correlation with left ventricular ejection fraction (r = -0.50, p less than 0.05). During atrial pacing, aortic plasma hANP concentration increased from 67 +/- 13 (SEM) to 151 +/- 33 pg/ml (p less than 0.01), CS plasma hANP concentration from 727 +/- 121 to 1205 +/- 228 pg/ml (p less than 0.01), and the hANP secretion rate from 45.4 +/- 14.8 to 86.8 +/- 28.2 ng/min (p less than 0.05, n = 12). The aortic plasma hANP concentration was significantly correlated with the CS plasma hANP concentration (r = 0.81, p less than 0.001) or the hANP secretion rate (r = 0.70, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Carbamazepine age-dose ratio relationship in children

Steady-state plasma carbamazepine (CBZ) concentrations were measured in 196 pediatric inpatients taking CBZ alone or CBZ combined with other drugs. The steady-state CBZ concentrations divided by the daily administered dose (dose ratio, reciprocal of apparent clearance) increased significantly (r = 0.183, p less than 0.01) with age. The correlation between dose and CBZ concentration, while significant (r = 0.265, p = 0.023), was weak because of wide interindividual differences in dose ratio. There was a negative correlation between CBZ daily dose and CBZ dose ratio. This negative correlation was significant in children 4-6 (r2 = 0.481, p less than 0.01), 7-11 (r2 = 0.399, p less than 0.01), and greater than 11 years of age (r2 = 0.401, p less than 0.01), but not in children less than 4 years of age (r2 = 0.172, p greater than 0.1). The CBZ dose ratio was significantly (p less than 0.001) lower in patients taking CBZ in combination with more than one other antiepileptic drug compared with those on CBZ monotherapy. No significant (p greater than 0.1) difference in CBZ dose ratio was found between male and female patients. These findings suggest that CBZ clearance was influenced by age, dose, and comedication with more than one other antiepileptic drug but not sex. The concentration necessary for efficacy is a clinical, not an analytical decision. However, the dose-concentration relationships show that recommended pediatric CBZ doses of 10-30 mg/kg/day are not enough to attain published therapeutic CBZ concentrations in many children.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of P-glycoprotein-mediated efflux on cerebrospinal fluid/plasma concentration ratio.

The ratio of drug levels in cerebrospinal fluid (CSF) to plasma (CSF/plasma) at equilibrium has been viewed as in vivo free fraction (fp) in plasma [CSF/plasma = fp], if no active transport is involved in brain penetration. We determined the CSF/plasma level following oral administration in rats and in vitro rat plasma protein binding for 20 compounds that were synthesized in our institute and have similar physicochemical properties. However, results indicated that the CSF/plasma was not only poorly correlated with fp but remarkably lower than fp in most of the compounds tested, suggesting that certain transporters such as P-glycoprotein (P-gp) located in blood-brain barrier (BBB) may decrease the unbound drug concentration in the brain. We evaluated P-gp-mediated transport activity of the 20 compounds with P-gp (mdr1a)-transfected LLC-PK1 cells and calculated P-gp efflux index (PEI), indicating the extent of P-gp-mediated transport. A plot of the CSF/plasma versus fp/PEI showed a strong correlation (r = 0.93), and the absolute values were almost identical [CSF/plasma = fp/PEI]. These results suggest that P-gp quantitatively shifts the equilibrium of unbound drugs across the BBB. Although we cannot rule out the possibility that endogenous transporters other than P-gp on BBB and/or blood-CSF barrier may affect CSF levels of compounds, the present study indicated that fp and PEI measurements may be useful in predicting in vivo CSF/plasma fractions for central nervous system-targeting drugs.     

Pharmacokinetics of IV and oral acetyl-L-carnitine in a multiple dose regimen in patients with senile dementia of Alzheimer type

Summary Acetyl-L-carnitine (ALC), a physiological component of the L-carnitine family, has been proposed for treating Alzheimer's disease in pharmacological doses. As this condition requires prolonged therapy, its kinetics has been examined after a multiple dose regimen, involving different routes of administration, in 11 patients suffering from Senile Dementia of Alzheimer Type.The study design comprised a 3-day basal observation period, sham treatment with repeated blood sampling; treatment with 30 mg·kg^–1 i.v. given twice for 10 days (plasma kinetics was studied on the 7th day), and 50 days of 2.0 g/day p.o. given in three daily doses. Total acid soluble L-carnitine, L-carnitine and acetyl-L-carnitine in plasma and CSF were evaluated using an enantioselective radioenzyme assay. Short chain L-carnitine esters were calculated as the difference between total and free-L-carnitine.The plasma concentrations of individual components of the L-carnitine family did not change during the three days of the basal period, nor were they affected during the sham therapy period.Following the i.v. bolus injections, the plasma concentrations showed a biphasic curve, with average t_1/2 of 0.073 h and 1.73 h, respectively.At the end of oral treatment, plasma acetyl-L-carnitine and L-carnitine short chain esters were significantly higher than during the run-in phase.The CSF concentrations paralleled those in plasma, suggesting that ALC easily crosses the blood-brain barrier.It is concluded that i.v. and oral administration of multiple doses of ALC can increase its plasma and CSF concentration in patients suffering from Alzheimer's disease.     

阿尔茨海默病患者血液及脑脊液中血糖和真胰岛素的测定比较

目的 检测阿尔茨海默病（Alzheimer＇s disease,AD）患者血液及脑脊液中血糖、真胰岛素水平,探讨AD患者体内胰岛素代谢异常.方法 随机选取70例正常人为对照Ⅰ组,55例AD患者,检验其空腹血糖、真胰岛素水平; 35例为对照Ⅱ组,48例AD患者,检验其脑脊液中葡萄糖,真胰岛素水平;将AD按轻、中重度分组后与对照组进行比较.结果 AD患者各组空腹血糖及脑脊液中葡萄糖与对照组比较,差异无统计学意义（P〉 0.05）;轻度AD组血液及脑脊液真胰岛素与对照组比较,差异无统计学意义（P〉 0.05）;中重度AD组血液中真胰岛素较对照组升高,差异有统计学意义（P〈 0.05）,脑脊液中真胰岛素较对照组降低,差异有统计学意义（P〈 0.05）.结论 AD患者体内及脑内胰岛素代谢异常,与疾病的严重程度相关.     

Assessment of semen function and lipid peroxidation among lead exposed men

The study population included healthy, fertile men, employees of Zinc and Lead Metalworks (n=63). Workers exposed to lead were divided into two groups: a group with moderate exposure to lead (ME) - blood lead level (PbB) 25-40 microg/dl and a group with high exposure to lead (HE) PbB=40-81 microg/dl. The control group consisted of office workers with no history of occupational exposure to lead. Evaluation of lead, cadmium and zinc level in blood and seminal plasma, zinc protoporphyrin in blood (ZPP), 5-aminolevulinic acid in urine (ALA), malondialdehyde (MDA) in seminal plasma and sperm analysis were performed. No differences were noted in the concentration of cadmium and zinc in blood and seminal plasma in the study population. Lipid peroxidation in seminal plasma, represented as MDA concentration, significantly increased by about 56% in the HE group and the percentage of motile sperm cells after 1 h decreased by about 34% in comparison to the control group. No statistically significant correlation between other parameters of sperm analysis and lead exposure parameters nor between lead, cadmium and zinc concentration in blood and seminal plasma were found. A positive association between lead intoxication parameters (PbB, ZPP, lead seminal plasma) and MDA concentration in sperm plasma and inverse correlation with sperm cells motility (PbB, ZPP) was found. An increased concentration of MDA was accompanied by a drop in sperm cells motility. In conclusion, we report that high exposure to lead causes a decrease of sperm motility in men most likely as a result of increased lipid peroxidation, especially if the level in the blood surpasses the concentration of 40 microg/dl.     

Relation between occupational exposure to lead, cadmium, arsenic and concentration of cystatin C

Lead, cadmium and arsenic represent well recognized toxic agents which in a specific manner disturb function of cardiovascular system. Cystatin C has been accepted to be a significant prognostic factor for cardiovascular diseases. The study aimed at defining relationship between occupational exposure to lead, cadmium and arsenic on one hand and concentration of cystatin C on the other. The studies were performed on 282 men occupationally exposed to lead, cadmium and arsenic. Among the tested individuals several groups of persons were distinguished: exposed exclusively to lead (Pb group), cadmium (Cd group), arsenic (As group), to lead and cadmium (Pb/Cd group), to lead and arsenic (Pb/As group) or to cadmium and arsenic (Cd/As group). In all the individuals serum concentration of cystatin C was estimated. Concentration of cystatin C was found to be significantly higher in Pb group than in Cd and As groups, also in Pb/Cd group higher than in Cd group and in Pb/As group than in As group. Positive linear correlations were established between Pb concentration in blood (Pb-B) and serum concentration of cystatin C (r=0.59; p<0.05) as well as between urinary concentration of As (As-U) and serum concentration of cystatin C (r=0.41; p<0.05). Regression analysis demonstrated that higher blood level of lead, higher urinary level of arsenic, more advanced age and higher body mass index represented independent risk factors of an increased serum concentration of cystatin C in the group of persons exposed to lead, cadmium and arsenic. Conclusions: Higher blood level of lead and higher urinary level of arsenic represented independent risk factors of an increased serum concentration of cystatin C in the group of persons occupationally exposed to lead, cadmium and arsenic. Concentration of lead in blood was significantly influencing serum concentration of cystatin C. The highest mean serum concentration of cystatin C was detected in the group of foundry workers exposed simultaneously to lead and arsenic.     

Chronic occupational lead exposure and testicular endocrine function

The effects of moderate lead exposure on testicular endocrine function were evaluated in a group of 90 males who were occupationally exposed to inorganic lead. Lead concentrations in blood and bone were measured as indices of short-term and long-term, cumulative exposure, respectively. The results of this study show that the lead exposure levels encountered in the UK at present may result in a subclinical increase in follicle stimulating hormone (FSH), which is related to blood lead levels. This suggest that lead may be causing some subclinical primary damage to the seminiferous tubules in the testes. However, at blood lead levels of less than 47 micrograms dl-1 this effect on serum FSH is not apparent. There was no significant effect on serum testosterone concentrations or the free testosterone index. The mean luteinizing hormone (LH) level in the exposed group was found to be lower than in the control population. However, there appeared a confoundingly significant positive correlation between serum luteinizing hormone levels and the length of occupational lead exposure within the exposed group.     

Influence of age, sex and body weight on the dapsone acetylation phenotype.

The acetylation of dapsone (DDS) was determined by estimation of the ratio of monoacetyldapsone (MADDS) to DDS concentrations in plasma following a single dose of DDS in 337 white British subjects (193 female; 144 male). The percentage of slow DDS acetylators in the whole group was 60.3%. There was no statistically significant difference in this proportion between 191 elderly subjects (age greater than 65 years) and 143 young subjects (age less than 30 years). Although there was a small (66.3%) but significant (P = 0.033) preponderance of slow acetylators in the young male group there was no difference in the distribution of acetylator phenotypes between the sexes among either the elderly group or in the whole population studied. No correlation was found between absolute body weight and MADDS/DDS ratios.