Miquel Rodamilans

Lead Toxicity on Endocrine Testicular Function in an Occupationally Exposed Population

The hypothalamo-pituitary-testicular axis was evaluated in a group of 23 men who worked in the lead smelting industry and had a history of occupational inorganic lead exposure. The endocrine status of the workers was related to lead poisoning biological markers. According to the duration of their lead exposure they were divided into three groups: group 1 < 1 year, n = 5; group 2 between 3 and 5 years, n = 8; group 3 > 5 years, n = 10. Serum testosterone (T), steroid binding globulin (SBG), free testosterone index (T/SBG), serum luteinizing hormone (LH), follicle stimulating hormone (FSH), Blood lead levels, and blood zinc protoporphyrin (ZPP) were measured in all workers. Groups 2 and 3 showed a decrease in serum testosterone levels, an increase in SBG levels, and a decrease in T/SBG index, suggesting a correlation between testicular dysfunction and duration of exposure. There was an increase in serum LH in group 1, which was not progressive. This suggests that prolonged lead exposure initially produces a direct testicular toxicity followed by hypothalamic or pituitary disturbance when longer periods of exposure take place.

Sulindac Reduces the Urinary Excretion of Prostaglandins and Impairs Renal Function in Cirrhosis with Ascites

In 5 patients with cirrhosis and ascites the glomerular filtration rate (GFR), free water clearance (CH2O) and urinary excretion of prostaglandin E2(PGE2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured before and after a 3-day treatment with sulindac (400 mg/day). The administration of sulindac induced a marked fall of urinary excretion of PGE2 (from 24.2 +/- 5.5 to 3.8 +/- 1.1 ng/h; p less than 0.05), 6-keto-PGF1 alpha (from 19.9 +/- 2.9 to 5.6 +/- 1.1 ng/h; p less than 0.02) GFR (from 111 +/- 15 to 67 +/- 10 ml/min; p less than 0.01) and CH2O (from 7 +/- 1.5 to 3.7 +/- 1.3 ml/min; p less than 0.02) in all patients studied. The plasma concentration of the active metabolite sulindac sulfide in cirrhotics was 400% of that found in 6 healthy volunteers (9.6 +/- 1.7 vs. 2.4 +/- 0.6 ng/ml). Our results indicate that sulindac, at a dose of 400 mg/day, inhibits the renal synthesis of prostaglandins and impairs renal function in cirrhotics with ascites. These effects are probably related to the marked alteration of sulindac kinetics that occurs in these patients.

Cadmium and zinc relationships in the liver and kidney of humans exposed to environmental cadmium

Concentrations of cadmium and zinc were determined in the liver and in the kidney (cortex and medulla) of subjects from the general population of Barcelona (Spain) by atomic absorption spectrometry. Tissues were collected from necropsies of 50 selected subjects without any occupational exposure to heavy metals. Cadmium levels calculated on a fresh tissue basis were 14.6 +/- 5.9 micrograms/g (2.4-31) in the kidney cortex, 8.6 +/- 4.3 micrograms/g (1.5-16.7) in the kidney medulla and 0.98 +/- 0.50 micrograms/g (0.32-2.32) in the liver. Zinc concentrations ranged between 18-53 micrograms/g, (mean +/- S.D.: 38.0 +/- 10 micrograms/g) in the kidney cortex, 25.0 +/- 7.7 micrograms/g (12-42 micrograms/g) in the kidney medulla and 41.7 +/- 18.3 micrograms/g (20-84 micrograms/g) in the liver. The aim of the present work was to study the association of cadmium and zinc in the kidney and in the liver of a human population with cadmium accumulation from an environmental origin. The results obtained showed a significant correlation between cadmium and zinc concentration in the liver (r = 0.86, P < 0.001), but not in the kidney.

Single-blind comparison of venlafaxine and nortriptyline in elderly major depression

The objective of this single-blind study was to compare the efficacy and safety of venlafaxine extended-release and nortriptyline in elderly patients with moderate to severe major depression. In- and out-patients (N=68) with unipolar major depression were randomized to receive 6-month treatment with either nortriptyline or venlafaxine. Outcomes of the two groups were compared using measures including the Hamilton Depression Rating Scale (HDRS) and the Newcastle Scale. Side effects were assessed with the UKU side-effect rating scale. Of the 34 venlafaxine-treated patients, 22 were remitters, 7 were nonremitters, and 5 dropped out. The intent-to-treat remission rate was 71% (22 of 31). Of the 34 who received nortriptyline, 21 were remitters, 7 were nonremitters, and 6 dropped out. The intent-to-treat remission rate was 70% (21 of 30). These results suggest that the remission rate with a therapeutic plasma level of nortriptyline is similar to the remission rate with a standard dose of venlafaxine in this group of elderly major depressed patients. No significant differences were observed between dropout rates in the two groups, but autonomic side-effects were significantly more frequent for nortriptyline than for venlafaxine. These results confirm the efficacy and safety of venlafaxine extended-release for treating elderly major depression.

Optimized procedure for lamotrigine analysis in serum by high-performance liquid chromatography without interferences from other frequently coadministered anticonvulsants

The authors have developed a simple isocratic high-pressure liquid chromatographic (HPLC) assay for the simultaneous determination of lamotrigine and other frequently coadministered antiepileptic drugs in serum samples. Lamotrigine extraction was performed on a reversed-phase Oasis HBL preparation column. The eluates containing butalbital as internal standard were separated with a 7-&mgr;m Chromsystems C18 250 × 4.0 mm I.D. reversed-phase column at a temperature of 40°C using a mobile phase consisting of pH 3.8 phosphate-acetonitrile buffer (55:45, v/v), at a flow rate of 0.8 mL/min. Ultraviolet detection was carried out at 210 nm. Measurement of the peak:height ratio allowed quantitative determination of the samples. The method was linear over a concentration range of 0.2 to 20 &mgr;g/mL for lamotrigine. Recovery was >90%. Within-day and between-day coefficients of variation ranged from 1.8% to 6.7%. The mean lamotrigine concentration was 8.01 ± 5.63 &mgr;g/mL. After studying sera from 130 patients treated with lamotrigine the authors confirmed that associated antiepileptic therapy affected the serum lamotrigine levels, which were significantly higher in patients under valproic acid treatment.

Effect of Demeclocycline on Renal Function and Urinary Prostaglandin E2 and Kallikrein in Hyponatremic Cirrhotics

8 cirrhotics with hyponatremia were given demeclocycline (DMC) 900 mg/day to investigate its effect on renal function, plasma renin activity, aldosterone and urinary excretion of prostaglandin E2 and kallikrein. In 7 patients DMC induced an increase of free water clearance (from -0.36 +/- 0.06 to 0.13 +/- 0.06 ml/min) and serum sodium concentration (from 125.4 +/- 0.09 to 131.1 +/- 1.0 mEq/l, mmol/l). In 5 of these patients DMC also induced a marked reduction of glomerular filtration rate (from 72.2 +/- 6.2 to 31,2 +/- 4.7 ml/min) and renal plasma flow (from 468 +/- 98 to 195 +/- 55 ml/min) which could not be explained on the basis of hypovolemia. In each case this renal impairment was not associated with changes in urinary concentration of beta 2-microglobulin, urinary casts excretion, fresh urine sediment or urine protein content and disappeared after discontinuation of the drug. DMC induced a marked increase in the urinary excretion of prostaglandin E2 (from 0.82 +/- 0.27 to 6.16 +/- 1.91 ng/min) in 6 out of the 7 patients who responded to DMC and a marked reduction in urinary kallikrein (from 16.1 +/- 4.4 to 4.2 +/- 1.6 pkat/min) in the 5 patients who developed renal insufficiency. The serum DMC concentration was greater than 5 micrograms/ml in all patients who responded to DMC, greater than 8 micrograms/ml in all cases who developed renal insufficiency and of 3 micrograms/ml in the case not responding to DMC. (ABSTRACT TRUNCATED AT 250 WORDS)

Pentachlorophenol and Hexachlorobenzene in Serum and Urine of the Population of Barcelona

1 Urinary chlorophenols of the general population of Barcelona, Spain were determined. Pentachlorophenol (PCP: 25.0 ± 3.9 ng/ml; x ± s.e.m., n = 50) and tetrachlorophenol (TCP: 6.2 ± 1.6 ng/ml; x ± s.e.m., n = 25) were found in all samples. 2 Pentachlorophenol and hexachlorobenzene were also determined in serum. Both were present in all samples (PCP: 21.9 ± 1.9 ng/ml; HCB: 11.1 ± 1.1 ng/ml; x ± s.e.m., n = 100). Their concentrations do not show any correlation, suggesting no metabolic relation between them.

Inhibition of intratesticular testosterone synthesis by inorganic lead

The alterations in testicular testosterone synthesis produced by exposure to inorganic lead were investigated in BALB/c+ mice. Lead concentration in blood and testes and the levels of testosterone and delta 4-androgen biosynthesis pathway precursors (4-androstenedione, 17-hydroxyprogesterone, and progesterone) were measured in animals which were exposed to lead acetate in the drinking water (366 mg/l, 0.97 +/- 0.12 mg lead/animal/day) during 6 months. The results showed a significant reduction of the intratesticular testosterone levels after 30 days of exposure and of the androstenedione levels after 150 days. Intratesticular progesterone and hydroxyprogesterone levels showed no changes during the assay.

Serum and urine fluoride concentration : Relationships to age, sex and renal function in a non-fluoridated population

Serum and urine fluoride levels were determined in 250 healthy subjects (15-90 years, 122 men and 128 women) residing in Catalonia, Spain, and in 150 patients (20-81 years, 84 men and 66 women) with chronic renal failure undergoing regular dialysis treatment, living in the same geographical area, to determine normal range and to investigate its relationships to age, sex and renal function. Serum and urine fluoride were determined by a fluoride ion specific electrode system. Mean (+/- S.D.) serum fluoride concentration was 17.5 +/- 9.5 micrograms/l, ranging from 1 to 47 micrograms/l, in the control group and 58 +/- 31 micrograms/l, ranging from 28 to 185 micrograms/l, in renal patients. Urine fluoride concentration in the healthy group was 671 +/- 373 micrograms/24 h, ranging from 156 to 1900 micrograms/24 h. Fluoride status in the patient group was significantly greater than the control group. There was significant correlation between serum fluoride and age. No sex related difference was found.

Blood chromium determination in assessing reference values in an unexposed Mediterranean population.

Plasma chromium levels were determined in 243 healthy subjects. The study group consisted of 134 men and 109 women, ages 19–71 yr, all residing in Barcelona in northeastern Spain. The study was designed to assess the reference levels for plasma chromium and to investigate its relationships to age and sex. The assays were performed by means of a graphite-furnace atomic absorption spectrometer. The mean plasma chromium concentration was 3.01 ±1.45 nmol/L, ranging from 0.6 to 6 nmol/L. The upper reference values in the 0.95 percentile for this population was 5 nmol/L. No significant differences were observed with respect to the subjects’ sex.