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Biomedical subjects

J Corbella

Publications and source records attributed to J Corbella.

At least 73 records · Page 4Linked to original sources
PubMed1995

Suitability of the YNZ22 (D17S5) VNTR polymorphism for legal medicine investigations in the population of Catalonia (Spain).

Allele and phenotype frequencies for the YNZ22 locus were determined in a population sample from Catalonia (Spain) using the polymerase chain reaction (PCR). In 311 unrelated individuals, 14 alleles and 56 phenotypes were observed. No deviation from Hardy-Weinberg equilibrium was found. The observed heterozygosity was 81.35%. The YNZ22 polymorphism is useful for paternity testing with a CE value of 70% and an Essen-Möller value of 9.35 (log.).

Adult↗
PubMed1995

Assessment of the developmental toxicity of deferoxamine in mice.

Deferoxamine (DFO), an efficient chelating agent available for the treatment of iron and aluminium overload, was evaluated for developmental toxicity in Swiss mice. Intraperitoneal injections of DFO were given to pregnant animals at 0, 44, 88, 176, and 352 mg/kg per day on gestational days 6 through 15. Maternal clinical status was monitored daily during and after treatment. Fetal parameters, including external, visceral, and skeletal malformations and variations, were assessed. Mice were killed on day 18. No maternal mortality was observed, but dams exhibited reduced body weight gain during treatment at 88, 176, and 352 mg/kg per day. Body weight at termination, corrected body weight, and food consumption were reduced in all groups. In contrast, the only significant treatment-related embryo/fetal effect was a decrease in the number of live fetuses per litter at 352 mg/kg per day. The no-observable-adverse-effect level (NOAEL) for maternal toxicity of DFO was < 44 mg/kg per day, whereas the NOAEL for developmental toxicity was 176 mg/kg per day. In summary, intraperitoneal administration of DFO to mice during organogenesis produced developmental toxicity in the presence of maternal toxicity. Because of the remarkable maternal toxicity of DFO, extreme caution in the use of this drug is recommended during pregnancy.

Animals↗
PubMed1995

Effects of maternal stress on methylmercury-induced developmental toxicity in mice.

The developmental toxicity of combined exposure to maternal restraint stress and methylmercury chloride (MMC) was assessed in Swiss mice. On day 10 of gestation, four groups of plug-positive female mice were treated (p.o.) with a single dose of 12.5 or 25 mg MMC/kg. Immediately after MMC exposure, two of those groups were subjected to restraint for 14 hr. Control groups included restrained and unrestrained pregnant mice nonexposed to MMC. Combined exposure to 25 mg MMC/kg and restraint enhanced MMC-induced maternal toxicity, which included deaths and decreased body weight gain and food consumption. The number of nonviable implants was also increased significantly following concurrent exposure to MMC (25 mg/kg) and restraint, with the percentage of postimplantation loss increased from 64% (MMC alone) to 100% (MMC plus restraint). However, the types and incidence of internal and skeletal anomalies observed after administration of 12.5 mg MMC/kg were not increased by maternal restraint. These results suggest that maternal stress would enhance the MMC-induced maternal and embryo/fetal toxicity at doses of MMC that are highly toxic to the dams, whereas at doses that are less acutely toxic the role of maternal stress would not be significant.

Abnormalities, Drug-Induced↗
PubMed1995

Effects of long-term antiepileptic therapy on the catabolism of testosterone.

The serum levels of testosterone, sex hormone binding globulin, and free testosterone index were measured in 51 epileptic men (age 18-45) in order to assess the possible effects of antiepileptic drugs on sexual dysfunction. An analytical gas chromatography-mass spectrometry method was developed to assess the urinary excretion of testosterone, epitestosterone, androsterone, etiocholanolone, 11-OH androsterone and 11-OH etiocholanolone and to evaluate if the catabolism of testosterone had been increased. Twenty normal healthy males of similar age, 18-45 years, served as control group. Patients receiving polytherapy (n = 34) or monotherapy with carbamazepine (n = 8) or phenytoin (n = 9) showed higher levels of sex hormone binding globulin and testosterone, and lower levels of free testosterone than did the controls (P < 0.03). Urinary excretion of the metabolites androsterone and 11-OH androsterone was significantly reduced (P < 0.02) in the polytherapy group, while the monotherapy group showed only significant differences (P < 0.02) in the elimination of 11-OH androsterone. Our results suggest that an induction of the hepatic synthesis of sex hormone binding globulin may be the mechanism by which the antiepileptic drugs lower the levels of free testosterone in serum. However, the reduced excretion of androsterone and the normal levels of etiocholanolone show that the antiepileptic drugs do not produce an increase in the main catabolism pathway of testosterone.

Adolescent↗
PubMed1995

Accumulation of hexachlorobenzene in humans: a long standing risk.

1. Hexachlorobenzene (HCB) internal dose in the general population of Barcelona (Spain) was estimated after new indications of the carcinogenicity of this chemical in humans were recently reported. Hospital blood bank facilities and randomly selected volunteers were used for HCB analyses in serum (n = 100) and cerumen (n = 25). Other main organochlorine residues often found in human tissues and blood (pp DDE, beta-HCH,) were also determined. 2. HCB serum levels currently found (Range 0.7-19.7 ng Ml-1; X +/- s.d.: 4.13 +/- 3.61; GM: 3.05) were compared to those found in a similar survey made in 1986 on the same population. The serum HCB levels showed a significant decrease (P < 0.001) when compared to the former results and correlated with age (P < 0.001) suggesting a progressive preponderance of a stable blood-adipose equilibrium with fewer variations due to recent and variable intake of the chemical. 3. Cerumen analyses revealed detectable concentrations of HCB in all samples (Range: 160-4790 ng g-1 in extractable lipid basis) and confirmed the suitability of this matrix to assess the body burden of residues accumulated in adipose and lipid-rich tissues. The set of results shows that, although HCB exposure has been reduced, the overall population under study still accumulates significant amounts of this possible carcinogen.

Cerumen↗
PubMed1995

Four-week oral toxicity study of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in uremic rats.

A short-term oral toxicity study of 1,2-dimethyl-3-hydroxypyrid-4-one (L1), a promising oral chelating agent for the treatment of iron and aluminum overload, was carried out in uremic rats. L1 was administered to male uremic rats by gastric intubation at 0, 20, 40, 80 or 160 mg/kg/d for 4 w. Body weight and food and fluid intake were monitored daily. Complete hematologic examinations, serum biochemical parameter determinations and histological examinations were carried out. Although body weight gain was significantly reduced at 80 and 160 mg/kg/d, there were no effects of L1 on food and fluid consumption. There were no significant differences between controls and L1-treated groups in most of the hematological and biochemical parameters analyzed. No significant dose-dependent changes in relative organ weights were noted. The non-observed-adverse-effect level (NOAEL) for L1 in uremic rats was 40 mg/kg/d. According to the results of this study, uremia did not increase the toxic effects of L1.

Administration, Oral↗
PubMed1994

Mercury concentrations in marine species from the coastal area of Tarragona Province, Spain. Dietary intake of mercury through fish and seafood consumption.

A total of 592 samples of 21 species of fish, cephalopods, crustaceans and molluscs were analyzed for mercury concentrations between November 1992 and February 1993 at four sites on the Tarragona coast in Catalonia, Spain. The results of this study show that mercury discharges into the marine environment of Tarragona Province have increased the mercury content of marine organisms, with fish and crustaceans being the groups which accumulated the highest levels of this element. In a subsequent study, the individual dietary intake of mercury from fish and seafood consumption by the population of Tarragona Province was estimated to be 16 micrograms day-1. This intake of mercury would not signify a health hazard for consumers of fish and seafood from the Tarragona coastal waters.

Animals↗
PubMed1994

Zinc and copper levels in serum and urine: relationship to biological, habitual and environmental factors.

Zinc and copper levels were determined in serum and urine of 434 subjects living in an industrial and an agricultural area of Tarragona Province, Spain. Zinc and copper concentrations were related to a range of factors such as sex, age, blood pressure, and drinking and smoking habits. Geometric mean serum zinc and copper concentrations were, respectively, 113.9 and 84 micrograms dl-1, while the mean values for urine zinc and copper concentrations were 698.7 and 26.6 micrograms g-1 creatinine. Serum zinc and copper levels and urine copper concentrations in men were significantly lower than in women, while there were no differences in serum or urinary zinc and copper levels with age. The consumption of alcohol significantly reduced the levels of zinc and copper in serum, whereas blood pressure had no influence on these values. The levels of zinc and copper in urine were not affected by the smoking and drinking habits, place of residence, or blood pressure. In general terms, the results of this study agree with previously reported values from different countries.

Adolescent↗
PubMed1994

Evaluation of the protective activity of 2,3-dimercaptopropanol and sodium 2,3-dimercaptopropane-1-sulfonate on methylmercury-induced developmental toxicity in mice.

The embryotoxic and teratogenic effects of methylmercury in experimental animals have been established by several investigators. The protective activity of 2,3-dimercaptopropanol (BAL) and sodium 2,3-dimercaptopropane-1-sulfonate (DMPS, a chelator used in the treatment of inorganic and organic mercury) on methylmercury chloride (MMC)-induced maternal and developmental toxicity in mice has been evaluated in the present study. BAL and DMPS were administered subcutaneously or by gavage to pregnant mice immediately after a single oral administration of 30 mg MMC/kg given on day 10 of gestation and at 24, 48, and 72 h thereafter. Amelioration by BAL and DMPS of MMC embryo/fetotoxicity was assessed at 15, 30, and 60 mg/kg/day and at 90, 180, and 350 mg/kg/day, respectively. Treatment with BAL did not ameliorate the maternal toxicity or the developmental toxicity of MMC observed in the mouse. In contrast, DMPS at 90, 180, and 360 mg/kg/day significantly reduced the maternal lethality of MMC, whereas treatment with 180 and 360 mg DMPS/kg/day showed significant protective activity against MMC-induced embryotoxicity and teratogenicity. Based on the present findings, DMPS might be a useful chelator against the maternal and developmental toxicity induced by methylmercury.

Abnormalities, Drug-Induced↗
PubMed1994

Effects of chronic lead and cadmium exposure on blood pressure in occupationally exposed workers.

An epidemiological study was performed to assess whether the occupational exposure to lead or cadmium is associated with an increase in blood pressure. Blood lead levels were determined in 36 male subjects who were occupationally exposed to lead, whereas urinary cadmium concentrations were determined in 40 male workers who were employed in cadmium pigment and resin factories from Barcelona (Spain). Blood lead and urine cadmium concentrations were also determined in 40 health volunteers who were not occupationally exposed to lead or cadmium (control group). The mean concentrations of blood lead were 9.8 micrograms/dL for controls and 39.5 micro/dL for lead-exposed workers, whereas 0.79 micrograms/g creatinine and 2.50 micrograms/g creatinine were the mean levels of urine cadmium for controls and for cadmium-exposed workers, respectively. After adjusting for age, body mass index, and drinking and smoking habits, a significant rise of blood pressure with the increases in blood lead levels was found in the group of lead-exposed workers, but not in the control group. In contrast, the results of this study did not corroborate the hypothesis that an increase in cadmium exposure implies a rise in blood pressure.

Adult↗
PubMed1994

Housing of pregnant rats in metabolism cages: maternal and developmental effects.

The influence of the caging conditions on maternal and gestational variables was assessed for pregnant rats housed individually in two cage types. Plug-positive Sprague-Dawley females were caged either in Makrolon or in metabolism (Tecniplast) cages, and were not disturbed throughout all the gestational period. Cesarean sections were performed on gestation day 20. All live fetuses were examined for external, internal, and skeletal malformations and variations. Pregnant rats were affected by the housing system, as evidenced by a significant weight loss and reduced food consumption in the animals housed in metabolism cages. A moderate increase in the number of total skeletal defects was also observed in the fetuses of dams housed in metabolism cages. An important implication of these results would be that in maternal and developmental toxicity studies of xenobiotics, pregnant animals should not be housed in metabolism cages.

Animals↗
PubMed1994

Developmental toxicity evaluation of monoisoamyl meso-2,3-dimercaptosuccinate in mice.

Monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS), a new dimercaptosuccinic acid (DMSA) analog with enhanced lipophilic properties, was evaluated for potential developmental toxicity. Intraperitoneal injections of Mi-ADMS were given to female Swiss mice (0, 47.5, 95, and 190 mg/kg) on gestational d 6-15. The maternal clinical status was monitored daily during treatment. At termination (gestational d 18), dams were evaluated for clinical status and gestational outcome. Each live fetus was weighed and examined for external, visceral, and skeletal abnormalities. Although no maternal mortality was observed, treatment with 95 and 190 mg/kg resulted in maternal toxicity, manifested as reduced body weight gain during treatment and increased relative liver weight. Embryo/fetal toxicity, consisting of a significant increase in the number of late resorptions as well as in the percentage of postimplantation loss, reduced (nonsignificant) fetal body weight, and an increase in the incidence of skeletal defects, was also observed at 190 mg/kg/d. However, no treatment-related external or soft-tissue malformations or developmental variations were found in any group. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 47.5 mg/kg/d, whereas the NOAEL for developmental toxicity was 95 mg/kg/d. These results indicate that Mi-ADMS did not produce developmental toxicity in mice in the absence of maternal toxicity.

Abnormalities, Drug-Induced↗
PubMed1994

Comparative aluminium mobilizing actions of several chelators in aluminium-loaded uraemic rats.

The relative effectiveness of deferoxamine (DFO), 1,2-dimethyl-1,3-hydroxypyrid-4-one (L1), and citric and succinic acids in mobilizing and promoting excretion of aluminium (Al) were compared in female uraemic rats which had previously received aluminium nitrate nonahydrate i.p. in a daily dose of 45 mg kg-1 for 3 weeks (5 days/week). Chelators were administered s.c. at doses equal to one-eighth of their respective LD50 for five days. L1 was also given p.o. in doses of 200 mg kg-1 day-1. Total urines were collected 24 h after each chelator administration. Total urinary Al excreted over the 5-day period, expressed as mg kg-1, were: controls, 3.4; DFO-treated, 4.5 (P < 0.05); citric acid-treated, 3.7; and succinic acid-treated, 2.7. Although the daily amounts of Al excreted into urine by L1-treated rats were significantly higher (P < 0.001) than those of the controls, most animals died during the period of treatment. Measurements of Al in selected tissues 24 h after the last administration of each chelator revealed that none of the compounds significantly altered the Al concentration in bone, kidney, and brain, whereas only DFO and succinic acid significantly reduced the levels of Al in spleen. Moreover, L1 (given s.c. or p.o.) and citric acid treatment led to a significant reduction in the liver Al burden. These results indicate the need for further investigations to determine the toxicity and the therapeutical safety margins of L1.

Aluminum↗
PubMed1994

Developmental toxicity of cyclohexanediaminetetraacetic acid (CDTA) in mice.

Cyclohexanediaminetetraacetic acid (CDTA), an effective antagonist for the treatment of zinc, lead, and manganese poisoning was evaluated for maternal and developmental toxicity in pregnant Swiss mice. CDTA was given intraperitoneally on gestation days 6-15 at doses of 0, 270, 540, and 1080 mg/kg/day. On gestational day 18, the fetuses were examined for external, visceral, and skeletal malformations and variations. Treatment with CDTA at 1080 mg/kg/day resulted in a high level of maternal deaths, as well as less severe clinical signs (significant reduction in weight gain and food consumption). Increased resorptions, fetal deaths, and decreased number of live fetuses per litter were observed at 1080 mg/kg/day. Mean fetal body weights were also significantly decreased in this group. At 1080 mg/kg/day, CDTA caused external malformations, while the development of skeletal tissues was less affected. The no observable adverse effect level (NOAEL) for maternal and developmental toxicity of CDTA in mice was 540 mg/kg/day. Analyses of maternal and fetal tissues revealed only slight effects of CDTA on concentrations of calcium, magnesium, zinc, copper and iron. According to these results, the alterations in mineral metabolism should not be the major reason for CDTA-induced developmental toxicity.

Abnormalities, Drug-Induced↗