Biomedical subjects

A Lafuente

Publications and source records attributed to A Lafuente.

At least 37 records · Page 2Linked to original sources

PubMed1999

Cadmium effects on hypothalamic activity and pituitary hormone secretion in the male.

Cadmium specifically modify amine metabolism at the central nervous system and pituitary hormone secretions. Thus, the physiological functions controlled by these hormones can be modulated by cadmium. This xenobiotic is associated with deleterious effects on the gonadal function and with changes in the secretory pattern of other pituitary hormones like prolactin, ACTH, GH or TSH. The observed changes in pituitary hormone secretion do not correlate with the modifications of central nervous system metabolism of the neurotransmitters involved in their regulation. The accumulative data indicates the existence of a disruption in the regulatory mechanisms of the hypothalamic-pituitary axis. The physiological significance of these effects remains to be elucidated.

Adrenocorticotropic Hormone↗

PubMed1999

Cadmium affects the episodic luteinizing hormone secretion in male rats: possible age-dependent effects.

Cadmium affects luteinizing hormone (LH) secretion through unknown mechanisms. The present study was undertaken to assess whether chronic exposure to low concentrations of cadmium may affect the episodic secretion of LH and if these effects are age-dependent. Male rats were given cadmium at a dose of 50 ppm in the drinking water, from day 30 to 60 or from day 60 to 90 of life. Age-matched rats with access to cadmium-free water were used as controls. At the end of the treatment, blood samples were collected every 7 min for 3 h, from 10:30 to 13.30 in conscious, freely moving rats. In control animals, mean serum LH levels and pulse duration increased with age (P < or = 0.001), and pulse frequency and the relative amplitude of LH pulses decreased (P < or = 0.001). Cadmium administration, from day 30 to 60 of life, decreased the pulse frequency and mean half-life of the hormone (P < or = 0.05, P < or = 0.01, respectively). However, no changes in any other parameters studied were observed as compared to the control group. When cadmium was administered from day 60 to 90, mean serum LH levels and the duration of LH pulses decreased (P < or = 0.05), whereas the pulse frequency increased (P < or = 0.05). The absolute and relative amplitude of the LH peaks and the mean half-life of the hormone were not changed after cadmium administration from day 60 to 90. These results indicate that low doses of cadmium change the pulsatile secretion of LH in male rats and that the effect of cadmium on episodic LH release was age-dependent.

Aging↗

PubMed1999

Pubertal dependent effects of cadmium on episodic prolactin secretion in male rats.

This work was undertaken to assess if exposure to cadmium related to puberty may affect the episodic pattern of prolactin. Male rats were submitted to cadmium exposure, from day 30 to 60 or from day 60 to 90 of life respectively, at a dose of 50 ppm in the drinking water. Control age-matched rats received cadmium-free water. Prepubertal cadmium administration decreased mean serum prolactin levels and the absolute amplitude of the prolactin pulses. Subchronic exposure to cadmium of adult rats decreased mean serum prolactin levels, the absolute amplitude of the prolactin pulses and their duration, and the mean half-life of the hormone. These results suggest that subchronic cadmium exposure changes the secretory pattern of prolactin in adult male rats in a puberty-dependent way.

Animals↗

PubMed1999

Environmental tobacco smoke interference in the assessment of the health impact of a municipal waste incinerator on children through urinary thioether assay.

The urinary elimination of thioethers urinary thioethers (UT) was studied in 83 schoolchildren living in two different areas of the city of Mataró, with special attention paid to the influence of a waste incinerator and of the smoking habits of their parents. The mean UT values were 8.79+/-3.23 and 7.52+/-3.23 mmol/mol creatinine in the area close to the incinerator (A1) and in the area far away from it (A2) respectively (statistically n.s.). Children exposed to environmental tobacco smoke (ETS) at home presented increased levels of UT (8.60+/-3.11 vs 5.93+/-3.22 mmol/mol creatinine; P=0.002). Considering the two exposures together (waste incinerator and ETS), no differences were found between the two areas studied (A1 and A2) in non-exposed (ETS) children, whereas slight differences were found when comparing highest ETS exposed children from the two areas (10. 18+/-2.70 vs 8.00+/-3.42 mmol/mol creatinine; P=0.04). Exposure to ETS could affect health more than pollutants from a waste incinerator and may interfere with non-selective assays such as urinary thioethers.

Air Pollutants↗

PubMed1999

Effects of chronic alternating cadmium exposure on the episodic secretion of prolactin in male rats.

Cadmium increases or decreases prolactin secretion depending on the dose and duration of the exposure to the metal. However, whether there are cadmium effects on the episodic prolactin secretion is less well known. This study was undertaken to address whether chronic alternating exposure to two different doses of cadmium affects the episodic pattern of prolactin and to what extent the effects of cadmium are age-dependent. Male rats were treated s.c. with cadmium chloride (0.5 or 1.0 mg/kg) from day 30 to 60, or from day 60 to 90 of age, with alteration of the doses every 4 days, starting with the smaller dose. Controls received vehicle every 4 days. The last dose of cadmium was given 48 h prior to the pulsatility study. Prolactin secretion in the 4 experimental groups studied was episodic and changed significantly after cadmium exposure. Cadmium administration from day 30 to 60 of life significantly decreased the mean half-life of prolactin. On the other hand, when administered from day 60 to 90 cadmium significantly decreased the mean as well as serum prolactin levels and the absolute amplitude of the prolactin pulses, their duration, the relative amplitude or the mean half-life of the hormone. The frequency of prolactin peaks was not changed by cadmium administration. The results indicate that low intermittent doses of cadmium chronically administered change the episodic secretion pattern of prolactin in rats. The effects of cadmium on prolactin secretion were age dependent.

Age Factors↗

PubMed1999

Recombinant tissue plasminogen activator (rtPA) for the treatment of hepatic veno-occlusive disease (VOD).

Seventeen patients who developed hepatic veno-occlusive disease (VOD) following hematopoietic stem cell transplantation were treated with recombinant tissue plasminogen activator (rtPA) with or without heparin. rtPA was started a median of 13 days post transplant (range 4-35). All patients received rtPA at a dose of 10 mg/day as a starting dose, and 12 patients also received heparin (1500 U bolus; then 100 U/kg/day as a continuous i.v. infusion). The median number of days of rtPA therapy was 2.5 (1-12). The median total serum bilirubin level was 116 mmol/l (range 63-194) at the beginning of treatment. Six patients showed a response to rtPA treatment (29%). It was observed that by day 2 of rtPA therapy, bilirubin levels in responders showed a downwards trend as compared to those in nonresponders. In all except one patient this response was observed after two doses of rtPA. Seven out of the 11 non-responders had a past history of liver dysfunction, compared with none of the responders. There were no differences between the two groups in terms of day of onset of liver dysfunction, manifestations of disease, maximum bilirubin and creatinine levels, and day of commencing treatment. No patient experienced severe hemorrhagic complications during therapy. Four responders survived for more than 100 days compared to none of the non-responders. Probability of survival was 33% at day 100. It is difficult to unequivocally establish the role of rtPA in the treatment of VOD. The importance of bilirubin levels on days 2 or 3 of therapy in predicting outcome should be established, as should the optimum dose of rtPA and optimum duration of therapy.

Adult↗

PubMed1999

Biotransformation of pentachlorophenol, aniline and biphenyl in isolated rainbow trout (Oncorhynchus mykiss) hepatocytes: comparison with in vivo metabolism.

1. The biotransformation of pentachlorophenol (PCP), aniline and biphenyl in rainbow trout (Oncorhynchus mykiss) isolated liver cells was investigated to examine if fish hepatocytes represent a suitable alternative to the in vivo approach for studying the biotransformation of chemicals. Each compound was incubated at two concentrations (10 and 60 microM) for 2 h. For comparison, the metabolic profile of these xenobiotics was also studied in urine and bile of trout orally exposed to 1.8-4.0 mg/kg wet wt of each compound. 2. In vitro as in vivo, PCP glucuronide and to a lesser extent PCP sulphate were the metabolites formed by trout from PCP. 3. Aniline was mainly metabolized to acetanilide and to a lesser extent to 2-aminophenol by isolated hepatocytes, but neither hydroxylated acetanilide nor conjugates were found in vitro whereas they were present in bile and urine of trout treated with this chemical. 4. Trout hepatocytes metabolized biphenyl to hydroxylated and dihydroxylated products and the corresponding glucuronides. These results correlated well with the metabolic profile obtained from the bile of trout exposed to this pesticide. 5. It is concluded that although hepatocytes are well suited for several types of biotransformation studies, the fact that this system may in some cases produce a different metabolic pattern than in vivo should be considered when attempting to extrapolate in vitro to in vivo data.

Aniline Compounds↗

PubMed1999

Aberrant methylation of p16INK4a in anatomic and gender-specific subtypes of sporadic colorectal cancer.

Colorectal cancer (CRC) occurring in the proximal colon and among women may represent a distinct subtype of the disease. In the present study of 120 sporadic CRCs, we used methylation-specific PCR to test whether methylation of the CpG island in the 5' region of the p16INK4a tumor suppressor gene was associated with anatomical location, gender, or other clinicopathological characteristics. Overall, 18.3% of the tumors had detectable p16INK4a methylation. A marked preponderance of methylated tumors occurred within the proximal colon; cancers occurring proximal to the sigmoid colon were 13.1 times more likely to contain methylated p16INK4a compared with distal tumors. In addition, female patients were 8.8 times more likely than males to have methylation-positive cancers, and p16INK4a methylation was also associated with poorly differentiated tumors. The localization of tumors with p16INK4a methylation within the proximal colon and among female patients specifically adds to a growing database of molecular alterations that define important subtypes of sporadic CRC. The potentially reversible nature of CpG methylation may provide novel therapeutic opportunities for this increasing subtype of the disease, which, due to anatomical location, presents a great challenge for early detection.

Aged↗

PubMed1998

Cadmium does not inhibit pulsatile prolactin secretion through TRH.

This work was undertaken to analyse the effects of acute cadmium administration on the pulsatile pattern of prolactin release, in adult male rats. For this purpose, animals were cannulated 40 h before the experiment to allow a continuous blood withdrawal. Two hours after the administration of one dose of cadmium chloride (4.5 mg kg1), the pulsatile pattern of prolactin, during three hours, was studied. The effects of two pulses of thyrotropin-releasing hormone (TRH) (1 microgram per rat), given 60 and 120 min after starting the period of blood sampling, were studied. The mean values of prolactin during the bleeding period and the absolute pulse amplitude were decreased by acute cadmium chloride administration. However, no changes in any other parameters of prolactin pulsatility were observed. TRH administration to control rats increased mean prolactin levels, and absolute and relative pulse amplitudes, but decreased the mean half-life of the hormone. In animals pretreated with cadmium, TRH increased the mean levels of prolactin, and absolute and relative amplitudes of the hormone pulses. No other parameter studied was changed by TRH in cadmium pretreated rats. These data suggest that acute administration of cadmium did not inhibit the pulsatile prolactin release through TRH.

Animals↗

PubMed1998

Modulation of episodic adrenocorticotropin hormone secretion by cadmium in male rats.

The effects of cadmium on adrenocorticotropin hormone (ACTH) secretion are controversial and seem to depend on the dose and duration of the exposure to the metal. This work was undertaken to analyze the effects of acute cadmium administration on the episodic pattern of ACTH release in adult male rats. For this purpose, animals were cannulated 40 h before the experiment to allow a continuous blood withdrawal. Two and a half hours after the administration of a single dose of cadmium chloride (4.5 mg kg-1 bodyweight), the episodic pattern of ACTH was analyzed during three hours (from 10:30 to 13:30, samples being collected every seven minutes) in conscious and freely moving adult male rats. The mean values of ACTH during the bleeding period and the absolute pulse amplitude were decreased by acute cadmium chloride administration (P < or = 0.001, P < or = 0.01, respectively). By contrast, the frequency of ACTH pulses increased (P < or = 0.01). However, no changes in any other parameters of episodic ACTH secretion were observed compared with control animals. These data suggest that cadmium interferes with the regulatory mechanism of ACTH.

Adrenocorticotropic Hormone↗

PubMed1997

Haematopoietic transplantation in pulmonary alveolar proteinosis associated with chronic myelogenous leukaemia.

Pulmonary alveolar proteinosis (PAP) is a disease of unknown etiopathogenesis sometimes associated with malignant haematological disorders. The potential reversibility of the process in these cases seems to be related to recovery from the underlying disease. GM-CSF has acquired an important, potentially pathogenic role and BMT presents one therapeutic option effective in certain forms of human PAP. We present the case of a 43-year-old female patient with Ph+ CML. During pretransplantation evaluation, unexpected pulmonary infiltrates were noted in the chest X-ray, PAP being diagnosed on biopsy. In view of the progressive respiratory symptomatology and her CML being in accelerated phase, the patient underwent haematopoietic transplantation. She died on day +12 from invasive pulmonary aspergillosis before a response could be observed. Pathogenic implications in PAP and the role of haematopoietic transplantation in this disease are discussed.

Adult↗

PubMed1997

Expression of glutathione S-transferase activity and glutathione content in squamous cell carcinoma of bladder associated with schistosomiasis in a population in Egypt.

The present study was designed to describe the expression of the glutathione S-transferase/glutathione system in squamous cell carcinoma of the bladder in a population in Egypt. The glutathione-S transferase activity was significantly higher in bladder cancer specimens (n = 40) in comparison with schistosomiasis cystitis tissue (n = 42) (4-fold, p = 1 x 10(-12)) and with healthy control samples (n = 9) (10-fold, p = 1 x 10(-6)). The glutathione content was also significantly higher in bladder cancer than in cystitis tissue (2-fold, p = 8 x 10(-6)) and in control samples (6-fold, 8 x 10(-6)). When control mucosa and cystitis samples were compared, 2-fold increased values were obtained for glutathione-S transferase (p = 4 x 10(-3)) and glutathione (p = 1 x 10(-3)) in schistosomiasis bladder tissue. Results describe an over-expression of glutathione-S transferase and glutathione levels in squamous cell carcinoma of the bladder, and indicate a possible role in chemoresistance to pharmacological therapy.

Adult↗

PubMed1997

Immunohistochemical study of alpha, mu and pi class glutathione S transferase expression in malignant melanoma. MMM Group. Multidisciplinary Malignant Melanoma Group.

Human pi, mu and alpha class glutathione S transferases (GST) have been localized immunohistologically in normal skin, naevi and melanoma. Pi GSTs were found principally in the stratum basalis and, to a lesser extent, in the superficial layers. Normal melanocytes showed strong nuclear and cytoplasmatic staining. Distribution of GST mu in the epidermis showed that only the stratum basale, where melanocytes are located, stained well but with weak nuclear staining. Normal melanocytes were also well stained. The alpha GSTs were relatively abundant in the upper strata and to a lesser extent, in the basal layers. The absence of nuclear staining gives these cells a target appearance. Normal melanocytes showed strong cytoplasmatic staining. The pi GSTs seem to be most persistently and strongly expressed in malignant melanoma (MM), but mu GSTs are also found, whereas the alpha GSTs were only occasionally present. The finding of the GST mu in the melanocytes of the basal layer raises new questions regarding the role of GST mu in these cells because of the inherent risk of MM in individuals with a congenital deficiency of this isoenzyme. The role of GSTs in the resistance of cells to chemotherapy is also discussed.

Cell Nucleus↗

PubMed1997

Effects of acute and subchronic cadmium administration on pituitary hormone secretion in rat.

Cadmium administration is known to be followed by deleterious effects on the endocrine system although its action mechanism is not well understood. The purpose of this study was to determine, in vivo, the effects of acute and/or subchronic cadmium chloride administration (6 mg/kg or 4 mg/kg/day during 14 days) on prolactin, luteinizing hormone (LH), follicle stimulating hormone (FSH), growth hormone (GH) and thyroid stimulating hormone (TSH) secretion in adult male rats. Six h after a single injection of CdCl2, a diminution of plasma levels of prolactin (4.52 +/- 0.53 vs. 16.2 +/- 2.7 ng/mL, p < 0.01), GH (3.39 +/- 0.41 vs. 6.71 +/- 1.30, ng/mL, p < 0.01), TSH (2.76 +/- 0.64 vs. 7.65 +/- 1.15 ng/mL, p < 0.01) and LH (4.1 +/- 1.3 vs. 5.18 +/- 0.28, p < 0.05) was observed, where as plasma FSH levels did not change. On the other hand, subchronic cadmium chloride administration for 14 days, increased plasma levels of GH (13.39 +/- 2.74 vs. 6.71 +/- 1.3 ng/mL, p < 0.05), TSH (27.8 +/- 4.42 vs. 6.65 +/- 1.15 ng/mL, p < 0.001), LH (11.1 +/- 1.3 vs. 5.18 +/- 0.28 ng/mL, p < 0.001) and FSH (53.16 +/- 3.66 vs. 12.51 +/- 1.45, p < 0.001), whereas plasma prolactin levels decreased (6.86 +/- 1.38 vs. 16.2 +/- 2.7 ng/mL, p < 0.01). In animals subchronically treated with CdCl2, body weight gain was lower than in control rats (p < 0.001). The present findings suggest that acute and subchronic cadmium administration modify pituitary hormone secretion differentially and specifically.

Animals↗

PubMed1996

Hyperprolactinaemia and cyclosporine treatment on secretion of adenohypophyseal hormones.

The possibility of interactions between the effects of cyclosporine (CyA) and prolactin to regulate various physiological functions has been suggested. To further analyze these interactions, the effect of chronic CyA administration on the secretion of adenohypophyseal hormones in hyperprolactinemic male rats, was studied. Male rats were grafted one pituitary gland under the kidney capsule or were sham-operated at 30 days of age. Both pituitary-grafted and sham-operated rats were given s.c. injections of vehicle or CyA (5 mg/kg/day) for 30 days beginning on the day of surgery. Pituitary-grafting increased the plasma levels of prolactin and decreased the plasma levels of luteinizing hormone (LH), whereas growth hormone (GH), thyroid stimulating hormone (TSH) and follicle stimulating hormone (FSH) did not change. CyA treatment to sham-operated rats did not modify plasma prolactin levels and decreased plasma levels of GH and LH. Administration of the immunosuppressor to pituitary-grafted rats decreased plasma prolactin levels and augmented plasma levels of LH and FSH. Plasma TSH levels did not change after CyA treatment either in sham-operated or in pituitary-grafted rats. These data suggest that CyA may modify the effects induced by prolactin on pituitary hormone secretion, although direct effects of the drug on the hypothalamic-pituitary axis cannot be excluded, according to the data obtained in sham-operated rats.

Animals↗

PubMed1996

Effects of cyclosporin treatment on prolactin pulsatility in chronic hyperprolactinemic male rats.

Neuroendocrine effects of cyclosporin (CsA) have been demonstrated, but the mechanisms involved are poorly understood. This work was designed to analyse (i) if chronic CsA administration could influence the episodic secretion of prolactin in adult male rats; and (ii) the effects of the chronic administration of the drug, in adult animals with elevated plasma prolactin levels. Male rats were implanted with one anterior pituitary gland under the kidney capsule or were sham-operated, at 30 days of age. Both pituitary-grafted and sham-operated rats were injected subcutaneously with vehicle or CsA (5 micrograms/kg/day) for 9 days beginning at the 60th day of age. In pituitary-grafted male rats, mean prolactin levels, absolute prolactin pulse amplitude and mean half-life of the hormone increased, while the pulse frequency and relative amplitude of the peaks decreased, as compared with sham-operated rats. CsA administration to sham-operated rats decreased the relative pulse amplitude of prolactin but increased the mean half-life of the hormone, the pulse duration and the mean hormone levels, as compared with rats of the same group treated with vehicle. However, CsA treatment to pituitary-grafted rats decreased mean prolactin levels and the absolute amplitude of its peaks and increased the relative amplitude of its pulses, whereas all the other parameters showed no change. When considering circulating values of prolactin in plasma from the trunk blood, CsA administration was followed by changes similar to those described when mean values of the serial samples were considered. These data suggest the existence of an interrelationship between elevated circulating prolactin levels and CsA, which probably takes place at the hypothalamic level, to regulate the pulsatile pattern of prolactin secretion in male rats, although a direct effect of the drug on the ectopic gland in pituitary-grafted male rats cannot be excluded.

Animals↗

PubMed1996

Influence of smoking in the glutathione-S-transferase M1 deficiency--associated risk for squamous cell carcinoma of the bladder in schistosomiasis patients in Egypt.

In this study we show an effect of the glutathione-S-transferase M1 (GSTM1) null phenotype on the risk for squamous cell carcinoma (SCC) of the bladder among male smokers in Egypt, with an adjusted odds ratio of 4.8 (95% confidence interval: 1.06-21.77). However, no overall effect of the GSTM1 null phenotype on the risk for bladder SCC was observed.

Adult↗

PubMed1996

Effects of luteinizing hormone-releasing hormone on pulsatile prolactin secretion in adult hyperprolactinemic female rats.

Regulation of prolactin secretion involves complex interactions of multiple inhibitory and stimulatory factors. Among them, luteinizing hormone-releasing hormone (LHRH) has been shown, when analyzed in single samples, to exert both stimulatory and inhibitory influences on prolactin secretion. In the present study, we have further examined the effects of LHRH on prolactin secretion by studying the pulsatile pattern of the hormone after the administration of the neuropeptide. For this purpose, adult sham-operated and pituitary-grafted female rats, exhibiting diestrus smears were bled for 3 hr during the morning (1030 to 1330 hr). Two pulses of LHRH (10 ng/kg body wt) were administered 60 and 120 min after starting the bleeding period. Pituitary grafting increased the mean serum prolactin levels, absolute amplitude of the hormone peaks, and its mean half-life, compared with control animals. In sham-operated rats, LHRH administration diminished mean serum prolactin levels, the absolute pulse amplitude and frequency of prolactin peaks. In pituitary-grafted animals, LHRH administration only decreased the pulse frequency of prolactin peaks. These data suggest that LHRH significantly suppressed pulsatile prolactin secretion, and that this effect was blunted by exposure to previously elevated circulating prolactin levels.

Animals↗