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Biomedical subjects

A Lafuente

Publications and source records attributed to A Lafuente.

At least 55 records · Page 3Linked to original sources

Possible interactions of cyclosporine and hyperprolactinemia modulating the episodic secretion of prolactin.

The interrelationship between the effects of prolactin and cyclosporine (CsA) appears to be very complex and until now poorly understood. The aim of the present work was to analyze whether chronic treatment with CsA could modify the episodic secretion of prolactin in male rats and whether the presence of an ectopic pituitary could counteract the effects of the drug on the pulsatile secretion pattern of this hormone. At 30 days of age, male rats were implanted with one anterior pituitary under the kidney capsule or where sham-operated. Both pituitary-grafted and sham-operated rats were injected sc for 30 days with the vehicle or CsA (5 mg/kg/day), beginning on the day of surgery. Pituitary grafting and/or CsA administration changed the pulsatile secretion pattern of prolactin. In pituitary-grafted male rats, mean serum prolactin levels, absolute pulse amplitude, and half-life of the hormone increased, while the pulse frequency decreased, compared with the values found in sham-operated rats. CsA administration to sham-operated rats increased the relative amplitude of prolactin peaks and diminished the half-life of the hormone, compared with rats of the same group treated with vehicle. However, CsA treatment in pituitary grafted rats led to lower mean serum prolactin levels and absolute amplitude, while the frequency, duration, and relative amplitude of prolactin pulses were not modified. Plasma prolactin levels did not change in control animals, whereas a reduction in circulating values of the hormone was found in pituitary grafted animals. These data suggest that CsA modifies the pulsatile secretory pattern of prolactin in pituitary-grafted male rats. The different effects observed in the control and pituitary-grafted animals might be due to a direct effect of the drug on the ectopic lactotrophs that are submitted to local regulatory influences different from those of the in situ pituitary which are submitted to the regulatory influence of the hypothalamus.

Animals↗

[Rhodococcus equi pneumonia in patients with HIV infection: report of 2 cases and review of the literature].

BACKGROUND: Pneumonia by Rhodococcus equi is infrequent and is associated with patients with important immunosuppression. To date 66 cases of pneumonia by Rhodococcus equi in patients with HIV infection have been published. The diagnosis, problems in determining diagnosis and treatment are discussed. MATERIALS AND METHODS: Two new cases of pneumonia by Rhodococus equi in C3 stage patients with HIV infection are reported. Diagnosis was achieved by study of bronchoalveolar lavage samples with the Apy-Coryne method and gas chromatography. RESULTS: The two patients presented pneumonia, one of which was necrotizing pneumonia with localization in the upper left lung and in the lower right lung, respectively. The clinical manifestations were characterized by respiratory involvement of a subacute course with pleural involvement in both cases and hemoptisis in one. Prolonged, combined antibiotic treatment was administered with good response in both cases. One patient died at one year of diagnosis from consumptive syndrome while the other remains asymptomatic. CONCLUSIONS: Infection by Rhodococcus equi should be suspected in HIV patients with slow evolution pneumonia, especially in the pneumonia is necrotizing. Combined i.v. antibiotic treatment is recommended and followed from 3 to 5 months with an association including clarithromycin.

Actinomycetales Infections↗

Effects of cyclosporine on circulating levels of prolactin, LH, FSH, TSH and GH in chronic hyperprolactinemic male rats.

The effects of cyclosporine (CyA) on pituitary hormone secretion in animals with previously high plasma prolactin levels have been studied. Hyperprolactinemia was either induced in 30 day old male rats by the transplantation of one anterior pituitary gland from a litter mate donor or they were sham-operated to be used as controls. Both pituitary-grafted and sham-operated animals were injected s.c. with the vehicle or CyA (5 mg/kg weight per day) for 10 days, beginning 30 days after surgery. As expected, pituitary grafting markedly increased plasma prolactin levels as compared with the values found in control animals. Hyperprolactinemia was associated with reduced plasma LH and GH levels, increased plasma TSH levels and with no changes in circulating FSH levels. CyA administration to control animals increased plasma prolactin and TSH levels, decreased plasma levels of LH and did not modify circulating values of FSH and GH. Furthermore, CyA administration to pituitary-grafted animals decreased plasma prolactin and TSH levels, whereas plasma concentrations of GH and gonadotropins did not change. These data suggest that CyA differentially affect the release of pituitary hormones and that there is an interrelationship between previously high plasma prolactin levels and CyA to modulate pituitary hormone secretion.

Animals↗

Phenotype of glutathione S-transferase Mu (GSTM1) and susceptibility to malignant melanoma. MMM group. Multidisciplinary Malignant Melanoma Group.

The isoenzyme Mu of glutathione S-transferase (GSTM1) is dominantly inherited, and the prevalence of this isoenzyme in the population is about 60%. The lack of GSTM1 has been linked with cancer risk. The frequency of the phenotypes of this isoenzyme in melanoma (MM) patients (n = 197) is reported here. A significantly higher proportion of individuals in the control group (n = 147) had measurable GSTM1 than MM patients (59.1% vs 42%, P = 0.002); there was a higher proportion of positive phenotypes in general among women than among men. Odds ratio analysis indicated that individuals with this polymorphic variant have an approximately 2-fold risk of developing these cancers. GSTM1 phenotype distribution depends on age, smoking habit and tumour pathology. A group of MM patients with dysplastic naevi was also studied.

Adult↗

Possible changes in the regulatory mechanisms of pulsatile luteinizing hormone secretion in adult pituitary-grafted female rats.

It is well known that LH is released in an episodic fashion. However, the effects of hyperprolactinemia on luteinizing hormone (LH) pulsatility are not fully understood. The present study was undertaken to describe hyperprolactinemia effects on the regulatory mechanism of LH pulsatility. For this purpose hyperprolactinemia was induced in female rats by the transplantation of two pituitary glands beneath the kidney capsule. Age-matched sham-operated animals were used as controls. We have evaluated the pulsatile pattern of LH in both groups of animals. As expected, pituitary grafting increased mean serum prolactin levels compared with the values found in control animals. Luteinizing hormone-releasing hormone (LHRH) administration did not change serum prolactin levels in control or in pituitary-grafted rats. Thyrotropin-releasing hormone (TRH) administration increased prolactin secretion in both groups. There is an increase in mean values of LH and in the absolute amplitude of LH peaks in pituitary-grafted compared with control rats. No other parameters of LH pulsatility were changed by pituitary grafting. After LHRH administration, LH release was increased and a priming effect after the second administration of LHRH is observed in control rats. In pituitary-grafted animals the responses of LH to LHRH administration was diminished compared with the response observed in control rats. The administration of two pulses of TRH to control rats only decreases the duration of LH pulses. However, in pituitary-grafted animals, TRH administration was followed by a decrease in the mean values of LH and in the absolute amplitude of the LH peaks. Vasoactive intestinal peptide (VIP) administration increased mean values of LH and the absolute and relative amplitudes of LH pulses in sham-operated animals, whereas only the relative amplitude of LH peaks was modified by VIP in pituitary-grafted rats. All these data suggest that hyperprolactinemia induced by pituitary-grafting interfere with the neuromodulator effects on the pulsatile regulatory center of the hypothalamus.

Animals↗

Characterization of quinone reductase, glutathione and glutathione S-transferase in human myeloid cell lines: induction by 1,2-dithiole-3-thione and effects on hydroquinone-induced cytotoxicity.

In this study, we have characterized quinone reductase (QR), glutathione (GSH), glutathione S-transferase (GST) and their induction by a chemoprotector, 1,2-dithiole-3-thione (D3T), in the human myeloid cell lines ML-1 and HL-60. In addition, we also examined the toxicity of hydroquinone (HQ), a benzene metabolite, to these two cell lines. Both of the cell lines contain a basal level of cellular GSH, which is similar in the two cell lines. Although ML-1 cells contain much higher QR specific activity than HL-60 cells, which are relatively QR deficient, the GST specific activity of ML-1 cells is 1.8 times less than that of HL-60 cells. Immunoblot experiments showed that the GST in these two cell lines is GST pi. In addition, HL-60 cells exhibit 4.5 times more myeloperoxidase specific activity than ML-1 cells. Inclusion of D3T in the cultures could induce significant increases in cellular GSH content and QR activity, but not GST activity in either cell line. Treatment with HQ caused both inhibition of cell proliferation and loss of cell viability in these two myeloid cell lines. HQ treatment also resulted in a significant depletion of cellular GSH, which preceded the loss of cell viability. Pretreatment of both cell lines with buthionine sulfoximine, an inhibitor of GSH biosynthesis, markedly increased HQ-induced toxicity. In contrast, the presence of dicumarol, a QR inhibitor, failed to potentiate HQ-induced toxicity in ML-1 cells. On the other hand, pretreatment of these two myeloid cell lines with D3T significantly protected against HQ-induced inhibition of cell proliferation and cell death. Therefore, the above results suggest that GSH but not QR is an important factor involved in the toxicodynamics of HQ in these myeloid cells.

Antimetabolites, Antineoplastic↗

Acute ethanol administration in diestrus-2 in the rat on pulsatile prolactin and LH release.

Exposure to ethanol is followed by changes in reproductive function in man and animals, characterized by modifications in the secretion patterns of prolactin and luteinizing hormone (LH). As both hormones are secreted in an episodic fashion, the present work was undertaken to study the effects of acute ethanol administration on pulsatile prolactin and LH secretion patterns in adult female rats. Rats were previously cannulated to allow a continuous blood withdrawal to study the pulsatile patterns of prolactin and LH. The mean values of prolactin during the bleeding period and the absolute pulse amplitude of prolactin peaks were significantly increased by acute ethanol administration, whereas a significant decrease of relative pulse amplitude and frequency of this hormone was observed. On the other hand, ethanol administration increased the mean serum LH levels and the absolute and relative amplitudes of LH peaks. Ethanol treatment did not modify either frequency or duration of LH peaks. These data suggest that acute ethanol administration in adult female rats is followed by changes in the pulsatile prolactin and LH secretory patterns, which might be part of the mechanism to explain ethanol effects on the endocrine system.

Animals↗

Myeloperoxidase activity and whole blood chemiluminescence in bladder cancer--influence of smoking.

Polymorphonuclear leukocytes (PMNs) from 63 male bladder cancer patients do not differ from 65 cases of the control group in myeloperoxidase activity (MPO) nor in whole blood chemiluminescence response (CL). MPO activity increased in control smokers compared with the control nonsmokers (p < 0.05) and correlated significantly with cigarette consumption. CL response was also higher in control smokers (p < 0.05) than in control nonsmokers, and correlates significantly with the MPO activity. Both MPO and CL showed significant association with the increased number of peripheral blood PMNs. Although substantial evidence implicates oxygen free radicals, not only in chemical carcinogenesis, but also in the antitumor system (especially the myeloperoxidase system), we were unable to establish either an increase or a decrease in the axidant generating capacities in bladder cancer patients, although a trend towards a higher MPO and CL activity was observed in nonsmokers of this group. In conclusion, we found an enhanced oxidant-generating status of the smokers' PMNs, but its biological significance in carcinogenesis of the bladder remains to be established.

Adult↗

Cyclosporine modifies the pulsatile secretory patterns of prolactin and luteinizing hormone in normal and pituitary-grafted female rats.

This study was designed to examine whether cyclosporine (CyA) acts on the endocrine system by modifying the pulsatile secretion pattern of prolactin and LH. Both pituitary-grafted and sham-operated rats were submitted to a subcutaneous vehicle or CyA (5 mg/kg) treatment daily for 10 days beginning on the day of surgery. Pituitary grafting and/or CyA administration changed the pulsatile pattern of prolactin observed in sham-operated animals. The mean values of serum prolactin were significantly increased by pituitary grafting and the treatment with CyA further increased them. The mean half-life of prolactin was significantly increased in pituitary-grafted rats and was not changed by CyA administration, although it was decreased in sham-operated rats. The frequency of prolactin pulses was significantly decreased in pituitary-grafted as compared to sham-operated controls and was not further modified by CyA administration. However, in sham-operated rats a significant decrease of this parameter was observed. Duration of the prolactin peaks was significantly increased by pituitary grafting, and was not modified by CyA administration in any of the groups studied. The absolute amplitude of the prolactin peaks was significantly increased in pituitary-grafted as compared to sham-operated animals, and the treatment with CyA further increased this parameter in both groups. Mean values of LH were significantly increased in pituitary-grafted as compared to control rats. CyA administration significantly increased LH levels in sham-operated rats and decreased them in pituitary-grafted animals. The mean half-life, the pulse frequency and the duration of LH peaks were not modified by either pituitary grafting or CyA administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Physiological roles of thyrotrophin-releasing hormone and vasoactive intestinal peptide on the pulsatile secretory patterns of prolactin in pituitary-grafted female rats.

Much is known about the fact that thyrotrophin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) stimulate prolactin secretion but areas of uncertainty remain. This work was undertaken to describe the effects of TRH and VIP on the pulsatile secretion pattern of prolactin, in adult sham-operated and pituitary-grafted hyperprolactinaemic female rats. Two pulses of TRH (1 microgram/rat) or one pulse of VIP (20 micrograms/rat) were given 60 or 120 min after the period of blood sampling. Pituitary grafting increased the mean values of prolactin, absolute amplitude and duration of the peaks and decreased their frequency, compared with control animals. In sham-operated rats, TRH elevated prolactin levels by increasing the absolute and relative amplitudes and duration of the pulses, along with a decrease in their frequency. No priming effects of TRH were observed in this study. Hyperprolactinaemia blunted TRH effects on the pulsatile secretion pattern of prolactin. In sham-operated rats, VIP administration increased the absolute and relative amplitudes of the prolactin peaks. None of the other parameters studied were changed. In pituitary-grafted animals, VIP administration increased the absolute and relative amplitudes of the prolactin peaks but to a lesser extent compared with controls. These data suggest that TRH and VIP affect prolactin pulsatility differentially. The effects of TRH and VIP were blunted to some extent by exposure to previously elevated circulating prolactin levels.

Animals↗

Ovariectomy at different stages of the estrous cycle modifies the pulsatile secretory pattern of prolactin in rat.

The role of estrogens in the synchronization of pulsatile prolactin secretion throughout the estrous cycle in the adult female rat is studied. Mean values of prolactin, in sham-operated animals increased from diestrus-2 to proestrus and then decreased to the values found at diestrus-1. Ovariectomy did not modify the pattern which follows mean serum levels of the hormone throughout the estrous cycle; although increased values of prolactin were found at both proestrus and estrus, when compared to control animals. No changes in mean values of the hormone were observed at any other phase of the estrous cycle. The number of peaks was fairly constant in sham-operated rats in any phase of the estrous cycle, but a decrease in its number, after ovariectomy, was observed at proestrus and estrus. The absolute amplitude of the peaks increased numerically but not statistically significant from diestrus-2 to proestrus, then decreasing to diestrus-1 in control animals whereas an increase in the absolute amplitude of the prolactin peaks was detected in proestrus and estrous after ovariectomy. The duration of the prolactin peaks was not changed either by the phase of the estrous cycle or by ovariectomy. The relative amplitude of the prolactin peaks was only changed in rats ovariectomized at diestrus-1, as compared to sham-operated animals. All these data indicated that changes in estrogen/secretion by ovariectomy throughout the estrous cycle of the rat induced a differential effect on the pulsatile pattern of prolactin, being more marked in proestrus and estrus, associated with the highest circulating estrogen levels.

Animals↗

Opioids and the pulsatile prolactin secretory pattern: effects of hyperprolactinemia.

It is well known that opioids regulate prolactin secretion through unknown mechanisms. The present study describes the effects of morphine and naloxone administration on pulsatile prolactin secretion in adult sham-operated and pituitary-grafted female rats. Animals were rendered hyperprolactinemic by transplanting 2 pituitary glands beneath the kidney capsule. Naloxone (2 mg/kg/h), morphine (50 mg/kg/h)+naloxone or saline (0.5 ml/h) were administered i.v. through a jugular cannula and bled at 7-min intervals for a period of 3 h. Pituitary grafting increased mean serum prolactin levels, the absolute amplitude and the duration of the pulses, but decreased their frequency. Naloxone, in sham-operated rats, reduced mean serum prolactin levels, the absolute amplitude and the frequency of the pulses. However, morphine+naloxone administration increased mean serum prolactin levels and the absolute amplitudes of prolactin pulses in pituitary-grafted rats. Naloxone administration did not decrease previously increased mean serum levels of prolactin in pituitary-grafted rats. These results suggest that opioids synchronize the pulsatile pattern of prolactin and that these effects are blunted in pituitary-grafted animals.

Animals↗

Effects of naloxone on pulsatile luteinizing hormone in experimental hyperprolactinemia.

It is well known that opioids regulate luteinizing hormone (LH) secretion through not fully understood mechanisms. This study describes the effects of naloxone on the episodic release of LH in adult sham-operated and pituitary-grafted female rats. Animals were rendered hyperprolactinemic by transplanting 2 pituitary glands beneath the kidney capsule. Naloxone (2 mg/kg/h) or saline (0.5 ml/h) were administered iv through jugular cannulae and subjects were bled at 7 min intervals for a period of 3 h. As expected, pituitary-grafting was followed by an increase in mean values of prolactin during the bleeding period. Naloxone administration decreased mean serum prolactin levels in sham-operated rats and did not further change them in pituitary-grafted animals. Hyperprolactinemia was associated with increases in mean serum LH levels during the bleeding period and in the absolute amplitude of LH peaks. Naloxone administration increased mean values of LH and the absolute amplitude of LH peaks, and decreased their frequency in sham-operated rats. Neither pituitary grafting nor naloxone administration modified the frequency, duration or relative amplitude of LH peaks. However, naloxone administration reduced the mean half-life of LH in sham-operated rats to a similar extent than did pituitary grafting. Naloxone failed to further change the mean half-life of LH in pituitary-grafted rats. These results suggest that opioids modulate the pulsatile pattern of LH and that these effects are blunted in pituitary-grafted animals.

Analysis of Variance↗

Human glutathione S-transferase mu (GST mu) deficiency as a marker for the susceptibility to bladder and larynx cancer among smokers.

The isoenzyme mu of glutathione S-transferase (GST mu) is dominantly inherited and the prevalence of this isoenzyme in the population is about 60%. An increased risk of lung cancer has been previously shown among smokers lacking GST mu in (Seidegard J., Pero R.W., Miller D.G., Beattie E.J. (1986) Carcinogenesis, 7, 751-753). The frequency of the phenotypes of this isoenzyme in bladder cancer patients (n = 75), in larynx cancer patients (n = 78) and healthy controls matched for age and smoking history is reported here. A significantly higher proportion of smokers in the control group had measurable GST mu compared with bladder cancer patients (54.6% vs. 33.3%, P < 0.01) and also compared to larynx cancer patients (55.1% vs. 33.3%, P < 0.01). Odds ratio analysis indicates that smokers with this polymorphic variant have an approximately 2-fold greater risk of developing these cancers.

Adult↗

Enhanced glutathione S-transferase activity and glutathione content in human bladder cancer. Followup study: influence of smoking.

Glutathione content and glutathione S-transferase activity have been studied in human bladder specimens obtained from controls and from patients with superficial transitional cell carcinoma (tumor samples and peri-tumor normal tissues from the same patient). After combining an earlier study from our laboratory with the additional material presented (9 healthy controls and 25 transitional cell carcinoma patients), it can be observed that glutathione S-transferase activity was significantly greater in tumor than in peri-tumor normal tissue (34 patients, p < 1 x 10(-7)) or in normal mucosa (17 controls, p < 1 x 10(-3)). Glutathione content was significantly greater in tumor than in peri-tumor normal tissue (p < 5 x 10(-3)) or in normal mucosa (p < 2 x 10(-2)), with this increase being evident only in smokers. When comparing normal mucosa and peri-tumor samples no significant differences were found either for glutathione S-transferase activity or for glutathione content. Results demonstrate the relationship between the glutathione S-transferase/glutathione system and development of transitional cell carcinoma, as well as its role in cellular resistance to chemotherapy.

Aged↗

Pulsatile prolactin secretory patterns throughout the oestrous cycle in the rat.

Prolactin secretion throughout the oestrous cycle in the rat remains at a low level and fairly constant, with the exception of the surge at pro-oestrus. The present study was designed to characterize possible changes in pulsatile patterns of prolactin during the oestrous cycle of the adult female rat. Mean values of prolactin increased from dioestrus-2 to pro-oestrus and then decreased to the values found at dioestrus-1. The number of peaks remained fairly constant in any phase of the oestrous cycle. The absolute amplitude of the peaks increased numerically but was not statistically significant from dioestrus-2 to pro-oestrus then decreasing until dioestrus-1. No changes in the relative amplitude or duration of the peaks throughout the oestrous cycle were detected. The results indicated that there is a similar pulsatile pattern of prolactin at any stage of the oestrous cycle, when samples were obtained during the morning.

Animals↗