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Biomedical subjects

A Lafuente

Publications and source records attributed to A Lafuente.

70 records · Page 4Linked to original sources

Effects of hyperprolactinemia on prolactin and LH pulsatile pattern in female rats.

Prolactin (PRL) and luteinizing hormone (LH) secretions are very closely-related. To further understand these mechanisms, the pulsatile secretion pattern of both hormones in experimentally-induced hyperprolactinemia has been studied in adult female rats. Hyperprolactinemia was induced by the transplanting of two pituitary glands. Nine days after the transplant operation, rats were bled (75 or 100 microliters/7 min for 3 h). Serum samples were analyzed for prolactin and LH values by RIA. Hyperprolactinemia modifies pulsatile PRL secretion by increasing the absolute amplitude and duration of the peaks together with a decrease in their frequency. Also, the mean values of the hormone during the whole studied period were increased. Hyperprolactinemia was followed by an increase in the mean values of LH and in the absolute amplitude of the peaks. All these results suggest that hyperprolactinemia induced by pituitary grafting in adult female rats, is followed by a significant change in prolactin and LH pulsatility, which may explain, to some extent, the effects of hyperprolactinemia on reproduction.

Animals↗

[Cluster headache. A clinical study].

The personal experience with cluster headache in 108 patients is reported. Significant clinical findings included a clear male predominance, with a male/female prevalence ratio of 4.7/1, the persistent homolateral character of pain during the attacks, seen in 100% of cases, and the tendency to repeat the attacks on the same side (96%). The cluster headache predominated during spring and the painful crisis, in our experience, had a clear nocturnal predominance. Regarding the signs and symptoms accompanying pain, our series was similar to those in the international literature, except for a smaller prevalence of Horner's sign in our cases. The association with tenderness of the carotid territory ipsilateral to pain is reported here for the first time. The importance of a correct anamnesis of all parameters associated with pain is emphasized in the present study, as in many patients only a detailed investigation permits an adequate clinical definition.

Adult↗

Glutathione-S-transferase activity in human superficial transitional cell carcinoma of the bladder. Comparison with healthy controls.

Glutathione-S-transferase (GST) activity and glutathione (GSH) content have been studied in human urinary bladder (UB) specimens obtained from healthy controls (HC) (n = 8) and from patients with superficial transitional cell carcinoma (TCC) (n = 9), either in TCC and in adjacent normal (ANE) tissues of the same patient. The GST activity was significantly higher in TCC in comparison with ANE (ten fold) and with HC (five fold). This activity was also significantly higher in HC than in ANE (two fold). The Km values obtained in the whole population (1.26 +/- 0.3 X 10(-3) mol/l) suggest that a unique form of isoenzyme is present in the UB epithelium and that it is the same acidic form "rho" described in erythrocytes. The GSH content was significantly higher in TCC than in ANE (2.5 fold) and also that in HC (three fold). A good correlation between GST activity and GSH content was observed in HC but not in TCC or ANE. These results demonstrate the relation between the activity of the GST system and the development of the TCC as well as its role in the cellular resistance to chemotherapy. A possible decrease of the GST activity before the development of the tumor is also discussed.

Aged↗

[Effect of progesterone and estradiol on the regulation of pulsatile secretion of LH in the various phases of the estrous cycle of rats].

The normal changes on LH pulse amplitude and frequency throughout the estrous cycle and the specific role of Progesterone (P) and Estradiol (E) on pulsatile LH release have been determined in rats at the different stages of the estrous cycle. The effects on pulsatile LH release 24 h after ovariectomy (OVX), have been studied, as well as the way the normal values of the pulsatile release was re-established, when the physiological levels of P and/or E were restored by implantation of either P, E, or both Silastic capsules in OVX rats 24 h early. Our data during the rat estrous cycle, have confirmed that the lowest pulsatile LH release was on estrus, and the largest LH pulses were obtained on diestrus day 1, when the plasmatic levels of both P and E were lowest. Moreover, a variable ovarian steroid effect has been found at the different stages of the cycle. In estrus and diestrus day 2, both steroids were necessary to restore the normal values of the pulsatile LH release in OVX rats 24 h before, while in proestrus, the main steroid was Estradiol, although a non steroidal ovarian factor was also necessary to restore the normal pulse amplitude. Finally, in diestrus day 1 there was an absence of an ovarian steroid negative feedback on pulsatile LH release, because the levels of both steroids were too low in this stage, to exert a regulatory role on pulsatile LH release.

Animals↗

Inhibition of growth hormone and glucagon release by Phe-4-somatostatin in patients with acromegaly.

We have studied growth hormone (GH), insulin (I), glucagon (Gl) and glucose in basal conditions, after somatostatin (SS) (3 micrograms/ml) and Phe-4-SS (0.75 microgram/ml) infusion and IV bolus of the latter in 3 acromegalic patients. In two patients, Phe-4-SS inhibited glucagon and growth hormone secretion in a similar way as SS, without modifying insulin secretion. These effects were short-lived and ceased after the infusion was stopped. From these results it appears that Phe-4-SS is both more potent and more specific than SS with respect to inhibition of GH and glucagon release, but it does not have prolonged biological action. Lack of suppression of GH by SS or Phe-4-SS in the acromegalic patient with post-surgical recurrence of the disease could be due to the existence of receptor abnormalities, and suggests a diversity in the physiopathology of the disease.

Acromegaly↗

Enhanced glutathione S-transferase (GST) activity in pregnant rats treated with benzo(a)pyrene.

Administration of Benzo(a)pyrene (BP, 50 mg/kg/d) to pregnant rats significantly increased Glutathione S-transferase (GST) activity in placental tissue-extract (Vmax = 40 nmol/min/mg protein and 69 nmol/min/mg protein in controls versus treated animals respectively; P less than 0.01) and total fetal tissue-extract (Vmax = 51 nmol/min/mg protein and 82 nmol/min/mg protein in controls versus treated animals respectively; P less than 0.01) indicating an induction effect of BP on the GST system. An increase in the Km values was also observed: 1.61 x 10(-3) M and 2.84 x 10(-3) M in control versus treated placentae; 1.38 x 10(-3) M and 2.05 x 10(-3) M in control versus treated fetuses. A competitive effect on the enzyme by the BP present in the sample may also be involved. The glutathione content in both tissues did not show any changes after the treatment with BP. This increase in the GST system was not sufficient to protect the fetus. BP affected the reproductive performance of pregnant rats by significantly increasing the number of resorptions and fetal wastage, and, also, by decreasing the fetal weight.

Animals↗

The use erythrocyte glutathione as a predictive marker for malignant melanoma.

BACKGROUND: Glutathione (GSH) may provide defense against reactive oxygen species (ROS) generated by ultraviolet radiation. Furthermore, some authors have demonstrated a relationship between the GSH of peripheral blood erythrocytes (GSHe) and resistance to chemotherapy. PATIENTS & METHODS: To observe the influence of GSH on the genesis and evolution of Malignant Melanoma (MM), we assessed the concentration of GSH in erythrocytes (GSHe) in MM patients (n = 566) and controls (n = 164) by the method of Beutler (1963). RESULTS: No differences were found between the two groups (5.94 +/- 1.61 cases vs 6.08 +/- 1.49 mmol/gr Hb, controls; p > 0.05). Fifty seven patients with poor evolution (disease-free survival < 2 years) had higher GSH levels than the remaining patients (6.35 +/- 1.83 vs 5.83 +/- 1.62 mmol/g Hb; p < 0.01). GSHe increased significantly after antineoplastic therapy (4.75 +/- 1.26 vs 7.73 +/- 1.39 mmoVg Hb; p < 0.001), thus indicating a possible role in chemoresistance. 2 CONCLUSIONS: GSHe is not related to the risk of developing MM. GSHe may be related to the evolution of MM, being higher in patients who suffer relapse or metastasis. GSHe increases significantly during cytostatic treatment.

Antineoplastic Agents↗

Glutathione S-transferase (GSTM1 and GSTT1)-dependent risk for colorectal cancer.

BACKGROUND: The deleted GSTT1 and GSTM1 genotypes (null genotypes) resulting in loss of transferase activity are found in 10-20% and 50-60% of the population, respectively. PATIENTS AND METHODS: The GSTT1- and GSTM1-dependent risk for sporadic colorectal cancer (CRC) was studied in 247 incident CRC cases and 296 hospital-based controls. RESULTS: The GSTT1-null genotype was found to be 1.5 times more prevalent in CRC patients (17.4%) compared with controls (11.1%) (crude OR 1.6; p = 0.03). The GSTM1-null genotype was found to be equally prevalent in cases and controls (53%). Multivariate analysis showed a significant 1.7-fold risk for CRC associated with the GSTT1-null genotypes (p = 0.04) and this increased to 2.9 for smokers (p = 0.02). CONCLUSION: This study provides evidence of gene-environment interaction and illustrates the importance of further research into the role of genetic susceptibility for CRC.

Aged↗

Glutathione and glutathione S-transferases in human squamous cell carcinomas of the larynx and GSTM1 dependent risk.

BACKGROUND: The aim of the present study was to establish the risk of squamous cell carcinoma (SCC) of the larynx associated with the congenital absence of glutathione S-transferase M1 (GSTM1), and to describe the expression of the isoenzymes GSTA1/2, GSTP1-1, and GSTM1 and glutathione (GSH) content in healthy and tumoral larynx tissue. MATERIAL AND METHODS: Blood samples from 160 SCC male patients and 158 controls were phenotyped for GSTM1 by ELISA. Using 37 paired samples (normal and tumour specimens) from cancer patients we carried out a descriptive study of enzyme activity by ELISA (GSTs) and Ellman's as say (GSH) RESULTS: GSTM1 null phenotype was more common in the SCC group than in controls (OR 1.9, CIs 1.18-3.05, p = 0.004). Total GST activity was higher in tumour samples than in matched healthy tissue (2.2-fold, p-0.00001), being largely determined by GSTP1-1 (1.9-fold increased in malignant tissue; p = 0.0003). The GSH content was also significantly higher in SCC than in normal mucosa (1.9-fold, p = 0.0007). CONCLUSIONS: We confirmed the GSTM1-dependent risk for larynx cancer among smokers. The overexpression of the GST/GSH system in tumours reported here indicates their possible role in chemoresistance to pharmacological therapy.

Carcinoma, Squamous Cell↗

Limitations in the use of glutathione S-transferase P1 in urine as a marker for bladder cancer.

BACKGROUND: GST pi (GSTPl) is overexpressed in bladder cancer and desquamation of the tumour may produce detectable levels of urinary GSTPl which could be used as a marker for the early diagnosis of bladder cancer. MATERIALS AND METHODS: A preliminary study in 27 transitional cell carcinoma (TCC) patients and 20 controls, using an ELISA methodl is presented here. RESULTS: 55.5% of TCC patients were positive for GSTP1, while all control samples were negative. Some of the GSTP1 positive cases also gave positive results for haematuria, which indicates that a limitation of this marker involves the contamination of the urine with erythocyte GSTP1. In 5 cases (18.5%) without haematuria detectable levels of GST pi were found. CONCLUSIONS: Further studies would be required to assess the advantages of this technique over clas sical cytology or as a complement to it, especially in patients in a phase of temporary negative haematuria.

Aged↗