Zinc reduces collagen degradation in demineralized human dentin explants.

OBJECTIVES: Dentin matrix metalloproteinases are implicated in the pathogenesis of caries and contribute to collagen degradation in resin-dentin interfaces. The objective was to determine if collagen degradation may be modulated by an excess of zinc or zinc chelators. METHODS: Mineralized and phosphoric acid demineralized human dentin specimens were tested. Chlorhexidine digluconate, doxycycline or ZnCl2 were added to the media. In half of the groups, active exogenous metalloproteinase-2 was incorporated into the solution. C-terminal telopeptide determinations (radioimmunoassay) were performed after 24 h, 1 and 3 weeks. RESULTS: Collagen degradation was prominent in demineralized dentin. Doxycycline fully blocked dentin proteolysis. Chlorhexidine digluconate reduced the degradation at the 24-h period. Zinc in excess strongly inhibits hydrolysis of collagen and its effect was maintained for 3 weeks. CONCLUSIONS: Zinc in excess reduces MMP-mediated collagen degradation. The hypothesis that binding of zinc to collagen results in protection of sensitive cleavage sites of metalloproteinases requires further validation.

Effects of raloxifene therapy on circulating osteoprotegerin and RANK ligand levels in post-menopausal osteoporosis.

Previous in vitro studies suggest that the anti-resorptive effect of raloxifene might be mediated by changes in several cytokines involved in the bone remodeling process. In this context, the osteoprotegerin (OPG)- receptor activator of NF kappa B ligand (RANKL) system is considered a key component in the osteoclastogenesis regulation. The aim of this study was to determine the effects of raloxifene treatment on serum concentrations of OPG, receptor RANKL and its relationship with biochemical markers of bone turnover and bone mineral density (BMD) in previously untreated women with post-menopausal osteoporosis. We selected 47 post-menopausal women (mean age 63+/-7 yr) with densitometric criteria of osteoporosis. We determined at baseline, 3, 6, and 12 months anthropometric parameters, biochemical markers of bone turnover, serum levels of 25(OH) D, serum levels of OPG and RANKL. BMD (dual-energy x-ray absorptiometry) in lumbar spine (LS) femoral neck and total hip was measured at baseline and 12 months after raloxifene (60 mg/day) treatment. Serum levels of OPG decreased in the 3rd and 6th month of treatment (p<0.001) and returned to basal levels in the 12th month. There was a significant decrease of RANKL levels and OPG/RANKL ratio after 1 yr of raloxifene treatment. In addition, BMD in LS increased significantly (2.5%) in the 12th month of treatment (p=0.031). Finally, the biochemical markers of bone turnover (total alkaline phosphatase, bone alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine cross-linked carboxi-terminal telopeptide of type I collagen) decreased significantly from the 3rd month of treatment. In conclusion, our results support the hypothesis that raloxifene may inhibit osteoclast activity, at least partly modulating the OPG-RANKL system.

[Plasma concentrations of beta-endorphins in the children of alcoholic patients]. / Niveles de beta-endorfinas en hijos de padres alcohólicos.

BACKGROUND: Of the factors identified in different studies as the possible causes of alcoholism, heredity appears to be the most important. However, environmental factors can increase or decrease the risk of an individual developing alcohol dependence. METHOD: To clarify the possible influence of heredity on alcoholism, we studied the plasma concentration of beta-endorphins in 25 families with alcoholic members: 27 children whose father was alcoholic and 7 whose father and mother were both alcoholics. The results were compared with finding in an age-matched control group of no-drinking adults and normal children in non-drinking families. RESULTS: The children of alcoholic parents had significantly lower beta-endorphin levels (p < 0.001) than control individuals, and concentrations were especially low when both parents were alcoholics. CONCLUSION: We conclude that plasma beta-endorphin concentration may have predictive value in identifying persons likely to become alcoholics.

Niveles de beta-endorfinas en hijos de padres alcohólicos / Plasma concentrations of beta-endorphins in the children of alcoholic parents

Introducción: En los últimos años son numerosos los trabajos acerca de las posibles causas del alcoholismo, donde parece intervenir varios factores, siendo la herencia uno de los más implicados, aunque se han destacado otros, como factores ambientales, que contribuirían a aumentar o disminuir el riesgo individual para desarrollar una dependencia alcohólica. Método: Para intentar aclarar la posible influencia de la herencia en el alcoholismo, hemos estudiado los niveles de beta-endorfinas (β-E) en 25 familias de alcohólicos, en las cuales había 27 hijos con un padre alcohólico y 7 hijos con los dos, así como en dichos padres alcohólicos, y comparado los resultados con unos grupos control: uno de adultos no bebedores y otro de niños normales en familias de no-bebedores, con edades similares. Resultados: Se ha encontrado que los hijos de alcohólicos tienen unos niveles de Beta-E significativamente más bajos (p < 0,001) que los controles, y estos niveles eran aún más bajos en los hijos cuyos dos padres eran alcohólicos. Conclusión: Se concluye que la determinación de β-E podía tener un valor predictivo a la hora de determinar quién es más propenso a ser alcohólico en el futuro

Background: Of the factors identified in different studies as the possible causes of alcoholism, heredity appears to be the most important. However, environmental factors can increase or decrease the risk of an individual developing alcohol dependence. Method: To clarify the possible influence of heredity on alcoholism, we studied the plasma concentration of beta-endorphins in 25 families with alcoholic members: 27 children whose father was alcoholic and 7 whose father and mother were both alcoholics. The results were compared with finding in an age-matched control group of no-drinking adults and normal children in non-drinking families. Results: The children of alcoholic parents had significantly lower beta-endorphin levels (p < 0.001) than control individuals, and concentrations were especially low when both parents were alcoholics. Conclusion: We conclude that plasma beta-endorphin concentration may have predictive value in identifying persons likely to become alcoholics

Plasma concentrations of beta-endorphin in smokers who consume different numbers of cigarettes per day.

The harmful effects of smoking on health have been widely documented, although it is as yet unclear whether tobacco dependence is only psychological in nature, or both psychological and physical. We studied plasma concentrations of beta-endorphin, cortisol, and adrenocorticotropic hormone (ACTH) in healthy persons who consumed different numbers of cigarettes per day, and compared the findings with those in a control group of nonsmokers. Beta-endorphin levels were significantly higher than in controls only in persons who smoked fewer than 10 cigarettes per day. Cortisol levels were significantly higher in smokers who consumed more than 20 cigarettes per day. There were no significant differences between any of the groups in plasma ACTH concentrations.

Plasma concentrations of beta-endorphin, adrenocorticotropic hormone, and cortisol in drinking and abstinent chronic alcoholics.

Previous studies of the relationship between the endogenous opioid system and alcohol consumption have reported contradictory results. To shed light on this connection, we compared plasma concentrations of beta-endorphin, adrenocorticotropic hormone, and cortisol in 70 alcoholic persons after different periods of abstinence and a group of 80 control subjects. Plasma beta-endorphin was decreased in alcoholics (18.61 +/- 1.38 vs. 39.31 +/- 3.44 pg/ml), even after more than 10 years' abstinence. This effect may mediated by the tetrahydroisoquinoline system, and may thus result from chronic alcohol consumption. On the other hand, lowered circulating concentrations of beta-endorphin may be a cause, rather than an effect, of alcoholism. Plasma levels of adrenocorticotropic hormone and cortisol did not differ in alcoholics and controls (19.29 +/- 1.66 vs. 13.27 +/- 1.85 pg/ml for ACTH, 20.37 +/- 0.78 vs. 17.22 +/- 0.64 ng/ml for cortisol), and thus appear to have no relation with chronic alcohol consumption.

Effect of acute alcohol intoxication on the opioid system in humans.

We investigated the possible relations between the endogenous opioid system and acute alcoholic intoxication in 21 subjects, of whom 13 were drinkers who came to the emergency service with evident symptoms of drunkenness, and 8 were nondrinkers who consumed 1 g alcohol per kg body weight over a short period. Different patterns of changes were found in the two groups for plasma concentrations of beta-endorphin and adrenocorticotropic hormone. In drinkers, plasma levels of both substances increased, whereas in nondrinkers both concentrations decreased, the declines being especially notable 15, 30, and 45 min after ingestion. We found no differences between the two groups in plasma cortisol concentrations. The different levels of these substances may reflect differences in drinking behavior between the two groups.

Hyperinsulinemia in polycystic ovary syndrome: relationship to clinical and hormonal factors.

We analyzed the association between hyperandrogenism and hyperinsulinemia, and their relationship to body mass index, in a large series of patients with polycystic ovary syndrome (PCOS). A characteristic hormonal profile was sought in women with marked hyperinsulinemia. The patient group consisted of 73 women with PCOS, ranging in age from 16 to 29 years. The control group consisted of 34 healthy women with no evidence of hyperandrogenism, aged 19-30 years. None of the patients or control women had a body mass index above 27 kg/m2. Follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, androstenedione, dehydroepiandrosterone sulfate, sex hormone binding globulin, 17-hydroxyprogesterone, and free cortisol were determined by radioimmunoassay. The free testosterone index was calculated. The oral glucose tolerance test was used to analyze basal insulinemia, maximum insulin peak, and the insulinemia/glycemia index. In the group with PCOS body mass index was greater, free testosterone index was higher, and levels of dehydroepiandrosterone sulfate, testosterone, 17-hydroxyprogesterone (P < 0.001) and androstenedione (P < 0.05) were higher than in the control group. Of the insulin parameters, basal insulinemia, maximum insulin peak, and insulinemia/glycemia index were higher in the patient group (P < 0.001). In patients with marked insulinemia, free testosterone index was more markedly elevated, and gonadotrophin levels were normal. Our data confirm that a characteristic pattern of hyperinsulinemia is associated with PCOS. We found no causal relationship between hyperinsulinemia and androgen levels. A characteristic hormonal pattern was found in patients with marked hyperinsulinemia.

Reduction of endogenous, ovarian and adrenal androgens with ketoconazole does not alter insulin response in the polycystic ovary syndrome.

Several different strategies were used to investigate the relationship between hyperandrogenism and hyperinsulinemia associated with polycystic ovary syndrome. Ketoconazole was given orally (400 mg/day) for 9 months to evaluate the effect of reduction in ovarian and adrenal androgens on insulin response (oral glucose tolerance test) in 35 women with polycystic ovary syndrome. Androgenic steroids (testosterone, androstenedione, dehydroepiandrosterone sulphate, and free testosterone index) decreased (p < 0.01), but basal insulinemia, maximum peak insulin, and insulin/glucose ratio showed no significant changes. One month after treatment was stopped, free testosterone index, and serum concentrations of androstenedione and testosterone, increased (p < 0.05), but no alterations were noted in insulin parameters. Body mass index was stable throughout the ten-month study period. Our findings suggest that endogenous androgens, no matter whether they are of ovarian or adrenal origin, do not play a major role in the modulation of hyperinsulinemia in patients with polycystic ovary syndrome.

Ketoconazole therapy: hormonal and clinical effects in non-tumoral hyperandrogenism.

The aim of this study was to assess the usefulness of ketoconazole as a therapeutic alternative to polycystic ovary syndrome. The study group comprised 37 women with signs of hyperandrogenism (hirsutism, acne) and oligomenorrhea. A low dose (400 mg/day) of ketoconazole was tested in a 9-month prospective clinical study. Clinical response (Ferriman & Gallway score, acne) and modifications in hormone pattern (luteinizing hormone, follicle-stimulating hormone, estradiol, testosterone, prolactin, 17-hydroxy-progesterone, androstenedione, steroid hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, adrenocorticotropin (ACTH) and free testesterone index) were measured, and ACTH stimulation tests were performed. Tolerance and side-effect also were assessed. After 9 months of ketoconazole treatment, the patients' Ferriman & Gallway scores (18.26 +/- 4.6 vs 12.4 +/- 4.1; p < 0.001) and acne had improved markedly. Hormone patterns also became more favorable, with decreases in androgenic steroids (testosterone, androstenedione, free testosterone index and dehydroepiandrosterone sulfate; p < 0.01) and increases in estradiol (p < 0.01). Basal cortisol levels and cortisol after ACTH stimulation were not changed significantly, remaining within the reference range. Increases in ACTH were observed only in the 3rd month (p < 0.01). Initial levels of androgenic steroids were correlated inversely with their percentage decrease in successive samplings. Decreases in adrenal androgenic steroids were associated with an increase in steroid hormone-binding globulin. The side-effects of treatment, although not severe, caused some discomfort and led to a high drop-out rate (30%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Lipid profile of hyperandrogenic women undergoing treatment with ketoconazole and its relationship with the evolution of the hormone pattern]. / Perfil lipídico de la paciente hiperandrogénica en tratamiento con ketoconazol y su relación con la evolución del patrón hormonal.

BACKGROUND: Previous studies have demonstrated changes in the lipidic profile following treatment with ketoconazole. However, the possible influence in patients with hyperandrogenism treated with this drug and its possible relation with the evolution of the hormonal pattern is unknown. RESULTS: Thirty-seven women with no tumoral hyperandrogenism treated with ketoconazole for 9 months (400 mg/day) were studied during treatment and one month after suppression of the medication. The study included the evaluation of total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol and hormonal determinations of estradiol, androstenedione, testosterone, dehydroepiandrosterone, sulphate and sex hormone binding globulin. RESULTS: A rapid and significant decrease of LDL cholesterol and total cholesterol was observed (p < 0.01) which was reversible upon discontinuation of treatment. The HDL cholesterol levels and triglycerides did not modify. The final hormonal profile was more favorable with a significant reduction of testosterone and dehydroepiandrosterone sulphate (p < 0.01) and an increase in estradiol (p < 0.01). No statistical correlation was observed between the changes of sexual steroids and the changes in the lipidic pattern. CONCLUSIONS: In patients with non tumoral hyperandrogenism treated with ketoconazole the modifications of the steroid hormone profile do not appear to be related with changes in lipidic metabolism.

Dehydroepiandrosterone sulfate and other possible influencing factors that modulate sex hormone-binding globulin levels in the hirsute patient.

This study was designed to investigate the most important factors affecting serum concentrations of sex hormone-binding globulin (SHBG) in women with hirsutism. We compared endocrine profiles based on biochemical measurements of LH, FSH, oestradiol, testosterone (T), prolactin, 17-hydroxy-progesterone, dehydroepiandrosterone sulphate (DHEAS), SHBG, cortisol and insulin in the follicular phase in 32 healthy women and 52 patients. The study group was subdivided according to SHBG levels into Group A (low level) and Group B (high level). Significant differences between Groups A and B were found in DHEAS and T levels, but not in body mass index or insulinaemia. There was a relationship between DHEAS and SHBG levels (r = 0.51) and between T and SHBG (r = 0.31). We conclude that DHEAS may be a significant modulator of SHBG in the female hirsute patient, an observation seldom mentioned in previous reports.

Effects of growth hormone in patients receiving total parenteral nutrition following major gastrointestinal surgery.

The purpose of the present study was to determine whether the administration of a biosynthetic human growth hormone was capable of enhancing the efficacy of total parenteral nutrition. Patients (n = 38) who had undergone major gastrointestinal surgery were randomly divided into two groups. Group I (n = 20) treated only with PN, and Group II (n = 18) treated as in Group I plus human growth hormone (4 IU daily). Our study shows that the administration of human growth hormone produces a statistically significant increase in serum levels of growth hormone, somatomedin-C, transferrin, albumin and total proteins. It also causes a positive nitrogen balance from the first 24 hours onward. These findings suggest that the administration of human growth hormone produces an increase in protein synthesis, perhaps through somatomedin-C as mediator.

[Dehydroepiandrosterone sulfate and lipids in acute myocardial infarct]. / Dehidroepiandrosterona-sulfato y lípidos en el infarto agudo de miocardio.

To establish the possible relationship between acute myocardial infarction (AMI) and dehydroepiandrosterone-sulfate (DHEA-S) in a group of 15 patients with AMI, blood levels of DHEA-S and certain lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides) were determined at admission in the hospital and after 10 days. As controls a group of healthy individuals or with minor diseases, and a group of 24 severely ill non-cardioischaemic patients have been studied. DHEA-S and HDL-cholesterol levels have been found significantly lowered both in patients with AMI (at 10th day) as well as in the severely ill non-cardioischaemic patients, in comparison with the healthy volunteers group. We conclude, then, than the lowering in DHEA-S and HDL-cholesterol seems not to be specifically relates with AMI but has a certain relationship with severe disorders in general.

[Derivatives of pro-opiomelanocortin (ACTH and beta-endorphin) in chronic alcoholics]. / Derivados de la pro-opiomelanocortina (ACTH y beta-endorfina) en alcohólicos crónicos.

The plasmatic concentration of beta-endorphins and ACTH were measured in 31 alcoholic patients and in a control group (N = 16), to test the possible relation between chronic alcohol intake and propiomelanocortin production. There were found a decrease of beta-endorphins plasmatic levels in chronic alcoholic group, apart of clinical manifestations or abstinence period (one month maximum). This decrease can be cause by the chronic alcohol intake, and can be mediated by the tetrahydroisoquinolines (TIQs) or otherwise be the cause and not the consequence of alcoholism. The global plasmatic levels of ACTH were decreased but it was significant in the subgroup of alcoholics with liver disfunction, mental illness and those who carry on drinking.

[Dehydroepiandrosterone sulfate, cortisol and their precursors in severely ill (acute and chronic) patients]. / Dehidroepiandrosterona-sulfato, cortisol y sus precursores en enfermos graves (agudos y crónicos).

This study tries to evaluate the interrelationship amongst certain corticoadrenal hormones (Dehydroepiandrosterones-Sulphate (DHEA-S), progesterone, 17-OH progesterone and cortisol) in male patients with severe organic processes (24 chronic and 22 acutely ill) and comparing them with a control group of 15 healthy male subjects or suffering mild processes. Corticoadrenal hormone behaviour in the presence of a severe disease show marked differences between the androgenic and the glucocorticoid pathways. While DHE-S shows a significant decrease in severe disease, independently of the underlying disease (acute or chronic), the contrary occurs with the glucocorticoid pathway, in which cortisol and specially its precursors, progesterone and 17-OH-progesterone, predominantly present in the acute situation, normal or significantly increased levels. These differences between the two adrenal pathways suggest that apart from ACTH there must be another regulatory mechanism of the androgenic pathway which may facilitate the androgenic adaptation to the situation of severe disease.

Plasma beta-endorphin levels in chronic alcoholics.

In order to test the possible relationship between the chronic consumption of alcohol and the opioid system, we have measured the plasma levels of beta-endorphin in a group of 31 alcoholic patients and compared the results with those of a control group of 16 subjects. Our results show that chronic consumption of alcohol induces a significant decrease in beta-endorphin (beta-end) plasma levels regardless of either the disease suffered by the alcoholic patient or of the time of abstinence studied (one month maximum). Thus we believe that the beta-end decrease may well be due to the patients' alcoholism and that it might be mediated by the tetrahydroisoquinoline system, or be a cause of alcoholism rather than a consequence.

[Beta-endorphin in acute focal cerebral infarct]. / Betaendorfina en el infarto cerebral focal agudo.

Experimental studies in animal models suggest that the endorphin system may be implicated in the pathogenetic mechanism of cerebral ischemic lesions. Naloxone has been shown to possess a beneficial effect on the neurologic deficit associated with cerebral ischemia in animal experiments, probably because of its endorphin antagonist properties. By contrast, the results of clinical trials are contradictory. Moreover, the true significance of high plasma levels of beta-endorphin in patients with acute focal cerebral infarct (AFCI) has not yet been elucidated. We have evaluated 23 patients with established AFCI, in whom plasma levels of beta-endorphin and corticotropin (ACTH) were simultaneously measured during the first 48 hours after the onset of the disease. The results were compared with those from a control group. In a subgroup of 9 cases new measurements were made after 7 days. In the patients with AFCI, significantly lower levels of beta-endorphin and ACTH than in the control group were found. One week later, a moderate nonsignificant increase in the plasma level of beta-endorphin was found. The localization and estimated size of the infarct area were not relevant. Probably, the plasma levels of beta-endorphin will need to be considered before naloxone therapy is indicated, and only if it is confirmed that the plasma levels of beta-endorphin reflect changes at the cerebral level, as the pathophysiological role of these opioids in AFCI has not yet been established.

Measurement of parathyrin in blood from thyroid veins: two radioimmunoassays compared in patients with primary hyperparathyroidism.

We measured parathyrin (PTH) in peripheral venous blood samples and in thyroid veins (both homolateral and contralateral to the lesion) in 13 patients with surgically confirmed parathyroid adenomas. Two different RIAs were used, one specific to the mid-region of the molecule (44-68, M-PTH), the other specific to the carboxy-terminal region (65-84, C-PTH). With the M-PTH assay we established a statistically significant multiple correlation (P less than 0.05) between the PTH concentrations in blood from the peripheral and thyroid veins; no significant correlation was found when we used the C-PTH assay. Our results confirm the superiority of the M-PTH RIA over the C-PTH RIA for study of hormonal secretion in primary hyperparathyroidism.