Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine.

Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting ß-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.

A link between bone mineral density and serum adiponectin and visfatin levels in acromegaly.

CONTEXT: Two adipokines highly expressed in fat mass, adiponectin with antiinflammatory and antiatherogenic properties and visfatin with an insulin-mimetic effect, are potential contributors to bone metabolism. In acromegaly, data on adiponectin are contradictory, and there are no data on visfatin. OBJECTIVES: The aim of the study was to evaluate adiponectin and visfatin in acromegaly, compared to control subjects, and to analyze their relationship with body composition and bone markers. METHODS: Bone markers [osteocalcin, total amino-terminal propeptide of type 1 procollagen (total P1NP), carboxy-terminal telopeptide (beta-Crosslaps)], body composition (by dual-energy x-ray absorptiometry), adiponectin (by ELISA), and visfatin (by immunoanalysis)] were evaluated in 60 acromegalic patients (24 males and 36 females) and in 105 age- and gender-matched healthy controls (33 males and 72 females). Acromegalic patients were classified as controlled, with normal IGF-I and nadir GH no greater than 1 microg/liter (n = 41), or active (n = 19). RESULTS: Acromegalic patients had lower adiponectin (P < 0.01), more lean body mass (P < 0.01), more total body mass (P < 0.01), higher bone formation markers (osteocalcin and total P1NP, P < 0.05 and P < 0.01, respectively), but less bone resorption markers (beta-Crosslaps, P < 0.001) than controls. No differences in visfatin and BMD were found between patients and controls. Adiponectin correlated negatively with BMD (r = -0.374; P < 0.05) and lean mass (r = -0.301; P < 0.05) and positively with age (r = 0.341; P < 0.001) in acromegaly. Visfatin correlated negatively with BMD (r = -0.359; P < 0.05). BMD was the predictor for adiponectin and visfatin. CONCLUSIONS: Acromegalic patients present hypoadiponectinemia and a favorable bone marker profile. Adiponectin and visfatin could be a link between fat mass and bone in acromegaly.

Deleterious effects of glucocorticoid replacement on bone in women after long-term remission of Cushing's syndrome.

Endogenous hypercortisolism and high-dose and long-term glucocorticoid (GC) therapy reduce bone mass. Patients in remission after successful treatment of Cushing's syndrome (CS) often present hypoadrenalism and require long-term GC replacement. The aim of our study was to evaluate whether this GC "replacement" had any further effect on bone in women after long-term remission of CS. Thirty-seven women (mean age: 50 +/- 14 yr; 27 of pituitary and 10 of adrenal origin) with cured CS (mean time of cure: 11 +/- 6 yr), 14 with active CS, and 85 sex-, body mass index (BMI)-, and age-matched controls were enrolled. BMD and BMC were measured by DXA scanning. Bone biochemical markers were also measured. Duration and dose of GC replacement and duration of endogenous hypercortisolism were calculated. Cured and active CS patients had less BMC, BMD, and osteocalcin than controls (p < 0.01). These differences were observed in estrogen-sufficient women but not in those with estrogen deficiency. Duration of GC treatment (mean: 42 mo; range, 2-420 mo) and endogenous hypercortisolism (mean: 70 mo; range, 13-241 mo) negatively correlated with BMC and lumbar spine BMD. After regression analysis, the main predictor of abnormal BMC and BMD was the duration of GC replacement (p < 0.01). Patients treated for CS persistently have less bone mass despite long-term cure. Both duration of endogenous hypercortisolism and mainly exogenous "replacement" therapy with GC negatively affect bone mass. Thus, the additional deleterious effect of GC for the treatment of adrenal axis suppression should be considered.

¿Es necesario modificar el límite superior de los valores de referencia de la tirotropina? / Should the upper reference limit of thyrotropin be changed?

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Hipotiroidismo central y dislipemia mixta secundarios a tratamiento con bexaroteno / Bexarotene-induced central hypothyroidism and mixed dyslipidemia

El bexaroteno es un análogo de retinoide sintético caracterizado por unirse selectivamente a un tipo de receptores retinoides (receptores X) que fue diseñado para el tratamiento, entre otros, de estadios avanzados de linfoma cutáneo de células T resistentes a tratamientos convencionales. Se ha descrito que hasta el 40% de los pacientes que reciben bexaroteno pueden desarrollar hipotiroidismo secundario y hasta el 70%, hiperlipemia mixta grave, efecto común a otros retinoides. Presentamos a 3 pacientes que desarrollaron hipotiroidismo central y dislipemia tras el inicio de tratamiento con bexaroteno; en uno de ellos pudimos observar que estas alteraciones remitían tras la supresión del tratamiento (AU)

Bexarotene is a synthetic retinoid analogue that joints selectively to retinoid X receptor and has been designed for treatment of advanced stages of cutaneous T- cell lymphoma. Up to a 40% of patients treated with bexarotene develop central hypothyroidism while severe mixed dyslipidemia may be present in up to 70%. We report 3 patients that developed central hypothyroidism and dyslipidemia after bexarotene treatment was initiated. In one of them, we observed normalization of the thyroid function when bexarotene treatment was stopped (AU)

Effects of bariatric surgery on vitamin D status and secondary hyperparathyroidism: a prospective study.

BACKGROUND: Morbidly obese patients have been reported to present with vitamin D insufficiency and secondary hyperparathyroidism. Scattered data are available regarding the effects of bariatric surgery on vitamin D status. We studied calcium metabolism and vitamin D status before and after bariatric surgery. METHODS: In this prospective study, 64 patients (M5/F59) fulfilled the inclusion criteria (i.e. 2 calcidiol serum determinations in the winter season) among 457 morbidly obese individuals who underwent Roux-en-Y gastric bypass (RYGBP) a mean of 36 months previously. Laboratory data (serum calcium, phosphorus, creatinine, alkaline phosphatase, albumin, calcidiol, albumin and iPTH) were determined before and after RYGBP. Pre- and postoperative calcidiol levels were categorized as being normal (>50 nmol/L), insufficient (25-50 nmol/L), and deficient (<25 nmol/L). Pre- and postoperative mild secondary hyperparathyroidism was defined as iPTH >7.3 pmol/L with simultaneous normal values for creatinine, calcium and phosphorus. RESULTS: RYGBP produced a significant weight loss coupled with a simultaneous increase in calcidiol (+28%, P<0.0005) and decrements in total alkaline phosphatase (-53%, P<0.0005) and iPTH (-74%, P=0.001). Corrected serum calcium, phosphorus, and creatinine levels were indistinguishable before and after RYGBP. Additionally, 37.5% of the patients maintained their calcidiol category, while 42.2 % improved it and 20.3% lost one category. CONCLUSIONS: RYGBP does not completely correct pre-existing vitamin D deficient states with secondary hyperparathyroidism. Low calcidiol bioavailability and or insufficient sunlight exposure do probably persist after bariatric surgery. While randomized controlled studies are warranted, it seems advisable to support vitamin D supplementation as well as increasing sunlight exposure in the morbidly obese population.

El laboratorio clínico: uso y abuso, modelos de gestión y gasto sanitario / Clinical laboratory: use and misuse, management models and health expenditure

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Metabolic syndrome at follow-up in women with and without gestational diabetes mellitus in index pregnancy.

We prospectively studied 262 women with prior gestational diabetes mellitus (GDM) and 66 control women to compare their prevalence of metabolic syndrome and its relationship with insulin secretion and sensitivity. A 75-g oral glucose tolerance test was scheduled 5 years after delivery along with lipid profile, anthropometrics, and blood pressure measurement. Metabolic syndrome was defined according to the National Cholesterol Education Program 2001, and insulin sensitivity and secretion were estimated with the homeostasis model assessment. Women with prior GDM had similar insulin sensitivity and lower insulin secretion than control women. In comparison with control women, women with prior GDM had higher blood pressure, waist circumference, very low-density lipoprotein cholesterol, and oral glucose tolerance test blood glucose values but, with the exception of fasting hyperglycemia, did not have an increased prevalence of metabolic syndrome or its components. The multivariate prediction of metabolic syndrome and its components was similar with age and current homeostasis model assessment-insulin secretion and resistance indexes or with age, obesity, and GDM. The main predictor was current insulin resistance in the first case and obesity in the second, obesity being the best predictor overall. We conclude that in our population and at midterm follow-up, women with prior GDM have a decreased insulin secretion and display a higher prevalence of fasting hyperglycemia but not the full-blown picture of metabolic syndrome. Obesity, a surrogate index of insulin resistance, is the best predictor of metabolic syndrome at follow-up.

Unchanged hypovitaminosis D and secondary hyperparathyroidism in morbid obesity after bariatric surgery.

BACKGROUND: Morbidly obese patients have been reported to present with vitamin D insufficiency and secondary hyperparathyroidism. We assessed whether bariatric surgery alters the 25-hydroxyvitamin D (calcidiol) and intact parathyroid hormone (iPTH) levels in patients presenting with morbid obesity. METHODS: A cross-sectional survey was conducted on 144 patients of whom 80 had not undergone bariatric surgery, while 64 had bariatric surgery at a mean of 36 months previously. Calcidiol levels were defined as being normal (>50 nmol/L), insufficient (2550 nmol/L) and deficient (<25 nmol/L). Mild secondary hyperparathyroidism was defined as iPTH >7.3 pmol/L with simultaneous normal values for creatinine, calcium and phosphorus. RESULTS: 80% of the patients presented low vitamin D levels and mild secondary hyperparathyroidism. Previous surgery or the presence of diabetes did not influence calcidiol levels. Corrected serum calcium, phosphorus, alkaline phosphatase, iPTH and Calcidiol were similar between subjects with and without surgery. CONCLUSIONS: Vitamin D deficient states with secondary hyperparathyroidism in the morbidly obese precede and are not significantly affected by bariatric surgery. Hypovitaminosis D with secondary hyperparathyroidism due to low calcidiol bio-availability should be added to the crowded list of sequelae of morbid obesity. While further studies are warranted, it seems advisable to support vitamin D supplementation in the morbidly obese population.

Evaluation of two nonisotopic immunoassays for determination of glutamic acid decarboxylase and tyrosine phosphatase autoantibodies in serum.

BACKGROUND: Autoantibodies for the 65-kDa form of glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase-like protein (IA-2) are measured for risk prediction and diagnosis of autoimmune diabetes mellitus. There is a lack of adequate nonisotopic alternatives to the most widely used method for both autoantibodies, which is a radiobinding assay (RBA). METHODS: We compared two commercially available immunoassays, an ELISA and a time-resolved immunofluorometric assay (TR-IFMA), with RBA. RESULTS: We found excellent agreement between the RBA and ELISA for measurement of GAD65 autoantibodies (GADAs); they showed comparable analytical precision in the cutoff range and achieved similar diagnostic specificity. The ELISA identified more GADA-positive individuals among patients with new-onset type 1 diabetes than did the RBA [89% (95% confidence interval, 78-95%), vs 71% (58-82%); P <0.03]. For IA-2 autoantibodies (IA-2As), only the TR-IFMA achieved analytical performance and diagnostic accuracy comparable to that of the RBA. These results with the GADA ELISA and IA-2A TR-IFMA were consistent with those obtained blindly in the Diabetes Antibody Standardization Program 2003. The performance of the GADA TR-IFMA and IA-2A ELISA was unsatisfactory, and these tests were not subjected to clinical evaluation. CONCLUSIONS: The GADA ELISA and IA-2A TR-IFMA behave comparably with RBA and are thus suitable for use in the clinical laboratory.

Falsely increased prostate-specific antigen concentration attributed to heterophilic antibodies.

We describe a 50-year-old man with a serum total prostatic-specific antigen concentration of 67.6 microg/L (reference range 0-4 microg/L) revealed as part of an annual health check programme. Clinical examination failed to identify any prostatic abnormality, and laboratory investigation indicated positive interference due to heterophilic antibodies.

Hipovitaminosis D en el anciano / Hypovitamonosis D in the elderly

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