Multifaceted physiological and therapeutical impact of curcumin on hormone-related endocrine dysfunctions: A comprehensive review.

Over the past five decades, Curcumin (Cur), derived from turmeric (Curcuma longa), has gained considerable attention for its potential therapeutic applications. Synthesizing insights from clinical trials conducted over the last 25 years, this review delves into diseases where Cur has demonstrated promise, offering a nuanced understanding of its pharmacokinetics, safety, and effectiveness. Focusing on specific examples, the impact of Cur on various human diseases is explored. Endocrine glands and associated signaling pathways are highlighted, elucidating how Cur influences cellular signaling. The article underscores molecular mechanisms such as hormone level alteration, receptor interaction, cytokine and adipokine expression inhibition, antioxidant enzyme activity, and modulation of transcription factors. Cur showcases diverse protective mechanisms against inflammation and oxidative damage by suppressing antiapoptotic genes and impeding tumor promotion. This comprehensive overview emphasizes the potential of Cur as a natural agent for countering aging and degenerative diseases, calling for further dedicated research in this realm.

The Pharmacological Activity of Camellia sinensis ( L. ) Kuntze on Metabolic and Endocrine Disorders: A Systematic Review.

Tea made from Camellia sinensis leaves is one of the most consumed beverages worldwide. This systematic review aims to update Camellia sinensis pharmacological activity on metabolic and endocrine disorders. Inclusion criteria were preclinical and clinical studies of tea extracts and isolated compounds on osteoporosis, hypertension, diabetes, metabolic syndrome, hypercholesterolemia, and obesity written in English between 2014 and 2019 and published in Pubmed, Science Direct, and Scopus. From a total of 1384 studies, 80 reports met inclusion criteria. Most papers were published in 2015 (29.3%) and 2017 (20.6%), conducted in China (28.75%), US (12.5%), and South Korea (10%) and carried out with extracts (67.5%, especially green tea) and isolated compounds (41.25%, especially epigallocatechin gallate). Most pharmacological studies were in vitro and in vivo studies focused on diabetes and obesity. Clinical trials, although they have demonstrated promising results, are very limited. Future research should be aimed at providing more clinical evidence on less studied pathologies such as osteoporosis, hypertension, and metabolic syndrome. Given the close relationship among all endocrine disorders, it would be of interest to find a standard dose of tea or their bioactive constituents that would be beneficial for all of them.

Endocrine disorders after heart transplantation: national cohort study.

BACKGROUND: Endocrine disorders in patients after heart transplantation (HT) remain understudied. We aimed to assess endocrine profiles and management of HT recipients in the early post- transplant period. METHODS: We conducted a retrospective cohort study on 123 consecutive HT recipients in the Advanced Heart Failure and Transplantation Programme between 2009 and 2018. All recipients had per-protocol endocrine follow-up within the first postoperative year. The median time to first post-transplant endocrine follow-up was 3 months (IQR 2-4). We assessed the incidence of vitamin D deficiency, bone mineral density, history of low energy fractures, hypogonadism in male recipients, posttransplant diabetes mellitus, and thyroid and parathyroid function. RESULTS: We enrolled 22 women and 101 men of median age 57 years (IQR 50-63). Post-transplant diabetes mellitus developed in 14 patients (11.4%). 18 of 25 patients (14.6%) with preexisting type 2 diabetes mellitus required intensification of antidiabetic therapy. 38 male patients (40.4%) had hypogonadism. 5 patients (4.6%) were hypothyroid and 10 (9.3%) latent hyperthyroid. Secondary hyperparathyroidism was present in 19 (17.3%), 25-hydroxyvitamin D deficiency in 64 (54.7%) of patients. Osteoporosis was present in 26 (21.1%), osteopenia in 59 (48.0%) patients. 47 vertebral fractures, 3 hip and 1 humerus fractures occurred in 21 patients. Most of the patients had coincidence of two or three disorders, while less than 5% did not have any endocrine irregularities. All patients received calcium and vitamin D supplements. Forty-six patients (37.4%) were treated with zoledronic acid, 12 (9.8%) with oral bisphosphonates. Two patients were treated with teriparatide. CONCLUSIONS: The prevalence of multiple endocrine disorders early after heart transplantation is high. Assessment and management of increased fracture risk and all other potentially affected endocrine axes should be considered as a standard of care in this early period.

[Effects of oral vitamin D3 supplementation in stage 3 chronic kidney disease subjects: insulin resistance syndrome and hormonal disturb interactions]. / Effets d'une supplémentation orale en vitamine D3 chez des sujets atteints de maladie rénale chronique au stade 3 : interactions avec le syndrome d'insulinorésistance et les perturbations hormonales.

The 1-25-hydroxyvitamine D (1-25OHD) or calcitriol deficiency in chronic kidney disease (CKD) patients was associated with increases vascular calcification risk, nephrons reduction, bone deficit and cardiovascular mortality by atherosclerosis. The objective of this study was to investigate the pleiotropic effects of 200.000 IU (D200 group) every 3 months versus 30.000 IU (D30 group) every month dose vitamin D supplementation in stage 3 CKD patients. A cohort of 132 adult subjects was randomized into 2 groups according to dose vitamin D supplementation in deficient subjects (25OHD <50 nmol/L or <20 ng/mL). Serum 25OHD levels were assessed before and after 6 and 12 months of vitamin D supplementation. Patients were phenotyped for IRS according to NCEP/ATPIII. Glomerular filtration rate (GFR) by the MDRD formula. Insulin resistance was evaluated by the Homa-IR model. IRS clusters by Cobas Integra 400®. PTH, Cortisol and IGF-1 were determined by radioimmunologic methods. The 25OHD profile was analyzed by LC-MS/MS. Results showed that vitamin D supplementation increased serum 25OHD concentrations (>75 nmol/L or >30 ng/mL) in both groups; however, the supplementation benefits are more significant in D30 group than in D200 group. We noted a highlighted improvement of kidney function, an inhibition of GFR collaps, a safe reduction of proteinuria, a significant PTH and C-reactive protein (inflammation) levels attenuation, concomitantly with cortisolemia normalization and decreased IGF-1 depletion. Nevertheless, homocysteine and Lp(a) concentrations remain increased, not modulated by vitamin D treatment. This study shows that continuous low doses (30.000 IU every month) are recommended for intermittent high doses (200.000 IU every 3 months) vitamin D supplementation. Our study suggests that the serum 25OHD profile can be considered a reliable biomarker in the bioclinic CKD status to stage stabilization and inhibit its evolution.

Iron Chelation Therapy as a Modality of Management.

Introduction of MRI techniques for identifying and monitoring tissue iron overload and the current understanding of iron homeostasis in transfusion-dependent (TDT) and non-transfusion-dependent thalassemia have allowed for a more robust administration of iron chelation therapies. The development of safe and efficient oral iron chelators and the insights gained from large-scale prospective studies using these agents have improved iron overload management. A significant reduction in iron toxicity-induced morbidity and mortality and improvements in quality of life were observed in TDT. The appropriate management of tissue-specific iron loading in TDT has been portrayed using evidence-based data obtained from investigational studies.

MANAGEMENT OF ENDOCRINE DISEASE: The effect of vitamin D supplementation on glycaemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: Epidemiologic studies suggest that vitamin D status plays a role in glycaemic control in patients with type 2 diabetes. However, intervention studies yielded inconsistent results. The aim of this study is to systematically review the effect of vitamin D supplementation on glycaemic control in patients with type 2 diabetes. METHODS: Systematic review and meta-analysis. We searched Medline, Embase and the Cochrane Library for RCTs examining the effect of vitamin D supplementation on glycaemic control in patients with type 2 diabetes. A random-effects model meta-analysis was performed to obtain a summarized outcome of vitamin D supplementation on HbA1c, fasting glucose and homeostasis model assessment - insulin resistance (HOMA-IR). RESULTS: Twenty-three RCTs were included in this systematic review representing a total of 1797 patients with type 2 diabetes. Mean (± s.d.) change in serum 25-hydroxyvitamin D varied from 1.8 ± 10.2 nmol/L to 80.1 ± 54.0 nmol/L. Nineteen studies included HbA1c as outcome variable. Combining these studies no significant effect in change of HbA1c was seen after vitamin D intervention compared with placebo. A significant effect of vitamin D supplementation was seen on fasting glucose in a subgroup of studies (n = 4) with a mean baseline HbA1c ≥ 8% (64 mmol/mol) (standardized difference in means: 0.36; 95% CI: 0.12-0.61, P = 0.003). CONCLUSIONS: Current evidence of RCTs does not support short-term vitamin D supplementation in a heterogeneous population with type 2 diabetes. However, in patients with poorly controlled diabetes, a favourable effect of vitamin D is seen on fasting glucose.

Actualización de las recomendaciones para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales. Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN / Update of recommendations for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology

Objetivo: Actualizar las recomendaciones previas formuladas por el Grupo de trabajo de osteoporosis y metabolismo mineral de la Sociedad Española de Endocrinología y Nutrición (SEEN) para la evaluación y el tratamiento de la osteoporosis asociada a diferentes enfermedades endocrinas y alteraciones nutricionales. Participantes: Miembros del Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN. Métodos: Las recomendaciones se formularon de acuerdo al sistema Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en PubMed de las nuevas acerca de cada enfermedad usando las siguientes palabras clave asociadas al nombre de cada proceso patológico: AND osteoporosis, fractures, bone mineral density, bone markers y treatment. Se revisaron artículos escritos en inglés con fechas de inclusión comprendidas entre el 18 de octubre de 2011 y el 30 de octubre de 2014. Tras la formulación de las recomendaciones estas se discutieron de forma conjunta por el Grupo de trabajo.Conclusiones: Esta actualización resume los nuevos datos acerca de la evaluación y tratamiento de la osteoporosis en las enfermedades endocrinas y nutricionales que se asocian a baja masa ósea o a un aumento del riesgo de fractura.(AU)

Objective: To update previous recommendations developed by the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition for the evaluation and treatment of osteoporosis associated to different endocrine and nutritional diseases. Participants: Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition. Methods: Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date between 18 October 2011 and 30 October 2014 were included. The recommendations were discussed and approved by all members of the Working Group. Conclusions: This update summarizes the new data regarding evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions.(AU)

Uncertainties in endocrine substitution therapy for central endocrine insufficiencies: growth hormone deficiency.

The growth hormone deficiency (GHD) syndrome is associated with several metabolic abnormalities and it has been postulated that the increased cardiovascular disease (CVD) morbidity and mortality in GHD patients may be related to the missing metabolic effects of GH. Many CVD risk factors show improvements after GH therapy. Reduced bone mineral density (BMD) has been recorded both in patients with isolated GHD and in those with multiple pituitary deficiencies, indicating that GHD per se is responsible for the low BMD in both types of patients. These matters are, however, more complicated, as hypopituitary patients with GHD may have different phenotypes due to differences in underlying diagnoses. These phenotypes may not be clear-cut in individual patients. Moreover, patients may transit between different phenotypes over time due to extension of the pathology in the pituitary and/or the consequences of the treatment (surgery and/or radiotherapy). Three different phenotypes of hypopituitary patients will be discussed, with a focus on CVD risk and bone health: (1) patients with isolated GHD, e.g. due to prophylactic cranial radiotherapy for lymphoblastic leukaemia in childhood; (2) patients with GHD and multiple hormone deficiencies due to pituitary macroadenomas treated by surgery; (3) patients with GHD caused by craniopharyngiomas with multiple hormone deficiencies and hypothalamic involvement, where hypothalamic damage frequently dominates the positive metabolic effects of GH therapy. These phenotypes illustrate the differential impact of various pituitary pathologies on the phenotype of patients with GHD.

Mechanisms in endocrinology: vitamin D as a potential contributor in endocrine health and disease.

OBJECTIVE: It has been suggested that vitamin D may play a role in the pathogenesis of several endocrine diseases, such as hyperparathyroidism, type 1 diabetes (T1DM), type 2 diabetes (T2DM), autoimmune thyroid diseases, Addison's disease and polycystic ovary syndrome (PCOS). In this review, we debate the role of vitamin D in the pathogenesis of endocrine diseases. METHODS: Narrative overview of the literature synthesizing the current evidence retrieved from searches of computerized databases, hand searches and authoritative texts. RESULTS: Evidence from basic science supports a role for vitamin D in many endocrine conditions. In humans, inverse relationships have been reported not only between blood 25-hydroxyvitamin D and parathyroid hormone concentrations but also with risk of T1DM, T2DM, and PCOS. There is less evidence for an association with Addison's disease or autoimmune thyroid disease. Vitamin D supplementation may have a role for prevention of T2DM, but the available evidence is not consistent. CONCLUSIONS: Although observational studies support a potential role of vitamin D in endocrine disease, high quality evidence from clinical trials does not exist to establish a place for vitamin D supplementation in optimizing endocrine health. Ongoing randomized controlled trials are expected to provide insights into the efficacy and safety of vitamin D in the management of endocrine disease.

Therapeutic effects of Chinese herbal medicine against neuroendocrinological diseases especially related to hypothalamus-pituitary-adrenal and hypothalamus-pituitary-gonadal axis.

This is a systemic review of plants used traditionally for neuroendocrinological diseases related to hypothalamus-pitutary-adrenal (HPA) and hypothalamus-pitutary-gland (HPG) axis. By searching from PubMed literature search system (1950-2013), Medline (1950-2013) and CNKI (China Journals of Full-text database; 1989-2013), 105 papers met the inclusion criteria were displayed in this review. 96 herbal drugs were classified into two parts which include hormones mainly related to HPA and HPG axis. The full scientific name of each herbal medicine, dose ranges and routes, models or diseases, affect on hormones and pertinent references are presented via synoptic tables. Herbal remedies that have demonstrable the activities of hormones have provided a potential to various diseases related to neunoendocrine and deserve increased attention in future studies. This review provides a basis for herbs use in neuroendocrinological diseases. The data collected here will benefit to further research associated to herbal medicines and hormones.

Consensus document of the Neuroendocrinology area of the Spanish Society of Endocrinology and Nutrition on management of hypopituitarism during transition.

The transition period from child to adult represents a crucial phase in the growth process where multiple physical and psychosocial changes occur. It has been arbitrarily defined as the period extending from late puberty to full adult maturity (i.e., from mid to late teenage years until 6-7 years after achievement of final height). The aim of this guideline is to emphasize the importance of adequate hormone replacement during this period and to review reassessment of pituitary function. In patients with GH deficiency diagnosed in childhood, an attempt is made to answer when to retest GH secretion, when to treat and how they should be monitored. Thyroxine, glucocorticoid, and sex steroid replacement are also reviewed.

Management of endocrine disease: value and limitations of assessing vitamin D nutritional status and advised levels of vitamin D supplementation.

The growing attention to the role of vitamin D in skeletal and extra-skeletal diseases over the last decade induced an increased demand for vitamin D determination as well as a dramatic rise of sales of vitamin D supplement. However, several critical points in this field remain to be clarified. We lack a clear consensus about the definition of vitamin D deficiency, insufficiency, and sufficiency. The identification of different thresholds defining vitamin D status has relevant implications in clinical practice. In fact, the worldwide prevalence of low vitamin D status is highly varying according to the level of 25(OH)D utilized to define sufficiency. Therefore, the assessment of 25-hydroxyvitamin D levels may have a critical role, but a number of different technical problems associated with its determination may interfere in interpreting the results. The hydrophobic nature of vitamin D and the tight binding to its carrier (vitamin D binding protein), the different forms circulating in blood, and the issue of standardization are among the most important factors influencing the measurement of this metabolite. Another controversial point relies on the conflicting guidance on prevention and treatment of vitamin D deficiency endorsed by different medical and scientific communities. In particular, uncertainty exists about how to replete vitamin D stores, how to maintain normal 25(OH)D levels after repletion, which form of vitamin D is preferable for supplementation, and which route of administration and dosing regimens are advisable. Finally, concerns have been raised regarding vitamin D toxicity and its adverse effects.

Diagnosis and treatment of mitochondrial myopathies.

Mitochondrial disorders are a heterogeneous group of disorders resulting from primary dysfunction of the respiratory chain. Muscle tissue is highly metabolically active, and therefore myopathy is a common element of the clinical presentation of these disorders, although this may be overshadowed by central neurological features. This review is aimed at a general medical and neurologist readership and provides a clinical approach to the recognition, investigation, and treatment of mitochondrial myopathies. Emphasis is placed on practical management considerations while including some recent updates in the field.

[Clinical practice guidelines for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Bone Metabolism Working Group of the Spanish Society of Endocrinology]. / Guías de práctica clínica para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales. Grupo de Metabolismo Mineral de la Sociedad Espa˜nola deEndocrinología y Nutrición.

OBJECTIVE: To provide practical recommendations for evaluation and treatment of osteoporosis associated to endocrine diseases and nutritional conditions. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology, a methodologist, and a documentalist. METHODS: Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed), using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date before 18 October 2011 were included. Current evidence for each disease was reviewed by two group members, and doubts related to the review process or development of recommendations were resolved by the methodologist. Finally, recommendations were discussed in a meeting of the Working Group. CONCLUSIONS: The document provides evidence-based practical recommendations for evaluation and management of endocrine and nutritional diseases associated to low bone mass or an increased risk of fracture. For each disease, the associated risk of low bone mass and fragility fractures is given, recommendations for bone mass assessment are provided, and treatment options that have shown to be effective for increasing bone mass and/or to decreasing fragility fractures are listed.

Systemic illness moderates the impact of N-acetyl cysteine in bipolar disorder.

OBJECTIVES: Bipolar disorder (BD) is intricately associated with chronic clinical conditions. Medical comorbidity is not only more prevalent in mood disorders, but is associated with increased costs, cognitive impairment and, ultimately, premature mortality. Oxidative stress and inflammation may mediate part of this association. To further investigate the association between medical comorbidity status and clinical improvement with adjuvant N acetyl cysteine (NAC) in the context of a placebo-controlled trial. METHODS: Placebo-controlled randomized clinical trial assessing the effect of NAC over 24 weeks. Symptomatic and functional outcomes were collected over the study period. Medical comorbidities were self-reported, and we took special interest in cardiovascular and endocrine conditions. We evaluated change from baseline to endpoint and the interaction between change and reported medical comorbidities. RESULTS: Fifty-one percent of patients reported have a cardiovascular or endocrine comorbidity. Although not found for depressive symptoms or quality of life, a significant interaction between medical comorbidity and change scores was consistently found for all functional outcomes. This indicated an advantage of NAC over placebo in those with a clinical comorbidity. CONCLUSION: Systemic illness moderated only the effect of NAC on functioning, not on depression. Demonstrating an improvement in functional outcomes with an agent that modulates redox and inflammatory pathways, this study lends empirical support to the idea that medical and psychiatric comorbidity are additive in contributing to allostatic states. One intriguing possibility is that comorbid clinical illness could be a marker for more severe oxidative stress states--and thus guide antioxidant use--in BD.

Melatonin: new applications in clinical and veterinary medicine, plant physiology and industry.

Novel functions of melatonin continue to be uncovered. Those summarized in this report include actions at the level of the peripheral reproductive organs and include functions as an antioxidant to protect the maturing oocyte in the vesicular follicle and during ovulation, melatonin actions on the developing fetus particularly in relation to organizing the circadian system, its potential utility in combating the consequences of pre-eclampsia, reducing intrauterine growth restriction, suppressing endometriotic growths and improving the outcomes of in vitro fertilization/embryo transfer. The inhibitory effects of melatonin on many cancer types have been known for decades. Until recently, however, melatonin had not been tested as a protective agent against exocrine pancreatic tumors. This cancer type is highly aggressive and 5 year survival rate in individuals with pancreatic cancer is very low. Recent studies with melatonin indicate it may have utility in the treatment of these otherwise almost untreatable pancreatic cancers. The discovery of melatonin in plants has also opened a vast new field of research which is rapidly being exploited although the specific functions(s) of melatonin in plant organs remains enigmatic. Finally, the described application of melatonin's use as a chemical reductant in industry could well serve as a stimulus to further define the utility of this versatile molecule in new industrial applications.

Evaluation of a stable gonadotropin-releasing hormone analog in mice for the treatment of endocrine disorders and prostate cancer.

Gonadotropin-releasing hormone (GnRH) receptor agonists have wide clinical applications including the treatment of prostate cancer and endocrine disorders. However, such agonists are characterized by poor pharmacokinetic properties, often requiring repeated administration or special formulations. Therefore, the development of novel peptide analogs with enhanced in vivo stability could potentially provide therapeutic alternatives. The pharmacological evaluation of a bioactive peptide [Des-Gly¹°,Tyr5(OMe),D-Leu6,Aze-NHEt9]GnRH, analog 1, is presented herein and compared with leuprolide. Peptide stability was evaluated using mouse kidney membrane preparations, followed by a liquid chromatography-tandem mass spectrometry-based approach that afforded identification and quantification of its major metabolites. The analog was significantly more stable in vitro in comparison with leuprolide. In vitro and in vivo stability results correlated well, encouraging us to develop a clinically relevant pharmacokinetic mouse model, which facilitated efficacy measurements using testosterone as a biomarker. Analog 1, an agonist of the GnRH receptor with a binding affinity in the nanomolar range, caused testosterone release in mice that was acutely dose-dependent, an effect blocked by the GnRH receptor antagonist cetrorelix. Repeated dosing studies in mice demonstrated that analog 1 was well tolerated and had potency similar to that of leuprolide, based on plasma and testis testosterone reduction and histopathological findings. Analog 1 also shared with leuprolide similar significant antiproliferative activity on androgen-dependent prostate cancer (LNCaP) cells. On the basis of pharmacokinetic advantages, we expect that analog 1 or analogs based on this new design will be therapeutically advantageous for the treatment of cancer and endocrine disorders.

Clinical uses of melatonin: evaluation of human trials.

During the last 20 years, numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. The objective of this article is to review, in depth, the science regarding clinical trials performed to date. The efficacy of melatonin has been assessed as a treatment of ocular diseases, blood diseases, gastrointestinal tract diseases, cardiovascular diseases, diabetes, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, infectious diseases, neurological diseases, sleep disturbances, aging and depression. Melatonin has been also used as a complementary treatment in anaesthesia, hemodialysis, in vitro fertilization and neonatal care. The conclusion of the current review is that the use of melatonin as an adjuvant therapy seems to be well funded for macular degeneration, glaucoma, protection of the gastric mucosa, irritable bowel syndrome, arterial hypertension, diabetes, side effects of chemotherapy and radiation in cancer patients or hemodialysis in patients with renal insufficiency and, especially, for sleep disorders of circadian etiology (jet lag, delayed sleep phase syndrome, sleep deterioration associated with aging, etc.) as well as in those related with neurological degenerative diseases (Alzheimer, etc.,) or Smith-Magenis syndrome. The utility of melatonin in anesthetic procedures has been also confirmed. More clinical studies are required to clarify whether, as the preliminary data suggest, melatonin is useful for treatment of fibromyalgia, chronic fatigue syndrome, infectious diseases, neoplasias or neonatal care. Preliminary data regarding the utility of melatonin in the treatment of ulcerative colitis, Crohn's disease, rheumatoid arthritis are either ambiguous or negative. Although in a few cases melatonin seems to aggravate some conditions, the vast majority of studies document the very low toxicity of melatonin over a wide range of doses.

Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major.

Cardiac and endocrine disorders are common sequelae of iron overload in transfused thalassaemia patients. Combined chelation with desferrioxamine (DFO) and deferiprone (DFP) is well tolerated and produces an additive/synergistic effect superior to either drug alone. 52 thalassaemia major patients were transitioned from DFO to combined chelation with DFO and DFP. Serum ferritin, cardiac and hepatic iron levels were monitored regularly for up to 7 years, as were cardiac and endocrine function. Patients' iron load normalized, as judged by ferritin and cardiac and hepatic magnetic resonance imaging findings. In all 12 patients receiving treatment for cardiac dysfunction, symptoms reversed following combined chelation, enabling nine patients to discontinue heart medications. In the 39 patients with abnormal glucose metabolism, 44% normalized. In 18 requiring thyroxine supplementation for hypothyroidism, 10 were able to discontinue, and four reduced their thyroxine dose. In 14 hypogonadal males on testosterone therapy, seven stopped treatment. Of the 19 females, who were hypogonadal on DFO monotherapy, six were able to conceive. Moreover, no patients developed de novo cardiac or endocrine complications. These results suggest that intensive combined chelation normalized patients' iron load and thereby prevented and reversed cardiac and multiple endocrine complications associated with transfusion iron overload.