Influence of physical exercise on ß-amyloid, α-synuclein and tau accumulation: an in vitro model of oxidative stress in human red blood cells.

A common pathological feature of neurodegenerative disorders (NDs), such as Alzheimer's (AD) and Parkinson's (PD) diseases, is the abnormal accumulation and misfolding of specific proteins, primarily α-synuclein (α-syn), ß-amyloid1-42 (Aß) and tau, in brain and in peripheral tissues too. Oxidative stress has been proved to be involved in NDs at various levels and, in particular, in such protein alterations, on the contrary physical activity is emerging as a counteracting factor in NDs. In the present work, the content of Aß, α-syn and tau in red blood cells (RBCs) derived from ten endurance athletes (ATHL) and ten sedentary volunteers (SED) were compared before and after in vitrooxidative stress treatment. Total Aß, α-syn and tau were quantified in RBCs (isolated from the subjects) by immunoenzymatic assays. Oxidative stress was induced by in vitro H2O2 administration to RBCs. H2O2 treatment was confirmed to significantly enhance ROS accumulation in RBCs. Total Aß content in RBCs was lower in the ATHL subgroup with respect to the SED one. In the SED subgroup, but not in the ATHL one, total Aß levels were increased by oxidative stress. Total α-syn content was lower in the ATHL subgroup with respect to the SED one and α-syn levels were increased by oxidative stress in both subgroups, with the percentage of increase higher in SED. Total tau content was comparable in both ATHL and SED and it was not affected by oxidative stress. Our data confirm previous findings evidencing that both oxidative stress and sedentary style contribute to aberrant folding and accumulation of NDs-related proteins, pointing to the importance of both anti-oxidant therapies and exercising in the prevention and treating of such diseases.

A case of GH deficiency and beta-thalassemia.

A 23-year-old male patient, who suffers from beta-thalassemia major, came to us for an endocrine-metabolic evaluation. Medical history showed a diagnosis of heart disease with heart failure since the age of 16, type 1 diabetes mellitus diagnosed at the age of 18, treated with an intensive insulin therapy with a poor glycometabolic control. Patient performed regular blood transfusions and iron chelation with deferasirox. An echocardiogram revealed an enlarged left ventricle. Patient had undergone a comprehensive study of buoyancy both basal and hormone-stimulated and it was therefore carried out a diagnosis of GH deficiency and hypogonadotropic hypogonadism. A recombinant GH replacement therapy was then prescribed. After six months of therapy, the patient reported a net improvement of asthenic symptoms. Physical examination showed a reduction in abdominal adiposity in waist and an increase of 5 cm in stature. Laboratory tests showed an amelioration of glycometabolic control, such as to justify a reduction in daily insulin dose. The stature observed was thought appropriate to begin the administration of testosterone. Moreover, the cardiological framework showed a reduction of left ventricular dilatation, good ventricular motility, global minimum persistent tricuspid but not mitral regurgitation and no alteration on ECG.

[Efficacy of external conventional radiotherapy in short and long term control of acromegaly; a comparison with stereotactic irradiation]. / Efficacia della Radioterapia Convenzionale nel controllo abreve e a lungo termine della malattia acromegalica: confrontocon la metodica stereotassica.

AIMS: The aim of this study was to follow up two groups of patients with active acromegaly, who underwent to external irradiation and radio-surgery and to value the efficacy of irradiation in the control of the growth of the adenoma, hypersecretion and incidence of adverse events. MATERIALS AND METHODS: In 2 groups of patients, (A) of 47 subjects treated with conventional irradiation at a dose of 45 Gy, (B) of 6 subjects irradiated with stereo taxis radiotherapy at a dose of 15-20 Gy, were evaluated GH, IGF1 levels and pituitary function at 2, 5, 10 and 15 years after treatment. A cerebral MRI scan with detailed study of the sellar region was performed every year. RESULTS: Group (A): decrease of GH levels in 9% of patients after 2 years from therapy, 29% after 5 years, 52% after 10 years, 77% after 15 years; normalization of IGF1 levels in 8% of cases after 2 years, 23%, 42% and 61% respectively after 5, 10 and 15 years; hypopituitarism in 57, 78, 85% of patients, respectively after 5, 10 and 15 years. Group (B):normalization of IGF1 levels in 4 of 6 patients after 5 years and in all subjects after 10 and 15 years; progressive decrease of GH levels in all patients and GH normalization in 2 of 6 cases after 10 years; hypopituitarism in 1 patient after 2 years. CONCLUSIONS: We confirm the long term efficacy of external Radiotherapy in active acromegaly. Stereo taxis annuls the risks of neurological and neurovascular complications of conventional RT. Although comparison between the two techniques is not statistical significant in our cases we can affirm a faster normalization of IGF1 levels after stereotactic treatment.

Prevalence of celiac disease in patients with autoimmune thyroiditis.

AIM: Many autoimmune disorders are associated to celiac disease (CD) but the association with autoimmune thyroiditis has been more frequently documented; this is in part explained by a shared immunogenetic make-up, and in part caused to time gluten-exposition, as suggested by the significant correlation observed in celiac patients between the increase occurrence of autoimmune diseases and the length of exposure to gluten. The aim of this study was to establish the prevalence of celiac disease in a group of subjects with autoimmune thyroiditis newly diagnosed on the basis of antibodies anti-peroxidase (TPO). METHODS: A total of 113 untreated patients with TPO >70 IU/mL were enrolled. CD was screened by measuring anti-endomysial antibodies (EMA) both IgA and IgG; an high prevalence of positive serology was resulting in this group, justified, in part, from EMA IgG investigation. RESULTS: In fact 31/113 patients showed IgA and/or IgG positivity and were diagnosed as celiacs with jejunal biopsy. CONCLUSION: On the basis of this paper, such as in according to current research-setting studies, the greater frequency of CD in association to autoimmune thyroid disease suggests that all subjects with TPO should be routinely screened for CD, through EMA IgA and IgG. However, the performance of this screening has never been evaluated until now, even if it could, in fact, be valid in order to increment diagnosis of CD, today still undiagnosed.

Polyglandular autoimmune endocrine insufficiency complicated by severe osteoporosis.

In literature different cases of polyglandular autoimmune type II syndrome (PGA II) are reported, where Addison's disease is associated with gonadal insufficiency. The lack in the production of sexual steroids causes a severe postmenopausal osteoporosis. The case we report is related to a 38-year-old woman we met in 1988 and who was suffering from deep asthenia, cramps, cutaneous hyperpigmentation, nausea, vomiting, abdominal pain, weight loss and hypotension. The biochemical data were indicative for autoimmune adrenal failure. Between 1988 and 1997 the patient developed a progressive insufficiency of other endocrine glands, leading to the classic feature of PGA II. In 1998, this clinical status was complicated by a severe osteoporosis. We thought that the sudden decrease in the bony mineral density was due to the lack of the protective role played by adrenal gland androgens in postmenopausal osteoporosis. They would directly act on the bony tissue, independently from oestrogens peripheral conversion, thus producing a stimulant effect on the bone formation. A new therapeutical approach, in case of osteoporosis, is today represented by DHEA replacement therapy in women showing low hormone levels.

Diabetes mellitus and retinopathy.

The role of somatostatin and growth hormone in eye diseases recently became a matter of interest because of its link with proliferative diabetic retinopathy. In diabetic patients the pathologic proliferation of blood vessels as a result of retinal ischemia is a major cause of blindness. The hypoxic portions of the retina release angiogenic factors, stimulating neovascularization. Somatostatin is a natural peptide hormone that affects the release of a number of other hormones, such as growth hormone, glucagon, insulin and gastrin. The somatostatin analog promises to be safe and effective treatment for severe diabetic retinopathy. This compound has been shown to block the local and systemic production of insulin-like growth factor 1 and growth hormone, which promote the angiogenesis and endothelial cell proliferation associated with proliferative retinopathy. Several studies have confirmed that using somatostatin analogs to block insulin-like growth factor 1 production is effective in reducing neovascularization and preventing disease progression to proliferative stage of diabetic retinopathy. Long-acting somatostatin analogs are currently being tested for the treatment of diabetic retinopathy. The development of somatostatin analogs with increased selectivity for receptor subtypes will provide improved outcomes in the management of patients with diabetic retinopathy.

Pure dislocation of the ankle: three case reports and literature review.

Ankle dislocation without fracture is an extremely rare injury. The results of treatment are reported for three patients who had a posteromedial open dislocation, a lateral open dislocation, and a posterior closed dislocation of the ankle. Management consisted of immediate reduction, debridement and capsular suture in the open dislocations, and immobilization with a short leg cast in all patients. At followup no patient had tibiotalar joint instability; a 10 degrees to 15 degrees loss in the range of dorsiflexion was observed in two patients. One patient reported paresthesia in the area of the superficial peroneal nerve. The three patients achieved good long-term functional and radiographic results. Predisposing factors that contribute to the pathogenesis of this lesion are internal malleolus hypoplasia, ligamentous laxity, weakness of the peroneal muscles, and previous ankle sprains. Among the three patients, medial malleolus hypoplasia was present in one patient and previous sprains were seen in the clinical history of another patient.

Pancreatic endocrine tumours.

Gastrointestinal endocrine neoplasms are rare tumours that have been classified by the peptides they secrete and the resulting clinical syndromes. The incidence of these tumours is estimated to be less than 1-1.5 cases/100,000 of the general population. These gastrointestinal endocrine cells are characterized by similar cytochemical and ultrastructural characteristics, contain amines and they are capable of uptake of amine precursors to amines or peptides. The function of these cells is the neuroendocrine regulation of normal homeostatic mechanisms including vasomotor tone as well as carbohydrate, calcium and electrolyte metabolism. Each amine precursor uptake and decarboxylation cell normally synthesizes, stores and secretes its single amine or polypeptide and is responsive to its environment for stimulation or suppression in the related clinical syndrome.