Indagine epidemiologica sull'apporto iodico e sulla prevalenza del gozzo in Liguria nell'ambito del monitoraggio della iodoprofilassi in Italia

Indagine epidemiologica sull'apporto iodico e sulla prevalenza del gozzo in Liguria nell\ubfambito del monitoraggio della iodoprofilassi in Itali

Long-term outcome of low-activity radioiodine administration preceded by adjuvant recombinant human TSH pretreatment in elderly subjects with multinodular goiter

<p>Abstract</p> <p>Background</p> <p>Large multinodular goiter (MNG) in elderly people is a common finding which can require intervention. The long-term effect of radioiodine therapy on thyroid volume (TV) and function after recombinant human (rh) TSH pre-treatment was evaluated.</p> <p>Methods</p> <p>After baseline evaluation, 40 subjects over 60 years old with a large MNG were treated with ¹³¹I up to the activity of 600 MBq. Nineteen patients were pretreated with rhTSH (0.1 mg on 2 consecutive days; group 1) while 21 subjects underwent treatment without rhTSH pretreatment (group 2). TV was monitored every 6–12 months by ultrasonography. The median follow-up period was 36 months.</p> <p>Results</p> <p>At the baseline, the groups matched in terms of TV, 24-h radioiodine uptake (RAIU), urinary iodine and neck complaints. The number of subjects pretreated with anti-thyroid drugs was significantly (P = 0.01) greater in group 2 than in group 1; TSH was more suppressed (P = 0.003) and f-T3 was more elevated (P = 0.005) in group 2 than in group 1 patients. RhTSH increased 24-h RAIU in group 1 up to the baseline level observed in group 2. The ¹³¹I activity administered was similar in both groups. Adverse events were slight and similar in both groups. A permanent post-radioiodine toxic condition was reported only in 2 patients in group 2. After radioiodine therapy, hypothyroidism was observed in significantly more group 1 patients than group 2 patients (P = 0.002). While TV was reduced in both groups, the percentage TV reduction recorded at the last examination was significantly higher (P = 0.03) in group 1 than in group 2. MNG-related complaints were significantly reduced in both group 1 (P = 0.0001 vs baseline) and group 2 (P = 0.001) patients.</p> <p>Conclusion</p> <p>Low radioiodine activities after pretreatment with low-dosage rhTSH are able to reduce TV and improve MNG-related symptoms in elderly subjects.</p

The Role of CTLA-4 Gene Polymorphisms in Autoimmune Disease Pathogenesis: A 2012 Update

Gene association studies are very appealing in autoimmune diseases. In recent years, access to other human gene sequences prompted investigators to focus on genes encoding the immune regulatory proteins such as the costimulatory, adhesion molecules, cytokines and chemokines and their receptors. Among them, cytotoxic T-lymphocyte antigen-4 (CTLA-4) has been extensively studied for its pivotal role in autoimmunity. As a central regulatory element of the immune responses magnitude, CTLA-4 could act as a double-edged sword and only the optimal expression ensures an effective, but at the same time, safe immune response. Thus, we can argue that CTLA-4 alleles associated with abnormal membrane expression could make a person more susceptible to tumor growth and/or manifestation of autoimmune diseases. Unfortunately, the relationship between the presence of SNP conferring susceptibility/protection to autoimmune disease and the genetic regulation/modification of CTLA-4 is the not yet fully clarified, and in some aspects conflicting

Clinical efficacy of radioiodine therapy in multinodular toxic goiter, applying an implemented dose calculation algorithm.

Radioiodine is a common therapeutic option for Multinodular Toxic Goiter (MTG). We evaluated an algorithm for personalized radioiodine activity calculation. Ninety-three (28 male, 65 female; 43-84 years) patients with MTG eligible for radioiodine treatment (131I-iodide) were studied. The quantity of 131I-iodide to be administered was estimated by Thyroid Volume Reduction (TVR) algorithm, developed for Graves' disease. It takes into account 131I uptake, its effective half-life (T1/2eff), thyroid volume, and its expected reduction during treatment. A comparison with the activity calculated by other dosimetric protocols and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid volume by ultrasonography (US), thyroid stimulating hormone (TSH), and thyroid hormones by standard immunometric methods. In a follow-up of 6-120 months, remission of hyperthyroidism after a single 131I-iodide treatment was observed in 76 patients (64 euthyroid, 12 hypothyroid). The thyroid volume reduction observed by US after the treatment fairly correlated with what predicted by our model; T1/2eff was highly variable and critically affected dose calculation. The administered activities (median 526 MBq, range 156-625 MBq) were slightly lower than the "fixed" activities (600 MBq) and with respect to the other protocols' prescriptions (-15/38%); the median 131I activity administered to relapsed patients (605 MBq) was significantly greater (P=0.01) with respect to the dose administered to cured patients (471 MBq). Our study shows that an effective cure of MTG can be obtained with relatively low 131I activities and probably with a relatively low incidence of hypothyroidism, using TVR method

Long-term outcome after radioiodine therapy with adjuvant rhTSH treatment: comparison between patients with non-toxic and pre-toxic large multinodular goitre.

Radioiodine is a common therapeutic option for Multinodular Toxic Goiter (MTG). We evaluated an algorithm for personalized radioiodine In multinodular goitre (MNG), low radioiodine (RAI) activity after recombinant human (rh) TSH is able to reduce thyroid volume (TV) and improve symptoms. Our aim was to evaluate the long-term outcome of RAI after rhTSH treatment in patients who were divided according to their baseline TSH levels. Eighteen patients (69.2 \ub1 6.1 year) presented non-toxic (TSH >0.3 mIU/l) MNG (TV: 61.0 \ub1 3.8 ml; group 1), while 13 patients (74.1 \ub1 7.9 year) had non-autoimmune pre-toxic (TSH 0.3 mIU/l were more frequently followed by a need for L-T4 therapy. Compressive symptoms improved in the majority of subjects

In depth functional characterization of human induced pluripotent stem cell-derived beta cells in vitro and in vivo

In vitro differentiation of human induced pluripotent stem cells (iPSCs) into beta cells represents an important cell source for diabetes research. Here, we fully characterized iPSC-derived beta cell function in vitro and in vivo in humanized mice. Using a 7-stage protocol, human iPSCs were differentiated into islet-like aggregates with a yield of insulin-positive beta cells comparable to that of human islets. The last three stages of differentiation were conducted with two different 3D culture systems, rotating suspension or static microwells. In the latter, homogeneously small-sized islet-like aggregates were obtained, while in rotating suspension size was heterogeneous and aggregates often clumped. In vitro function was assessed by glucose-stimulated insulin secretion, NAD(P)H and calcium fluctuations. Stage 7 aggregates slightly increased insulin release in response to glucose in vitro. Aggregates were transplanted under the kidney capsule of NOD-SCID mice to allow for further in vivo beta cell maturation. In transplanted mice, grafts showed glucose-responsiveness and maintained normoglycemia after streptozotocin injection. In situ kidney perfusion assays showed modulation of human insulin secretion in response to different secretagogues. In conclusion, iPSCs differentiated with equal efficiency into beta cells in microwells compared to rotating suspension, but the former had a higher experimental success rate. In vitro differentiation generated aggregates lacking fully mature beta cell function. In vivo, beta cells acquired the functional characteristics typical of human islets. With this technology an unlimited supply of islet-like organoids can be generated from human iPSCs that will be instrumental to study beta cell biology and dysfunction in diabetes

In depth functional characterization of human induced pluripotent stem cell-derived beta cells in vitro and in vivo

In vitro differentiation of human induced pluripotent stem cells (iPSCs) into beta cells represents an important cell source for diabetes research. Here, we fully characterized iPSC-derived beta cell function in vitro and in vivo in humanized mice. Using a 7-stage protocol, human iPSCs were differentiated into islet-like aggregates with a yield of insulin-positive beta cells comparable to that of human islets. The last three stages of differentiation were conducted with two different 3D culture systems, rotating suspension or static microwells. In the latter, homogeneously small-sized islet-like aggregates were obtained, while in rotating suspension size was heterogeneous and aggregates often clumped. In vitro function was assessed by glucose-stimulated insulin secretion, NAD(P)H and calcium fluctuations. Stage 7 aggregates slightly increased insulin release in response to glucose in vitro. Aggregates were transplanted under the kidney capsule of NOD-SCID mice to allow for further in vivo beta cell maturation. In transplanted mice, grafts showed glucose-responsiveness and maintained normoglycemia after streptozotocin injection. In situ kidney perfusion assays showed modulation of human insulin secretion in response to different secretagogues. In conclusion, iPSCs differentiated with equal efficiency into beta cells in microwells compared to rotating suspension, but the former had a higher experimental success rate. In vitro differentiation generated aggregates lacking fully mature beta cell function. In vivo, beta cells acquired the functional characteristics typical of human islets. With this technology an unlimited supply of islet-like organoids can be generated from human iPSCs that will be instrumental to study beta cell biology and dysfunction in diabetes