E Guastamacchia

Università degli Studi di Bari Aldo Moro, Bari, Apulia, Italy

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Publications (63)82.73 Total impact

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    ABSTRACT: The regulation of neurohypophyseal peptides secretion reflects the convergence of a large number of afferent neural pathways on vasopressinergic and oxytocinergic neurons of supraoptic (SON) and paraventricular nuclei (PVN). In addition to afferent input, vasopressin and oxytocin can also exert an autocrine regulation of neuronal activity. In fact, magnocellular neurons (MCNs) of SON and PVN are able to secrete these hormones not only at the endings of their terminal axons, but also from their dendrites and this local release, by activating a range of ion gated, ion channel and G protein coupled receptors, partecipate in pre- and post-synaptic modulation of neural activity of MCNs. In this review we analyzed the molecular mechanisms involved in the control of neurohypophyseal hormones secretion and related possible pharmacological targets-
    Current Pharmaceutical Design 10/2014; · 3.31 Impact Factor
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    ABSTRACT: We report a the case of a young woman affected by hypothyroidism due to Hashimoto's thyroiditis, previously well compensated with a full replacement therapy (150 mcg/day of levothyroxine), presenting a clinical picture of myxedema, with a TSH=650 mU/L. Two years before she had started a dialysis treatment because of a chronic renal failure and she had been treated for the last 18 months with sevelamer carbonate, a phosphate binder. No improvement of clinical conditions nor reduction in TSH serum levels were obtained by increasing the dose of levothyroxine up to 300 mcg/day, whereas the euthyroidism was finally restored by administering the first morning dose of sevelamer carbonate at least 4 hours after the levothyroxine administration. This case shows that sevelamer carbonate, in analogy with what has been already reported for sevelamer hydrochloride, can interfere with levothyroxine absorption leading to a condition of hypothyroidism in patients previously well compensated with a given replacement dose.
    Endocrine Metabolic & Immune Disorders - Drug Targets(Formerly Current Drug Targets - Immune Endocrine & Metabolic Disorders) 09/2014;
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    ABSTRACT: Afferent renal nerves stimulate vasopressin (VP) secretion by activation of VPergic neurons of SON and PVN. Intrarenal infusion of bradykinin (BK), which excites afferent renal nerves, increases VP release. However, BK is also a potent intrarenal vasodilator hence BK may modulate VPsecretion stimulating its release via afferent renal nerves and inhibiting its renal effects as intrarenal vasodilator via a paracrine control. BK impaired the mechanism of phosphorilation that induces the traslocation of vescicles containing aquaporin-2 to the apical plasma membrane thus inhibitins the osmotic water permeability of collecting duct cells provoked by VP via its V2 receptor, In addition, BKB2 receptor knockout mice exhibit decreased urine output and increased urine osmolality following water deprivation. Oxytocin (OT) increases urine volume and sodium excretion in rats. Icatibant, a BKB2 antagonist, suppress these effects showing that BK mediates diuresis and natriuresis induced by OT. Infusion of OT down-regulated myometrial OT and BK receptors indicating the existence of a common final pathway of OT and BK in the contractile responsiveness of uterine myometrial cells
    Journal of Autacoids. 06/2014;
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    ABSTRACT: Rates of depression are significantly increased in diabetic patients, and even more in the elderly. About 20-30 % of patients with diabetes suffer from clinically relevant depressive disorders, 10 % of which being affected by the major depression disorder. Moreover, people with depression seem to be more prone to develop an associated diabetes mellitus, and depression can worsen glycemic control in diabetes, with higher risk to develop complications and adverse outcomes, whereas improving depressive symptoms is generally associated with a better glycemic control. Thus, the coexistence of depression and diabetes has a negative impact on both lifestyle and quality of life, with a reduction of physical activity and an increase in the request for medical care and prescriptions, possibly increasing the healthcare costs and the susceptibility to further diseases. These negative aspects are particularly evident in the elderly, with further decrease in the mobility, worsening of disability, frailty, geriatric syndromes and increased mortality. Healthcare providers should be aware of the possible coexistence of depression and diabetes and of the related consequences, to better manage the patients affected by these two pathological conditions.
    Endocrine. 06/2014;
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    ABSTRACT: This study examined whether the AR-CAG repeat length might affect clinical characteristics (testis volume) seminal parameters (sperm count and its mobility) along with hormonal serum profile [FSH, LH, Testosterone (T) and Inhibin B (InhB)] both in idiopathic male infertility (IM) and in infertility due to a previous condition of cryptorchidism (CryM) or to Y chromosome long arm microdeletions (YM). Observational study without intervention(s). One hundred and ten IM patients [90 idiopathic olizoospermic males (IOM) and 20 idiopathic azoospermic males (IAM)], 19 CryM male and 10 YM patients were included. Sixty-one age-matched healthy men who had fathered within 3 years were involved representing the control group (FM). AR-CAG repeats stretch was significantly longer in IOM (p < 0.05), CryM (p < 0.05) and YM (p < 0.001) than FM. When the AR-CAG repeat tracts were subdivided in three subgroups according to the length of CAG repeats tract assessed in fertile subjects (the one with the middle (n 19-21) belonging to the 25 and 75 % inter-quartile, the ends belonging to the <25 % inter-quartile and >75 % inter-quartile, respectively), there was a statistically significant difference of distribution of AR-CAG tract length among fertile and different groups of infertile men (p = < 0.0005; chi-square test). Moreover, the subgroup of AR-CAG repeat stretch with 22-28 triplets was associated with lower levels of InhB both in idiopathic oligozoospermic (Scheffe, Bonferroni and Dunett tests p = < 0.01) and azoospermic men (Scheffe, Bonferroni and Dunett test p = < 0.05), while, when FM and men with idiopathic infertility were gathered in a single group, both the subgroup of AR- CAG tract with 15-18 repeats and the one with 22-28 repeats are associated with lower testis volume, reduced sperm count and serum InhB levels. Our study showed that the outliers of AR-CAG repeat length seem to influence the function of AR, affecting testis volume and Sertoli cell function and consequently sperm production in both fertile and idiopathic infertile men.
    Journal of Assisted Reproduction and Genetics 04/2014; · 1.82 Impact Factor
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    ABSTRACT: In addition to release of vasopressin (VP) and oxytocin (OT) from terminal axons, magnocellular neurons (MCNs) of supraoptic (SON) and paraventricular nuclei (PVN) are able to release these hormones from their dendrites. This local release plays a role in pre- and post-synaptic modulation of MCNs thus showing an autocrine regulation of neural activity via dendritic release of VP and OT by activation of a range of ion gated, ion channel and G protein coupled receptors (GPCRs). In this review we analyzed VP and OT gene expression, synaptogenesis of MCNs in the SON and PVN, transient receptor potential vanilloid cation channel, GPCRs, estrogen receptors, neuromodulators of SON and PVN functions and aquaporin 2 from molecular mechanisms to behavioral responses. Genetic approaches help us to discriminate axonal versus dendritic process and to separate the release of VP and OT from astrocytes, intra-MCNs, to axons, extra-MCNs, in the control of several behaviors as drinking and eating behavior, defensive-aggressive behavior, and maternal behavior.
    Pharmacology Biochemistry and Behavior 12/2013; · 2.82 Impact Factor
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    ABSTRACT: In many instances it is difficult or even impossible to distinguish parathyroid lesions from those of thyroid origin at ultrasound as well as at scintiscan and even at cytology, because they often share common features with thyroid nodules. Given the importance of reaching a correct diagnosis, because of the different behaviour of these lesions, their frequent coexistence and the different management, the aim of this study is to evaluate the contribute of Parathyroid Hormone (PTH) determination in the aspirates to the differential diagnosis of parathyroid from thyroid lesions in an area of mild iodine deficiency and high prevalence of thyroid nodules. Forty-six consecutive patients were suspected to have one o more nodule(s) of parathyroid origin because of the localization of the lesions in the posterior aspect of thyroid lobes at ultrasound examination. In 13 cases there were also laboratory findings suggestive for primary hyperparathyroidism, with clinical evidence in 6 of these patients. A total of 55 lesions suspected to be of parathyroid origin because of their position, shape and/or associated clinical or laboratory findings were selected. After obtaining cytological preparations, the needle used to perform the fine-needle aspirate (FNA) was then washed using 1 ml of normal saline. Intact PTH determination on the washout was done whereas, in case of cystic lesions, the evaluation was performed directly in the liquid aspirated. The values of PTH in the aspirates ranged from 6.7 to 16640 pg/ml. Sixteen patients underwent to surgical intervention and the histological examination of the 23 operated lesions previously submitted to PTH-FNA showed 11 parathyroid adenomas, 5 hyperplasic parathyroid lesions and 7 benign thyroid nodules. In one case the lesions aspirated (low PTH in the aspirates) resulted thyroid nodules at histology, but a parathyroid adenoma in ectopic location was found at surgery. A strong positive correlation between high levels of PTH in the aspirate and the histological finding of parathyroid lesions was found. A value over 190 pg/ml was constantly associated to the parathyroid origin of the lesion. Our results confirmed the high accuracy of PTH-FNA determination in differentiating parathyroid lesions from thyroid nodules and this is of special value in an area of mild iodine deficiency with a high prevalence of thyroid nodules.
    Endocrine, metabolic & immune disorders drug targets. 12/2013; 13:351-358.
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    ABSTRACT: The clinical occurrence of ectopic thyroid gland is an infrequently encountered condition, resulting from the developmental abnormality during the migration of the thyroid anlage from the floor of the primitive foregut to its final position in the neck. It can be found along the way of thyroid descent, in the midline, or laterally in the neck or even in the mediastinum or under the diaphragm. This condition is often asymptomatic, whereas symptoms could be related to ectopic thyroid size, to its relationships with surrounding organs or to diseases affecting the ectopic thyroid in the same way they involve orthotopic glands. Sometimes, a growing mass can lead to the clinical suspicion of a tumor disease. On the other hand, thyroid ectopy must be distinguished from metastasis of thyroid cancer. Scintigraphy and ultrasonography are the main diagnostic means for evaluating ectopic thyroid tissue, whereas fine needle aspiration could be useful in the presence of a nodular ectopic gland or when the coexistence of an orthotopic thyroid can arise the suspicion of a metastasis from a thyroid cancer. Surgical removal is indicated in symptomatic cases, whereas radioiodine ablation is reserved to recurrent disease. In this paper we report an emblematic case of ectopic thyroid gland and a review of the literature dealing with this condition.
    Endocrine, metabolic & immune disorders drug targets. 10/2013;
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    ABSTRACT: In this review, we analyzed the anatomical and functional role played by central and peripheral chemoreceptors (CHRs), as well as the relationship between CHR activation and vasopressin (AVP) release. The most important site of central chemoreception has been localized at level of the rostral ventrolateral medulla (RVLM) in the retrotrapezoid nucleus (RTN, even if several brain areas partecipate in chemoreception mechanisms as nucleus tractus solitarius (NTS), ventrolateral nucleus (A1) and locus coeruleus (A6), brainstem raphe nuclei (B7-B8-B9), pre-Botzinger complex, fastigial nucleus (FN), and the hypothalamus. Functionally, these central CHRs are able to detect very small pH/CO2 fluctuations, and play a role on brain blood flow, acid-base balance, blood pressure via sympathetic tone and arousal. They receive, also, synaptic inputs from 5-HTergic raphe nuclei and NAergic A1 and A6 cell group, as well as are regulated by ATP released from astrocytes via activation of P2X and P2Y purinergic receptors, activation of protein kinase C, gene transcription and sustained increase of Ca++. Afferent nerve fibers from carotid CHRs reach the CNS via the glossopharyngeal and vagus nerve. They transduce low arterial O2 tension into increased action potential activity, which causes bradycardia and coronary vasodilatation via vagal stimulation and systemic vasoconstriction via catecholaminergic stimulation. Electrophysiological studies showed the existence of two renal CHRs. R1 CHRs do not have a resting discharge but are activated by renal ischemia and hypotension. R2 CHRs have a resting discharge and respond to backflow of urine into the renal pelvis. Stimulation of carotid CHRs, induced by bilateral carotid occlusion, increases AVP release. This response is blocked by lesions of the septal forebrain nuclei, medial preoptic area and anterior hypothalamus. A high proportion of A1 and A6 NAergic neurons receive peripheral CHR inputs that play an excitatory role on AVPergic neurons of SON and PVN. Indeed, we showed that microinjection of the presynaptic alpha2-adrenergic agonist clonidine into the NTS blocked AVP release induced by hypovolemia and this effect was prevented by the alpha2-adrenoceptor blocker yohimbine. Cardiovascular responses, as heart rate and blood pressure, induced by peripheral CHRs activation are mediated by NMDA receptors in the RVLM and stiumulate AVP release. Axons arising from 5-HTergic B7-B8-B9 raphe nuclei synapse in the RTN and play a stimulatory role on AVP release. Hypoxic-hypoxia increases neurohypophyseal blood flow and AVP release, an effect inhibited by CHR denervation. Decreases in arterial pH and increases in arterial pCO2 stimulate AVP release. The peripheral vasodilaltation induced by warm with a decrease in central blood volume stimulates AVP release via CHR mechanism. Activation of R1 and R2 CHRs, following increased intrapelvic pressure with solutions of mannitol, NaCl and KCl produces a significant increase of AVP secretion. Intrarenal infusion of bradykinin, which excites afferent renal nerves, increases the activity of AVPergic neurones in the SON, an effect inhibited by renal denervation. Electrical stimulation of renal afferent nerves increases the activity of AVPergic neurons in the PVN, thus showing that signals arising from renal CHRs modulate the activity of hypothalamic AVPergic neurons. Therefore, it is interesting to underline that the central neural pathways subserving osmotic and non-osmotic control of AVP secretion are correlated to brain areas partecipating to chemoreception mechanisms.
    Endocrine Metabolic & Immune Disorders - Drug Targets(Formerly Current Drug Targets - Immune Endocrine & Metabolic Disorders) 09/2013; 13(3):250-255.
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    ABSTRACT: In this review, we analyzed the role played by central and peripheral chemoreceptors (CHRs) in vasopressin (AVP) secretion control. Central neural pathways subserving osmotic and non-osmotic control of AVP secretion are strictly correlated to brain areas participating in chemoreception mechanisms. Among the different brain areas involved in central chemoreception, the most important site has been localized in the retrotrapezoid nucleus of the rostral ventrolateral medulla. These central CHRs are able to detect very small pH/CO2 fluctuations, participating in brain blood flow regulation, acid-base balance and blood pressure control. Decreases in arterial pH and increases in arterial pCO2 stimulate AVP release by the Supraoptic and Paraventricular Nuclei. Carotid CHRs transduce low arterial O2 tension into increased action potential activity, leading to bradycardia and coronary vasodilatation via vagal stimulation, and systemic vasoconstriction via catecholaminergic stimulation. Stimulation of carotid CHRs by hypoxia increases neurohypophyseal blood flow and AVP release, an effect inhibited by CHRs denervation. Two renal CHRs have been identified: Type R1 CHRs do not have a resting discharge but are activated by renal ischemia and hypotension; Type R2 CHRs have a resting discharge and respond to backflow of urine into the renal pelvis. Signals arising from renal CHRs modulate the activity of hypothalamic AVPergic neurons: activation of R1 and R2 CHRs, following increased intrapelvic pressure with solutions of mannitol, NaCl and KCl, produces a significant increase of AVP secretion and the same effect has been obtained by the intrarenal infusion of bradykinin, which excites afferent renal nerves, as well as by the electrical stimulation of these nerves.
    Endocrine, metabolic & immune disorders drug targets. 09/2013; 13(3):250-255.
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    ABSTRACT: Testosterone deficiency syndrome (TDS) presents several sequences that generally involve different organs such as testis, bone, skeletal muscle, and heart, inducing osteoporosis, strongly reducing muscle mass, facilitating heart insufficiency and decreasing exercise capacity and strength. Approximately 25% of patients affected by chronic heart failure (CHF) are characterized by plasma Testosterone (T) levels below normal ranges also related to disease progression. In addition, reduction of testosterone concentration may contribute to some specific features of TDS syndrome such as abnormal energy handling, weakness, dyspnoea and cachexia in particular. According to some recent evidence it has emerged that testosterone replacement therapy (TRT) may be able to improve muscle strength and functional pulmonary capacity in CHF men with TDS. This review will place emphasis either on the pathophysiologic role of testosterone deficiency in CHF men or on the effects of testosterone replacement therapy.
    Endocrine, metabolic & immune disorders drug targets. 01/2013;
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    ABSTRACT: Epidemiological studies have recently shown that obesity, and abdominal obesity in particular, is an independent risk factor for the development of heart failure (HF). Higher cardiac oxidative stress is the early stage of heart dysfunction due to obesity, and it is the result of insulin resistance, altered fatty acid and glucose metabolism, and impaired mitochondrial biogenesis. Extense myocyte hypertrophy and myocardial fibrosis are early microscopic changes in patients with HF, whereas circumferential strain during the left ventricular (LV) systole, LV increase in both chamber size and wall thickness (LV hypertrophy), and LV dilatation are the early macroscopic and functional alterations in obese developing heart failure. LV hypertrophy leads to diastolic dysfunction and subendocardial ischemia in obesity, and pericardial fat has been shown to be significantly associated with LV diastolic dysfunction. Evolving abnormalities of diastolic dysfunction may include progressive hypertrophy and systolic dysfunction, and various degrees of eccentric and/or concentric LV hypertrophy may be present with time. Once HF is established, overweight and obese have a better prognosis than do their lean counterparts with the same level of cardiovascular disease, and this phenomenon is called "obesity paradox". It is mainly due to lower muscle protein degradation, brain natriuretic peptide circulating levels and cardio-respiratory fitness than normal weight patients with HF.
    Endocrine, metabolic & immune disorders drug targets. 01/2013;
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    ABSTRACT: Nowadays, erectile dysfunction (ED) is considered an increasingly important clinical condition in men with heart failure (HF) which might influence the therapeutic approach to these patients. Since there is cogent evidence that ED is a "sentinel marker" of acute cardiovascular events especially in men younger than 65 years old or in those affected by type 2 diabetes mellitus, it deserves an early diagnosis and an appropriate treatment. In NYHA III-IV class HF patients, sexual activity could lead to acute cardiovascular events and this should be taken into account when approaching ED patients. Moreover, it is well known that some classes of drugs, normally employed in the treatment of HF patients (e.g.thiazide diuretics, spironolactone and ß-blockers), might worsen or even contribute to ED development. However, growing evidence suggests that PDF 5 inhibitors (vardenafil, tadalafil and sildenafil) seem to better satisfy the needs of NYHA HF I- II class men suffering from ED. In fact, they show a few side effects, while improving both cardiopulmonary parameters and quality of life. Therefore, the aim of this review is to sum up the most recent evidences regarding the management of ED in men suffering from HF.
    Endocrine, metabolic & immune disorders drug targets. 01/2013;
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    ABSTRACT: A cohort of 66 healthy overweight and obese patients, 53 women and 13 men were examined. Waist circumference and fasting 25(OH)D, insulin, glucose, lipid (cholesterol, HDL cholesterol, and triglyceride), C-reactive protein (CRP), and complement 3 (C3), and 4 (C4) serum concentrations were measured. Insulin resistance was assessed by the homeostasis model assessment (HOMAIR). Results. 25(OH)D levels showed a significant negative correlation with BMI (P < 0.01), waist circumference (P < 0.05), fasting insulin (P < 0.01), HOMAIR (P < 0.01), triglycerides (P < 0.01), CRP (P < 0.01), C3 (P < 0.05), and C4 (P < 0.05). Multiple regression analyses were performed with 25(OH)D as the dependent variable and BMI (or waist circumferences), fasting insulin (or HOMAIR), triglycerides, and CRP (or C3 or C4) as independent variables. Only insulin or HOMAIR maintained a significant independent association with 25(OH)D levels, whereas vitamin D did not maintain a significant independent association with CRP or C3 or C4 concentrations. Conclusions. The present study, performed in overweight and obese subjects, shows that 25(OH)D levels are negatively associated with inflammatory parameters such as CRP and C3 and C4 levels, but not independently of BMI, body fat distribution, insulin levels, or insulin resistance. Our results suggest that hyperinsulinemia and/or insulin resistance are directly responsible for decrease of 25(OH)D levels in obesity.
    BioMed research international. 01/2013; 2013:921348.
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    ABSTRACT: Background. I-131 total body scintigraphy is a commonly used post thyroidectomy imaging procedure in the management of differentiated thyroid cancer, in particular in patients with intermediate or high risk of persistent or recurrent disease, in combination with serum thyroglobulin determinations and ultrasound of the neck. It can show the persistence of residual thyroid tissue after thyroidectomy and local and distant metastases. Although this is a highly sensitive method for detecting normal and pathologic thyroid tissue, especially when performed after a radio-ablative dose, false-positive scans (i.e. uptake in the absence of residual thyroid tissue or metastases) can occur in different situations. Patient Findings. We report a case of a 42-yr-old woman with recurrent chest infections and bronchiectasis, who had a total thyroidectomy and I-131 treatment because of a papillary thyroid carcinoma. She presented with marked bilateral I-131 uptake in the lungs mimicking metastatic involvement of the lungs by thyroid cancer but interpreted as nonspecific bilateral uptake by her bronchiectatic bronchial tree. Summary. Our case, as well as others reported in the literature, calls attention to the fact that radioiodine lung uptake may be related to chronic inflammatory lung disease, thus representing a potential diagnostic pitfall in patients with differentiated thyroid cancer. Conclusions. I-131 uptake should be interpreted on the bases of clinical context, imaging and laboratory findings (serum Tg). Recognition of potential false-positive I-131 scans is critical to avoid unnecessary exposure to further radiation from repeated therapeutic doses of radioactive iodine with possible side effects and even worsening of lung disease itself.
    Thyroid: official journal of the American Thyroid Association 08/2012; · 2.60 Impact Factor
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    ABSTRACT: Vasopressin (AVP) secretion and release are regulated by a number of central nervous system sites that receive peripheral signals from the osmoreceptors and baroreceptors. Aim of this paper is to review anatomical pathways and neurotransmitters involved as well as drugs affecting AVP secretion. We focalize some observations indicating the different role of brain organs on the synthesis and transport of AVP. Several data indicate that the integrity of circumventricular organs (CVOs) is essential for the transmission of information, concerning plasma osmolality, from the periphery to AVPergic neurons of SON and PVN. Indeed, lesions of the organum vasculosum lamina terminalis (OVLT), subfornical organ (SFO) and area postrema (AP) reduce significantly AVP release to hyperosmotic stimuli. On the other hand, when the lesion is localized only to medioventral septal (MVS) nuclei, we observed that the synthesis of AVP is present because unreleased neurosecretory material is accumulated in the cytoplasm and axons of SON and PVN neurons but not transported to posterior pituitary, whereas normal rats showed a depletion of neurosecretory granules during dehydratation. These data might indicate that CVOs inform SON and PVN to synthesize AVP in response to dehydration, whereas MVS nuclei might regulate axoplasmic transport of AVP to posterior pituitary, therefore AVP release might be under the synergistic control of CVOs and MVS nuclei. We focused, also, the mechanism of the neuroendocrine reflex arc that regulates posterior pituitary hormones. The hormones of the anterior pituitary are submitted to feed-back control regulation by hormones, glucose, etc., whereas neurohypophyseal hormones respond to peripheral stimuli, such as hyperosmolality and hypovolemia for AVP and nipple-suction and cervix dilatation for oxytocin, via the neuroendocrine reflex arc which involve step by step sensory receptors (osmoreceptors, baroreceptors, chemoreceptors), synaptic connections, anatomical pathways and brain nuclei and structures.
    Current pharmaceutical design 07/2012; · 4.41 Impact Factor
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    ABSTRACT: Familial Adenomatous Polyposis, Cowden's Syndrome, and Peutz-Jeghers Syndrome are well known as Intestinal Polyposis Syndromes, inherited conditions characterized by the development of polyps of the gastro-intestinal tract in association with extra-intestinal manifestations, in particular malignant tumors at different sites. Thyroid carcinoma is sometimes part of the clinical picture of these syndromes. The aim of this paper is to review the literature dealing with the association between differentiated thyroid carcinomas and Intestinal Polyposis Syndromes in order to point out peculiar aspects, providing suggestions for the screening and the management of thyroid tumors in these patients.
    Endocrine, metabolic & immune disorders drug targets. 03/2012;
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    ABSTRACT: Prepuberal-onset (PRHH) and postpuberal-onset (PSHH) Hypogonadotropic Hypogondism (HH) refer to a heterogeneous group of patients, showing a broad spectrum of clinical signs and symptoms of androgen deficiency in consideration of the different possible aetiologies and the age at onset. These patients, though, required Gonadotropin treatment (GnTh) by means of administration of both the β Human Chorionic Gonodadotropin (β HCG) and the Follicle Stimulating Hormone (FSH) to obtain mature sperms in the ejaculate aiming to reach fertility levels. However, the response to GnTh is always unpredictable concerning either the effectiveness or the duration of the therapy. Consequently, different studies have been carried out to identify clinical (i.e. cryptorchidism, gynecomastia, testis size, etc) and biochemical markers [serum Testosterone (T) and Inhibin B (IB)] that can be useful to predict the effectiveness of GnTh. Given that the actions of T, even those directed at inducing and maintaining spermatogenesis, are mediated by its interaction with the Androgen Receptor (AR), we measured the AR CAG repeat polymorphism in men with HH, in order to examine whether the CAG polymorphism extensions could co-regulate the GnTh effectiveness. Twenty-three HH subjects were subdivided according to the age at onset (pre- and postpubertal) and treated with the same scheme and doses of GnTh, extending the period of treatment up to 30 months. Thirty-five healthy and fertile men served as a control group (CG). Twelve HH subjects (3 PRHH and 9 PSHH), who reached complete spermatogenesis within 12 months, showed the length of AR CAG repeat number [20 (19-23) = median (interquartile range 25th - 75th percentile)] not statistically different from our CG [20 (19-22)], while CAG repeat number [23 (20-25)] of 11 HH patients (9 PRHH and 2 PSHH) who obtained mature sperms in their ejaculate beyond a year to within 30 months, was significantly higher. Our results suggest that the length of AR CAG repeat polymorphism might affect the response to GnTh in men suffering from HH, in particular in those patients with prepubertal-onset hypogonadism.
    Endocrine, metabolic & immune disorders drug targets. 03/2012; 12(3):236-42.
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    ABSTRACT: While overt hypothyroidism is associated with reversible dementia in the elderly, the relationship of subclinical hypothyroidism with cognition remains a controversial issue. Our aim was to investigate the correlation between subclinical hypothyroidism and cognition in the elderly, with particular reference to long term memory and selective attention. We selected 337 outpatients (177 men and 160 women), mean age 74.3 years, excluding the subjects with thyroid dysfunction and those treated with drugs influencing thyroid function. The score of Mini Mental State Examination (MMSE) was significantly lower in the group of patients with subclinical hypothyroidism than in euthyroid subjects (p < 0.03). It was observed that patients with subclinical hypothyroidism had a probability about 2 times greater (RR = 2.028, p < 0.05) of developing cognitive impairment. Prose Memory Test (PMT) score resulted significantly lower in subjects with subclinical hypothyroidism (p < 0.04). Considering the Matrix Test (MT) score, the performance was slightly reduced in subclinical hypothyroidism (NS). Furthermore, TSH was negatively correlated with MMSE (p < 0.04), PMT (p < 0.05) and MT score (NS). No correlation was found between FT4 and FT3 and MMSE, PMT and MT score. In the elderly, subclinical hypothyroidism is associated with cognitive impairment, and its impact on specific aspects of cognition (long term memory and selective attention) is less evident.
    Endocrine, metabolic & immune disorders drug targets. 03/2012; 12(3):260-7.
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    ABSTRACT: It has been demonstrated that hypothyroidism can lead to significant hemodynamic alterations favoring the onset of chronic heart failure (CHF) as well as its progression. Furthermore, amiodarone, an iodine-containing antiarhythmic drug frequently used in CHF patients, is often the cause of primary hypothyroidism. To define the prevalence and incidence of hypothyroidism in a group of CHF outpatients in stable clinical conditions, with particular reference to the role of amiodarone therapy. Among the 422 enrolled patients (326 males, aged 65±12 years), 51 (12%) had a previous diagnosis of hypothyroidism while 21 (5%) were newly diagnosed at the enrolment. Then, the overall prevalence of hypothyroidism at the first evaluation was 17%and, as expected, it was significantly higher in females than males (33% vs 13%; p < 0.001). During follow-up (median 28 months) hypothyroidism occurred in further 19 patients (incidence rate: 26/1000/year) and it was mainly attributable to amiodarone therapy. Considering all together the hypothyroid patients, either those affected by thyroid failure at the enrolment than those developing hypothyroidism during the follow-up, levothyroxine therapy was continued or started in 69% of them; however, normal serum TSH values were obtained only in 76% of treated cases (mean levothyroxine dose: 69±44 mcg/day). In any case, in the group of patients affected by hypothyroidism a significantly greater occurrence of heart failure progression was observed. Hypothyroidism, especially the subclinical form, frequently occurs in patients affected by CHF receiving amiodarone therapy. Given the unfavorable impact of hypothyroidism on the progression and prognosis of CHF, and the opportunity to adequately manage thyroid failure by means of levothyroxine replacement therapy without the need to withdraw amiodarone, we recommend regular testing of thyroid function in CHF patients, in particular in those submitted to amiodarone therapy, in order to early diagnose a condition of hypothyroidism and titrate substitutive treatment.
    Endocrine, metabolic & immune disorders drug targets. 12/2011; 12(1):86-94.