Michele Iovino

Vasopressin secretion control: central neural pathways, neurotransmitters and effects of drugs.

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.

Synaptic Inputs of Neural Afferent Pathways to Vasopressin- and Oxytocin-Secreting Neurons of Supraoptic and Paraventricular Hypothalamic Nuclei

BACKGROUND Magnocellular neurosecretory neurons of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei synthesize vasopressin and oxytocin in response to signals generated by osmoreceptors and baroreceptors and, respectively, by receptors of the nipples and cervix. METHODS We analyzed the literature identifying relevant articles dealing with synaptic inputs of neural afferent pathways to Vasopressin-and Oxytocin-secreting neurons of SON and PVN. RESULTS This article focuses on the multisynaptic pathways involved in the regulation of Vasopressin and Oxytocin secretion. CONCLUSION An updated topographic description of the afferent pathways involved in the regulation of VPergic and OTergic neurons and their synaptic inputs inducing the stimulus-secretion-coupling has been depicted.

False positive diagnosis on 131 iodine whole-body scintigraphy of differentiated thyroid cancers

Abstract131Iodine is used both to ablate any residual thyroid tissue or metastatic disease and to obtain whole-body diagnostic images after total thyroidectomy for differentiated thyroid cancer (DTC). Even though whole-body scan is highly accurate in showing thyroid residues as well as metastases of DTC, false positive results can be found, possibly leading to diagnostic errors and unnecessary treatments. This paper reviews the physiological and pathological processes involved as well as the strategy to recognize and rule out false positive radioiodine images.

Sevelamer Carbonate Markedly Reduces Levothyroxine Absorption

We report the case of a young woman affected by hypothyroidism due to Hashimotos 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 earlier she had started a dialysis treatment because of a chronic renal failure and had been under treatment for the last 18 months with sevelamer carbonate, a phosphate binder. No improvement of clinical conditions nor reduction in TSH serum levels was observed even on increasing the dose of levothyroxine up to 300 mcg/day, whereas euthyroidism finally restored by administering the first morning dose of sevelamer carbonate at least 4 hours after 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.

Parathyroid Hormone Determination in Ultrasound-Guided Fine Needle Aspirates Allows the Differentiation between Thyroid and Parathyroid Lesions: Our Experience and Review of the Literature

In many cases, it is difficult or even impossible to distinguish parathyroid lesions from thyroid ones at ultrasound as well as at scintiscan and even at cytology, because they often share common features. The aim of this study was to evaluate the role of Parathyroid Hormone (PTH) determination in the aspirates in 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 or more nodule(s) of parathyroid origin because of their position in the posterior aspect of thyroid lobes and/or their shape and echo-pattern 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 were selected. After obtaining cytological preparations, the needle used to perform the fine-needle aspirate (FNA) was washed using 1 ml of normal saline. Intact PTH determination in the washout was done whereas the evaluation was performed directly in the aspirated fluid in case of cystic lesions. The values of PTH in the aspirates ranged from 6.7 to 16640 pg/ml. Sixteen patients underwent surgical intervention and the histological examination of the 23 operated lesions previously submitted to FNA-PTH showed 11 parathyroid adenomas, 5 hyperplasic parathyroid lesions and 7 benign thyroid nodules. A strong positive correlation between high levels of PTH in the aspirate and the histological findings of parathyroid lesions was found. A value over 245 pg/ml was constantly associated to the parathyroid lesions. Our results confirmed the high accuracy of FNA-PTH 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.

Vasopressin in Heart Failure

BACKGROUND AND OBJECTIVE The nonapeptide hypothalamic hormone vasopressin (VP), exerts important effects on cardiovascular system via its receptors V1, V2 and V3. Patients with congestive heart failure (CHF) present elevated plasma VP levels. Aim of this paper is to review the role of vasopressin in CHF. METHODS We analyzed the best of published literature dealing with the role of VP in patients affected by CHF, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on August 2017. RESULTS Scientific articles dealing with the relationship between VP and CHF show that circulating high VP levels found in CHF despite an exaggerated increase in circulatory blood volume can contribute to CHF exacerbation. In particular, the stimulation of V1R induces vascular constriction responsible for increased systemic vascular resistance and afterload, and, in addition, coronary vasoconstriction with consequent reduced coronary circulation and cardiac contractility, whereas the stimulation of V2R induces free water reabsorption and this is responsible of preload increase and congestion of pulmonary vascular bed with edema and hyponatremia, markers of advanced CHF. CONCLUSION VP can play an important role among the derangements of the endocrine system in CHF even being a possible target in the treatment of this condition. Vaptans, antagonists of VP receptors, in fact, are able to increase urine output and plasma sodium levels without the increased risk of arrhythmic death induced by diuretics, even though, further studies are needed to establish a possible role of these drugs in the treatment of CHF.

The Role of Neurohypophyseal Hormones Vasopressin and Oxytocin in Neuropsychiatric Disorders

BACKGROUND AND OBJECTIVE Although the neurohypophyseal hormones vasopressin (VP) and oxytocin (OT) are mostly known for their role respectively in antidiuresis, and in labour, lactation and maternal behavior, both might exert widespread influences either on emotion and cognition in healthy subjects, showing some gender-related differences. They interact with each other facilitating shifts between positive socially- oriented and defensive states. In fact, VP amplifies the reactivity to stressors showing also beneficial effects on attention, verbal learning as well as memory, whereas OT reduces the amplitude of the stress response, improves emotion processing, and can play a negative effect on memory and verbal learning in healthy individuals. Several data indicate the possible involvement of these neuropeptides in the pathophysiology of psychiatric conditions involving social interactions, such as autism, as well as in schizophrenia and depression. The aim of this paper is to review the literature relating to the role played by neurohypophyseal hormones in neuropsychiatric disorders. METHODS We analyzed the best of published literature dealing with the relationships between neurohypophyseal hormones and neuropsychiatric conditions like autism (AD), major depressive disorder (MDD), bipolar disorder (BD) and schozophrenia, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on December 2017. RESULTS Several studies indicate a role played by OT and VP in AD, schizophrenia, MDD and BD. Even if conflicting data have been reported, several mechanisms may be involved in these behavioral diseases, such as differences in aminoacid sequence and peptide biological activity, neurotransmission and genetic disorders involving OT and VP receptors. CONCLUSION The involvment of VP and OT in neurpopsychiatric disorders can support a possible beneficial therapy with OT or with VP antagonists. The target may be obtained using effective drug delivery methods as well as the association with other drugs.

Molecular Mechanisms Involved in the Control of Neurohypophyseal Hormones Secretion

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, participate 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.

Role of Central and Peripheral Chemoreceptors in Vasopressin Secretion Control

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.

Bradykinin Signal Pathways Modulate Neurohypophyseal Hormones Secretion

Afferent renal nerves stimulate vasopressin (VP) secretion by activation of VPergic neurons of supraoptic (SON) and paraventricular nuclei (PVN). Therefore, intrarenal infusion of bradykinin (BK), which excites afferent renal nerves, increases VP release. However, BK is also a potent intrarenal vasodilatator hence BK may modulate VP secretion not only by stimulating its release via afferent renal nerves, but also inhibiting its renal effects as intrarenal vasodilator via a paracrine control. Furthermore, BK impaires the mechanism of phosphorilation that induces the traslocation of aquaporin 2 containing vesicles to the apical plasma membrane thus inhibiting the osmotic water permeability of the collecting duct cells induced by VP via its V2 receptor, a Gs protein-coupled receptor. In addition, BKB2 receptor knockout mice exhibit decreased urine volume and increased urine osmolality following water deprivation. Oxytocin (OT) increases urine output and sodium excretion in rats. Icatibant, a BKB2 antagonist, suppresses these effects showing that BK mediates diuresis and natriuresis induced by OT. Infusion of OT down-regulates 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. The frequency of uterine contractions induced by OT and BK are stimulated by nitric oxide via prostaglandins release.