Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study.

BACKGROUND: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. OBJECTIVE: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. METHODS: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. RESULTS: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. CONCLUSIONS: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

Alterations in Hypothalamic Mechanisms Associated with Reduced Suckling-Induced Prolactin Secretion in the Lactation-Deficient OFA hr/hr Rat.

INTRODUCTION: OFA hr/hr rats have deficient lactation with impaired suckling-induced PRL release. Unlike their background strain, Sprague-Dawley (SD) rats, OFA rats display abnormal mediobasal hypothalamus (MBH) dopaminergic tone during late pregnancy and lactation. We explored if the expression of MBH components, including various receptors (R) and proteins that regulate the dopaminergic system, is altered in mid-lactating OFA compared to SD rats, which may be associated with the abnormality. METHODS: Four groups of mid-lactating rats were used: continuous lactation; pups separated overnight; 30-min suckling (S); and 2 h or 4 h S after separation. Mothers were sacrificed to obtain serum for PRL RIA and MBHs to determine tyrosine hydroxylase (TH), PRL-R, PRL signaling molecules (activator: STAT5b; inhibitors: SOCS1, SOCS3, CIS), opioids (PENK, PDYN), and µ- and κ-opioid R (MOR, KOR) mRNA expression by qPCR and phospho-TH (p-TH) and TH proteins by Western blot. RESULTS: Suckling-induced PRL was lower in OFA and p-TH expression diminished in both strains. Separation increased TH mRNA and protein in SD, which decreased after 4 h S, but OFA protein levels remained unchanged. Separation of pups also resulted in decreased PRL-R and CIS expression in SD but increased PRL-R and SOCS3 in OFA. Despite the lower PRL-R, STAT5b, SOCS1, and SOCS3 levels in OFA compared to SD, suckling diminished them further. We observed subtle changes in SD opioids and their R, but in OFA, suckling decreased PENK, KOR, and MOR. CONCLUSION: The different patterns of TH, opioids, their R, and PRL signaling inhibitor expression with conserved TH activation by suckling may disturb the balance between stimulation and inhibition of PRL release resulting in impaired suckling-induced PRL secretion in OFA rats.

Mast cells, cortistatin, and its receptor, MRGPRX2, are linked to the pathogenesis of chronic prurigo.

BACKGROUND: Chronic prurigo (CPG) is characterized by intensive itch and interactions among nerves, neuropeptides, and mast cells (MCs). The role of some neuropeptides such as cortistatin (CST) and its receptor, Mas-related G protein-coupled receptor X2 (MRGPRX2), in CPG remains poorly investigated. OBJECTIVES: We evaluated first whether CST activates human skin MCs, and second whether CST and MRGPRX2 are expressed in the skin of CPG patients, and by which cells. METHODS: Skin prick tests and microdialysis with CST were performed in 6 and 1 healthy volunteers, respectively. Degranulation of human skin MCs was assessed using ß-hexosaminidase and histamine release assays. Skin samples from 10 patients with CPG and 10 control subjects were stained for CST, MCs, and MRGPRX2 (protein and mRNA) using immunohistochemistry, immunofluorescence, and/or in situ hybridization. Flow cytometry was used to assess CST in human skin MCs. MRGPRX2 levels were measured in serum by ELISA. RESULTS: CST induced concentration-dependent degranulation of human skin MCs in vivo and ex vivo. Skin lesions of CPG patients exhibited markedly higher numbers of CST-expressing cells, CST-expressing MCs, MRGPRX2-expressing cells, and MRGPRX2 mRNA-expressing cells than nonlesional skin. MCs were the main MRGPRX2 mRNA-expressing cells in the lesions of most CPG patients (70%). Stimulation of human skin MCs with anti-IgE led to a release of CST. The number of MRGPRX2-expressing cells correlated with disease severity (r = 0.649, P = .04). MRGPRX2 serum levels in CPG patients correlated with disease severity (r = 0.704, P = .023) and quality-of-life impairment (r = 0.687, P = .028). CONCLUSIONS: CST and MRGPRX2 may contribute to the pathogenesis of CPG and should be evaluated in further studies as potential biomarkers and novel therapeutic targets.

Late Gadolinium Enhancement by Cardiac Magnetic Resonance and Speckle Tracking Echocardiography in the Evaluation of Cardiac Complications in Chagas Cardiomyopathy: A Systematic Review.

Background: Chagas cardiomyopathy (CC) increases cardiovascular mortality associated with congestive heart failure (CHF), ventricular arrhythmias (VA), and sudden cardiac death (SCD). Different imaging techniques have been tested to assess disease progression and cardiac risk in individuals with Chagas disease (ChD). In this systematic review, we evaluated the accuracy in detecting cardiac complications in CC patients using cardiac magnetic resonance (CMR) and speckle tracking echocardiography (STE). Methods: A search was done on PubMed, Cochrane, and Embase for studies in humans over 18 years of age with ChD. Demographic data, research methodology, imaging parameters, and cardiac outcomes were extracted, and study quality was assessed, resulting in a narrative description. Results: Twelve studies with 1124 patients were analyzed. One study discovered a contractility pattern by STE. Four studies assessed the identification of Early Cardiac Impairment (ECI) and VA risk, respectively, while three studies evaluated the risk of SCD. Global Longitudinal Strain (GLS) identified patients with ECI (-18.5 ± 3.4% non-fibrosis vs -14.0 ± 5.8% fibrosis, p = 0.006 and -18 ± 2% non-fibrosis vs -15 ± 2% fibrosis, p = 0.004). The amount of fibrosis > 11.78% or in two or more contiguous transmural segments were markers for VA risk. GLS and the amount of fibrosis were found to be predictors of SCD. Conclusions: STE may be considered a screening technique for identifying the subclinical status of CHF. CMR using Late Gadolinium Enhancement (LGE) is considered a relevant parameter for stratifying patients with ChD who are at risk of SCD. Fibrosis and GLS can be used as markers to categorize patients at risk for arrhythmias.

Survival of pediatric Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) at a single institution.

BACKGROUND: Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD), the de facto standard of care in adult-onset Hodgkin lymphoma (HL), has not been directly compared to doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC), a pediatric-aimed regimen designed to reduce late effects. We aimed to describe the single-institution experience of using both regimens in patients with pediatric HL. METHODS: This retrospective cohort study evaluated a total of 224 patients diagnosed with HL between 1999 and 2018 at Children's Hospital Los Angeles (CHLA), of which 93 patients were eligible having received ABVD (n = 46) or ABVE-PC (n = 47) chemotherapy as their initial treatment. Descriptive analyses were performed using the Student's t-test or Fisher's exact test. Survival analysis used the Kaplan-Meier method. Events included death, relapse, and secondary malignancy. We also describe the use of radiation therapy, pulmonary toxicity, and cardiomyopathy determined by shortening fraction <29%. Analyses followed an intention-to-treat principle. RESULTS: There was no difference in baseline characteristics between the patients receiving ABVE-PC or ABVD in regard for stage, risk group, or prognostic variables, such as the presence or absence of "B" symptoms, bulky disease, and extra-nodal involvement. A greater proportion of patients treated with ABVE-PC received consolidating external beam radiation treatment (XRT) either by randomization or by response compared to ABVD (59.6% vs. 32.6%, respectively, p = .01). While not statistically significant, response to therapy, assessed by positron emission tomography/computerized tomography (PET/CT) where available, mirrored the use for radiation (rapid response 58.3% vs. 90.0%, n = 34, p = .11). The median dose of anthracycline (doxorubicin) was the same in patients receiving ABVE-PC versus ABVD (200 vs. 200 mg/m2 , interquartile range 200-250 vs. 200-300 mg/m2 , p = .002). There was no difference in event-free survival (p = .63) or overall survival (p = .37) with a median follow-up length of 3.9 years. CONCLUSIONS: ABVD and ABVE-PC achieved similar survival outcomes in our single-institution cohort.

Managing Disruptions in Early Care & Education: Lessons from COVID-19.

Families face challenging decisions about early care and education (ECE) for their children. Decisions about what is best for each child and family are constrained by family and contextual factors and are prone to disruptions. This study provides a descriptive look at patterns of ECE settings children were in the year prior to kindergarten, beginning in Fall 2019 through Spring 2021, a period during which most ECE arrangements were disrupted by the COVID-19 pandemic, and into the 2020-2021 kindergarten year. Analyses of survey (N = 121) and interview (n = 25) data from families whose children entered kindergarten in Fall 2020 revealed multiple and cascading disruptions during this time. Disruptions were nearly universal, and families made continual accommodations as they juggled employment needs and children's ECE needs. Findings from this study have implications for how actual and anticipated disruptions may have a greater influence on families' child care decision-making into the future.

The real life experience goes on: update after 4 years on the first cohort treated with lanadelumab at our center.

Introduction: Lanadelumab is a first-line long-term prophylaxis (LTP) in hereditary angioedema (HAE). Real-life data on its long-term efficacy and safety are limited. It is unknown whether patients using lanadelumab need short-term prophylaxis (STP). Objectives: To provide 4-year follow-up data for our first 34 patients treating with lanadelumab. Methods: Patients were assessed for their current injection interval, attacks, treatment satisfaction, disease control (AECT), quality of life impairment (AE-QoL), events that can induce attacks, and the use of STP since the start of their treatment with lanadelumab. Results: Of 34 patients who started lanadelumab treatment, 32 were still using it after 4 years, with a median injection interval of 33 (range 14-90) days. HAE patients (n=28) reported longer intervals, i.e. 35 (14-90) days, than patients with angioedema due to acquired C1 inhibitor deficiency (n=4, 23 (14-31) days). With their current injection intervals, used for a mean duration of 29 ± 17 months, patients reported a yearly attack rate of 0.3 ± 0.1. More than 70% of patients were attack-free since starting their current injection interval. All patients reported well-controlled disease, i.e. ≥10 points in the AECT; 21 patients had complete control (16 points). AE-QoL scores improved further compared to our initial report, most prominently in the fears/shame domain (-6 points). Treatment satisfaction was very high. No angioedema occurred after 146 of 147 potentially attack-inducing medical procedures without STP. Conclusions: Our results demonstrate the long-term efficacy and safety of lanadelumab in real-life and question the need for STP in patients who use effective LTP.

Biotransformation of lignocellulosic biomass into industrially relevant products with the aid of fungi-derived lignocellulolytic enzymes.

Lignocellulosic material has drawn significant attention among the scientific community due to its year-round availability as a renewable resource for industrial consumption. Being an economic substrate alternative, various industries are reevaluating processes to incorporate derived compounds from these materials. Varieties of fungi and bacteria have the ability to depolymerize lignocellulosic biomass by synthesizing degrading enzymes. Owing to catalytic activity stability and high yields of conversion, lignocellulolytic enzymes derived from fungi currently have a high spectrum of industrial applications. Moreover, these materials are cost effective, eco-friendly and nontoxic while having a low energy input. Techno-economic analysis for current enzyme production technologies indicates that synthetic production is not commercially viable. Instead, the economic projection of the use of naturally-produced ligninolytic enzymes is promising. This approach may improve the economic feasibility of the process by lowering substrate expenses and increasing lignocellulosic by-product's added value. The present review will discuss the classification and enzymatic degradation pathways of lignocellulolytic biomass as well as the potential and current industrial applications of the involved fungal enzymes.

Differential effects of hypo- and hyperthyroidism on remodeling of contacts between neurons expressing the neuropeptide EI and tyrosine hydroxylase in hypothalamic areas of the male rat.

The Neuropeptide EI (NEI, glutamic acid- isoleucine amide) participates in neuroendocrine function. Previously we demonstrated that NEI concentration is regulated by thyroid hormones in discrete hypothalamic areas in rats. We observed that the thyroid status affects the dopaminergic regulation of the pituitary hormones. In this study we explored possible interactions between NEI and tyrosine hydroxylase (TH) containing elements in selected hypothalamic areas of male rats. Neuronal somas, terminals and boutons were assessed by confocal microscopy, in hypo- and hyperthyroid animals. We observed a remodeling of the contacts between the TH and NEI immunoreactive elements in the incerto-hypothalamic area (IHy, also known as rostromedial zona incerta) according to thyroid function. However, in the dorsolateral zone of the peduncular part of the lateral hypothalamus (DL-PLH) the thyroid hormones affect the dendritic trees of the neurons without perturbing the overall NEI/TH contacts. Also, we demonstrated that TRH Receptor 1 (TRH-R1) is colocalized in NEI immunoreactive neurons in the peduncular part of the lateral hypothalamus (PLH) and NEI precursor mRNA expression increased by hypothyroidism indicating that NEI neurons are responsive to the feedback mechanisms of the Hypothalamic Pituitary-Thyroid Axis (HPT). In conclusion, the hypothyroid status seems to increase the interactions between the NEI neurons and the dopaminergic pathways while hyperthyroidism either decreases or displays no effects. Altogether these observations support the participation of the IHy and PLH NEI as a modulating component of the HPT suggesting that altered neuroendocrine, behavioral and cognitive dysfunctions induced by dysthyroidism could be in part mediated by NEI.

Cardiovascular Magnetic Resonance Imaging Evidence of Edema in Chronic Chagasic Cardiomyopathy.

The persistence of inflammatory processes in the myocardium in varying degrees of chronic Chagas heart disease has been poorly investigated. We hypothesized that edema could occur in patients with chronic chagasic cardiomyopathy and corresponds to the persistence of inflammatory processes in the myocardium. Eighty-two Chagas disease (CD) seropositive patients (64.6% females; age = 58.9 ± 9.9) without ischemic heart disease or conditions that cause myocardial fibrosis and dilation were considered. Late gadolinium enhancement (LGE) and T2-weighted magnetic resonance imaging of edema were obtained and represented using a 17-segment model. Patients were divided into three clinical groups according to the left ventricular (LV) ejection fraction (EF) as G1 (EF > 60%; n=37), G2 (35% > EF < 60%; n=33), and G3 (EF < 35%; n=12). Comparisons were performed by the Fisher or ANOVA tests. Bonferroni post hoc, Spearman correlation, and multiple correspondence analyses were also performed. Edema was observed in 8 (9.8%) patients; 2 (5.4%) of G1, 4 (12.1%) of G2, and 2 (16.7%) of G3. It was observed at the basal inferolateral segment in 7 (87.5%) cases. LGE was observed in 48 (58.5%) patients; 16 (43.2%) of G1, 21 (63.6%) of G2, and 11 (91.7%) of G3 (p < 0.05). It was observed in the basal inferior/inferolateral/anterolateral segments in 35 (72.9%) patients and in the apical anterior/inferior/lateral and apex segments in 21 (43.7%), with midwall (85.4%; n=41), subendocardial (56.3%; n=27), subepicardial (54.2%; n=26), transmural (31.2%; n=15), and RV (1.2%; n=1) distribution. Subendocardial lesions were observed only in patients with LVEF < 35%. There was no involvement of the mid-inferolateral/anterolateral segments with an LVEF > 35% (p < 0.05). Deteriorations of the LV and RV systolic functions were positively correlated (r s =0.69; p < 0.05) without evidence of LGE in the RV. Edema can be found in patients with chagasic cardiomyopathy in the chronic stage. In later stages of cardiac dilation with low LVEF, the LGE pattern involves subendocardium and mid locations. Deteriorations of RV and LV are positively correlated without evidence of fibrosis in the RV.

Severe symptomatic hyponatremia during citalopram therapy--a case report.

BACKGROUND: Hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone is an uncommon complication of treatment with the new class of antidepressant agents, the selective serotonin reuptake inhibitors. The risk of hyponatremia seems to be highest during the first weeks of treatment particularly, in elderly females and in patients with a lower body weight. CASE PRESENTATION: A 61-year-old diabetic male was admitted to the hospital because of malaise, progressive confusion, and a tonic/clonic seizure two weeks after starting citalopram, 20 mg/day. On physical examination the patient was euvolemic and had no evidence of malignancy, cardiac, renal, hepatic, adrenal or thyroid disease. Laboratory tests results revealed hyponatremia, serum hypoosmolality, urine hyperosmolarity, and an elevated urine sodium concentration, leading to the diagnosis of inappropriate secretion of antidiuretic hormone. Citalopram was discontinued and fluid restriction was instituted. The patient was discharged after serum sodium increased from 124 mmol/L to 134 mmol/L. Two weeks after discharge the patient denied any new seizures, confusion or malaise. At that time his serum sodium was 135 mmol/L. CONCLUSIONS: Because the use of serotonin reuptake inhibitors is becoming more popular among elderly depressed patients the present paper and other reported cases emphasize the need of greater awareness of the development of this serious complication and suggest that sodium serum levels should be monitored closely in elderly patients during treatment with citalopram.

Effects of thyroid status on NEI concentration in specific brain areas related to reproduction during the estrous cycle.

We previously showed that short-term hypo- and hyperthyroidism induce changes in neuropeptide glutamic-acid-isoleucine-amide (NEI) concentrations in discrete brain areas in male rats. To investigate the possible effects of hypo- and hyperthyroidism on NEI concentrations mainly in hypothalamic areas related to reproduction and behavior, female rats were sacrificed at different days of the estrous cycle. Circulating luteinizing hormone (LH), estradiol and progesterone concentrations were measured in control, hypothyroid (hypoT, treated with PTU during 7-9 days) and hyperthyroid (hyperT, l-T4 during 4-7 days) animals. Both treatments blunted the LH surge. Hypo- and hyperthyroidism increased estradiol concentrations during proestrus afternoon (P-PM), although hypoT rats showed lower values compared to control during proestrus morning (P-AM). Progesterone levels were higher in all groups at P-PM and in the hyperT during diestrus morning (D2). NEI concentrations were lower in hypoT rats during the estrous cycle except in estrus (E) in the peduncular part of the lateral hypothalamus (PLH). They were also reduced by both treatments in the perifornical part of the lateral hypothalamus (PeFLH) during P-PM. Hypothyroidism led to higher NEI concentrations during P-PM in the organum vasculosum of the lamina terminalis and anteroventral periventricular nucleus (OVLT+AVPV). The present results indicate that NEI concentration is regulated in a complex manner by hypo- and hyperthyroidism in the different areas studied, suggesting a correlation between NEI values and the variations of gonadal steroid levels during estrous cycle. These changes could be, in part, responsible for the alterations observed in the hypothalamic-pituitary-gonadal axis in these pathologies.

Hypo- and hyperthyroidism affect NEI concentration in discrete brain areas of adult male rats.

To date, there has been only one in vitro study of the relationship between neuropeptide EI (NEI) and the hypothalamic-pituitary-thyroid (HPT) axis. To investigate the possible relationship between NEI and the HPT axis, we developed a rat model of hypothyroidism and hyperthyroidism that allows us to determine whether NEI content is altered in selected brain areas after treatment, as well as whether such alterations are related to the time of day. Hypothyroidism and hyperthyroidism, induced in male rats, with 6-propyl-1-thiouracil and l-thyroxine, respectively, were confirmed by determination of triiodothyronine, total thyroxine, and thyrotropin levels. All groups were studied at the morning and the afternoon. In rats with hypothyroidism, NEI concentration, evaluated on postinduction days 7 and 24, was unchanged or slightly elevated on day 7 but was decreased on day 24. In rats with hyperthyroidism, NEI content, which was evaluated after 4 days of l-thyroxine administration, was slightly elevated, principally in the preoptic area in the morning and in the median eminence-arcuate nucleus and pineal gland in the afternoon, the morning and afternoon NEI contents being similar in the controls. These results provide the bases to pursue the study of the interaction between NEI and the HPT axis.

Experimental autoimmune oophoritis and α-melanocyte-stimulating hormone.

This article focuses on primary ovarian insufficiency and the experimental models used in recent years to explain the probable mechanisms of autoimmune oophoritis and idiopathic primary ovarian insufficiency. The relationship between the immune system and the neuroendocrine system is also an important focus of this article. Activation of the immune system is necessary for maintaining homeostasis and this requires multiple interactions and regulation between the immune system and the neuroendocrine system. Neuropeptides, neuroendocrine mediators, are expressed and released primarily, but not exclusively, by the nervous system and have profound effects on the immune system. As an example of one of these peptides we describe the α-melanocyte-stimulating hormone and its anti-inflammatory properties.

Efectos del Hipo-E Hipertiroidismo sobre la regulación de nei en áreas encefálicas relacionadas con la reproducción / Effects of Hypo-and hyperthyroidism on the regulation of nei in brain areas related to reproduction

El hipo- y el hipertiroidismo afectan el correcto funcionamiento del eje hipotálamohipófiso-gonadal (eje HHG) y del sistema nervioso central (SNC), el estudio de estas disfunciones en animales de experimentación ha permitido demostrar que las hormonas tiroideas (THs) pueden ser responsables de dichas alteraciones actuando en forma directa, o indirecta mediante la regulación a nivel central de moléculas neurotransmisoras y neuromoduladoras. El neuropéptido ácido-glutámico-isoleucina-amida (NEI) actúa como neuromodulador en la iberación de la hormona luteinizante (LH) y como neurotransmisor en ciertos comportamientos como la actividad motora (MA) y el comportamiento de aseo excesivo (CAE). El presente trabajo de tesis fue realizado con la finalidad de estudiar la posible regulación de las THs sobre la expresión de NEI en distintas áreas hipotalámicas y de correlacionar las modificaciones de la misma con las manifestaciones clínicas que se producen en estas patologías. Para esto se desarrolló un modelo de hipo- en hipertiroidismo en ratas macho adultas y en hembras durante el ciclo estral en las que se estudiaron distintas regiones hipotalámicas involucradas en el controlde la reproducción y del comportamiento. El análisis de lasmismas fue realizado midiendo la concentración del péptido por radioinmunoanálisis y su expresión por estudios de inmunohistoquímica e inmunofluorescencia. La relación de NEI con la expresión de enzimas como tirosina hidroxilasa (TH) y descarboxilasa del ácido- glutámico (GAD) y su posible modificación secundaria a la disfunción tiroidea también fue estudiada. Para determinarsi la hormona liberadora de tirotropina (TRH) podría ejercer algún efecto regulatorio sobre la neurona de NEI, sedeterminó la presencia de su receptor 1 (TRH-R1) en los somas que expresan el péptido.

Hypo- and hyperthyroidism affect the proper functioning of the hypothalamic-pituitarygonadal axis (HPG axis) and the central nervous system (CNS), studies done in experimental animals have demonstrated that in the CNSthyroid hormones (THs) are responsible of these changes acting directly or indirectly trhough the modulation of neurotransmitters and neuromodulators. The neuropeptide glutamic-acid-isoleucineamide (NEI) acts as a euromodulator in the release of luteinizing hormone (LH) and as a neurotransmitter in certain motivated behaviors as motor activity (MA) and excessive grooming behavior (EGB).This thesis work was performed in order to study the possible regulation of TSH on NEI expression in varioushypothalamic areas and to correlate that changes with the clinical manifestations that occur in these pathologies at the reproductive and central levels. For this aim a rat model ofhypo- and hyperthyroidism was developed in adult male and females during the estrous cycle. A series of hypothalamic regions involved in the control of reproduction and motivated behaviors were studied. NEI was determined by radioimmunoassay, immunohistochemistry and immunofluorescence methods. The relation of NEI with other molecules such as tyrosine hydroxylase (TH) and glutamic-acid-decarboxylase (GAD) and its possible modification secondary to the changes on thyroid hormones levels was studied.