Calcitonin gene-related peptide (CGRP) concentrations outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine / Concentrações de peptídeo relacionado ao gene da calcitonina (CGRP) fora dos ataques de enxaqueca no sangue periférico como um potencial biomarcador para enxaqueca crônica

Introduction: Chronic migraine is a debilitating condition that affects a significant portion of the population. Accurate diagnosis and treatment of chronic migraine remain a challenge due to the lack of objective biomarkers. Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in the pathophysiology of migraine and has been proposed as a potential biomarker for migraine. Methods: We measured CGRP levels in peripheral blood samples collected from 142 participants with chronic or episodic migraine and 24 healthy controls during ictal periods, i.e., outside migraine attacks. We compared CGRP levels between the three groups and assessed the correlation between CGRP levels and clinical features of chronic migraine. Conclusion: Our study provides evidence that CGRP levels in peripheral blood during ictal periods may serve as a potential biomarker for chronic migraine. Further studies are needed to validate these findings and to explore the clinical utility of CGRP as a biomarker for chronic migraine.

Introdução: A enxaqueca crônica é uma condição debilitante que afeta uma parcela significativa da população. O diagnóstico preciso e o tratamento da enxaqueca crónica continuam a ser um desafio devido à falta de biomarcadores objetivos. O peptídeo relacionado ao gene da calcitonina (CGRP) é um neuropeptídeo envolvido na fisiopatologia da enxaqueca e foi proposto como um potencial biomarcador para enxaqueca. Métodos: Medimos os níveis de CGRP em amostras de sangue periférico coletadas de 142 participantes com enxaqueca crônica ou episódica e 24 controles saudáveis ​​durante períodos ictais, ou seja, fora das crises de enxaqueca. Comparamos os níveis de CGRP entre os três grupos e avaliamos a correlação entre os níveis de CGRP e as características clínicas da enxaqueca crônica. Conclusão: Nosso estudo fornece evidências de que os níveis de CGRP no sangue periférico durante os períodos ictais podem servir como um potencial biomarcador para enxaqueca crônica. Mais estudos são necessários para validar estes resultados e explorar a utilidade clínica do CGRP como biomarcador para enxaqueca crónica.

O valor prognóstico da reserva microvascular isquêmica periférica na sepse não está vinculado ao peptídeo relacionado ao gene da calcitonina ou à substância P / The prognostic value of peripheral ischemic microvascular reserve in sepsis is not related to calcitonin gene-related peptide or substance P

RESUMO Objetivo: Avaliar possíveis mecanismos atribuídos ao valor prognóstico da reserva microvascular isquêmica periférica em pacientes com sepse. Métodos: Este estudo de coorte observacional incluiu 46 pacientes consecutivos com sepse em uma unidade de terapia intensiva entre novembro de 2020 e outubro de 2021. Após a ressuscitação volêmica com fluidos, avaliou-se a reserva microvascular isquêmica periférica mediante a associação dos testes hiperemia reativa pós-oclusão e índice de perfusão periférica. Adicionalmente, amostras de sangue venoso periférico foram coletadas para avaliar os níveis dos neuropeptídeos substância P e peptídeo relacionado ao gene da calcitonina no membro superior do paciente antes e imediatamente após o teste de hiperemia reativa pós-oclusão. Resultados: Não houve correlação estatisticamente significativa (p > 0,05) entre os valores basais ou variações dos níveis de neuropeptídeos e a reserva microvascular isquêmica periférica. Conclusão: Embora o peptídeo relacionado ao gene da calcitonina e a substância P possam desempenhar papel prognóstico na sepse, esses neuropeptídeos não parecem contribuir para a reserva microvascular isquêmica periférica.

ABSTRACT Objective: To evaluate the mechanisms attributed to the prognostic value of peripheral ischemic microvascular reserve in patients with sepsis. Methods: This observational cohort study enrolled 46 consecutive septic patients in the intensive care unit between November 2020 and October 2021. After fluid resuscitation, the peripheral ischemic microvascular reserve was evaluated using the association of postocclusion reactive hyperemia with the peripheral perfusion index. Additionally, peripheral venous blood samples were used to evaluate the neuropeptide calcitonin gene-related peptide and substance P levels in the upper limb before and immediately after postocclusion reactive hyperemia Results: There was no statistically significant correlation (p > 0.05) between basal values (pg/mL) or variations from neuropeptide levels (%) and the peripheral ischemic microvascular reserve (%). Conclusion: Although calcitonin gene-related peptide and substance P may have a prognostic role in sepsis, these neuropeptides do not appear to contribute to peripheral ischemic microvascular reserve.

Research progress on the role of neuropeptides in the pathogenesis of dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

Dry eye(DE)is a multi-factorial ocular surface disease. The mechanisms underlying the pathogenesis of DE is still unclear. Inflammation and immune response are considered to be one of the core mechanisms among the pathogenesis of DE. Neuropeptides are small molecular peptides generated after the sensory nerve endings damaged or stimulated. They play an important role in triggering and regulating inflammatory response. Thus, they are important mediums between the nervous system and immune system. Recent studies have revealed that neuropeptides secreted by ocular surface nerves are considered to be an important factor involved in the pathogenesis of DE. Therefore, this paper summarized the research progress on the roles of neuropeptides underlying the mechanisms of the pathogenesis of DE, analyzed the latest points of view and research hot spots, so as to provide references for the prevention and treatment of DE.

Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study

SUMMARY OBJECTIVE: Epilepsy is a common disorder that affects the nervous systems of 1% of worldwide population. In epilepsy, one-third of patients are unresponsive to current drug therapies and develop drug-resistant epilepsy. Alterations in ghrelin, nesfatin-1, and irisin levels with epilepsy were reported in previous studies. Vasoactive intestinal peptide is among the most common neuropeptides in the hippocampus, which is the focus of the seizures in temporal lobe epilepsy. However, there is also lack of evidence of whether these four neuropeptide levels are altered with drug resistant temporal lobe epilepsy or not. The aim herein was the evaluation of the serum levels of nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide in drug-resistant temporal lobe epilepsy patients and temporal lobe epilepsy (TLE) without drug resistance, and to compare them to healthy controls. METHODS: This cross-sectional study group included 58 temporal lobe epilepsy patients (24 with drug resistant temporal lobe epilepsy and 34 with temporal lobe epilepsy who were not drug-resistant) and 28 healthy subjects. Nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide serum levels were determined using enzyme-linked immunosorbent assay. RESULTS: The serum ghrelin levels of patients with drug resistant temporal lobe epilepsy were seen to have significantly decreased when compared to those of the control group (p<0.05). Serum nesfatin-1, vasoactive intestinal peptide, and irisin levels were seen to have decreased in the drug resistant temporal lobe epilepsy group when compared to those of the control and temporal lobe epilepsy groups; however, the difference was non-significant (p>0.05). CONCLUSIONS: The results herein suggested that ghrelin might contribute to the pathophysiology of drug resistant temporal lobe epilepsy. However, further studies are needed to confirm this hypothesis.

Low Electrical Resistance Properties of Acupoints: Roles of NOergic Signaling Molecules and Neuropeptides in Skin Electrical Conductance / 中国结合医学杂志

Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical resistance. New devices are developing to increase the reliability of electrical skin impedance measurements for counteracting the factors including skin dryness, skin thickness, size of the sensing electrode, pressure applied on the electrode, interelectrode distance, room temperature, and humidity. Morphological studies have identified that blood vessels, hair follicles, and nervous components are enhanced in the meridians/acupoints, which represent areas of potentially high neuronal activity. Recent evidence shows that nitric oxide (NO) concentrations are enhanced in skin acupoints/meridians. L-arginine-derived NO synthesis modifies skin norepinephrine (NE) synthesis/release in acupoints/meridians, and NO-NE activations play an important role in mediating the skin conductance responses to electrical stimulation. NOergic signaling molecules interact with gap junction and transient receptor potential vanilloid type-1. Other studies reported that the high conductance at acupoints is a result of the release of the neuropeptides substance P and calcitonin gene-related peptide during neurogenic inflammation in the referred pain area. Pathological body conditions caused considerable changes in skin conductance or impedance at acupoints. Although systematic research with an improved equipment and research design to avoid the influencing factors are requested for a definite answer in this field, the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of nervous components, and NOergic signaling molecules and neuropeptides involved in the skin low resistance at acupoints. The increased interest in the acupoints/meridians has led to an open-minded attitude towards understanding this system, which is fundamental important to establish the valid aspects of scientific basis of Chinese medicine mechanisms and therapies.

Biomarkers in migraine: a sea of something

Migraine is the most common headache disorder with high prevalence. Clinical features which forms basis for diagnosis are heterogenous, varying from person to person and in an individual patient from one headache to the next. In most of the migraineurs treatment is delayed, until the disease severity is high leading to significant disability and socioeconomic burden. Many patients receive various combination of prolonged therapy with no significant benefits. Identifying a biomarker for migraine might help in assessing the susceptibility, diagnosing the disease early, choosing appropriate therapeutic target and monitoring the disease course. Here in this review authors discuss most studied, promising biomarkers emerging in field of migraine. The keywords migraine, and biomarkers were used in the search engines of PubMed and Google scholar and articles identified were extensively reviewed. Genetic biomarkers ascertain susceptibility or predisposition to migraine and are valuable in diagnosis, developing novel therapeutic agents, assessing treatment response. This review briefs about most studied genetic and circulatory biomarkers of migraine. Further research into existing biomarkers with higher sample size, excluding confounding factors is necessary. Search for newer biomarkers which can be of great value in diagnosis and therapy is needed. Identifying a biomarker which is reliable, replicable, easily available and cost-effective is need of the hour in management of migraine.

Aspectos clínicos e inmunopatogénicos de la alopecia areata / Clinical and immunopathogenical aspects of alopecia areata

Resumen La alopecia areata en una enfermedad autoinmune caracterizada por pérdida no cicatricial de pelo, en forma de parches localizados o generalizados, en la que se pierde el privilegio inmunológico del folículo piloso. Factores ambientales, neuroendocrinos y/o psicológicos en individuos genéticamente predispuestos llevan a la activación inmunológica que conduce a la alopecia. La tercera parte de los pacientes tienen familiares afectados y se ha descrito asociación con antígenos del HLA clase I y II, y de polimorfismos de nucleótido único en genes relacionados con la activación del linfocito T. Neuropéptidos como la sustancia P, el péptido relacionado con el gen de la calcitoninay el péptido intestinal vasoactivo, producidos por los nervios cutáneos, participan en la inmunopatogénesis. Como otras entidades dermatológicas, puede ser subestimada y catalogada como un problema estético, sin tener en cuenta que tiene alto impacto en la calidad de vida y se asocia a comorbilidades psiquiátricas, autoinmunes y endocrinas.

Summary Alopecia areata (AA) is an autoimmune disease characterized by non-cicatricial hair loss, in the form of localized or generalized patches, in which the immunological privilege of the hair follicle is lost. Environmental, neuroendocrine and / or psychological factors in genetically predisposed individuals lead to immune activation and hence, alopecia. One third of the patients has affected relatives, association with HLA class I and II antigens, and single nucleotide polymorphisms in genes related to the activation of the T lymphocyte. Neuropeptides such as substance P, the peptide related to the Calcitonin gene and vasoactive intestinal peptide, produced by cutaneous nerves, participate in the immunopathogenesis of AA. Like other dermatological entities, it can be underestimated and cataloged as an aesthetic problem, without considering its high impact on quality of life and its association with psychiatric, autoimmune and endocrine comorbidities.

The role of neuropsychiatric factors in the occurrence of psoriasis / 中华皮肤科杂志

Considerable evidence has indicated that psychological factors,such as anxiety,nervousness and mental stress,can induce or exacerbate psoriasis and affect therapeutic effects to a certain degree,suggesting that psychological factors may play an important role in the occurrence of psoriasis.Current researches on neuropsychiatry-related pathogenesis of psoriasis mainly include two aspects:on the one hand,acting as stressors,psychological factors can activate the following two neuroendocrine systems,including hypothalamic-pituitary-adrenocortical axis and sympathetic-adrenal medullary system;on the other hand,neuropeptides and nerve growth factors induce in vivo neurogenic inflammation.Neuropsychiatric factors may participate in the occurrence of psoriasis through the above pathways.

Short-term Haze Exposure Predisposes Healthy Volunteers to Nasal Inflammation

PURPOSE: This study aimed to investigate the impact of short-term haze exposure on nasal inflammation in healthy volunteers. METHODS: Thirty-three healthy university students were assessed for nasal symptoms, nasal patency, upper and lower respiratory tract nitric oxide (NO) as well as inflammatory mediators and neuropeptides in nasal secretions before and after a 5-day haze episode. Peripheral blood mononuclear cells (PBMCs) were stimulated with particulate matter with an aerodynamic diameter of less than 2.5 μm (PM(2.5)), and cytokines in the supernatants were examined. RESULTS: Mild nasal symptoms were reported by some participants during the haze episode. Objective measures of nasal patency demonstrated that nasal airway resistance was significantly increased from baseline levels, while nasal cavity volume and minimum cross-sectional area were significantly decreased. Similarly, the levels of nasal and exhaled NO, eotaxin, interleukin (IL)-5, chemokine (C-C motif) ligand 17, IL-8, substance P, nerve growth factor and vasoactive intestinal peptides in nasal secretions were significantly increased from baseline values following the haze episode. In contrast, the levels of interferon-γ, IL-10, transforming growth factor-β and neuropeptide Y were significantly decreased. Incubation with 0.1-10 μg/mL PM(2.5) significantly increased release of IL-1β, IL-4, IL-5, IL-8 and IL-10 from PBMCs. CONCLUSIONS: Short-term haze exposure may lead to nasal inflammation and hypersensitivity in healthy subjects predominantly by Th2 cytokine-mediated immune responses.

Relationship between panic disorder and plasma neuropeptide-S level

Abstract Background: Panic disorder has long been associated with the changes in various neurotransmitters, such as Neuropeptide-S (NPS). Objective: In this study we aimed to determine whether there is a relationship between blood NPS levels and panic disorder. Methods: Twenty nine patients with panic disorder and thirty two healthy control subjects who were age and gender matched were enrolled to the study. Blood samples were taken from participants and plasma NPS levels were quantified by using an ELISA kit. Results: In the study group, median NPS blood level was 16.7 pg/mL and in the control group it was 32.5 pg/mL. There was a statistically significant difference (p = 0.021). Using receiver operating characteristics (ROC) curve, sensitivity and specificity of NPS blood level, for diagnosing panic disorder was calculated, and it was found 79.3% and 56.25% respectively (AUC:0.672, 95% CI: 0.540-0.787). Discussion: Malfunction at the NPS modulatory system in the cortical areas (which is causing excitations in brain areas, such as amygdala and hypothalamus) does not only increase anxiety symptoms and risk of panic disorder but also causes panic disorder patients to have lower plasma NPS levels than the control group. Therefore it can be argued that such malfunction can be treated with a systemic treatment. Baykan H et al. / Arch Clin Psychiatry. 2018;45(4):79-81

Ecdysis-related pleiotropic neuropeptides expression during Anopheles albimanus development / Expresión de neuropéptidos pleiotrópicos asociados con ecdisis durante el desarrollo del mosquito Anopheles albimanus

Abstract: Objective: To analyze the transcription pattern of neuropeptides in the ontogeny of a malaria vector, the mosquito Anopheles albimanus. Materials and methods: The transcription pattern of Crustacean CardioActive peptide (CCAP), corazonin, Ecdysis Triggering Hormone (ETH), allatostatin-A, orcokinin, Insulin Like Peptide 2 (ILP2), Insulin Like Peptide 5 (ILP5) and bursicon was evaluated using qPCR on larvae (1st - 4th instar), pupae and adult mosquitoes. Results: Unlike in other insects, transcripts of CCAP (70.8%), ETH (60.2%) and corazonin (76.5%) were expressed in 4th instar larvae, probably because these three neuropeptides are associated with the beginning of ecdysis. The neuropeptide ILP2 showed higher transcription levels in other stages and orcokinin decreased during the development of the mosquito. Conclusion: The CCAP, corazonin and ETH neuropeptides are potential targets for the design of control strategies aimed at disrupting An. albiamnus larval development.

Resumen: Objetivo: Describir la expresión de neuropéptidos durante la ontogenia del mosquito vector de la malaria Anopheles albimanus. Material y métodos: Se midió la expresión de CCAP, corazonina, ETH, allatostatina, orcokinina, ILP2, ILP5 y bursicon en larvas de primer (2mm), segundo (4mm), tercer (5mm) y cuarto (6mm) estadio, pupas y mosquitos adultos, mediante qPCR. Resultados. A diferencia de otros insectos en donde, CCAP, corazonina y ETH se expresan principalmente en estadios pupales, en An. albimanus se expresaron mayoritariamente en larvas de cuarto estadio, CCAP tuvo 70.8% de expresión relativa, corazonina 76.5% y ETH 60.2%. ILP2 fue el neuropéptido que más se expresó en el primer, segundo y tercer estadio y orcokinina disminuyó durante el desarrollo del mosquito. Conclusión. Los péptidos estudiados se expresaron en todos los estadios de desarrollo del mosquito. Sin embargo, su expresión varió en cada uno de ellos. Los neuropéptidos CCAP, corazonina y ETH, que son esenciales para la transformación de lavas a pupas, pueden ser blancos potenciales para el diseño de estrategias de control dirigidas a interrumpir el desarrollo larvario de An. albimanus.

Spinal Mechanisms of Itch Transmission / 神经科学通报·英文版

Peripheral itch stimuli are transmitted by sensory neurons to the spinal cord dorsal horn, which then transmits the information to the brain. The molecular and cellular mechanisms within the dorsal horn for itch transmission have only been investigated and identified during the past ten years. This review covers the progress that has been made in identifying the peptide families in sensory neurons and the receptor families in dorsal horn neurons as putative itch transmitters, with a focus on gastrin-releasing peptide (GRP)-GRP receptor signaling. Also discussed are the signaling mechanisms, including opioids, by which various types of itch are transmitted and modulated, as well as the many conflicting results arising from recent studies.

Identification of mouse brain neuropeptides by high throughput mass spectrometry / 生物工程学报

Neuropeptides play an important role in the physiological functions of the human body. The physiological activities such as pain, sleep, mood, learning and memory are affected by neuropeptides. Neuropeptides mainly exist in the nerve tissue of the body, and a small amount of them are distributed in body fluid and organs. At present, analysis of large-scale identification of neuropeptides in whole brain tissue is still challenging. Therefore, high-throughput detection of these neuropeptides is greatly significant to understand the composition and function of neuropeptides. In this study, 1 830 endogenous peptides and 99 novel putative neuropeptides were identified by extraction of endogenous peptides from whole brain tissue of mice by liquid phase tandem mass spectrometry (LC-MS / MS). The identification of these endogenous peptides provides not only a reference value in the treatment and mechanism studies of diseases and the development of drugs, but also the basis for the study of a new neuropeptides and their functions.

Effect of intracerebroventricular injection of leptin on proopiomelanocortin and neuropeptide Agouti related protein in type Ⅱ diabetic rats / 重庆医学

Objective To study the effect of intracerebroventricular injection of leptin on proopiomelanocortin(POMC) and neuropeptide Agouti related protein (AGRP) and fasting blood glucose (FBG) in rats with type 2 diabetes mellitus (T2DM).Methods Eighty male 8-week-age SD rats with T2DM were selected and divided into two groups:intracerebroventricular injection of leptin group(n=40)and intracerebroventricular injection of vehicle control group(n =40).Intracerebroventricular injection of 5 μL/kg(fasting leptin level 15 ng/mL) leptin was performed in the leptin injection group,and the control group was injected with same amount of vehicle instead.After 48 h,the FBG level was determined,and the levels of POMC and AGRP were detected by the titer method.Results The level of FBG in the leptin injection group was significantly lower than that in the control group(P＜ 0.05),the expression of serum POMC in the leptin injection group was significantly higher than that in control group(P＜0.05),The expression of AGRP in the leptin injection group was significantly decreased than control group(P＜0.05).Conclusion intracerebroventricular injection of leptin can significantly reduce the FBG level in rats with T2DM,increases POMC expression and decreases AGRP associated protein expression.

Relationship between neuropeptide S in amygdala and 5-hydroxytryptamine and GABA in spinal dorsal horns of rats with neuropathic pain / 中华麻醉学杂志

Objective To evaluate the relationship between neuropeptide S (NPS) in the amygdala and 5-hydroxytryptamine (5-HT) and GABA in spinal dorsal horns of rats with neuropathic pain.Methods Eighty pathogen-free healthy male Sprague-Dawley rats,weighing 200-260 g,aged 2 months,were divided into 4 groups (n =20 each) using a random number table:sham operation group (group Sham),neuropathic pain group (group NP),low dose NPS group (group L-NPS) and high dose NPS group (group H-NPS).The neuropathic pain model was established by left L5,6 spinal nerve ligation (SNL) in anesthetized rats.NPS was injected into the bilateral amygdala at 3,6,9,12,15 and 18 days after SNL in LNPS group (10 pmol per side) and H-NPS group (100 pmol per side).The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 2 days before SNL and 1,4,7,11,14,17 and 21 days after SNL.Five rats were selected at 7,14 and 21 days after SNL and sacrificed,and the lumbar segment (L5) of the spinal cord was removed for detection of the expression of 5-HT and GABA in spinal dorsal horns by immunofluorescence histochemistry.Results Compared with group Sham,the MWT was significantly decreased,the TWL was shortened,and the expression of 5-HT and GABA in spinal dorsal horns was down-regulated in NP,L-NPS and H-NPS groups (P＜0.05).Compared with group NP,the MWT was significantly increased,the TWL was prolonged,and the expression of 5-HT and GABA in spinal dorsal horns was up-regulated in L-NPS and H-NPS groups (P＜0.05).Compared with group L-NPS,the MWT was significantly increased,the TWL was prolonged,and the expression of 5-HT and GABA in spinal dorsal horns was up-regulated in group H-NPS (P＜0.05).Conclusion The spinal mechanism of endogenous analgesia induced by NPS in the amygdala may be related to up-regulation of the expression of 5-HT and GABA in spinal dorsal horns of rats with neuropathic pain.

Advances in mass spectrometry-based approaches for neuropeptide analysis / 生物工程学报

Neuropeptides are an important class of endogenous bioactive substances involved in the function of the nervous system, and connect the brain and other neural and peripheral organs. Mass spectrometry-based neuropeptidomics are designed to study neuropeptides in a large-scale manner and obtain important molecular information to further understand the mechanism of nervous system regulation and the pathogenesis of neurological diseases. This review summarizes the basic strategies for the study of neuropeptides using mass spectrometry, including sample preparation and processing, qualitative and quantitative methods, and mass spectrometry imagining.

Atopic dermatitis: allergic dermatitis or neuroimmune dermatitis?

Abstract: Advances in knowledge of neurocellulars relations have provided new directions in the understanding and treatment of numerous conditions, including atopic dermatitis. It is known that emotional, physical, chemical or biological stimuli can generate more accentuated responses in atopic patients than in non-atopic individuals; however, the complex network of control covered by these influences, especially by neuropeptides and neurotrophins, and their genetic relations, still keep secrets to be revealed. Itching and airway hyperresponsiveness, the main aspects of atopy, are associated with disruption of the neurosensory network activity. Increased epidermal innervation and production of neurotrophins, neuropeptides, cytokines and proteases, in addition to their relations with the sensory receptors in an epidermis with poor lipid mantle, are the aspects currently covered for understanding atopic dermatitis.

Improvement of autism spectrum disorder symptoms in three children by using gastrin-releasing peptide / Melhoria nos sistemas do transtorno do espectro autista em três crianças, utilizando peptídeo liberador de gastrina

Abstract Objective: To evaluate the safety, tolerability and potential therapeutic effects of gastrin-releasing peptide in three children with autistic spectrum disorder. Methods: Case series study with the intravenous administration of gastrin-releasing peptide in the dose of 160 pmol/kg for four consecutive days. To evaluate the results, parental impressions the Childhood Autism Rating Scale (CARS) and the Clinical Global Impression (CGI) Scale. Each child underwent a new peptide cycle after two weeks. The children were followed for four weeks after the end of the infusions. Results: The gastrin-releasing peptide was well tolerated and no child had adverse effects. Two children had improved social interaction, with a slight improvement in joint attention and the interaction initiatives. Two showed reduction of stereotypes and improvement in verbal language. One child lost his compulsion to bathe, an effect that lasted two weeks after each infusion cycle. Average reduction in CARS score was 2.8 points. CGI was "minimally better" in two children and "much better" in one. Conclusions: This study suggests that the gastrin-releasing peptide is safe and may be effective in improving key symptoms of autism spectrum disorder, but its results should be interpreted with caution. Controlled clinical trials-randomized, double-blinded, and with more children-are needed to better evaluate the possible therapeutic effects of gastrin-releasing peptide in autism.

Resumo Objetivo: Avaliar a segurança, a tolerabilidade e os possíveis efeitos terapêuticos do peptídeo liberador de gastrina em três crianças com transtorno do espectro autista. Métodos: Estudo de casuística com administração intravenosa de peptídeo liberador de gastrina na dose de 160 pmol/kg por quatro dias consecutivos. Para avaliar os resultados, foram usadas a impressão dos pais, a Escala de Classificação de Autismo na Infância (CARS) e a Escala de Impressão Clínica Global (CGI). Cada criança foi submetida a novo ciclo de peptídeo após duas semanas. As crianças foram acompanhadas por quatro semanas após o término das infusões. Resultados: O peptídeo liberador de gastrina foi bem tolerado e nenhuma criança apresentou efeitos adversos. Duas crianças apresentaram melhoria na interação social, com melhoria na atenção compartilhada e nas iniciativas de interação. Duas mostraram redução dos estereótipos e melhoria na linguagem verbal. Uma criança perdeu sua compulsão por banhos, efeito que durou duas semanas após cada ciclo de infusão. A redução média no escore da CARS foi de 2,8 pontos. Quanto à CGI, os resultados foram "minimamente melhor em duas crianças" e "muito melhor" em uma. Conclusões: Este estudo sugere que o peptídeo liberador de gastrina é seguro e pode ser efetivo na melhoria dos principais sintomas do transtorno do espectro autista, porém seus resultados devem ser interpretados com cautela. Ensaios clínicos controlados, randomizados, duplo-cegos e com maior número de crianças são necessários para melhor avaliar os possíveis efeitos terapêuticos do peptídeo liberador de gastrina sobre o autismo.

Neuropeptidomics: Mass Spectrometry-Based Identification and Quantitation of Neuropeptides

Neuropeptides produced from prohormones by selective action of endopeptidases are vital signaling molecules, playing a critical role in a variety of physiological processes, such as addiction, depression, pain, and circadian rhythms. Neuropeptides bind to post-synaptic receptors and elicit cellular effects like classical neurotransmitters. While each neuropeptide could have its own biological function, mass spectrometry (MS) allows for the identification of the precise molecular forms of each peptide without a priori knowledge of the peptide identity and for the quantitation of neuropeptides in different conditions of the samples. MS-based neuropeptidomics approaches have been applied to various animal models and conditions to characterize and quantify novel neuropeptides, as well as known neuropeptides, advancing our understanding of nervous system function over the past decade. Here, we will present an overview of neuropeptides and MS-based neuropeptidomic strategies for the identification and quantitation of neuropeptides.

Stressful Events and Serum Concentration of Substance P in Acne Patients

BACKGROUND: Psychological stress is an important factor of acne pathogenesis. Stress related production of hormones, cytokines and neuropeptides may result in the chronic course and exacerbations of the disease. OBJECTIVE: The aim of the study was to evaluate the relationship between acne severity, intensity of emotional stress and serum concentration of substance P (scSP), to compare the intensity of adversities, psychological stress and scSP in acne patients with healthy controls and to compare coping techniques for stress. METHODS: The study consisted of 80 patients. Emotional stress was analyzed with the use of social readjustment rating scale, whereas the methods of coping with stress were assessed with the coping inventory for stressful situation questionnaire. The blood concentration of substance P was analyzed by enzyme-linked immunosorbent assay method in a group of 40 patients with acne vulgaris and in control subjects. RESULTS: There was no statistically significant difference between the severity of acne and the intensity of stress. Acne patients presented a higher average scSP than the controls. No statistically significant correlation was observed between the severity of acne and scSP; however, the intensity of stress correlated with scSP in the control group. The evaluation of methods of coping with stress showed significantly higher rate for the avoidance-oriented coping among acne patients. CONCLUSION: The number of stressful events is not a factor that determines the severity of acne. The course of the disease may depend on tolerance to stress and methods of coping with stress.