Níveis de cortisol salivar e sérico, alfa-amilase e fluxo de saliva total não estimulada em gestantes e não gestantes

OBJETIVO: Comparar os níveis de cortisol sérico e salivar, alfa-amilase salivar (sAA) e fluxo de saliva não estimulada (UWS) em gestantes e não gestantes. MÉTODOS: Trata-se de um estudo longitudinal realizado no centro de promoção da saúde de um hospital universitário. Nove gestantes e 12 não gestantes participaram do estudo. Foram coletados e analisados soro e UWS nos três trimestres gestacionais e duas vezes por mês durante o ciclo menstrual. A análise do cortisol salivar e sérico foi realizada com o uso de quimiluminescência e a atividade da sAA foi determinada por meio de analisador automático para bioquímica. RESULTADOS: Foi verificado que a mediana (intervalo interquartil) dos níveis de cortisol sérico no grupo de gestantes foi maior que 23,8 µL/dL (19,4-29,4) quando comparado ao grupo de não gestantes, que teve média de 12,3 (9,6-16,8; p<0,001). Os níveis de sAA seguiram o mesmo padrão, com médias de 56,7 U/L (30,9-82,2) e 31,8 (18,1-53,2; p<0,001), respectivamente. Foram observadas diferenças dos níveis de cortisol sérico e salivar (µL/dL) e de sAA entre a fase folicular versus a fase lútea (p<0,001). As medianas dos fluxos salivares (UWS) foram semelhantes em gestantes (0,26 [0,15-0,30] mL/min) e não gestantes (0,23 [0,20-0,32] mL/min). Foram encontradas correlações significativas entre o cortisol salivar e o sérico (p=0,02) e entre o cortisol salivar e a sAA (p=0,01). CONCLUSÕES: Os níveis de cortisol sérico de sAA durante a gestação elevam-se. Na fase lútea do ciclo ovariano, os níveis de cortisol salivar aumentam ao passo que os níveis de cortisol sérico e sAA diminuem. _______________________________________________________________________________________ ABSTRACTPURPOSE: To compare salivary and serum cortisol levels, salivary alpha-amylase (sAA), and unstimulated whole saliva (UWS) flow rate in pregnant and non-pregnant women. METHOD: A longitudinal study was conducted at a health promotion center of a university hospital. Nine pregnant and 12 non-pregnant women participated in the study. Serum and UWS were collected and analyzed every trimester and twice a month during the menstrual cycle. The salivary and serum cortisol levels were determined by chemiluminescence assay and the sAA was processed in an automated biochemistry analyzer. RESULTS: Significant differences between the pregnant and non-pregnant groups were found in median [interquartile range] levels of serum cortisol (23.8 µL/dL [19.4-29.4] versus 12.3 [9.6-16.8], p<0.001) and sAA (56.7 U/L [30.9-82.2]versus 31.8 [18.1-53.2], p<0.001). Differences in salivary and serum cortisol (µL/dL) and sAA levels in the follicularversus luteal phase were observed (p<0.001). Median UWS flow rates were similar in pregnant (0.26 [0.15-0.30] mL/min) and non-pregnant subjects (0.23 [0.20-0.32] mL/min). Significant correlations were found between salivary and serum cortisol (p=0.02) and between salivary cortisol and sAA (p=0.01). CONCLUSIONS: Serum cortisol and sAA levels are increased during pregnancy. During the luteal phase of the ovarian cycle, salivary cortisol levels increase, whereas serum cortisol and sAA levels decline

Animal models of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) constitutes a clinical syndrome in which the diagnostic criteria of heart failure are not accompanied by gross disturbances of systolic function, as assessed by ejection fraction. In turn, under most circumstances, diastolic function is impaired. Although it now represents over 50% of all patients with heart failure, the mechanisms of HFpEF remain understood, precluding effective therapy. Understanding the pathophysiology of HFpEF has been restricted by both limited access to human myocardial biopsies and by the lack of animal models that fully mimic human pathology. Animal models are valuable research tools to clarify subcellular and molecular mechanisms under conditions where the comorbidities and other confounding factors can be precisely controlled. Although most of the heart failure animal models currently available represent heart failure with reduced ejection fraction, several HFpEF animal models have been proposed. However, few of these fulfil all the features present in human disease. In this review we will provide an overview of the currently available models to study HFpEF from rodents to large animals as well as present advantages and disadvantages of these models

Hepatic immune-mediatedadverseeffects of immune checkpoint inhibitors: analysis of real-life experience

Introduction and objectives: Immune Checkpoint Inhibitors (ICI) have shifted the paradigm of cancer therapy treatment. Despite their efficacy, ICIs may induce immune-related adverse events (irAE), which can affect various organs, namely the liver. This study intends to perform a comprehensive clinical description of the hepatic irAEs associated with ICI in a Portuguese population of a tertiary hospital centre. Materials and methods: A retrospective analysis of patients who developed immune-mediated liver injury (IMLI), among a cohort of patients treated with ICIs between March 15th of 2015 and December 15th of 2019 in a tertiary hospital. We used both Common Terminology Criteria for Adverse Events (CTCAE) and Drug-Induced Liver Injury Network (DILIN) criteria to define liver injury. Results: Among 151 patients, eight (5.3%) patients developed liver injury grade ≥3, of which five had hepatic metastasis. As such, only 3 cases were classified as IMLI. All IMLI presented with cholestasis pattern; the median duration from ICI initiation to IMLI was 84 days and/or 4 ICI cycles; one patient registered IMLI one month after nivolumab suspension; all were treated with steroids and one was successfully submitted to ICI re-challenge; a favourable outcome was seen in all patients; the median time to hepatic biochemistries normalization was 150 days. Among 10 patients with previous hepatic conditions, only one developed liver injury grade 2. Conclusions: Clinically significant ICI-related hepatotoxicity was uncommon; Immune-mediated liver injury may present a cholestatic pattern predominance. There was a low rate of liver injury of any kind in patients with previous hepatic disease while on ICI.info:eu-repo/semantics/publishedVersio

Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension

Falcao-Pires I, Goncalves N, Henriques-Coelho T, Moreira-Goncalves D, Roncon-Albuquerque R Jr, Leite-Moreira AF. Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 296: H2007-H2014, 2009. First published April 3, 2009; doi: 10.1152/ajpheart.00089.2009.-We investigated the endogenous production of apelin and the cardiac and pulmonary effects of its chronic administration in monocrotaline (MCT)-induced pulmonary hypertension (PH). Male Wistar rats were injected with MCT (60 mg/kg sc) or vehicle (day 0). One week later, these animals were randomly treated during 17 days with pyroglutamylated apelin-13 (Pyr-AP13; 200 mu g.kg(-1).day(-1) ip) or a similar volume of saline, resulting in four groups: sham (n = 11), sham-AP (n = 11), MCT (n = 16), and MCT-AP (n = 13). On day 25, right ventricular (RV) and left ventricular (LV) hemodynamic and morphometric parameters were assessed. Tissue and plasma samples were collected for histological and molecular analysis. When compared with sham, the MCT group presented a significant increase of RV mass (166 +/- 38%), diameter of cardiomyocyte (40 +/- 10%), myocardial fibrosis (95 +/- 20%), peak systolic pressure (99 +/- 22%), peak rate of ventricular pressure rise (dP/dt(max); 74 +/- 24%), peak rate of ventricular pressure decline (dP/dt(min); 73 +/- 19%), and time constant tau (55 +/- 16%). In these animals, RV expression of apelin (-73 +/- 10%) and its receptor APJ (-61 +/- 20%) was downregulated, whereas mRNA expression of type B natriuretic peptide (9,606 +/- 713%), angiotensinogen (191 +/- 147%), endothelin-1 (RV, 497 +/- 156%; and LV, 799 +/- 309%), plasmatic levels of apelin (104 +/- 48%), and angiotensin 1-7 (161 +/- 151%) were increased. Chronic treatment with Pyr-AP13 significantly attenuated or normalized these changes, preventing apelin-APJ mRNA downregulation and PH-induced neurohumoral activation of several vasoconstrictors, which exacerbates apelin-APJ vasodilator effects. Therefore, apelin delayed the progression of RV hypertrophy and diastolic dysfunction. Together, these observations suggest that the apelin-APJ system may play an important role in the pathophysiology of PH, representing a potential therapeutic target since it significantly attenuates RV overload and PH-induced neurohumoral activation

Centauri honey: a promising medicinal ingredient?

Honey is a natural product that has been used over the centuries as a medicine due to its biological activities. Centauri Cave Nymph Honey is a Cave honey extracted from 2500 meters high altitude above sea level from a deep cave by professional speleologists and is located at Caucasus Mountains of Turkey. The Apis mellifera Caucasica bee colony is located 50 kilometers away from human residences, ensuring its isolation from other colonies and maintaining a varroa mite-free status. The aim of this work is to analyze the physicochemical parameters and the bioactivity of Centauri honey. The physiochemical parameters that have been examined include color, moisture content, conductivity, pH, acidity, HMF (5-hydroxymethylfurfural), diastase index, and proline. In addition, it was also evaluated the ash, protein, sugars, carbohydrates, and energy. The biological activity was evaluated through the antioxidant (TBARS), antimicrobial activities and cytotoxicity in different cell lines (AGS, CaCo-2, MCF-7, NCI-H460, PLP2, HFF-2, and HaCat), and anti-inflammatory activity (RAW 264.7 macrophages). Ongoing research is focusing on the potential protetive effects of consuming Centauri Cave Honey against lung and prostate cancers. In vivo studies are expected to shed more ligt on the additional health benefits that this honey may offer.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES (PIDDAC) to CIMO (UIDB/00690/2020 and UIDP/00690/2020) and SusTEC (LA/P/0007/2021).info:eu-repo/semantics/publishedVersio

Medicinal centauri honey: a promising ingredient?

Honey is a natural product with antioxidant and antimicrobial properties, has been used as a medicinal substance for centuries. Thisnatural product is main- ly composed of a supersaturated solution of sugars, containing low water con- tent and trace amounts of bioactive compounds. The flower source, climate, geographical origin, harvesting process and storage conditions are factors that influence the composition of the nectar, leading to significant changes in the chemical composition, physical properties, and bioactivity of honey1. Centau- ri Honey is harvested from bee colonies located in the wild Alps of Turkey ́s mountainous region, approximately 2,500 meters above the Black Sea. The bees live in caves far from human settlements and other bees, and they have access to medicinal endemic blooms throughout the year. The aim of this work was to investigate the quality, physicochemical, nutrition- al parameters, and bioactivity of honey. The quality and physiochemical pa- rameters was analysed by colour, moisture content, conductivity, pH and acidity, 5-HMF (5-Hydroxymethylfurfural), diastase index and proline. The nutritional values were determined assessing ash, protein content, sugars, carbohydrates and energy. The biological activity was evaluated through the antioxidant, antimicrobial activity (broth microdilution method) and cytotox- icity in cell lines (AGS, CaCo-2, MCF-7, NCI-H460, PLP2, HFF-2, and HaCat), and anti-inflammatory activity (using RAW 264.7 macrophages). Further studies are ongoing to scientifically validate the medicinal properties of Centauri Honey due to its exceptional chemical composition and thus to become an innovative Ingredient.info:eu-repo/semantics/publishedVersio

Sialometry : aspects of clinical interest

A saliva total é um complexo de secreções multiglandulares composto de fluido gengival, células epiteliais descamadas, microrganismos, produtos do metabolismo bacteriano, resíduos alimentares, leucócitos, muco da cavidade nasal e da faringe. A saliva possui diversas funções, incluindo reparação tecidual, tamponamento, proteção, digestão, gustação, ação antimicrobiana, manutenção da integridade do dente e sistema de defesa antioxidante. A redução do fluxo salivar (hipossalivação) é um distúrbio comum, e estima-se que cerca de 20% da população geral tenham esta alteração. A hipossalivação pode ser decorrente de diabetes mellitus, hipotireoidismo, desidratação, comprometimento do parênquima glandular por processos infecciosos, doenças granulomatosas ou condições autoimunes e inflamatórias (como a síndrome de Sjögren e a artrite reumatoide), radioterapia da região cefálica e/ou cervical, bem como pode estar associada a distúrbios do humor, efeitos adversos ocasionados pelo uso de algumas medicações ou, ainda, ser de causa idiopática. As terapias convencionais para o tratamento da redução do fluxo salivar, com o uso de sialogogos gustatórios e químicos, ainda apresentam restrições. Contudo, novas alternativas têm mostrado grande perspectiva no tratamento deste problema. Diagnosticar um paciente como hipossalivador crônico é um desafio na prática clínica, e os métodos de avaliação do fluxo salivar são pouco conhecidos pelos reumatologistas. A avaliação seriada do fluxo salivar é importante para o correto diagnóstico e prognóstico de determinadas condições bucais e sistêmicas. Esta revisão aborda alguns aspectos relacionados à função da saliva, às consequências da hipossalivação e aos métodos de medição da taxa de fluxo salivar, conceitos úteis na prática diária do reumatologista.Whole saliva is a multiglandular secretion complex consisting of gingival fluid, desquamated epithelial cells, microorganisms, products of bacterial metabolism, food debris, leukocytes mucus from the nasal cavity and the pharynx. Saliva has many functions, including tissue repair, tamponage, protection, digestion, taste, antimicrobial action, maintaining tooth integrity and antioxidant defense system. A decrease in salivary flow (hyposalivation) is a common disorder and it is estimated that approximately 20% of the general population have this alteration. Hyposalivation may be due to diabetes mellitus, hypothyroidism, dehydration, impaired glandular parenchyma by infectious processes, granulomatous diseases or autoimmune and inflammatory conditions (such as Sjogren's syndrome and rheumatoid arthritis), radiotherapy of head and/or neck region, or it may be associated with mood disorders, adverse effects caused by the use of some medications or even be idiopathic. Conventional therapies for the treatment of reduced saliva flow with the use of chemical and gustatory secretagogues are still limited. However, new alternatives have shown great perspective in the treatment of this disorder. To diagnose a patient as having chronic hyposalivation is a challenge in clinical practice and methods of salivary flow assessment are little known by rheumatologists. The serial evaluation of salivary flow is important for the diagnosis and prognosis of certain oral and systemic conditions. This review addresses some aspects related to the role of saliva, the consequences of hyposalivation and methods of salivary flow rate measurement, useful concepts in the daily practice of rheumatology

O que o reumatologista deve saber sobre as manifestações orofaciais das doenças reumáticas autoimunes

Manifestações orofaciais ocorrem com frequência nas doenças reumáticas e, comumente, representam sinais iniciais ou de atividade da doença que ainda são negligenciados na prática clínica. Entre as doenças reumáticas autoimunes com possíveis manifestações orais, incluem-se a artrite reumatoide (AR), miopatias inflamatórias (MI), esclerose sistêmica (ES), lúpus eritematoso sistêmico (LES), policondrite recidivante (PR) e síndrome de Sjögren (SS). Sinais e sintomas orofaciais como hipossalivação, xerostomia, disfunções temporomandibulares, lesões na mucosa bucal, doença periodontal, disfagia e disfonia podem ser a primeira expressão dessas doenças reumáticas. Esse artigo revisa as principais manifestações orofaciais das doenças reumáticas que podem ser de interesse do reumatologista, para diagnóstico e acompanhamento das doenças reumáticas autoimunes.Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases