First survey on the diagnosis and treatment of primary aldosteronism by Spanish Endocrinology and Nutrition specialists.

OBJECTIVE: To evaluate the indication and the resources for the screening/diagnosis of primary aldosteronism (PA) in Endocrinology units in Spain. MATERIAL AND METHODS: An anonymous 2-phase (2020/2021) online survey was conducted by the AdrenoSEEN group among SEEN members with data about screening, confirmation tests, availability of catheterisation and the treatment of PA. RESULTS: Eighty-eight (88) specialists completed the survey. Plasma aldosterone concentration and plasma renin activity were available at all centres; urinary aldosterone was available in 55% of them. The most frequent indications for determining the aldosterone/renin ratio (ARR) were adrenal incidentaloma (82.6%), hypertension with hypokalaemia (82.6%), hypertension in patients <40 years (79.1%) and a family history of PA (77.9%). 61% and 18% of the respondents used an ARR cut-off value of PA of ≥30 and 20ng/dl per ng/mL/, respectively. The intravenous saline loading test was the most commonly used confirmatory test (66.3%), followed by the captopril challenge test (24.4%), with the 25mg dose used more than the 50mg dose (65% versus 35%). 67.4% of the participants confirmed the availability of adrenal vein catheterization (AVC). 41% of this subgroup perform it with a continuous infusion versus 30.5% with an ACTH (1-24) bolus, whereas 70.3% employ sequential adrenal vein catheterization. 48% of the participants reported an AVC success <50%. Total laparoscopic adrenalectomy was the treatment of choice (90.6%), performed by specialists in General and Digestive Surgery specialising in endocrinological pathology. CONCLUSION: PA screening and diagnostic tests are extensively available to Spanish endocrinologists. However, there is a major variability in their use and in the cut-off points of the diagnostic methods. The AVS procedure remains poorly standardised and is far from delivering optimal performance. Greater standardisation in the study and diagnosis of PA is called for.

Involvement of NO/cGMP Signaling Pathway, Ca2+ and K+ Channels on Spasmolytic Effect of Everlasting Flower Polyphenolic Extract (Helichrysum stoechas (L.) Moench).

Functional gastrointestinal diseases (FGID) are worldwide prevalent conditions. Pharmacological treatments can be ineffective, leading the population to turn to herbal or traditional remedies. Helichrysum stoechas (L.) Moench is a medicinal plant traditionally used in the Iberian Peninsula to treat digestive disorders, but its effects on gastrointestinal motility have not been scientifically demonstrated. The aim of this work was to evaluate the antispasmodic effect of a polyphenolic extract of H. stoechas (HSM), its mechanism of action and its antioxidant activity. Isometric myography studies were performed in rat ileum, and malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) levels were measured in rat jejunum. HSM reduced the integrated mechanical activity of spontaneous contractions. In Ca2+-free medium, HSM reduced the concentration-response curve of CaCl2 similarly to verapamil. Pre-incubation with the extract blocked the contraction induced by Bay K8644, KCl and carbachol. L-NAME, ODQ, Rp-8-Br-PET-cGMPS, KT-5823, apamin, TRAM-34 and charybdotoxin reduced the relaxant effect of the extract on spontaneous contractions. MDA+4-HDA levels in LPS-treated tissue were reduced by the extract, showing antioxidant activity. In conclusion, HSM showed antispasmodic activity through inhibition of Ca2+ influx, activation of the NO/PKG/cGMP pathway and opening of Ca2+-activated K+ channels. The results suggest that H. stoechas could help in the prevention or treatment of FGIDs.

The Potential Role of Everlasting Flower (Helichrysum stoechas Moench) as an Antihypertensive Agent: Vasorelaxant Effects in the Rat Aorta.

Helichrysum stoechas (L.) Moench (H. stoechas) is a medicinal plant traditionally used in the Iberian Peninsula to treat different disorders such as arterial hypertension. The aim of this study was to investigate the vascular effects of a polyphenolic methanolic extract of H. stoechas, which has high antioxidant activity, and its mechanism of action. Isometric myography studies were performed in an organ bath with rat aortic rings with intact endothelium. The H. stoechas extract produced vasorelaxation in the aortic rings that were precontracted by phenylephrine or KCl. L-NAME and Rp-8-Br-PET-cGMPS but not indomethacin or H-89; it also reduced the relaxant response evoked by H. stoechas extract on the phenylephrine-induced contractions. H. stoechas extract reduced the response to CaCl2 similar to verapamil and reduced the phenylephrine-induced contractions comparable with heparin. TRAM-34, apamin and glibenclamide reduced relaxation induced by the H. stoechas extract. The combination of L-NAME+TRAM-34+apamin almost completely inhibited the H. stoechas-induced effect. In conclusion, the relaxant effect of the H. stoechas extract is partially mediated by endothelium through the activation of the NO/PKG/cGMP pathway and the opening of Ca2+-activated K+ channels. Furthermore, the decrease in the cytosolic Ca2+ by the inhibition of Ca2+ influx through the L-type Ca2+ channels and by the reduction of Ca2+ release from the sarcoplasmic reticulum via the IP3 pathway is also involved.

Regionalização e Rede de Atenção à Saúde em Mato Grosso / Regionalization and Health Care Network in Mato Grosso, Brazil

Resumo Este estudo analisa a estruturação da Rede de Atenção à Saúde nas regiões de saúde do estado de Mato Grosso, considerando as ações planejadas nos instrumentos de gestão do governo do estado e da Secretaria de Estado de Saúde (SES), nos anos de 2012 a 2017, em conformidade com as diretrizes da Portaria MS/GM nº 4.279, de 30 de dezembro de 2010, que orienta o processo de conformação das redes de atenção à saúde no âmbito do Sistema Único de Saúde (SUS). Trata-se de estudo qualitativo, de natureza exploratório-descritiva, do tipo documental, que analisou os documentos públicos referentes ao planejamento do governo na especificidade do setor de saúde, o que inclui o Plano Plurianual, o Plano Estadual de Saúde e o Plano Estratégico da SES. Os achados do estudo mostram que, embora algumas ações/atividades relacionadas às diretrizes da portaria estivessem contempladas nos documentos pesquisados, ainda não foram suficientes para o estabelecimento de uma rede de atenção regionalizada de qualidade e para o fortalecimento da Atenção Primária à Saúde (APS) com capacidade de ser coordenadora do cuidado e ordenadora da rede no estado de Mato Grosso.

Abstract This study analyzes the structuring of the Health Care Network in the health regions of the state of Mato Grosso, considering the actions planned in the management instruments of the State government and the State Department of Health (SES), in the years of 2012 to 2017, in accordance with the guidelines of Ordinance MS/GM No 4.279, of December 30, 2010, which guides the process of conformation of Health Care Networks within the scope of the Brazilian National Health System (SUS). This is a qualitative, exploratory-descriptive study, of documentary type, which analyzed the public documents related to government planning on the specificity of the health sector, which includes the Pluriannual Plan, the State Health Plan and the Strategic Plan of the SES. The findings of the study show that, although some actions/activities related to the guidelines of the Ordinance were included in the researched documents, they were not yet sufficient for establishing a quality regionalized care network and for strengthening the Primary Health Care (PHC) with the capacity to coordinate care and order the network in the state of Mato Grosso.

Practical guide on the initial evaluation, follow-up, and treatment of adrenal incidentalomas Adrenal Diseases Group of the Spanish Society of Endocrinology and Nutrition. / Guía práctica sobre la evaluación inicial, seguimiento y tratamiento de los incidentalomas adrenales. Grupo de patología adrenal de la Sociedad Española de Endocrinología y Nutrición.

Initial evaluation of adrenal incidentalomas should be aimed at ruling out malignancy and functionality. For this, a detailed clinical history should be taken, and an adequate radiographic assessment and a complete blood chemistry and hormone study should be performed. The most controversial condition, because of the lack of consensus in its definition, is autonomous cortisol secretion. Our recommendation is that, except when cortisol levels <1.8µg/dL in the dexamethasone suppression test rule out diagnosis and levels ≥5µg/dL establish the presence of autonomous cortisol secretion, diagnosis should be based on a combined definition of dexamethasone suppression test ≥3µg/dL and at least one of the following: elevated urinary free cortisol, ACTH level <10 pg/mL, or elevated nocturnal cortisol (in serum and/or saliva). During follow-up, dexamethasone suppression test should be repeated, usually every year, on an individual basis depending on the results of prior tests and the presence of comorbidities potentially related to hypercortisolism. The initial radiographic test of choice for characterization of adrenal incidentalomas is a computed tomography scan without contrast, but there is no unanimous agreement on subsequent monitoring. Our general recommendation is a repeat imaging test 6-12 months after diagnosis (based on the radiographic characteristics of the lesion). If the lesion remains stable and there are no indeterminate characteristics, no additional radiographic studies would be needed. We think that patients with autonomous cortisol secretion with comorbidities potentially related to hypercortisolism, particularly if they are young and there is a poor control, may benefit from unilateral adrenalectomy. The indication for unilateral adrenalectomy is clear in patients with overt hormonal syndromes or suspected malignancy. In conclusion, adrenal incidentalomas require a comprehensive evaluation that takes into account the possible clinical signs and comorbidities related to hormonal syndromes or malignancy; a complete hormone profile (taking into account the conditions that may lead to falsely positive and negative results); and an adequate radiographic study. Monitoring and/or treatment will be decided based on the results of the initial evaluation.

Jasonia glutinosa (L.) DC., a traditional herbal medicine, reduces inflammation, oxidative stress and protects the intestinal barrier in a murine model of colitis.

Jasonia glutinosa (L.) DC., known as rock tea (RT), is traditionally used in Spain as a digestive due to its beneficial properties in bowel disorders. The pharmacological nature of these properties has not been established yet. The aim of this work was to evaluate the therapeutic utility of RT in experimental colitis and to identify chemical constituents with anti-inflammatory and/or anti-oxidative properties. RT extract was prepared with ethanol in a Soxhlet apparatus and analysed by HPLC-DAD. Superoxide radical scavenging properties, xanthine oxidase and lipoxygenase (5-LOX) inhibitory activity, and capability to lower nitric oxide (NO) and tumor necrosis factor α (TNF-α) levels were measured in cell-free and cell-based assays. In the 2.5%-dextran-sodium sulphate (DSS) injury-repair model of ulcerative colitis (UC), mice were daily treated with sulfasalazine (SSZ, as reference drug, 100 mg/kg bw), RT (5, 25 and 50 mg/kg bw, p.o.), or vehicle over 20 days. Colitis was scored daily. Colon samples were examined macroscopically and histopathologically. Protein levels of myeloperoxidase (MPO), interleukins 6, and 10 (IL-6, IL-10), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) were studied as markers of oxidative stress and inflammatory activity. The integrity of the apical epithelial layer was assessed by immunofluorescence staining of zonula ocludens-1 (ZO-1). Finally, intestinal contractility was also evaluated by isometric myography. Fifteen phenolic compounds and three pigments were identified and quantified, of which caffeoylquinic acids, and the flavonoid, quercetin-3-O-galactoside, were the most abundant. RT extract significantly scavenged superoxide radicals, inhibited 5-LOX activity, and lowered NO and TNF-α levels. DSS-treated mice receiving RT scored clinically lower than controls during the first 3 days of DSS treatment and during the recovery period. SSZ was less effective than RT. Anatomical and histological examination of colon samples revealed that RT significantly prevented colon shortening, increased colon thickness, and lowered the macroscopic damage score. RT also significantly prevented the increase of MPO activity, IL-6 levels, iNOS and COX-2 expression, the loss of ZO-1 apical expression, and normalized contractility disturbances. In conclusion, daily administration of RT showed therapeutic properties in the DSS-model of UC. The benefits of RT can likely be attributed to its anti-inflammatory and antioxidant phenolic and flavonoid constituents.

Antibody responses to influenza vaccine in patients on biological therapy: Results of RIER cohort study.

BACKGROUND AND OBJECTIVES: Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. MATERIAL AND METHODS: Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. RESULTS: 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054). CONCLUSIONS: Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule.

El síndrome de realimentación. Importancia del fósforo / The refeeding syndrome. Importance of phosphorus

El síndrome de realimentación es una enfermedad compleja que ocurre cuando se inicia el soporte nutricional después de un periodo de ayuno. La característica principal es la hipofosfatemia, sin embargo, también son comunes otras alteraciones bioquímicas como la hipomagnesemia, el déficit de tiamina y las alteraciones hídrico-electrolíticas. Su incidencia es desconocida, ya que no existe una definición universalmente aceptada, pero con frecuencia está infradiagnosticado. El síndrome de realimentación es un trastorno potencialmente fatal pero prevenible. Identificar a los pacientes en riesgo es crucial para mejorar su manejo. Si se diagnostica existen unas guías (NICE 2006) para orientar su tratamiento (pero basadas en un bajo grado de evidencia). Los objetivos de esta revisión son: destacar la importancia de este problema en pacientes desnutridos, discutir su fisiopatología y características clínicas y dar una serie de recomendaciones finales para disminuir el riesgo de desarrollarlo y facilitar su tratamiento

Refeeding syndrome (RS) is a complex disease that occurs when nutritional support is initiated after a period of starvation. The hallmark feature is the hypophosphataemia, however other biochemical abnormalities like hypokalaemia, hypomagnesaemia, thiamine deficiency and disorder of sodium and fluid balance are common. The incidence of RS is unknown as no universally accepted definition exists, but it is frequently underdiagnosed. RS is a potentially fatal, but preventable, disorder. The identification of patients at risk is crucial to improve their management. If RS is diagnosed, there is one guideline (NICE 2006) in place to help its treatment (but it is based on low quality of evidence). The aims of this review are: highlight the importance of this problem in malnourished patients, discuss the pathophysiology and clinical characteristics, with a final series of recommendations to reduce the risk of the syndrome and facilitate the treatment

The refeeding syndrome. Importance of phosphorus. / El síndrome de realimentación. Importancia del fósforo.

Refeeding syndrome (RS) is a complex disease that occurs when nutritional support is initiated after a period of starvation. The hallmark feature is the hypophosphataemia, however other biochemical abnormalities like hypokalaemia, hypomagnesaemia, thiamine deficiency and disorder of sodium and fluid balance are common. The incidence of RS is unknown as no universally accepted definition exists, but it is frequently underdiagnosed. RS is a potentially fatal, but preventable, disorder. The identification of patients at risk is crucial to improve their management. If RS is diagnosed, there is one guideline (NICE 2006) in place to help its treatment (but it is based on low quality of evidence). The aims of this review are: highlight the importance of this problem in malnourished patients, discuss the pathophysiology and clinical characteristics, with a final series of recommendations to reduce the risk of the syndrome and facilitate the treatment.

Efecto espasmolítico de Jasonia glutinosa en intestino de roedores / Spasmolytic effect of Jasonia glutinosa on rodent intestine

Antecedentes: Jasonia glutinosa es una planta utilizada en la Península Ibérica y en el sur de Francia por su efecto espasmolítico, pero sin evidencia científica sobre ello. Objetivo: examinar el efecto espasmolítico de un extracto de té de roca. Métodos: estudiamos el efecto de dicho extracto sobre las contracciones espontáneas en duodeno de rata in vitro y sobre el tránsito gastrointestinal en el ratón in vivo. Resultados: el extracto de té de roca redujo las contracciones espontáneas en el músculo liso longitudinal del duodeno de rata, inhibió las contracciones inducidas por KCl, bloqueó la contracción causada por la entrada de Ca2+ extracelular y la contracción inducida por el Bay K8644, agonista de los canales de Ca2+ tipo L. El efecto inhibitorio del extracto de té de roca fue similar al del verapamilo, inhibidor de los canales de Ca2+ tipo L. El té de roca no modificó el tránsito gastrointestinal total en ratones sanos. Sin embargo, tras el tratamiento con dextrano sulfato de sodio, un inductor de colitis, el extracto de té de roca revirtió el aumento del tránsito gastrointestinal asociado a dicho tratamiento. Conclusión: el extracto de té de roca relajó el músculo liso duodenal a través de canales de Ca2+ tipo L y normalizó el tránsito gastrointestinal en un modelo de colitis. Estos resultados validan el uso tradicional de Jasonia glutinosa en alteraciones digestivas. Así, el té de roca podría ser utilizado como espasmolítico en el tratamiento de diversas patologías gastrointestinales (AU)

Introduction: Jasonia glutinosa is an endemic plant species of the Iberian Peninsula and Southern France traditionally used in infusions as a spasmolytic; this plant is also known as "té de roca" (rock tea) but there is no scientific evidence about the effects of this plant. Aim: To evaluate the spasmolytic effect of rock tea. Methods: We have studied the in vitro effect of a rock tea extract on rat duodenum spontaneous contractions and the in vivo effect on mice gastrointestinal transit. Results: Rock tea extract reduced the spontaneous contractions of rat duodenal smooth muscle, inhibited KCl-induced contractions and blocked the contractions invoked by both extracellular Ca2+ and the agonist of L-type calcium channels Bay K8644. This inhibitory effect was similar to the one observed after the addition of the antagonist of L-type calcium channels verapamil. Rock tea did not modify gastrointestinal transit in healthy mice. However, after the treatment with dextran sulfate sodium, an inducer of colitis, rock tea extract reverted the increase in the gastrointestinal transit associated with this treatment. Conclusion: Rock tea extract relaxed duodenal smooth muscle via L-type calcium channels and normalized gastrointestinal transit in a model of colitis. These results may validate the traditional use of Jasonia glutinosa in patients with gastrointestinal alterations. Thus, rock tea may be used as a spasmolytic agent to treat gastrointestinal disorders (AU)

Spasmolytic effect of Jasonia glutinosa on rodent intestine.

INTRODUCTION: Jasonia glutinosa is an endemic plant species of the Iberian Peninsula and Southern France traditionally used in infusions as a spasmolytic; this plant is also known as "té de roca" (rock tea) but there is no scientific evidence about the effects of this plant. AIM: To evaluate the spasmolytic effect of rock tea. METHODS: We have studied the in vitro effect of a rock tea extract on rat duodenum spontaneous contractions and the in vivo effect on mice gastrointestinal transit. RESULTS: Rock tea extract reduced the spontaneous contractions of rat duodenal smooth muscle, inhibited KCl-induced contractions and blocked the contractions invoked by both extracellular Ca2+ and the agonist of L-type calcium channels Bay K8644. This inhibitory effect was similar to the one observed after the addition of the antagonist of L-type calcium channels verapamil. Rock tea did not modify gastrointestinal transit in healthy mice. However, after the treatment with dextran sulfate sodium, an inducer of colitis, rock tea extract reverted the increase in the gastrointestinal transit associated with this treatment. CONCLUSION: Rock tea extract relaxed duodenal smooth muscle via L-type calcium channels and normalized gastrointestinal transit in a model of colitis. These results may validate the traditional use of Jasonia glutinosa in patients with gastrointestinal alterations. Thus, rock tea may be used as a spasmolytic agent to treat gastrointestinal disorders.

Diferentes mecanismos de acción de la genisteína y quercetina en las contracciones espontáneas del duodeno de conejo / Different mechanisms of actions of genistein and quercetin on spontaneous contractions of rabbit duodenum

Los flavonoides son conocidos por relajar el músculo intestinal precontraído y retrasar el tránsito o la peristalsis intestinal. El objetivo de este estudio era determinar los efectos de la genisteína y quercetina sobre las contracciones espontáneas del duodeno de conejo in vitro en un baño de órganos. La genisteína o quercetina (0,1-10 μM) redujeron la amplitud de las contracciones espontáneas en el músculo liso longitudinal y circular de duodeno de conejo sin modificar la frecuencia. El Bay K8644 (activador del canal de Ca2+ tipo L), apamina, caribdotoxina y tetraetilamonio (inhibidores de los canales de K+) revertieron la inhibición de la amplitud de las contracciones espontáneas inducidas por la genisteína en el músculo longitudinal y circular. El H-89 (inhibidor de la proteína kinasa A) antagonizó la reducción inducida por la quercetina sobre la amplitud de las contracciones espontáneas del músculo longitudinal y circular de duodeno, mientras la 2,5-dideoxiadenosina (inhibidor de la adenil ciclasa) revertió solamente la reducción de la amplitud en el músculo circular. En conclusión, la genisteína y la quercetina reducen las contracciones espontáneas del duodeno por diferentes mecanismos de acción. El efecto de la genisteína actuaría sobre canales de Ca2+ y de K+, y el efecto de la quercetina actuaría sobre el AMPc y la proteína kinasa A

Flavonoids are known to relax precontracted intestinal smooth muscle and delay intestinal transit or intestinal peristalsis. The aim of this study was to determine the effects of genistein and quercetin on spontaneous contractions of rabbit duodenum in vitro in an organ bath. Genistein and quercetin (0.1-10 μM) reduced the amplitude of spontaneous contractions in the longitudinal and circular smooth muscle of rabbit duodenum, but they did not modify the frequency. Bay K8644 (L-type Ca2+ channel activator), apamin, charybdotoxin, and tetraetylammonium (K+ channel blockers) reverted the inhibition of amplitude of spontaneous contractions induced by genistein in longitudinal and circular smooth muscle

Community-associated methicillin-resistant Staphylococcus aureus in children treated in Uruguay.

INTRODUCTION: Staphylococcus aureus produces a variety of diseases among children, ranging from skin and soft tissue infections to invasive life-threatening diseases. Since 1990, an increasing number of diseases produced by community-associated methicillin-resistant S. aureus (CA-MRSA) isolates have been reported. The aim of this study was to describe the importance and the microbiological characteristics of S. aureus isolates recovered from children treated at the Hospital Pediátrico del Centro Hospitalario "Pereira Rossell" (HP-CHPR); focusing on invasive diseases caused by CA-MRSA isolates, as well as some clinical aspects of the diseases they have produced. METHODOLOGY: One hundred and twenty-five S. aureus isolates recovered from the HP-CHPR between 2003 and 2006 from children with invasive (n=89) and superficial diseases (n=36) were included. Genotypic and phenotypic characteristics of S. aureus isolates and relevant clinical aspects of each child were studied. RESULTS: CA-MRSA isolates accounted for 73% of all S. aureus recovered from invasive (mainly bone and joint) infections, pneumonia and bacteraemia. The most common CA-MRSA strain recovered from invasive (n=65) and superficial (n=36) diseases had the following features: pulsotype A (type USA1100), SCCmec cassette type IV, Panton-Valentine Leukocidin genes positive, susceptibility to trimethoprim-sulfamethoxazole without the inducible macrolide-lincosamide-streptogramin B (iMLSB) resistance phenotype. No association between genotypic characteristics of invasive CA-MRSA isolates and clinical outcomes was found. CONCLUSIONS: CA-MRSA isolates produced a wide spectrum of invasive diseases in a public paediatric hospital between 2003 and 2006. Microbiologic characterization suggests the spread of an adapted CA-MRSA clone lacking erm genes.