AIM: The aim of this preliminary clinical study is to compare the stress level of non-hypertensive and hypertensive subjects by measuring changes in Chromogranin A (CgA) level in saliva before and after non-surgical periodontal treatment, scaling and root planing (SRP), subjects and to determine if the dental treatment affects the patient’s stress level. We will also measure the changes in arterial blood pressure before and after non-surgical periodontal treatment. Finally, compare if the duration of treatment affects the CgA level and blood pressure between non-hypertensive and hypertensive subjects. MATERIALS AND METHODS: Twenty patients participated in the study and only 17 evaluated. Four hypertensive patients and 13 non-hypertensive patients. Blood pressure was measured and saliva samples were collected at consultation visit (T0) and before (T1) and after (T2) non-surgical periodontal treatment (SRP). Duration of treatment was recorded. RESULTS: Concentration of CgA (pmol/ml) in the hypertensive group between T0 – T2 and T1 – T2 was a decrease of 15% and 46.5% respectively. The non-hypertensive group a decrease of 71% and 64.4% respectively. For the whole population, there was a significant decrease in CgA concentration between T0 – T2 (p-value = 0.046) and T1 – T2 (p-value = 0.032) with no statistical significance between T0 – T1 (p-value =0.873). No significant difference in change of blood pressure. CONCLUSION: Within the limitations of this study, there was no significant difference in blood pressure measurements. Concentrations of CgA decreased significantly after SRP compared to before SRP in all groups. A larger sample size is needed in the future.

Os serviços de banho e tosa vem apresentando um grande crescimento, sendo o segundo maior faturamento do mercado pet no Brasil. Em um ambiente de banho e tosa, a presença de agentes estressores é inevitável, podendo levar o animal a óbito. Sendo assim, este trabalho visa analisar as alterações nos níveis de cortisol e cromogranina A salivares, as alterações comportamentais e de parâmetros fisiológicos antes e depois do banho e tosa, como também avaliar os fatores ambientais que possam desencadear um quadro de estresse agudo e causar danos à saúde do animal, em 33 cães de dois estabelecimentos de banho e tosa da cidade de São Paulo. A saliva foi coletada por meio de um swab introduzido oralmente entre os dentes e a bochecha do cão e posteriormente armazenada a -80ºC até a realização dos testes. Para a mensuração dos níveis de cortisol e cromogranina A salivares foram realizados ensaios imunoenzimáticos (ELISA). Os resultados apontam que, independente da raça, sexo ou idade, os cães demonstraram aumento dos níveis de cortisol salivar em 61% após o banho e os níveis de cromogranina A salivar aumentaram em 55% antes mesmo do inicio dos procedimentos. Alguns comportamentos relacionados ao estresse, como rigidez dos membros e lambedura do plano nasal foram observados durante todo o procedimento, porém se intensificaram durante a secagem do pelo, principalmente quando da utilização do soprador. Alguns itens da estrutura do estabelecimento devem ser avaliados periodicamente, tais como secadores, tesouras e escovas, banheiras, mesas de procedimentos e gaiolas, evitando assim quaisquer danos à integridade física do animal. Este estudo demonstra que os procedimentos de banho e tosa geram estresse à grande maioria dos cães e que a estrutura dos estabelecimentos pode apresentar pontos críticos que causem danos à saúde do animal. A presença de um médico veterinário no estabelecimento e o correto treinamento dos funcionários garante uma maior qualidade na prestação dos serviços de banho e tosa, prevenindo riscos e atuando de forma eficiente e eficaz em quaisquer intercorrências que possam surgir durante o banho e tosa / Pet grooming is a growing service and the second largest grossing business in Brazil’s pet market. In a grooming environment, the presence of stressors is inevitable, and sometimes the stress may lead the animal to death. This study aims to evaluate the acute stress provided in a grooming environment in 33 dogs from two pet shops in Sao Paulo, Brazil, through paired analysis of before and after grooming changes in salivary cortisol and chromogranin A levels, changes in behavioral and physiological parameters and also describe the environmental factors that can trigger an acute stress frame and cause risks to dog’s health. The saliva was collected by a swab inserted orally between the dogs teeth and cheek and then frozen at -80 º C until the tests. Salivary cortisol and chromogranin A levels were measured through immunoenzymatic assays (ELISA). The results show that regardless of breed, gender or age, the dogs increased their cortisol levels by 61% after grooming, while chromogranin A levels increased by 55% even before grooming. Some stress-related behaviors, such as stiffness of the limbs and licking the nasal plane were observed during the entire grooming procedure, but intensified during the drying, especially when the blower was used. To avoid risks to the animals’s physical integrity some items in the pet shop structure should be periodically assessed such as dryers, scissors and brushes, baths , procedures tables and cages. This study demonstrated that grooming procedures cause stress in the majority of dogs and that pet shops may present environmental critical points that could be a risk to the animal’s health. The presence of a veterinarian and the proper training of employees ensure a higher quality in the grooming services, preventing risks and providing efficient and effective actions through any complications that may arise during grooming procedures

Os serviços de banho e tosa vem apresentando um grande crescimento, sendo o segundo maior faturamento do mercado pet no Brasil. Em um ambiente de banho e tosa, a presença de agentes estressores é inevitável, podendo levar o animal a óbito. Sendo assim, este trabalho visa analisar as alterações nos níveis de cortisol e cromogranina A salivares, as alterações comportamentais e de parâmetros fisiológicos antes e depois do banho e tosa, como também avaliar os fatores ambientais que possam desencadear um quadro de estresse agudo e causar danos à saúde do animal, em 33 cães de dois estabelecimentos de banho e tosa da cidade de São Paulo. A saliva foi coletada por meio de um swab introduzido oralmente entre os dentes e a bochecha do cão e posteriormente armazenada a -80ºC até a realização dos testes. Para a mensuração dos níveis de cortisol e cromogranina A salivares foram realizados ensaios imunoenzimáticos (ELISA). Os resultados apontam que, independente da raça, sexo ou idade, os cães demonstraram aumento dos níveis de cortisol salivar em 61% após o banho e os níveis de cromogranina A salivar aumentaram em 55% antes mesmo do inicio dos procedimentos. Alguns comportamentos relacionados ao estresse, como rigidez dos membros e lambedura do plano nasal foram observados durante todo o procedimento, porém se intensificaram durante a secagem do pelo, principalmente quando da utilização do soprador. Alguns itens da estrutura do estabelecimento devem ser avaliados periodicamente, tais como secadores, tesouras e escovas, banheiras, mesas de procedimentos e gaiolas, evitando assim quaisquer danos à integridade física do animal. Este estudo demonstra que os procedimentos de banho e tosa geram estresse à grande maioria dos cães e que a estrutura dos estabelecimentos pode apresentar pontos críticos que causem danos à saúde do animal. A presença de um médico veterinário no estabelecimento e o correto treinamento dos funcionários garante uma maior qualidade na prestação dos serviços de banho e tosa, prevenindo riscos e atuando de forma eficiente e eficaz em quaisquer intercorrências que possam surgir durante o banho e tosa / Pet grooming is a growing service and the second largest grossing business in Brazil’s pet market. In a grooming environment, the presence of stressors is inevitable, and sometimes the stress may lead the animal to death. This study aims to evaluate the acute stress provided in a grooming environment in 33 dogs from two pet shops in Sao Paulo, Brazil, through paired analysis of before and after grooming changes in salivary cortisol and chromogranin A levels, changes in behavioral and physiological parameters and also describe the environmental factors that can trigger an acute stress frame and cause risks to dog’s health. The saliva was collected by a swab inserted orally between the dogs teeth and cheek and then frozen at -80 º C until the tests. Salivary cortisol and chromogranin A levels were measured through immunoenzymatic assays (ELISA). The results show that regardless of breed, gender or age, the dogs increased their cortisol levels by 61% after grooming, while chromogranin A levels increased by 55% even before grooming. Some stress-related behaviors, such as stiffness of the limbs and licking the nasal plane were observed during the entire grooming procedure, but intensified during the drying, especially when the blower was used. To avoid risks to the animals’s physical integrity some items in the pet shop structure should be periodically assessed such as dryers, scissors and brushes, baths , procedures tables and cages. This study demonstrated that grooming procedures cause stress in the majority of dogs and that pet shops may present environmental critical points that could be a risk to the animal’s health. The presence of a veterinarian and the proper training of employees ensure a higher quality in the grooming services, preventing risks and providing efficient and effective actions through any complications that may arise during grooming procedures

Some aspects of the stress response during acute intensive care for severe burns are described and quantified by measuring hormonal and neuroendocrine patterns and relating these to organ function in the short term. This includes an assessment of whether there are markers for the severity of stress that are better than conventional descriptors of the severity of a burn in predicting failing organ function. P-CgA after a major burn injury is an independent and better predictor of organ dysfunction assessed as SOFA score than the traditionally used TBSA% burned. The results also suggest that the extent of neuroendocrine activation is related to organ dysfunction, and this motivates a more extensive effort to evaluate P-CgA as a prognostic marker with respect to mortality and long-term outcome. P-NT-proBNP exhibited a complex pattern with considerable inter-individual and day-to-day variations. Values of P-NT-proBNP were related to size of burn, water accumulation and systemic inflammatory response. A considerable covariation with trauma response and SOFA scores was observed in day by day analyses, but with weight change only on day 2. Maximum P-NT-proBNP showed a stronger correlation with SOFA score on day 14, with mortality, and with LOS, than did age and TBSA% burned. High values were also independent predictors of all subsequent SOFA scores up to two weeks after injury. P-NT-proBNP and NT-proANP reflect and predict organ function after burn injury similarly, notwithstanding a significantly larger intra-individual variability for P-NT-proBNP. P-NT-proBNP, but not NT-proANP, reflects the systemic inflammatory trauma response. Free cortisol concentration was related to the size of burns, as was the circadian cortisol rhythm. This effect of burn size was, at least in part, related to its effect on organ function. This thesis points to the fact that the stress response is richly interwoven, and cannot be adequately assessed by one biomarker only. All biomarkers studied here can be viewed as representing efferent limbs of the stress reaction, and they would need to be supplemented by biomarkers representing individual physiologic responses that follow the stress signaling.

No description available.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 4 uppsatser.

This thesis describes studies in patients with inflammatory bowel disease (IBD) and collagenous colitis (CC). We investigated mucosal eosinophil and neutrophil granulocytes and T-cells involved in the inflammatory processes and aimed at determining whether these processes are reflected in the faecal (F) contents of specific proteins secreted by cells in the intestinal mucosa. Thus, we measured eosinophil cationic protein (ECP) and eosinophil protein X (EPX) and the neutrophil derived myeloperoxidase (MPO) and calprotectin (C); and in addition, chromogranin A (CgA), Chromogranin B (CgB) and secretoneurin (SN), derived from EEC cells and cells in the enteric nervous system. We found that a normalised FC level can serve as a surrogate marker for successful treatment in patients with IBD, but persistently high FC levels need further evaluation (study I). Furthermore, FC and F-MPO appear to relate better than F-EPX to treatment outcome in IBD. We evaluated F-ECP, F-EPX, F-MPO and FC as markers of disease activity and treatment outcome in patients with CC (study III) and concluded that F-ECP was the best discriminator of detecting active CC. Normalised F-ECP and F-EPX could serve as markers of successful treatment. We showed that the inflammation in CC is characterised by activated eosinophils, but that there is no neutrophil activity (study II). T-cells have a lower grade of activity in active CC than in control subjects. During budesonide treatment the normal activation of eosinophils and T-cells is restored, with concomitant clinical remission. The findings in studies II and III indicate that the eosinophils have an essential role in the pathophysiology of CC. Markedly higher values of F-CgA, F-CgB and F-SN were found in patients with CC than in those with IBD and controls (study IV) indicating a crucial role for the intestinal neuro-endocrine system in the pathogenesis of collagenous colitis.

Diss. (sammanfattning) Göteborg : Univ., 2010.

Die transkriptionelle Aktivierung des HDC Gens sowie des Chromogranin A Gens in ECL-Zellen der Magenmucosa repräsentiert einen zentralen Mechanismus der Säureregulation durch Gastrin und scheint ausserdem Bedeutung für die Pathogenese der gastroduodenalen Ulkuskrankheit zu haben. Unsere Untersuchungen identifizieren erstmals die molekularen Mechanismen der Gastrin-abhängigen Regulation beider Gene und definieren die beteiligten Transkriptionsfaktoren, regulatorischen DNA-Elemente und intrazellulären Signalwege. Des weiteren wurde durch transgene Untersuchungen die transkriptionelle Regulation des ChromograninA Gens in vivo bestätigt und die neuroendokrin-spezifische Expression eines 4.8kB-langen CgA-Promotorfragmentes demonstriert. Als pathobiologisch relevante Aktivatoren des HDC Gens konnten oxidativer Stress sowie die H. pylori Infektion identifiziert und hinsichtlich ihrer molekularen Wirkungen auf das Schlüsselgen der Histaminsynthese im Magen charakterisiert werden. Diese Ergebnisse dokumentieren einen potentiellen Mechanismus für die Interaktion beider Stimuli mit den physiologischen Regelkreisen der Magensäureregulation und können durch die Definition neuer molekularer Angriffspunkte möglicherweise zur Entwicklung innovativer Therapieansätze beitragen. / Transcriptional activation of the genes encoding histidine decarboxylase and chromogranin A represents a key mechanism of gastrin-dependent acid regulation and also appears to be involved in the pathogenesis of gastroduodenal ulcer disease. Our results for the first time identify the molecular mechanisms underlying gastrin-dependent activation of both genes, and define the transcription factors, regulatory DNA elements and signal transduction pathways involved in this process. Furthermore, transgenic studies confirmed the principle of gastrin-dependent transcriptional activation of the chromogranin A gene in vivo, and demonstrated neuroendocrine-specific expression of a 4.8kB-CgA promotor fragment. In addition, the pathobiological stimuli oxidative stress and H. pylori were molecularly characterized regarding their activating effects on the key gene of gastric histamine sythesis. These results provide potential mechanisms for the interaction of both stimuli with regulatory circuits of gastric acid secretion, and can probably contribute via definition of new molecular targets to the development of inovative therapeutic strategies.

L'utilisation excessive d'agents antifongiques, aggravée par la pénurie de nouveaux médicaments introduits sur le marché, provoque l'accumulation de phénotypes de multi-résistance de nombreuses souches fongiques. Dans ce contexte alarmant, le développement de nouvelles molécules alternatives aux agents antifongiques conventionnels constitue un enjeu majeur de santé publique afin de prévenir l’émergence de nouvelles résistances fongiques pour limiter les problèmes socio-économiques. Dans ce contexte, la cateslytine (CTL), un peptide naturel issu de la maturation endogène de la chromogranine A, et déjà décrit comme un agent antimicrobien efficace contre de nombreux agents pathogènes, dont Candida albicans, présente un intérêt particulier. Dans la présente étude, nous avons ainsi comparé l'activité antimicrobienne de deux conformations de CTL, L-CTL et D-CTL contre différentes souches de Candida. Nos résultats démontrent que D-CTL est l'agent antifongique le plus efficace et le plus sûr. De plus, contrairement à L-CTL, D-CTL n'est pas dégradé par les protéases sécrétées par Candida albicans et est également stable dans la salive. La vidéo-microscopie révèle une invasion rapide de Candida albicans par D-CTL, et démontre l’importance de la division cellulaire pour la propagation de D-CTL d'une cellule mère à une cellule fille. La microscopie électronique en transmission permet d’illustrer la perméabilisation de la membrane fongique induite par les deux peptides. Enfin, nos résultats révèlent un effet antifongique additif de la combinaison entre D-CTL et le voriconazole, un agent antifongique de référence dans le traitement des infections liées à Candida. En conclusion, D-CTL peut être considéré comme un agent antifongique efficace, sûr et stable et pourrait être utilisé seul ou en association avec le voriconazole pour traiter les infections orales liées à Candida et servir dans le futur à l’élaboration de biomatériaux actifs. / The excessive use of antifungal agents, compounded by the shortage of new drugs being introduced into the market, is causing the accumulation of multi-resistance phenotypes in many fungal strains. Consequently, new alternative molecules to conventional antifungal agents are urgently needed to prevent the emergence of fungal resistance. In this context, Cateslytin (CTL), a natural peptide derived from the processing of Chromogranin A, has already been described as an effective antimicrobial agent against several pathogens including Candida albicans. In the present study, we compared the antimicrobial activity of two conformations of CTL, L-CTL and D-CTL against various strains of Candida. Our results show that D-CTL was the most efficient and safe antifungal agent. Moreover, in contrast to L-CTL,D-CTL was not degraded by proteases secreted by Candida albicans and was also stable in saliva. Using video-microscopy, we also demonstrated that D-CTL can rapidly enter Candida albicans, but is unable to spread within a yeast colony unless from a mother cell to a daughter cell during cellular division. Besides, transmission electron microscopy illustrated the permeabilization of the fungal membrane induced by both peptides. Finally, we revealed that the antifungal activity of D-CTL could be synergized by voriconazole, an antifungal of reference in the treatment of Candida related infections. In conclusion, D-CTL can be considered as an effective, safe and stable antifungal and could be used alone or in a combination therapy with voriconazole to treat Candida associated infections including oral candidosis.