Orientadores: Antônio Fernando Ribeiro, Jose Dirceu Ribeiro, Francisco Ubaldo Vieira Júnior / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T21:55:40Z (GMT). No. of bitstreams: 1 Servidoni_MariadeFatimaCorreaPimenta_D.pdf: 12508528 bytes, checksum: b3b02333b5c69daaf09a90ff457cc849 (MD5) Previous issue date: 2014 / Resumo: A Fibrose Cística (FC) é uma doença genética autossômica recessiva, comum em caucasianos. Tem incidência de 1: 2.500 a 1: 6.000 nascidos vivos e 1: 25 em portadores sãos na Europa e EUA e no Brasil a incidência estimada é de 1:10.000 nascidos vivos. É causada pela presença de dois genes CFTR (do inglês Cystic Fibrosis Transmembrane Conductance Regulator) mutados, que codificam uma proteína também denominada CFTR. A CFTR é o principal canal de Cloro (Cl-), é expressa na membrana apical das células epiteliais dos tratos respiratório e digestório (pâncreas, fígado e intestino), nas glândulas sudoríparas e salivares, e no aparelho reprodutor masculino. Regula o transporte de iôns e de água. O comprometimento ou a ausência da função da CFTR promove a desidratação das mucosas com produção de um muco viscoso com consequente obstrução das vias respiratórias e ductos das glândulas exócrinas determinando o fenótipo da FC. O grau de função da CFTR será determinante da gravidade da doença. Até à data, já foram descritas cerca de 2000 mutações no gene CFTR. A F508del é a mutação mais prevalente, está presente em 85% dos pacientes a nível mundial e em 65% no Brasil. As mutações podem ser classificadas em 6 grupos de acordo com o defeito molecular e celular e determina o fenótipo da FC. Pode ser classificado em: clássico e não-clássico. O clássico é o mais conhecido e frequente e apresenta sintomas graves. O não-clássico ocorre em cerca de 15% dos doentes e apresenta sintomas mais brandos, com diagnóstico em geral complexo e tardio. A FC é assim um "espectro de doenças" e o seu rastreio precoce na triagem neonatal (TNN), antes mesmo dos primeiros sintomas, abre novas perspectivas de prognóstico por isso é emergente a necessidade de métodos acurados que determinem a função da CFTR, direcionando uma terapia individualizada, em busca da cura. A primeira parte deste trabalho procurou consolidar a medição da função do canal CFTR em biopsias retais como um marcador biológico para diagnóstico e prognóstico da FC; a segunda descreveu a realização da biópsia retal e suas particularidades sob a ótica dos pacientes e da técnica. A terceira abordou a realização do teste do suor (TS) no estado de São Paulo (SP) expressando o panorama brasileiro do TS. Desta forma, entre 2007 e 2010 foi realizado estudo prospectivo de pacientes atendidos no ambulatório de FC do Hospital das Clínicas (HC) da Universidade Estadual de Campinas (Unicamp) com e sem FC submetidos à biópsia retal. Em 2013 foi aplicado em 14 serviços (9 públicos, 5 privados) que realizam o TS, um questionário qualitativo através de visita às sete cidades que contam com Centros de Referência para atendimento de pacientes com FC em SP. Nossos resultados demonstraram que a determinação de Cl- em biópsias retais mediadas pela CFTR é um biomarcador robusto, sensível, preditivo e reprodutível para o diagnóstico e prognóstico da FC e com potencial uso para ensaios pré-clínicos de terapias moduladoras da CFTR. A pinça jumbo e a solução salina fisiológica determinaram as melhores amostras para os estudos bioquímicos e de eletrofisiologia, a grande maioria dos indivíduos entrevistados não relataram maiores desconforto (76%), sendo a técnica utilizada segura e reprodutível. O estudo do TS em SP demonstrou a necessidade urgente de equipamentos adequados de estimulação e dosagem do Cl- no suor, associado à normatização da técnica e treinamento de pessoal capacitado para a sua realização. Dando seguimento a este trabalho, estamos implementando novas ferramentas diagnósticas para a FC: a avaliação eletrofisiológica da CFTR em câmara de Ussing através da cultura de células nasais e/ou organoides e da unção da CFTR na glândula sudorípara pelo evaporímetro. Por fim, todos os métodos de avaliação diagnóstica devem respeitar procedimentos operacionais padrão (POP), sendo que alguns nomeadamente os de eletrofisiologia, ainda dispõem de aplicação limitada a poucos centros no mundo / Abstract: Cystic Fibrosis (CF) is an autosomal recessive genetic disease, common among Caucasians. In Europe and USA, it has an incidence of 1:2,500-1:6,000 in newborns and 1: 25 for healthy carriers. In Brazil, the estimated incidence is 1:10,000 in newborns. It is caused by the presence of two mutated CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) genes encoding for CFTR protein, a Chloride (Cl-) channel expressed at the apical membrane of epithelial cells. CFTR is the main regulator of ion transport and water. Its defect leads to dehydrated epithelia and to the production of viscous mucus secretions that clogs the airways and ducts of exocrine glands, leading to the clinical manifestations of CF disease, mostly affecting the respiratory and digestive tracts (pancreas, liver and intestine). CFTR is also expressed in the sweat and salivary glands, and in the male reproductive system. The degree of CFTR function will determine the severity of the disease. About 2000 mutations have been already described in the CFTR gene. The F508del is the most prevalent, present in 85% of patients worldwide and 65% in Brazil. Mutations can be classified into six groups, depending on the molecular and cellular defect, and also determining the severity of the CF phenotype: Classical and Non-Classical. The Classical phenotype is best-known and frequent, presenting severe symptoms; but the Non-Classical phenotype, representing ~15 % of all CF patients, shows atypical symptoms, with variable organ involvement, which make the diagnosis difficult and often late. CF thus includes a "spectrum of diseases" and its early detection in newborn screening, even before the first symptoms, opens up new perspectives for prognosis. Since CF diagnosis requires proof of CFTR dysfunction, there is an emerging need for accurate methods capable of detecting CFTR function with high sensitivity and of directing CF therapy, in the quest for the most appropriate treatment. The first part of this study sought to consolidate the measurements of CFTR channel function in rectal biopsies as a biomarker for CF diagnosis and prognosis. The second part focused on the rectal biopsies procedure and its technical aspects and also on how it is perceived in the patients' perspective. The third part, approached how the sweat test (ST) procedure is carried out in CF centers in the state of São Paulo (SP), so as to assess the Brazilian scenario for the ST. To this end, between 2007 and 2010, we conducted a prospective study of patients seen at CF outpatient clinic, of the Clinical Hospital (HC) ¿ State University of Campimas (Unicamp) who underwent rectal biopsy and we also included non-CF subjects as controls. In 2013, a qualitative questionnaire was applied to 14 services (9 public, 5 private) which perform the ST by visiting the 7 cities of SP which have reference CF care centers. Data shown that determination of CFTR-mediated Cl- secretion in rectal biopsies proved to be a robust, sensitive, and reproducible predictive biomarker for CF diagnosis and prognosis, besides being a safe technique with the potential for use in preclinical trials of CFTR modulating therapies. The jumbo forceps and saline solution determined the best samples for electrophysiology and biochemical studies. Moreover, the great majority of the individuals tested by this procedure did not report major discomfort (76%). The work assessing the achievement of ST in SP, demonstrated an urgent need for adequate equipment for the stimulation of sweat and also for the measurement of Cl- in sweat, associated with standardization and training of specialized personnel for its implementation. As a follow up of this work, we are already implementing new diagnostic tools for CF, namely: the study of CFTR function in the sweat gland by the evaporimeter and in cultured nasal cells by Ussing chamber. Finally, all diagnostic methods must comply with strict standardized operation procedures (SOP) and some, including electrophysiology, still have limited use in few centers worldwide / Doutorado / Saude da Criança e do Adolescente / Doutora em Ciências

Orientador: Marco Antonio Garcia de Carvalho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Tecnologia / Made available in DSpace on 2018-08-27T14:19:19Z (GMT). No. of bitstreams: 1 Rodrigues_LucasCerqueira_M.pdf: 3544177 bytes, checksum: ffa0c5e0ad4701affb1f2910bdd85ca4 (MD5) Previous issue date: 2015 / Resumo: Na pesquisa médica, o exame de sudorese é utilizado para destacar as regiões do corpo onde o paciente transpira, sendo estas úteis para o médico identificar possíveis lesões no sistema nervoso simpático. Os estudos acerca deste exame apontam a inexistência de um processo de identificação automática das regiões do corpo. Neste projeto, utilizou-se o Kinect® para ajudar nesta solução. Este dispositivo é capaz escanear objetos 3D e possui uma biblioteca para desenvolvimento de sistemas. Este trabalho tem o objetivo de construir um sistema computacional cujo propósito é desenvolver uma solução semi-automática para análise de imagens digitais provenientes de exames de sudorese. O sistema em foco permite classificar as regiões do corpo onde o paciente transpira, por intermédio de seu escaneamento 3D, utilizando o Kinect®, e gerar um relatório para o médico com as informações consolidadas de forma a realizar o diagnóstico com facilidade, rapidez e precisão. O projeto teve início em 2013, no laboratório IMAGELab da FT/UNICAMP em Limeira/SP e contou com o apoio de uma das equipes do Hospital das Clínicas da USP de Ribeirão Preto/SP que realiza os estudos sobre o Exame de Sudorese iodo-amido. A contribuição do trabalho consistiu na construção do aplicativo, que utiliza o algoritmo de segmentação de imagem K-Means para segmentação das regiões sobre a superfície do paciente, além do desenvolvimento do sistema que inclui o Kinect®. A aplicação validou-se por meio de experimentos em pacientes reais / Abstract: In medical research, the Sweat Test is used to highlight regions where the patient sweats, which are useful for the doctor to identify possible lesions on the sympathetic nervous system. Studies on this test indicate some difficulties in the automatic identification of body regions. In this project, we used the Kinect® device to help in this solution. Created by Microsoft®, the Kinect® is able to identify distance and has a library for systems development. This work aims to build a computer system intending to resolve some of the difficulties encountered during the research in the examination of sweating. The system created allows classify regions of the body where the patient sweats, through its 3D scanning, using the Kinect®, and export to the doctor the consolidated information in order to make a diagnosis quickly, easily and accurately. The project began in 2013 in ImageLab laboratory FT / UNICAMP in Limeira / SP and had the support of one of the USP Clinical Hospital teams in Ribeirão Preto / SP that performs studies on the Sweating Exam Iodine-Starch. The contribution to knowledge was in the software construction using the Kinect® and the image segmentation using K-Means algorithm for targeting regions on the surface of the patient. The application is validated by experiments on real patients / Mestrado / Tecnologia e Inovação / Mestre em Tecnologia

L'adénosine est un nucléotide purinergique ubiquitaire qui exerce plusieurs fonctions dans l'organisme, notamment au sein du tissu cardiovasculaire, via ses 4 récepteurs RCPGs: A1, A2a, A2B, A3. Le système adénosinergique est donc particulièrement impliqué dans la pathologie cardiovasculaire et en particulier dans la maladie coronarienne et dans la fibrillation auriculaire.Dans la maladie coronarienne, le rôle du récepteur A2a est crucial puisqu'il participe au contrôle du flux coronaire. Nous avons comparé le niveau d’expression de ce récepteur dans les cellules mononuclées circulantes et dans des fragments d’artères coronaires prélevés chez des patients atteints de coronaropathie. L’expression du récepteur A2a dans les PBMCs est corrélée à celle mesurée dans les artères coronaires. Ces résultats indiquent que le récepteur A2a exprimé par les PBMCs a un comportement similaire à celui de son homologue in situ.L’adénosine affecte également le rythme cardiaque. Nous avons donc étudié son implication, via les récepteurs A1 et A2a, dans la fibrillation auriculaire. Nous avons observé une élévation très importante de l’adénosine dans la cavité auriculaire au cours de l’épisode de fibrillation auriculaire, et cette augmentation de l’adénosinémie pourrait participer à la permanence de la fibrillation.Dans une troisième partie nous avons évalué la corrélation entre les valeurs de l’ionogramme sanguin et celles de l’ionogramme sudoral et nous avons observé une corrélation entre la kaliémie et le potassium sudoral. Cela pourrait permettre de surveiller de manière continue etnon invasive les dyskaliémies, actrices des troubles du rythme. / The adenosine is an ubiquitous purinergic nucleotide which performs several functions in the body, in particular within the cardiovascular system, via his 4 receptors GPCRs: A1, A2a, A2B, A3. Thus the adenosinergic system is particularly involved in the cardiovascular pathology and in particular in the coronary disease and in the atrial fibrillation.In the coronary disease, the role of the A2a receptor is crucial because it participates in the control of the coronary flow. We compared the level of expression of this receptor in PBçCs and in fragments of coronary arteries taken from patients with coronaropathie. The expression of the A2a receptor in the PBMCs is correlated with that measured in the coronary arteries. These results indicate that the A2a receptor expressed by the PBMCs has a behavior similar to that of his in situ counterpart.The adenosine also modulates the heart rhythm. We thus studied her implication, via the A1 and A2a receptor, in the atrial fibrillation. We observed a very important rise of the adenosine in the left atrium during the episode of fibrillation, and we suggest that this increase in peripheral adenosine concentration could participate in the durability of the fibrillation.In the third part we estimated the correlation between the values of the blood ionogramme and those of the sweat ionogramme and we observed a correlation between the bllod concentration of potassium and the sweatpotassium. It could allow monitoring in a continuous and non-invasive way changes in blood potassium concentration which has a major role in cardiac rhytm diseases.

Background: Cystic fibrosis (CF) is a hereditary disorder caused by genetic mutations, which affect the chloride ion channels, leading to disrupted salt balance in different organs. A lack of properly functioning chloride ion channels can lead to formation of thick mucus, which hinders organ function, especially in the lungs where repeated inflammation occurs. Early diagnosis is critical to prevent further deterioration of the patient's condition. Current method of analysis of CF diagnostics uses conductivity meters to measure sweat electrolytes. However, current guidelines suggest using a chloridometer to directly measure chloride concentration, is the most reliable marker of cystic fibrosis. The aim of this project was to conduct a comprehensive evaluation of the new instrument's safety, reliability, validity, and conformity of the reference range to international chloride meter guidelines. Additional aims were to investigate the effect of storage conditions on sweat chloride concentration levels and examine the effect of increased salt intake on sweat test results. The study recruited healthy participants and took samples of their sweat by inducing sweat gland secretion. The chloride ion concentration was determined using a coulometric method. The results of the study found that the new method was reliable and matched international protocols. It also revealed that an increased salt consumption can impact chloride concentration in sweat, but not to an extent that it can affect medical decisions. Additionally, the study demonstrated that sweat samples can be frozen for up to two weeks without affecting the outcome of the chloride determination.

Depuis la fin des années 1980, le phénomène de revitalisation culturelle amérindienne observé à l’échelle continentale s’est enraciné au Québec. Ce phénomène panindien, qui se définit entre autres par un mouvement de guérison dit communautaire – c’est- à-dire qui s’organise à l’intérieur-même des communautés (par opposition à ce qui vient de l’extérieur) – est caractérisé par la prise en charge des problèmes sociaux rencontrés par les populations amérindiennes. Par l’analyse du rite de la tente à sudation, une pratique emblématique de la spiritualité panindienne et du mouvement de guérison, ce mémoire explore la dualité des stratégies de relation d’aide qui y sont déployées. Pour ce faire, l’expérience en milieu carcéral et en communauté d’aînés et d’intervenants autochtones a été prise à témoin. L’enquête de terrain révèle ainsi qu’en parallèle avec la fonction de mobilisation sociale et politique associée à la revitalisation culturelle amérindienne, on assiste à une instrumentation du rituel à des fins psychothérapeutiques. Tout en s’inscrivant dans la structure cosmologique commune à plusieurs traditions orales algonquiennes, cet usage particulier de la symbolique du rituel met à jour une vision plus clinique, plus individualisée et plus dépolitisée de la guérison autochtone habituellement revendiqué dans le discours panindien. / Since the end of the 1980’s, the Native cultural revitalization observed in North America has taken hold in Québec. This panindian phenomenon has defined itself through the aboriginal healing movement. In turn, this healing movement has been addressing the numerous social problems encountered by the Native populations both inside and outside of their communities. While connecting these events, this thesis explores, through the study of the sweat lodge ceremony, the duality of the counseling strategies deployed both in the panindian spirituality and the aboriginal healing movement. In this regard, the counseling experience of elders and professionals in prison and in the community reveals that besides the social and political functions usually associated with aboriginal healing, we can observe a psychotherapeutic instrumentation of the sweat lodge ritual. While capturing the cosmological structure of many Algonquian oral traditions, this particular use of the sweat lodge symbolism shows a more clinical, more individualized and more apolitical vision of aboriginal healing than the one that is usually described in the panindian discourse.

(in English): The diploma thesis examines phenomenon of stigmas and stigmatised persons in the Middle Ages. This diploma thesis contains of three parts. The goal of first part is description of Crucifixion symbolism from beginning of Christianity up to first stigmas about Francis of Assisi from 1224. Main part presents its own phenomenon of stigmas: their definition, base and reception in religious and expert field. Final part focuses on significant middle-aged holders of stigmas and analysis of their hagiography. Klíčová slova (anglicky): Stigmas, Jesus Christ, cross, crucifixion, bloody sweat, bloody tears, thorn crown, mysticism, self-identification.

Title: Impact textile membranes on the dynamics of changes physiological indicators of workload Goals: Compare measurements of clothing technical parameters and laboratory measurement workload in this outfit. Describe and explain the relationship between the results of the technical and functional measurements and physiological issues associated with the use of different textile membranes during a workout. Method: Laboratory quantitative measurement of selected physiological parameters, clothings technical parameters, skin temperature and subjective perception of thermophysiological comfort. Subsequent comparative analysis of measurement results. Key words: clothes, textile membranes, workload, oxygen consuption (VO2), thermophysiological comfort, sweat, clothing physiology

O lactato é um metabólito chave formado pelo metabolismo anaeróbico da glicose nos músculos, e tem se tornado um biomarcador importante no âmbito clínico e esportivo. Atualmente, existem biossensores eletroquímicos portáteis que são capazes de determinar os níveis de lactato no organismo em tempo real. No entanto, tal método é invasivo uma vez que requer amostras de sangue. O presente projeto tem como objetivo desenvolver um biossensor eletroquímico descartável para detecção de lactato no suor. Para isto a configuração do dispositivo foi feita utilizando a celulose bacteriana como substrato para obtenção de um dispositivo que seja resistente à deformação mecânica, especialmente quando molhado e, também, permeável ao suor. A impressão dos eletrodos de carbono neste substrato foi efetuada utilizando o processo de serigrafia. Com os dispositivos produzidos foram realizados experimentos de voltametria cíclica e espectroscopia de impedância eletroquímica, a fim de caracterizar o sensor desenvolvido e investigar a influência do pré-tratamento eletroquímico na sua performance analítica. A partir da modificação da superfície eletródica com nanocubos de Azul da Prússia foi possível desenvolver um sensor eletroquímico para detecção de peróxido de hidrogênio. A cronoamperometria foi utilizada para a determinação da curva analítica para o peróxido de hidrogênio. Com todos os parâmetros da cronoamperometria otimizados, uma dependência linear da corrente catódica com a concentração de peróxido de hidrogênio foi obtida, com a equação: Ip = 0,1 + 4,30 [H2O2], com r2 = 0,999 (n = 3). Esta curva analítica mostrou que a metodologia apresenta um Limite de Detecção e de Quantificação de mol L-1 e mol L-1, respectivamente. Para a configuração do biossensor eletroquímico a enzima lactato oxidase foi incorporada à superfície do papel pelo método de ligação covalente. Adotando esta metodologia foi verificado um aumento da área eletroativa que possibilitou uma melhora significativa no desempenho do sensor desenvolvido. No qual se obteve uma região linear de 1-24,0 mmol L-1 em suor sintético, obtendo-se Limites de detecção e Quantificação de e mol L-1. Tais parâmetros se mostraram adequados já que o suor pode apresentar níveis de aproximadamente 25 mmol L-1 de lactato. De modo geral, foi possível desenvolver uma plataforma eletroquímica no substrato de celulose bacteriana para a detecção de lactato em amostras de suor sintético. O dispositivo desenvolvido apresentou uma boa durabilidade e resistência ao se executarem sucessivas medidas corroborando a viabilidade deste substrato na projeção de sensores vestíveis para a aplicação direta na pele e monitoramento dos níveis de lactato em tempo real. / Lactate is a key metabolite formed in the anaerobic metabolism of glucose in the muscles. It has become an important biomarker in the clinical and sport scopes. Currently, there are portable biosensors that are able to determine lactate levels in real time. However, these methods are invasive since they require blood samples. Herein, we aim to develop a disposable wearable electrochemical biosensor for detection of lactate in sweat. For this purpose the configuration of the device was made with bacterial cellulose substrate in order to be permeable to sweat and resistant to mechanical deformation, especially when wet. The fabrication of the electrodes was made through screen printing technique. Electrochemical impedance spectroscopy and cyclic voltammetry were used to characterize the sensor developed in order to investigate the influence of the electrochemical pre-treatment in the analytical performance of the electrodes. To develop an electrochemical sensor for the detection of hydrogen peroxide the screen printed electrode was modified with Prussian blue nanocubes. Chronoamperometry experiments were used to detect of hydrogen peroxide. From optimized chronoamperometry parameters, a linear dependence of the cathodic current with the hydrogen peroxide concentration was obtained with the equation: Ip = 0.1 + 4.30 [H2O2], with r2 = 0.999 (n = 3). The limit of detection (LOD) and the limit of quantification (LOQ) were mol L-1 e mol L-1, respectively. For the configuration of the electrochemical biosensor the lactate oxidase enzyme was immobilized on the paper surface by the covalent bonding method. Adopting this methodology was verified an increase of the electroactive area that allowed a significant improvement in the performance of the developed sensor. In which a linear concentration range of 1-24.0 mmol L-1 was obtained in the synthetic sweat, obtaining LOD and LOQ of mol L-1 e mol L-1, respectively. Such parameters were adequate since sweat may have lactate levels of approximately 25 mmol L-1. Finally, it was possible to develop an electrochemical platform using the bacterial cellulose substrate for the detection of lactate in samples of synthetic sweat. The developed device presented a good durability and resistance when performing electrochemical measurements assuring the feasibility of this substrate in the projection of wearable sensors for the direct application to skin and monitoring of lactate levels in real time.

Objectives: To determine the physiological strain on industrial workers under thermal stress on extended shifts. To continuously measure deep body core temperatures, heart rates, fluid intake, changes in hydration state and physical fatigue in order to establish acceptable levels of physiological strain. To develop a rational heat stress index compatible with these limits. To design working-in-heat protocols for a self-paced workforce. Methods: A series of studies was conducted over 77 shifts on a group of approximately 50 male volunteers working in thermally stressful environments. Continuously- recorded deep body core temperatures, heart rates, fluid consumption, urinary specific gravity and physical fatigue were measured and recorded. A new field protocol was developed to assess physical fatigue over the working shift. An original methodology was developed to allow any heat stress index to be assessed on a comparative basis with any other index. A review of the commonly used occupational heat stress indices was conducted. A new rational heat stress index was developed, based on existing biophysical relationships and recommended physiological strain limits of deep body core temperature and sweat rate. New protocols designed for self-paced work incorporating the significant risk factors for heat illness were developed and implemented in a workforce of approximately 2000 workers exposed to heat stress. The previous protocols used a shortened shift as the primary intervention to protect worker health. The subsequent protocols removed the shortened shift and replaced this with a range of other interventions. Deep body core temperature, heart rate, fluid consumption, hydration state and fatigue were measured before and after the changes in protocols. / Results: Comparisons of heat stress indices confirmed the wide divergence in guidance provided by many of the commonly-used indices in terms of acceptable working environments. It also highlighted a number of serious shortcomings in the most widely-used indices, especially WBGT and ISO7933. A new, rational heat stress index called Thermal Work Limit (TWL) was developed. This included development of a computer model incorporating key thermal physiological parameters (deep body core temperature, mean skin temperature, sweat rate, skin wettedness). There was no increase in heat stress (as indicated by average workplace environmental conditions), deep body core temperature, mean heart rate, or changes in hydration status after the changes in protocols. Average environmental conditions were severe (WBGT 30.9° C, sd 2.0° C, range 25.7-35.2° C). Environmental conditions in the study were much hotter than those considered acceptable under standards such as the ACGIH. The results showed that miners regularly exceeded those limits allowable under most current indices in terms of maximum deep body core temperature (avg 38.3° C, std dev 0.4° C), maximum temperature rise (1.4° C, 0.4° C) and maximum heat storage (431 kJ, 163 kJ), without reporting any symptoms of heat illness. A significant component of the observed elevated core temperatures was due to the normal circadian rhythm, which was measured at 0.9° C (std dev 0.2° C). Evidence was found that workers "self-pace" when under thermal stress. Fluid intake averaged 0.8 l/h during exposure (sd 0.3 l/h, range 0.3-1.5 1/h). Average urinary specific gravity at start-, mid- and end of shift was 1.0251, 1.0248 and 1.0254 respectively; the differences between start and mid-shift, mid and end-shift, and start and end-shift were not significant. / However, a majority of workers were coming to work in a moderately hypohydrated state (urinary specific gravity avg 1.024, std dev 0.0059). Involuntary dehydration was not found to occur in the study group. This is in contrast to several other studies and some of the leading heat stress standards, which are based on the premise that workers are unable to maintain their hydration status when working in the heat, even when their fluid consumption is equal to their sweat rate. Continuous heart rates measured over a shift (avg 103 bpm, 14% of shifts exceeding avg 110 bpm, 5% exceeding avg 120 bpm) were in excess of those allowable under most current indices On average, workers experienced a peak 10- minute heart rate of 140 bpm and a peak 30-minute heart rate of 130 bpm during their shifts. There was a significant increase in fatigue in the first half of the working shift (P=0.001), with workers on average showing a significant recovery in the second half of their shift (p=0.04). Conclusions: Current heat stress indices provide little common agreement as to acceptable levels of thermal strain or stress for workers, at equivalent levels of environmental stress. IS07933 is seriously flawed and the ACGIH WBGT guidelines are too conservative for acclimatised workers and are unlikely to become widely adopted by industries with well-acclimatised workers. Many of the existing indices show internal inconsistencies. / Most of the physiological heat strain limits used in existing rational heat stress indices (in terms of deep body core temperature and heart rate) are conservative for self-paced, acclimatise d, non-dehydrating male workers. Involuntary dehydration is not unavoidable when acclimatised workers are exposed to thermal stress. Heat stress standards should not limit heat exposure durations for self- paced workers who have access to water on the basis of an unavoidable body water loss. Physical fatigue does occur in workers under heat stress on extended shifts; however, most workers show a significant increase in fatigue in the first half of their shift; whereas data indicates self-paced workers undergo significant recovery in terms of fatigue in the second half of the shift. As the heat exposures in this study cover a wide range of temperatures, humidity levels, wind speeds, body morphology and VO2max, these conclusions are applicable to most thermally stressful settings involving well-informed, well-acclimatised and self-paced male workers. The major category of work type not covered by this study is that of workers in fully-encapsulated (vapour-barrier) protective clothing. In addition, this study examined acute effects of heat stress and strain, not effects that might only be manifest with chronic exposure to heat.

Palmoplantar pustulosis (PPP) is a chronic disease of unknown pathogenesis. Most of the patients were smokers. High prevalence of a number of autoimmune diseases was observed among the patients (thyroid disease 14%, gluten intolerance 8%, diabetes type 1 3%). Eosinophils and neutrophils were found in large numbers in the pustules. Massive infiltrates of lymphocytes and mast cells in the dermis below the pustule and an abnormal acrosyringial pattern indicate that the acrosyringium is the target for the inflammation. Immunofluorescence (IF) revealed decreased innervation of the sweat gland, outward migration of substance P-positive granulocytes in the acrosyringium and an increased number of contacts between mast cells and nerve fibres in the dermis. Distributions of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were studied, since they regulate the level of acetylcholine, the main inducer of sweating. The most intense AChE-like immunoreactivity (LI) was observed in the acrosyringium in the lowest part of the stratum corneum, corresponding to the site of the pustule in PPP. ChAT-LI in granulocytes and AChE-LI in mast cells were demonstrated, which may have implications for inflammatory processes in general. Nicotinic acetylcholine receptors (nAChR) are activated by acetylcholine but also by nicotine. Immunohistochemstry of α-3 and α-7 subtypes of the nAChRs showed that the nAChR expression in healthy skin was influenced by smoking. A highly abnormal α-7 nAChR distribution in PPP skin was observed. The levels of nAChR antibodies were elevated in 42% of the PPP sera, and 68% of these sera gave specific endothelial IF in the papillary dermis in skin from non-smokers. Positive IF in the acrosyringium was also noted in skin from smokers. Conclusions: Smoking seems to induce up-regulation of an antigen in palmar skin. The results indicate that PPP is an autoimmune disease and that nicotine might have a role in the onset of the inflammation.