963 resultados para Diseases in Twins
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Propolis has shown activity against pathogenic microorganisms that cause diseases in humans and animals. The ethanol (Et-Blg) and acetone (Ket-Blg) extracts from a Bulgarian propolis, with known chemical compositions, presented similar activity against tissue culture-derived amastigotes. The treatment of Trypanosoma cruzi-infected skeletal muscle cells with Et-Blg led to a decrease of infection and of the intracellular proliferation of amastigotes, while damage to the host cell was observed only at concentration 12.5 times higher than those affecting the parasite. Ultrastructural analysis of the effect of both extracts in epimastigotes revealed that the main targets were the mitochondrion and reservosomes. Et-Blg also affected the mitochondrion-kinetoplast complex in trypomastigotes, offering a potential target for chemotherapeutic agents.
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The Egyptian Pharaoh Akhenaten initiated worship of a single god and established a new capital city (Tell Amarna) that was built and occupied only once from 1350-1330 BCE. This single short occupation offers a unique opportunity to study a short time period. The royal tombs have long been known and studied, but the location of graves for the common inhabitants has been an archaeological puzzle for more than 50 years. Recently four cemeteries have been located and the analysis of commingled bones from the South Tombs cemetery is presented here. The remains yield the following demographic profile: 53 adults with 19 females and 18 males; 14 juveniles between the ages of 5 and 17; and 3 infants. Arthritis and degenerative joint disease of the spine and joints indicates that DJD was not excessive. Only 2 to 8% of the adult population exhibits arthritis. There are 3 healed fractures of the arm (2 to 8% of the adult sample). There is 1 healed compressed fracture of the skull suggesting violence. The adult infection rate is between 2 and 8% with 3 healed and 1 active case of periostitis and no severe infections. Anemia is implicated by 23% of adult frontals exhibiting cribra orbitalia. Life for the common residents of Amarna appears to not have been as good as initially postulated.
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Background: Cardiovascular diseases are ranked among the leading causes of death in the industrialized countries. This study is aimed at ascertaining the mortality trends by ischemic heart disease (IHD) and cerebrovascular diseases (CVD) in Andalusia within the 1975-2004 period. Method: Based on the official IHD and CVD death statistics and the related populations, the gross rates (GR) and age-adjusted rates (TS) and the Potential Years of Life Lost (PYLL) were calculated. To quantify the trends and their change points, a joinpoint regression analysis was made. Results: The number of IHD deaths for females rose from 2,086 deaths in 1975 to 3,336 in 2004, the TS having dropped from 74.29 to 50.94 deaths/100,000 females, the PYLL having dropped from 173.65 years to 90.56 years/100,000 females. The number of deaths for males rose from 2,854 deaths in 1975 to 4,085 in 2004, the TS having dropped from 147, 67 to 104.96 deaths /100,000 males. The PYLL showed a like behaviour from the first to the last year of the series, showing values of 716.46 and 460.04 years / 100,000 males. For the IHD in females, the number of deaths in absolute numbers dropped from 4,712 to 4,221, the TS having dropped from 166.00 to 62.08 deaths in females, and the PYLL from 338.08 to 87.63 years / 100,000 females. For males, the number of deaths dropped from 3,714 to 2,951, the TS from 206.88 deaths /100,000 males in 1975 to 76.12 /100,000 males in 2004, and the PYLL dropping from 533.12 to 182.38 years / 100,000 males. Conclusions: The trend in mortality due to IHD was not constant either among females or males, although it has always been a downward trend, the drop being statistically significant. The drop in the CVD has been such a major one that both the absolute numbers and the gross rates are lower for the most recent years that the first years in the series studied despite the aging of Andalusia’s population.
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Abstract : This thesis investigates the pathogenicity and biology of Parachlamydia acanthamoebae and other obligate intracellular bacteria related to chlamydiae. All these Chlamydia-like organisms replicate in amoebae. Some evolved to resist to macrophages and represent possible new agents of respiratory tract infection. Using serological and molecular approaches, we showed that Parachlamydia acanthameobae likely plays a role as an etiological agent of pneumonia [1,2]. We also showed that Parachlamydia was able to enter and survive within pneumocytes and lung fibroblasts [3]. Moreover, we developed an animal model of lung infection in mice, which fulfilled the third and fourth Koch postulate [4]. Given the likely role of Parachlamydia in pneumonia, we studied its antibiotic susceptibility. We showed that Chlamydia-related organisms were resistant to quinolones, mainly due to mutations in the QRDR of gyrA [5]. To have tools to investigate the role of other Chlamydia-related bacteria in pneumonia, we developed immunofluorescence assays and assessed the rate of serological cross-reactivity between all these Chlamydia-related bacteria [6]. We also developed new diagnostic specific PCRs [2,7] and sequenced additional genes that are useful for both taxonomic and diagnostic purposes [8]. Then, we applied these serological and molecular approaches to patients with and without respiratory tract infections. This led to the identification of a possible role of Protochlamydia naegleriophila [7] and of Waddlia chondrophila in pneumonia [1]. A significant part of the thesis also investigated interactions of Parachlamydia with macrophages [9] and the host range of Chlamydia-related bacteria [10]. In conclusion, there are growing body of evidence supporting the role of Chlamydia-like organisms as agents of pneumonia. Further studies are needed to precise their pathogenic role in this setting. The diagnostic tools developed during this thesis will be useful to investigate the role of these strict intracellular bacteria in other diseases in both humans and animals [11,12]. Résumé : Le but de cette thèse est de déterminer le rôle pathogène de Parachlamydia et des bactéries apparentées aux Chlamydia ainsi que d'étudier leur biologie. Parachlamydia acanthamoebae est une bactérie intracellulaire apparentée aux Chlamydia, et qui est résistante non seulement aux amibes mais aussi aux macrophages. Par une approche sérologique et moléculaire, nous avons montré que les bactéries apparentées aux Chlamydia jouent probablement un rôle comme agent de pneumonie [1,2]. De plus, nous avons démontré que P. acanthameobae est capable d'entrer et de survivre dans les pneumocytes et fibroblastes pulmonaires [3]. Nous avons ensuite développé un modèle animal remplissant les troisième et quatrième postulats de Koch [4]. Nous avons aussi démontré que les bactéries apparentées aux Chlamydia sont résistantes aux quinolones, en raison de mutations dans la région QRDR de gyrA [5]. Afin de mieux déterminer le rôle pathogène de ces bactéries, nous avons mis au point des techniques d' immunofluorescence et déterminé la cross-réaction sérologique entre les différentes bactéries apparentées aux Chlamydia [6]. Différentes PCR diagnostiques ont aussi été développées [2,7] et des gènes supplémentaires ont été séquencés, qui seront utiles à la taxonomie ainsi qu'au développement de nouvelles méthodes diagnostiques [8]. Ces méthodes ont été appliquées à des échantillons provenant de patient avec ou sans pneumonie et ont permis l'identification du possible rôle pathogène de Protochlamydia naegleriophila [7] et de Waddlia chondrophila [1]. L'interaction de Parachlamydia avec les macrophages [9] et la permissivité de différentes cellules aux bactéries apparentées aux Chlamydia [10] ont également été étudiés dans le cadre de cette thèse. En conclusion, plusieurs nouveaux éléments viennent renforcer l'hypothèse que les bactéries apparentées aux Chlamydia sont des agents de pneumonies. Cependant, d'autres études doivent être menées pour confirmer leur rôle dans cette maladie. Les méthodes diagnostiques développées ici seront très utiles pour déterminer le rôle pathogène de ces bactéries chez les humains et animaux [11,12]
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Many arthropod species have adopted vertebrate blood as their main food source. Blood is rich in nutrients and, except for the presence of parasites, sterile. However, this food source is not freely available, nor is obtaining it devoid of risk. It circulates inside vessels hidden underneath the skin of mobile hosts that are able to defend themselves and even predate the insects that try to feed on them. Thus, the haematophagous lifestyle is associated with major morphological, physiological and behavioural adaptations that have accumulated throughout the evolutionary history of the various lineages of blood-sucking arthropods. These adaptations have significant consequences for the evolution of parasites as well as for the epidemiology of vector-transmitted diseases. In this review article, we analyse various aspects of the behaviour of triatomine bugs to illustrate how each behavioural trait represents a particular adaptation to their close association with their hosts, which may easily turn into predators. Our aim is to offer to the reader an up-to-date integrative perspective on the behaviour of Chagas disease vectors and to propose new research avenues to encourage both young and experienced colleagues to explore this aspect of triatomine biology.
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This review investigates ancient infectious diseases in the Americas dated to the pre-colonial period and considers what these findings can tell us about the history of the indigenous peoples of the Americas. It gives an overview, but focuses on four microbial pathogens from this period: Helicobacter pylori, Mycobacterium tuberculosis, Trypanosoma cruzi and Coccidioides immitis, which cause stomach ulceration and gastric cancer, tuberculosis, Chagas disease and valley fever, respectively. These pathogens were selected as H. pylori can give insight into ancient human migrations into the Americas, M. tuberculosis is associated with population density and urban development, T. cruzi can elucidate human living conditions and C. immitis can indicate agricultural development. A range of methods are used to diagnose infectious disease in ancient human remains, with DNA analysis by polymerase chain reaction one of the most reliable, provided strict precautions are taken against cross contamination. The review concludes with a brief summary of the changes that took place after European exploration and colonisation.
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Chagas disease is one of the most important yet neglected parasitic diseases in Mexico and is transmitted by Triatominae. Nineteen of the 31 Mexican triatomine species have been consistently found to invade human houses and all have been found to be naturally infected with Trypanosoma cruzi. The present paper aims to produce a state-of-knowledge atlas of Mexican triatomines and analyse their geographic associations with T. cruzi, human demographics and landscape modification. Ecological niche models (ENMs) were constructed for the 19 species with more than 10 records in North America, as well as for T. cruzi. The 2010 Mexican national census and the 2007 National Forestry Inventory were used to analyse overlap patterns with ENMs. Niche breadth was greatest in species from the semiarid Nearctic Region, whereas species richness was associated with topographic heterogeneity in the Neotropical Region, particularly along the Pacific Coast. Three species,Triatoma longipennis, Triatoma mexicana and Triatoma barberi, overlapped with the greatest numbers of human communities, but these communities had the lowest rural/urban population ratios. Triatomine vectors have urbanised in most regions, demonstrating a high tolerance to human-modified habitats and broadened historical ranges, exposing more than 88% of the Mexican population and leaving few areas in Mexico without the potential for T. cruzitransmission.
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This article intended to general practitioners brings an overview on current diseases in urology such as stone disease, benign prostatic hyperplasia, sexual dysfunction and localized cancers of prostate, bladder and kidney.
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Exposure to fine particles and noise has been linked to cardiovascular diseases and elevated cardiovascular mortality affecting the worldwide population. Residence and/or work in proximity to emission sources as for example road traffic leads to an elevated exposure and a higher risk for adverse health effects. Highway maintenance workers spend most of their work time in traffic and are exposed regularly to particles and noise. The aims of this thesis were to provide a better understanding of the workers' mixed exposure to particles and noise and to assess cardiopulmonary short term health effects in relation to this exposure. Exposure and health data were collected in collaboration with 8 maintenance centers of the Swiss Road Maintenance Services located in the cantons Bern, Fribourg and Vaud in western Switzerland. Repeated measurements with 18 subjects were conducted during 50 non-consecutive work shifts between Mai 2010 and February 2012, equally distributed over all seasons. In the first part of this thesis we tested and validated measurements of ultrafine particles with a miniature diffusion size classifier (miniDiSC) - a novel particle counting device that was used for the exposure assessment during highway maintenance work. We found that particle numbers and average particle size measured by the miniDiSC were highly correlated with data from the P-TRAK, a condensation particle counter (CPC), as well as from a scanning mobility particle sizer (SMPS). However, the miniDiSC measured significantly more particles than the P-TRAK and significantly less than the SMPS in its full size range. Our data suggests that the instrument specific cutoffs were the main reason for the different particle counts. The first main objective of this thesis was to investigate the exposure of highway maintenance workers to air pollutants and noise, in relation to the different maintenance activities. We have seen that the workers are regularly exposed to high particle and noise levels. This was a consequence of close proximity to highway traffic and the use of motorized working equipment such as brush cutters, chain saws, generators and pneumatic hammers during which the highest exposure levels occurred. Although exposure to air pollutants were not critical if compared to occupational exposure limits, the elevated exposure to particles and noise may lead to a higher risk for cardiovascular diseases in this worker population. The second main objective was to investigate cardiopulmonary short-term health effects in relation to the particle and noise exposure during highway maintenance work. We observed a PM2.5 related increase of the acute-phase inflammation markers C-reactive protein and serum amyloid A and a decrease of TNFa. Heart rate variability increased as a consequence of particle as well as noise exposure. Increased high frequency power indicated a stronger parasympathetic influence on the heart. Elevated noise levels during recreational time, after work, were related to increased blood pressure. Our data confirmed that highway maintenance workers are exposed to elevated levels of particles and noise as compared to the average population. This exposure poses a cardiovascular health risk and it is therefore important to make efforts to better protect the workers health. The use of cleaner machines during maintenance work would be a major step to improve the workers' situation. Furthermore, regulatory policies with the aim of reducing combustion and non-combustion emissions from road traffic are important for the protection of workers in traffic environments and the entire population.
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Infection by intracellular bacteria can lead to several diseases in both veterinary and human medicine. Unfortunately, the biology of these intracellular bacteria is highly complex due to their interactions with their host cells. Thus, it is very important to develop several tools in order to better understand the complex intracellular life of these pathogens, so allowing to improve the diagnosis options and the treatments of infectious diseases that they are causing. The workshop organised in Villars-sur-Ollon (Switzerland) by the ESCMID Study group on intracellular bacteria was a good opportunity to enhance our knowledge on these fastidious pathogens. During 5 days, 15 speakers gave 41 talks, covering all fields, from biology to clinic of different intracellular bacteria such as Bartonella, Chlamydia, Coxiella, Ehrlichia, Listeria, Parachlamydia, Rickettsia, and Waddlia. The format of this postgraduate course, which took place in the Swiss mountains, allowed interactive sessions and living discussions between the participants coming from all around the world. One of the major strength was to gather epidemiologists, clinical microbiologists, infectious diseases specialists, entomologists, veterinarians as well as bioinformaticians, biochemists and biologists to deliver a unique "one-health science" on intracellular bacteria. Here, we summarise the main take-home messages delivered during this meeting.
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This statewide profile describes the epidemiology of HIV, AIDS, and other sexually transmitted diseases in Iowa through December, 2002. The report characterizes the distribution of these diseases in terms of geography, race, gender, age, and associated causal factors. This epidemiological profile has been prepared to assist in developing a comprehensive HIV/AIDS Prevention and Care Plan. This description of the HIV epidemic in the state serves to guide prevention and service efforts, to quantify unmet need for prevention and care programs, and to evaluate programs and policies in Iowa. Five key questions are addressed: 1. What are the sociodemographic characteristics of Iowa’s population? 2. What is the epidemiology, including the geographical distribution, of HIV, AIDS, and other sexually transmitted diseases (STDs) in Iowa? 3. Who is at the greatest risk of becoming infected with HIV and other STDs in Iowa? 4. What are the patterns of utilization of HIV services throughout the state? 5. What are the number and characteristics of persons who know they are HIV-positive, but who are not receiving primary medical care?
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Abstract : Apoptosis is an evolutionarily conserved cellular suicide mechanism that can be triggered by activation of various pathways, such as the Fas-Pathway. Upon stimulation by its specific ligand (FasL), present at the surface of Cytotoxic Τ lymphocytes, the death receptor Fas initiates a signaling cascade culminating in the activation of cellular caspases, leading thus to cell death of the target cell (e.g. transformed cell). Dysregulation of apoptosis in general, and of Fas pathway in particular, was shown to contribute to pathogenesis of cancers and many human diseases. Even though, during the last decades the molecular mechanisms of apoptosis have been widely studied, it is important to better understand the mechanisms leading to apoptosis, to improve our understanding of pathological processes, and generate more subtle apoptosis-modulating therapies to fight cancer and other diseases. In order to identify new components of the Fas signaling pathway, a screen based on the mechanism of RNA interference was undertaken. After a first and a second manual whole-kinome screen, we identified several strong positive hits that showed a protection against Fas ligand-induced apoptosis with distinct siRNAs, notably STK11, an interesting tumor suppressor mutated in several sporadic and inherited cancers. The STK11 functional characterization reveals that this kinase represents an apically acting general pro-apoptotic modulator of the extrinsic pathway (FasL, TRAIL, TNF-induced apoptosis), but not of the intrinsic apoptotic pathway. The STK11 action on the Fas pathway was shown to be dependent on its kinase activity, but independent of AMPK, a well-characterized STK11 downstream substrate. Furthermore, STK11 was shown to interact with caspase-8, a major mediator of the extrinsic pathway, and modulate its activity through an unclear mechanism that may involve an STK11-dependant caspase-8 phosphorylation. This modification may allow a proper caspase-8 polyubiquitination and activation in p62 sequestosmes aggregates, but may also increase the activation of caspase-8 at the DISC level. In addition, we observed that STK11 modulate not only the apoptotic pathway induced by Fas engagement, but also FasL-induced JNK and NF- KB, sustaining an upstream role of this kinase in the pathway. In conclusion, our report reveals that STK11 is an important pro-apoptotic modulator of the Fas pathway in particular, and extrinsic pathway in general. Our finding could explain, at least partially, why inactivating mutations of the kinase leads to cancer, by allowing resistance to apoptosis and accordingly evasion of immune surveillance. Résumé : L'apoptose est un mécanisme de suicide cellulaire, conservé dans diverses espèces, et qui au niveau moléculaire est déclenché par différentes voies de signalisation, comme par exemple lors de l'activation du récepteur Fas. La liaison du ligand FasL au récepteur de la mort Fas, induit une cascade de signalisation qui conduit à l'activation des caspases. Les lymphocytes Τ cytotoxiques peuvent utiliser la voie Fas pour induire la mort et se débarrasser de cellules dangereuses pour le reste de l'organisme, tel que les cellules transformées. La dysrégulation de l'apoptose en général, et de la voie Fas en particulier, peut contribuer à diverses maladies telles que le cancer. Même si ces dernières décennies, les mécanismes moléculaires conduisant à l'apoptose ont été extensivement étudiés, il reste néanmoins important de mieux comprendre le phénomène d'apoptose, pour améliorer notre compréhension des processus pathologiques, mais surtout dans le but de développer de nouvelles thérapies ciblant l'apoptose contre le cancer et d'autres pathologies. Pour identifier de nouveau constituants de la voie Fas, un criblage génétique basé sur l'interférence à l'ARN a été entrepris. Après un premier et un deuxième criblage d'une librairie du kinome, nous avons identifié différentes protéines qui pourraient jouer un rôle positif dans la voie Fas, et en particulier la protéine suppresseur de tumeur STK11, qui est fréquemment mutée dans divers cancers sporadiques et héréditaires. La caractérisation fonctionnelle de STK11 a révélé que cette kinase était un modulateur apical de la voie extrinsèque de l'apoptose en général (Fas, TNF, TRAIL), mais pas de la voie intrinsèque. L'action de STK11 sur la voie Fas est dépendante de sa fonction kinase, mais indépendante de l'AMPK, un substrat bien caractérisé de STK11. De plus, STK11 interagît avec la caspase-8, un constituant majeur de la voie Fas, et module son activité, par un mécanisme encore peu clair qui pourrait impliquer une phosphorylation de la caspase-8 par STK11. Cette modification pourrait permettre une activation optimale de la caspase-8 en jouant un rôle dans le processus de polyubiquitination de la caspase-8, phénomène qui semble être important pour l'activation de la caspase-8 dans des agrégats protéiques avec p62, mais qui pourrait aussi augmenter son activation au niveau du DISC. Finalement, nous avons observé que STK11 modulait non seulement la voie apoptotique déclenchée par l'activation de Fas, mais aussi les voies non-apoptotiques de Fas, comme JNK et NF-KB. En conclusion notre étude, révèle que STK11 est un important modulateur pro- apoptotique de la voie Fas, et de la voie extrinsèque en général. Cette découverte pourrait expliquer, du moins partiellement, pourquoi les mutations inactivatrices de STK11 conduisent au cancer, par une augmentation de la résistance à l'apoptose et donc par l'évasion de la surveillance immunitaire.
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The Framework Convention on Tobacco Control (FCTC) isa global and comprehensive legal framework for reducing demand for tobacco (e.g. price measures; ban on smoking in enclosed places; contents of tobacco products; packaging and labeling; advertising, promotion and sponsorship; liability, tobacco cessation, etc.) and supply (e.g. illicit trade; sales to/by minors, etc.). Adopted in 2003, the FCTC has been ratified by 174 countries so far. Switzerland has signed the treaty in 2004 but ratification will necessitate the implementation of stronger tobacco control measures at the national level. The FCTC is a priority of any strategy to reduce noncommunicable diseases in populations. Broad implementation of the FCTC has the potential to prevent a substantial proportion of the billion of tobacco-related deaths expected in the 21st
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Pulmonary arterial hypertension is a rare disease with a poor prognosis. Epidemiological data are scarce, particularly in the paediatric population. A registry was recently developed in order to collect epidemiological data on patients with pulmonary arterial hypertension (PAH) in Switzerland. This is the first description of the paediatric data. Paediatric patients aged 0-18 years with the diagnosis of PAH were enrolled in the registry from 1999 to 2005 with informed consent from their parents. Patient characteristics, PAH aetiology, functional capacity, exercise capacity, treatments and outcome were among the most important data collected. A total of 23 patients (12 male, 11 female) have been thus far included in the registry. Median age at time of diagnosis was 3 years (range 1 month-18 years) and median follow-up was 3.47 years (range 1 day-12.6 years). PAH aetiologies are diagnosed as idiopathic in 8/23 patients (34.8%) and associated with congenital heart diseases in 12/23 (52.2%) or with pulmonary diseases in 3/23 patients (13.0%). Death occurred in 1 patient before treatment was initiated. Single treatments include medications with a calcium channel blocker in 2/23 patients, with bosentan in 10/23, and with inhaled iloprost in 1/23. Combined therapies include bosentan and inhaled iloprost in 7/23 patients, bosentan and sildenafil in 2/23 patients, and bosentan, sildenafil and inhaled iloprost in 2/23 patients. Additional oral anticoagulation is given to 14/23 patients and 8/23 patients are on oxygen therapy. NYHA class at baseline visit was obtained in 22/23 patients (4 NYHA 2, 17 NYHA 3 and 1 NYHA 4). Changes in NYHA class were observed over a 2-year period in 3/22 patients who improved from NYHA 3 to NYHA 2. Initial improvement of 6-minute walk distance was observed in 6/13 patients with a sustained improvement in 4. These preliminary results provide information on the epidemiology of PAH in children in Switzerland and demonstrate that most paediatric patients show stabilisation of the disease under new treatments. This underscores the utility of registries for rare diseases in providing crucial information in the era of new therapies. It may also help to improve the future medical approach.
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The diagnosis of muscular dystrophies or the assessment of the functional benefit of gene or cell therapies can be difficult, especially for poorly accessible muscles, and it often lacks a singlefiber resolution. In the present study, we evaluated whether muscle diseases can be diagnosed from small biopsies using atomic force microscopy (AFM). AFM was shown to provide a sensitive and quantitative description of the resistance of normal and dystrophic myofibers within live muscle tissues explanted from Duchenne mdx mice. The rescue of dystrophin expression by gene therapy approaches led to the functional recovery of treated dystrophic muscle fibers, as probed using AFM and by in situ wholemuscle strength measurements. Comparison of muscles treated with viral or non-viral vectors indicated that the efficacy of the gene transfer approaches could be distinguished with a single myofiber resolution. This indicated full correction of the resistance to deformation in nearly all of the muscle fibers treated with an adeno-associated viral vector that mediates exon-skipping on the dystrophin mRNA. Having shown that AFM can provide a quantitative assessment of the expression of muscle proteins and of the muscular function in animal models, we assessed myofiber resistance in the context of human muscular dystrophies and myopathies. Thus, various forms of human Becker syndrome can also be detected using AFM in blind studies of small frozen biopsies from human patients. Interestingly, it also allowed the detection of anomalies in a fraction of the muscle fibers from patients showing a muscle weakness that could not be attributed to a known molecular or genetic defect. Overall, we conclude that AFM may provide a useful method to complement current diagnosis tools of known and unknown muscular diseases, in research and in a clinical context.