O papel da IL-23 na resposta imunitária ao Mycobacterium tuberculosis

Dissertação de mestrado em Ciências da SaúdeO Mycobacterium tuberculosis é o agente etiológico da tuberculose e a principal causa de morte por um só agente infecioso em humanos. Esta bactéria é um exemplo ideal de um agente infecioso para o qual a resposta protetora depende da imunidade celular, uma vez que o organismo vive dentro de células, normalmente macrófagos. Assim, os mecanismos efetores mediados por células T, em vez de anticorpos, são necessários para controlar a infeção. No entanto, estas respostas demoram a ser ativadas sendo detetadas apenas 3 semanas após a infeção. Assim, a imunidade inata desempenha um papel crítico na proteção do hospedeiro contra a infeção com M. tuberculosis, visto que muitos indivíduos infetados controlam a infeção, apesar do atraso na resposta imunitária adquirida. Macrófagos infetados com M. tuberculosis produzem IL-23 em poucas horas de infeção; A nossa hipótese para este trabalho é que a IL-23 desempenha um papel fundamental na resposta inata contra M. tuberculosis, inclusive induzindo a expressão de peptídeos antimicrobianos que podem ajudar no controle da infeção. Por esse motivo, procuramos explorar o papel desta citoquina durante a infeção por M. tuberculosis in vivo e in vitro. Começamos por determinar a expressão de peptídeos antimicrobianos por macrófagos infetados com M. tuberculosis na presença ou ausência de IL-23. Os nossos dados mostram que a IL-23 não induz a expressão de peptídeos antimicrobianos em macrófagos infetados por M. tuberculosis. De seguida, determinamos o papel da IL-23 na resposta imunitário e no controle do M. tuberculosis in vivo. Para isso, infetamos ratinhos deficientes em IL-23R e comparamos sua capacidade de controlar M. tuberculosis com a de ratinhos C57BL/6. Os nossos dados mostram que, durante as primeiras semanas de infeção a IL-23 pode desempenhar um papel fundamental no controle de M. tuberculosis. No entanto, durante os estadios finais da infeção, os ratinhos com deficiência no IL-23R são mais suscetíveis à infeção. Apesar disso, os nossos dados não revelaram alteração significativa na resposta imunitária protetora, no que diz respeito à ativação e função efetora de células T. Também determinamos o potencial da IL-23 na proteção conferida pela vacinação da mucosa. Mostramos que ratinhos vacinados com BCG e ratinhos vacinados com BCG+IL-23 controlam a infeção por M. tuberculosis da mesma forma; no entanto, ratinhos vacinados com BCG+IL-23 exibem uma arquitetura melhorada de tecido pulmonar, o que sugere um papel importante da IL-23 na vacinação via mucosa. Em conjunto, os nossos dados justificam mais estudos para definir o papel da IL-23 durante a vacinação da mucosa e após a infeção por M. tuberculosis. Especificamente, o uso de uma dose maior de infeção poderá desvendar novos mecanismos inatos de proteção contra o M. tuberculosis mediados por IL-23.Mycobacterium tuberculosis is the etiological agent of tuberculosis and the leading cause of death due to a single infectious agent in humans. M. tuberculosis is an ideal example of a pathogen for which the protective response relies on cell-mediated immunity, since the organism lives within cells, typically macrophages. Therefore, T cell effector mechanisms, instead of antibody, are required to control the bacterium. However, these responses are slow to be activated and are detectable only 3 weeks after infection, giving the pathogen time to spread. Innate immunity plays a critical role in protecting the host from early infection with M. tuberculosis, as many M. tuberculosis-infected individuals can control the infection despite the delay in the acquired immune response. M. tuberculosis-infected macrophages produce IL-23 within hours infection; in this work, we hypothesized that IL-23 plays a pivotal role in the innate response to, including by inducing the production of antimicrobial peptides which may help in the control of infection. For this reason, we sought to explore the role of this cytokine during M. tuberculosis infection both in vivo and in vitro. We began by determining the expression of antimicrobial peptides by M. tuberculosis-infected macrophages in the presence and/or absence of IL-23. We showed that IL-23 does not induce the expression of antimicrobial peptides. We next determined the role of IL-23 in the immune response and control of M. tuberculosis in vivo. To do this, we infected IL-23R-defficient mice and compared their ability to control M. tuberculosis with that of C57B/6 mice. We showed that during early infection IL-23 might play a key role in the control of infection. However, during the late stages of infection IL-23R-defficient mice were more susceptible to M. tuberculosis infection. Despite this, our data did not reveal significant alteration in the protective immune response, in what regard T cell activation and effector function. We also determined the potential of IL-23 in enhancing protection conferred by mucosal vaccination. We showed that mice vaccinated with BCG and mice vaccinated with BCG+IL-23 control M. tuberculosis infection equally; however, BCG+IL-23 vaccinated mice display improved lung tissue architecture suggesting a potential role of IL-23 in mucosal vaccination. Taken together, these data warrant further studies to define the role of IL-23 during mucosal vaccination and following infection with M. tuberculosis. Specifically, the use of a higher dose of infection might unravel novel innate mechanisms of protection against M. tuberculosis mediated by IL-23.The work presented in this thesis was performed in the Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, and ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal. Financial support was provided by the ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01-0145- FEDER-022122), and by National funds through the Foundation for Science and Technology (FCT) - projects PTDC/SAU-INF/28463/2017, PTDC/MED-ONC/28658/2017, UIDB/50026/2020 and UIDP/50026/2020

Evaluation of the Level of Food Security in Households in the Health Area of Lwiro, Health Zone of MITI-MURHESA in 2022

Study framework: health area of Lwiro in the health zone of Miti-Murhesa, in DR Congo. General objective: The general objective of the present work was to contribute in ameliorating household food security in order to reduce sanitary risks linked to food insecurity in the health area of Lwiro, health zone of Miti-Murhesa in Democratic Republic of Congo. Material and method: In order to fulfill the specific objectives of this work, we appealed to the technique of simple random sampling on 358 households. Sampling was done using a questionnaire. MS Excel and SPSS were used for data analyses and treatment. Results: After data analyses and treatment it was observed that, most of those who were investigated had no level of instruction, that is 31,2% with the size of the household less that 7 people, and 17,3% had a low food diversification score that is ¼, that means haven consumed a group of food amongst the 4 main groups of food during the week that preceded the investigations. Conclusion: Food insecurity is at its best in the health zone of Miti-Murhesa. This is a reason to recommend to the population of this health zone to diversify their feeding, in order to ameliorate their level of food security and their nutritional state.&nbsp

Dechlorination of Lindane in the Multiphase Catalytic Reduction System with Pd/C, Pt/C and Raney-Ni

Dechlorination of -hexachlorocyclohexane (lindane) is carried out in the multiphase catalytic system, composed by isooctane and aqueous KOH phases, a phase transfer agent (Aliquat 336) and a metal catalyst, e.g. 5% Pd/C, 5% Pt/C, or Raney-Ni. At 50 ◦C and atmospheric pressure the full conversion of lindane to 1,2,4-tricholorobenzene (1,2,4-TCB) is achieved in 5–10 min via the base assisted dehydrochlorination, followed by the metal catalyzed hydrodechlorination with hydrogen to benzene. Aqueous KOH and Aliquat 336 strongly affect the reaction: if present together they co-promote both dehydrochlorination and hydrodechlorination steps; if KOH is absent, the reaction is forced to follow a different catalytic pathway, which involves a removal of a pair of chlorines at every reaction step by zerovalent metal followed by reduction of metal with hydrogen. This is proven by the formation of 3,4,5,6-tetrachlorocyclohex-1-ene and 5,6-dichlorocyclohexa-1,3-diene as intermediates in the reaction over Raney-Ni, and by the absence of TCBs in the reactions on all the catalysts studied. The final yield of benzene via this pathway can be achieved in shorter times than in a system with KOH. The presence of Aliquat 336 in the isooctane-water system produces a 10-fold rate increase, the presence of alkaline water is also important since it avoids catalyst poisoning by neutralizing the hydrochloric acid formed

Physical chemistry of sulphide self-heating

ABSTRACTA prerequisite step towards building a self-heating (SH) model for sulphide materials is the determination of physico-chemical parameters such as the specific heat capacity (Cp), and the energy of activation (Ea). The specific heat capacity of one copper and three nickel concentrates was determined over the temperature range 50 to 80oC in the presence of 6% moisture using the self-heating (SH) apparatus and confirmed by Drop Calorimetry. The Cp values from both techniques were comparable. The Cp values were similar for all concentrates increasing from 0.4 to 1.4 Jg-1K-1 as temperature increased from 50 to 80oC. From the Cp values, the enthalpy change (ΔH), the entropy change (ΔS) and the Gibbs free energy change (ΔG) for self-heating, were determined. The ΔG was negative, demonstrating that self-heating of the concentrates was spontaneous.Using the self-heating apparatus the, activation energy (Ea) was determined for the Ni-and Cu-concentrates and for pairs of sulphide minerals. The Ea ranged from 22 to 30 kJ.mol-1, implying a common reaction. Further support for a common reaction is the strong positive correlation between Ea and ln(QA/Cp) where Q (J.kg-1) is the heat of reaction causing self-heating and A the Arrhenius pre-exponential factor (s-1). Comparing to literature, the Ea values correspond to partial oxidation of hydrogen sulphide, supporting the contention that H2S may be an intermediate product in the self-heating of sulphide minerals. A positive relationship between Ea and the rest potential difference (ΔV) for the sulphide pairs and a negative relationship between Cp and ΔV were demonstrated which support a connection between self-heating and the galvanic effect.RESUMÉLa réalisation d'un modèle mathématique de l'auto-échauffement des concentrés sulfurés de nickel et de cuivre et des mélanges des minerais sulfurés, enjoint à la détermination des paramètres physico-chimiques tels que les capacités de chaleur spécifiques (Cp), et les énergies d'activation (Ea). Les capacités de chaleur spécifiques d'un concentré de cuivre et de trois concentrés de nickel contenant 6% d'humidité, ont été déterminées par utilisation d'un instrument de mesure de vitesse d'auto – échauffement et validées par la calorimétrie de chute dans l'intervalle de températures allant de 50 à 80oC. Les Cp (0.4 à 1.4 Jg-1K-1) obtenues sont similaires pour tous les échantillons. A partir des valeurs des Cp, les variations de l'enthalpie (ΔH), l'entropie (ΔS) et de l'énergie libre de Gibbs (ΔG) de l'auto échauffement ont été déterminées. La valeur négative de ΔG confirme le caractère spontané de l'auto échauffement des minerais sulfurés.Les énergies d'activation (Ea) pour l'auto-échauffement des concentrés de nickel et cuivre et des paires de minerais sulfurés étaient déterminées en faisant usage de l'appareil d'auto-échauffement. Les Ea ainsi obtenues oscillent entre 22 et 30 kJ.mol-1 : Ce qui est suggestif d'une rèaction chimique commune gouvernant l'auto-échauffement de ces matériaux. Ce fait est corroboré par la forte corrélation obtenue entre Ea et ln(QA/Cp) (Q (J.kg-1) est la chaleur de la rèaction chimique responsable de l'auto-échauffement et A (s-1) la constante d'Arrhenius).Ensuite celles-ci sont similaires à celle de l'oxydation partielle du H2S. Il se pourrait, ce faisant, que H2S soit un composé intermediaire lors de l'auto–échauffement des sulfures.Enfin, la corrélation positive entre Ea et la difference de potential (ΔV) dans les paires de minerais sulfurés et celle negative entre Cp et ΔV sont une preuve qu'il existe bel et bien une connection entre l'auto-échauffement et l'effet galvanique

Trends of chlordane and toxaphene in ambient air of Columbia, South Carolina.

A long-term record of chlordane and toxaphene (chlorobornanes, CHBs) measurements in Columbia, South Carolina is presented. Chlordane was used as a termiticide in the city and toxaphene was applied to cotton, soybeans and other crops in the region. Ratios among chlordane compounds in ambient air agreed well with those in technical chlordane when weighted for differences in volatility. Atmospheric concentrations (Ca, pgm-3) in pre-ban years (1988 for chlordane, 1986 for toxaphene) are compared to those made more recently by normalizing concentrations for the effect of varying ambient temperature. Plots of log Ca vs 1/T suggest that chlordane concentrations at 20˚C declined by about 40% between pre-ban years and 1994Ð1995, but no change is apparent at 5¡C. Recent concentrations of CHBs are lower than those measured when toxaphene was in use. Temperature slopes are flatter in post-ban years, possibly because of retarded evaporation of old residues as compared to freshly applied pesticide. The 1994-1995 concentrations of chlordanes and CHBs in Columbia air were several times higher than those found in the Great Lakes region. No distinct trend in CHB levels with air transport direction was noted, suggesting that volatilization from local or regional soils is supplying CHBs to Columbia air

La dialyse péritonéale en République du Congo : historique et problématique actuelle (lettre)

Introduction Peritoneal dialysis (PD) is an extrarenal purification technique using the peritoneum as an exchange membrane. The objectives of this work were to review the history of peritoneal dialysis in Congo Brazzaville and to describe a catheterization technique for peritoneal dialysis using the nasogastric tube, due to the unvailibility of Tenckhoff catheter. Method We reviewed the literature on PD in the Republic of Congo and described the current technique.  Results   Our review of the literature on PD in the Congo reveals that the first PD in the Republic of Congo was performed in 1989 by MPIO and colleagues. Our current PD technique uses only a nasogastric tube placed subumbilically by a paediatric surgeon under local anaesthetic, and a locally manufactured dialysate infused at a dose of 50ml per kilogram per day of a mixture of ringer lactate and hypertonic glucose serum with 1 ampoule of 30% hypertonic glucose or icodextrin serum in case of acute pulmonary oedema (APO). Of the 6 patients who benefited from PD, 2 recovered. Conclusion The description of the PD technique reveals that any developing country can do it. Our overall results encourages the pursuit of PD and motivate the creation of a PD unit at CHU/B.Introduction La dialyse péritonéale (DP) est une technique d'épuration extrarénale utilisant le péritoine comme membrane d'échange. Les objectifs de ce travail étaient de faire l'historique de la dialyse péritonéale au Congo Brazzaville et de décrire une technique de cathétérisme pour la dialyse péritonéale à l'aide de la sonde nasogastrique en l’absence de disponibilité de cathéter spécifique pour DP. Méthode Nous avons passé en revue la littérature sur la DP en République du Congo et décrit la technique actuelle.  Résultats   Notre revue de la littérature sur la DP au Congo révèle que la première DP en République du Congo a été réalisée en 1989 par MPIO et ses collègues. Notre technique actuelle de DP n'utilise qu'une sonde nasogastrique placée en sous-ombilical par un chirurgien pédiatre sous anesthésie locale, et un dialysat de fabrication locale perfusé à la dose de 50ml par kilogramme et par jour d'un mélange de ringer lactate et de sérum glucosé hypertonique avec 1 ampoule de sérum glucosé hypertonique à 30% ou d'icodextrine en cas d'œdème aigu du poumon (OAP). Sur les 6 patients qui ont bénéficié de la DP, 2 se sont rétablis. Conclusion La description de la technique de DP révèle que n'importe quel pays en développement peut le faire. Nos résultats globaux encouragent la poursuite de la DP et motivent la création d'une unité de DP au CHU/B

IDENTIFIKASI TANDA TANGAN MENGGUNAKAN PENGOLAHAN CITRA DIGITAL DAN METODE MACHINE LEARNING

Signature is used to legally approve an agreement, treaty, and state administrative activities. Identification of the signature is required to ensure ownership of a signature and to prevent things like forgery from happening to the owner of the signature. In this study, data signatures were obtained from 25 people over the age of 50. The signers provided 20 signatures and were free to choose the stationery used to write the signature on white paper. The total data obtained in this study was 500 signature data. The obtained signature was scanned to create a signature image, which was then pre-processed to prepare it for feature extraction, which can characterize the signature images. The HOG method was used to extract features, resulting in a dataset with 4,536 feature vectors for each signature image. To identify the signature image, the classification methods SVM, Decision Tree, Nave Bayes, and K-NN were compared. SVM achieved the highest accuracy, which is 100%. When K=5, the K-NN method achieved a fairly good accuracy of 97.3%. Meanwhile, Naive Bayes and Decision Tree achieved accuracy significantly lower than K-NN (61%). Because the HOG method produced a large feature vector for each signature, it is recommended that important features that represent signatures be optimized or extracted to produce smaller features to speed up computation without sacrificing accuracy, and that the HOG method be compared to other extraction feature methods to obtain a better model in future research