Preparation and In Vitro Release of Drug-Loaded Microparticles for Oral Delivery Using Wholegrain Sorghum Kafirin Protein

Kafirin microparticles have been proposed as an oral nutraceutical and drug delivery system. This study investigates microparticles formed with kafirin extracted from white and raw versus cooked red sorghum grains as an oral delivery system. Targeted delivery to the colon would be beneficial for medication such as prednisolone, which is used in the management of inflammatory bowel disease. Therefore, prednisolone was loaded into microparticles of kafirin from the different sources using phase separation. Differences were observed in the protein content, in vitro protein digestibility, and protein electrophoretic profile of the various sources of sorghum grains, kafirin extracts, and kafirin microparticles. For all of the formulations, the majority of the loaded prednisolone was not released in in vitro conditions simulating the upper gastrointestinal tract, indicating that most of the encapsulated drug could reach the target area of the lower gastrointestinal tract. This suggests that these kafirin microparticles may have potential as a colon-targeted nutraceutical and drug delivery system.

The third dimension: new developments in cell culture models for colorectal research

Cellular models are important tools in various research areas related to colorectal biology and associated diseases. Herein, we review the most widely used cell lines and the different techniques to grow them, either as cell monolayer, polarized two-dimensional epithelia on membrane filters, or as three-dimensional spheres in scaffoldfree or matrix-supported culture conditions. Moreover, recent developments, such as gut-on-chip devices or the ex vivo growth of biopsy-derived organoids, are also discussed. We provide an overview on the potential applications but also on the limitations for each of these techniques, while evaluating their contribution to provide more reliable cellular models for research, diagnostic testing, or pharmacological validation related to colon physiology and pathophysiology.

Nivel de ansiedad del paciente de enfermedad inflamatoria crónica intestinal en tratamiento con granulocitoaféresis

La ansiedad desarrollada en las personas que se enfrentan a tratamientos en el medio hospitalario produce un efecto negativo pudiendo perjudicar el correcto desarrollo de la terapia. El presente trabajo ha consistido en evaluar la ansiedad (Código NANDA:000146) de una muestra de pacientes con Enfermedad Inflamatoria Crónica Intestinal (EICI) sometidos a tratamiento con Granulocitoaféresis realizado con Adacolumn®, respecto al número de sesiones recibidas en la sala de donantes del Complejo Hospitalario Universitario de Canarias (CHUC) de forma ambulatoria y en un entorno nuevo reservado para dicha terapia. En 2012, se acondicionó un espacio de la sala de donantes de sangre y se formó al personal de enfermería en la realización de este tratamiento. Este trabajo se ha realizado por el método de estudio observacional descriptivo retrospectivo, la muestra recogida fueron el total de los pacientes que se sometieron a este tratamiento en nuestro servicio por medio de entrevistas telefónicas llevadas a cabo por enfermería. Se deduce que las condiciones ambientales de sala influyen en la disminución del nivel de ansiedad del paciente, favoreciendo la calidad asistencial, a la vez no hay relación entre el número de sesiones del tratamiento y nivel de ansiedad que manifestaron los pacientes, se definen la venopunción y el ingreso hospitalario como parámetros que producen más ansiedad. Se deben estudiar mejoras en el futuro para seguir aumentando la calidad asistencial de estos pacientes, disminuyendo la ansiedad producida ante el peligro percibido de la terapia y así tener una mayor respuesta positiva al tratamiento.

Perception of health benefits of dietary fibre among the Portuguese population

Introduction: Dietary iber (DF) has been part of human diet since ever, and its beneits for the human health have been well estab-lished and scientiically conirmed. Among these stand improved gastrointestinal functions, prevent cholesterol, diabetes or CVD. Objectives: To study the level of knowledge of people residing in Portugal about the health effects related to an adequate ingestion of DF. Methods: This is a descriptive cross-sectional study carried out on a non-probabilistic sample of 382 adults residing in Portugal. The questionnaire included a section about the socio-demographic characteristics (age, gender, level of education and living environ- ment) and another about the relation between dietary iber and possible beneicial effects to treat and prevent diseases. The data was treated using the SPSS software (V22). Results: The results allowed concluding that people were dif- ferently informed about the effects of DF in preventing and/or treating different diseases, being constipation the most recog- nized, followed in decreasing order by obesity, bowel cancer, cholesterol, cardiovascular diseases, diabetes and breast can- cer. The results also showed that signiicant differences were encountered between age groups for most of the diseases evalu- ated, but not between genders, levels of education or living en- vironments. Conclusions: Generally, it was concluded that the participants in this study were relatively well informed about the roles of DF in preventing and/or treating various diseases.

Acute mesenteric ischemia of arterial origin: importance of early revascularization

Voir aussi : F. Plumereau, S. Mucci, P. Le Naoures, J.B. Finel, A. Hamy. Ischémie mésentérique aiguë d’étiologie artérielle : intérêt d’une revascularisation précoce. Journal de Chirurgie Viscérale, Volume 152, Issue 1, February 2015, pp. 16-21. doi:10.1016/j.jchirv.2014.07.014

Effets préventifs et thérapeutiques des polyphénols dans un modèle in vitro et in vivo de maladie inflammatoire de l’intestin : caractérisation des polyphénols de la pelure de pomme et de la canneberge par spectrométrie de masse

La muqueuse intestinale est exposée à des agents oxydants provenant de l’ingestion d’aliments modifiés, de cellules immuno-inflammatoires et de la flore intestinale. Une diète élevée en fruits et légumes peut diminuer le stress oxydant (SOx) ainsi que l’inflammation via plusieurs mécanismes. Ces effets bénéfiques peuvent être attribuables à leur contenu élevé en polyphénols. La première étude de mon doctorat consistait à tester l’hypothèse que les polyphénols extraits de pelures de pomme (DAPP) pouvaient diminuer le stress oxydant et l'inflammation impliqués dans les maladies inflammatoires de l'intestin (MII). Nous avons caractérisé les polyphénols des DAPP par spectrométrie de masse (LC-MS) et examiné leur potentiel antioxydant et anti-inflammatoire au niveau des cellules intestinales. L’identification des structures chimiques des polyphénols a été effectuée par LC-MS. Le SOx a été induit par l’ajout du complexe fer/ascorbate (Fe/Asc, 200 µM/2 mM) et l’inflammation par la lipopolysaccharide (LPS, 200µg/mL) à des cellules intestinales Caco-2/15 pré-incubées avec les DAPP (250 µg/mL). L’effet du SOx est déterminé par le dosage du malondialdéhyde (MDA), de la composition des acides gras polyinsaturés et de l’activité des enzymes antioxydantes endogènes (SOD et GPx). L’impact des DAPP sur l’inflammation a été testé par l’analyse de l’expression des marqueurs inflammatoires: cyclooxygénase-2 (COX-2), le facteur de nécrose tumorale alpha (TNF-a et l’interleukine-6 (IL-6) et les facteurs de transcription NF-KB, Nrf-2 et PGC1α par immunobuvardage. Nos données ont montré que les flavonols et les flavan-3-ols constituent les composés polyphénoliques majoritaires des DAPP. L’ajout de Fer2+/Asc a provoqué une augmentation de la peroxidation lipidique comparativement aux cellules contrôles, un appauvrissement des acides gras polyinsaturés n-3 et n-6, et une modulation des enzymes antioxydantes, se traduisant par une augmentation de l’activité de la SOD et une diminution de la GPx. En contrepartie, les DAPP ont exhibé leur potentiel à corriger la plupart des perturbations, y compris l’expression protéique anormalement élevée du COX-2 et la production de la prostaglandine E2 (PGE2), ainsi que l’inflammation telle que réflétée par les facteurs NF-κB, TNF-α et IL-6. Par ailleurs, les mécanismes sous-jacents à ces changements bénéfiques des DAPP ont fait intervenir les facteurs de transcription antioxydants (Nrf-2, PGC1α). Vraisemblablement, cette première étude a permis de démontrer la capacité des DAPP à amoindrir le SOx et à réduire l’inflammation, deux processus étroitement impliqués dans les MII. Dans la deuxième étape de mon doctorat, nous avons voulu comparer les résultats de DAPP à ceux des polyphénols dérivant de la canneberge qui est considérée par la communauté scientifique comme le fruit ayant le plus fort potentiel antioxydant. À cette fin, nous avons caractérisé l’effet des composés polyphénoliques de la canneberge (CPC) sur le SOx, la défense antioxydante et l’inflammation au niveau intestinal tout en définissant leur métabolisme intraluminal. Les différents CPC ont été séparés selon leur poids moléculaire par chromatographie et leurs structures chimiques ont été identifiées par LC-MS. Suite à une pré-incubation des cellules Caco-2/15 avec les extraits CPC (250 µg/mL), le Fe/Asc et la LPS ont été administrés comme inducteurs du SOx et de l’inflammation, respectivement. La caractérisation globale des CPC a révélé que les acides phénoliques composaient majoritairement l’extrait de canneberge de petit poids moléculaire (LC) alors que les flavonoïdes et les procyanidines dimériques/trimériques représentaient l’extrait de poids moléculaire moyen (MC) tout en laissant les procyanidines oligo et polymériques à l’extrait de haut poids moléculaire (HC). Les CPC ont permis de restaurer la plupart des perturbations engendrées dans les Caco-2/15 par le Fe/Asc et le LPS. Les CPC exhibaient le potentiel d’abaisser les niveaux de MDA, de corriger la composition des acides gras polyinsaturés n-3 et n-6, d’augmenter l’activité des enzymes antioxydantes (SOD, GPx et CAT) et d’élever l’expression de Nrf2 et PGC1α. En outre, les CPC pouvaient aussi réduire les niveaux élevés des protéines inflammatoires COX-2, TNF-α et IL-6 ainsi que la production des PGE2 par un mécanisme impliquant le NF-κB. Au niveau mitochondrial, les procyanidines oligomériques ont réussi à corriger les dysfonctions reliées à la production d’énergie (ATP), l’apoptose (Bcl-2, Cyt C et AIF) et le statut des facteurs de transcription mitochondriaux (mtTFA, mtTFB1, mtTFB2). Dans le but de bien comprendre les mécanismes d’action des CPC, nous avons défini par LC-MS les composés polyphénoliques qui ont été transportés ou absorbés par l’entérocyte. Nos analyses soulignent le transport (i) des acides cinnamiques et benzoïques (LC); (ii) la quercétine glycosylée et conjuguée et les procyanidines dimériques de type A (MC); et (iii) l’épicatéchine et les procyanidines oligomériques (HC). Les processus de métabolisation (méthylation, glucuronidation et sulfatation) au niveau de l’entérocyte ont probablement permis le transport de ces CPC surtout sous leur forme conjuguée. Les procyanidines oligomériques ayant un degré de polymérisation supérieur à 2 (HC) ont semblé adhérer aux cellules Caco-2/15. L’épicatéchine suivi par les procyanidines dimériques de type A ont été trouvés majoritaires au niveau des mitochondries. Même si nous ignorons encore l’action biologique de chaque composé polyphénolique, nous pouvons suggérer que leurs effets combinatoires exercent des fonctions antioxydantes, anti-inflammatoires et mitochondriales dans le modèle intestinal Caco-2/15. Dans une troisième étape, nous avons procédé à l’évaluation des aspects préventifs et thérapeutique des DAPP tout en sondant les mécanismes sous-jacents dans une étude préclinique. À cette fin, nous avons exploité le modèle de souris avec colite expérimentale provoquée par le Dextran Sulfate de Sodium (DSS). L’induction de l’inflammation intestinale chez la souris C57BL6 a été effectuée par l’administration orale de DSS à 2.5% pendant 10 jours. Des doses physiologiques et supra-physiologiques de DAPP (200 et 400 mg/kg/j, respectivement) ont été administrées par gavage pendant 10 jours pré- et post-DSS. L’inflammation par le DSS a provoqué une perte de poids, un raccourcissement du côlon, le décollement dystrophique de l’épithélium, l’exulcération et les infiltrations de cellules mono et polynucléaires au niveau du côlon. De plus, le DSS a induit une augmentation de la peroxidation lipidique, une régulation à la baisse des enzymes antioxydantes, une expression protéique à la hausse de la myéloperoxidase (MPO), du COX-2 et de la production des PGE2. Par ailleurs, les DAPP ont permis de corriger ou du moins d’alléger la plupart de ces anomalies en situation préventive ou thérapeutique, en plus d’abaisser l’expression protéique de NF-κB et des cytokines inflammatoires (TNF-a et l’IL-6) tout en stimulant les facteurs de transcription antioxydants (Nrf-2, PGC1α). Conséquemment, les polyphénols des DAPP ont exhibé leur puissant pouvoir antioxydant et anti-inflammatoire au niveau intestinal dans un modèle in vivo. Leurs actions sont associées à la régulation des voies de signalisation cellulaire et des changements dans la composition du microbiote. Ces trois projets de recherche permettent d’envisager l’évaluation des effets préventifs et thérapeutiques des DAPP cliniquement chez les patients avec des désordres inflammatoires de l’intestin.

Implication of gut microbiota in nonalcoholic fatty liver disease

International audience

Experiences of patients undergoing chemotherapy - a qualitative study of adults attending Uganda Cancer Institute

Background: Cancer is a global public health challenge and how patients in countries with poor healthcare infrastructure experience cancer treatment is largely unknown. Purpose: The objective of this study was to describe adult Ugandan cancer patients’ experiences of undergoing chemotherapy treatment. Methodology: Using a qualitative descriptive design, seven in-patients with varying cancer diagnoses at the Uganda Cancer Institute were interviewed about their experiences of undergoing chemotherapy treatment; the interviews were transcribed and analysed thematically. Results: The analysis resulted in nine subthemes, which were categorized under three main themes: ‘experiences related to the body’, with the subthemes dry and sensitive skin, changes in eating and bowel habits, fever and feelings of abnormal body sensation; ‘thoughts and feelings’, with four subthemes reflecting the psychosocial impact of chemotherapy; and ‘actively dealing with discomfort’, with three subthemes describing how patients dealt with side effects, such as by sticking to a diet. Conclusion: Receiving chemotherapy treatment is difficult, and the side effects negatively influenced patients’ bodies and moods. Dealing actively with discomfort and accepting negative impacts in hope of a cure helped the participants manage the acute complications related to the treatment. We recommend the development of interventions to ease discomfort due to chemotherapy.

Calidad de vida relacionada con la salud en pacientes con enfermedad inflamatoria intestinal

Fundamento. Determinar la calidad de vida relacionada con la salud en pacientes con enfermedad de Crohn y colitis ulcerosa, así como evaluar las diferencias en función del sexo, tipo de enfermedad y otras variables sociodemográficas. Método. Estudio observacional, descriptivo y transversal en 100 pacientes atendidos en el servicio de Digestivo del Complejo Hospitalario de Navarra. Se empleó un cuestionario con variables sociodemográficas y clínicas, además del Inflammatory Bowel Disease Questionnaire-32, en su versión adaptada al castellano, para medir la calidad de vida. Resultados. La media de la puntuación total del cuestionario de calidad vida es de 166 puntos (D.T.=40,06) sobre un máximo de 232. Se han hallado diferencias estadísticamente significativas en función del tipo de enfermedad (p=0,005) y el sexo (p=0,001). Conclusiones. Las personas con enfermedad de Crohn o sexo femenino perciben peor calidad de vida relacionada con la salud respecto a pacientes con colitis ulcerosa u hombres.

Biopsy case mix and diagnostic yield at a Malawian central hospital

Cancer is a major disease burden worldwide resulting in high morbidity and mortality. It is the leading cause of mortality in developed countries and is one of the three leading causes of death for adults in developing countries. Pathological examination of tissue biopsies with histological confirmation of a correct cancer diagnosis is central to cancer care. Without an accurate and specific pathologic diagnosis, effective treatment cannot be planned or delivered. In addition, there are marked geographical variations in incidence of cancer overall, and of the specific cancers seen. Much of the published literature on cancer incidence in developing countries reflects gross estimates and may not reflect reality. Performing baseline studies to understand these distributions lays the groundwork for further research in this area of cancer epidemiology. Our current study surveys and ranks cancer diagnoses by individual anatomical site at Queen Elizabeth Central Hospital (QECH) which is the largest teaching and referral hospital in Malawi. A retrospective study was conducted reviewing available pathology reports over a period of one full year from January 2010 to December 2010 for biopsies from patients suspected clinically of having cancer. There were 544 biopsies of suspected cancer, taken from 96 anatomical sites. The oesophagus was the most common biopsied site followed by breast, bladder, bone, prostate, bowel, and cervical lymph node. Malignancies were found in biopsies of the oesophagus biopsies (squamous cell carcinoma, 65.1%; adenocarcinoma, 11.6%), breast (57.5%), bladder (squamous cell carcinoma, 53.1%) and stomach (37.6%). Our study demonstrates that the yield of biopsy for clinically suspected malignancy was greater than 50% for the 11 most common sites and provides a current survey of cancer types by site present in the population reporting to our hospital.

Qualidade de vida da pessoa portadora de ostomia na unidade local de saúde nordeste

Uma ostomia de eliminação intestinal resulta de um procedimento cirúrgico que consiste na ligação de uma parte do intestino delgado ou grosso, a um orifício externo na cavidade abdominal designado de estoma. O utente portador de uma ostomia de eliminação intestinal, devido à sua situação clínica, manifesta um misto de emoções resultante do enorme impacto físico e emocional devido à doença e ao tratamento. A sua própria vida vai desencadear alterações profundas no seu EU, nos estilos de vida, nas relações familiares e sociais, na sua imagem corporal e na autoestima (Pinto, 2012). Foi objetivo deste estudo analisar a perceção que a pessoa portadora de ostomia de eliminação intestinal, seguida na Unidade Local de Saúde Nordeste (ULSNE), tem sobre a sua qualidade de vida (QV). A investigação enquadra-se no domínio da investigação observacional, optando-se pela realização de um estudo descritivo, analítico e transversal, de abordagem quantitativa. Como instrumento de colheita de dados foi utilizado um formulário com questões relativas às características sociodemográficas, a escala de Graffar e a escala de avaliação da qualidade de vida do utente ostomizado. Aceitaram participar no estudo 105 utentes portadores de eliminação intestinal. O sexo predominante é o masculino (50,5%). A classe etária mais representativa é a dos 65 aos 92 anos (78,1%) e o estado civil predominante antes (67,6%) e depois (55,2%) da cirurgia é o de casado. Quanto à atividade laboral, o abandono do trabalho a tempo inteiro, devido à nova situação clínica, foi referido por 94,3% dos inquiridos. Em relação às habilitações académicas, 46,7% sabe ler e escrever, enquadrando-se na classe social média (57,1%). A consulta de estomaterapia na ULSNE ainda não está implementada, mas os inquiridos consideram que a sua implementação seria pertinente (93,3%), facilitando principalmente a adaptação à nova realidade (40%), a ultrapassar dificuldades (28,6%), a evitar complicações/resolver os problemas (9,5%). A média da QV dos participantes neste estudo é de 279,92, superior à média teórica da escala (215), indicando os inquiridos evidenciam um bom nível de qualidade de vida. O enfermeiro estomaterapeuta é o profissional que melhor pode proporcionar toda a informação e suportes necessários, que permitam ultrapassar os problemas e as limitações sentidas pelo ostomizado e pelas pessoas significativas na sua vida.

Atypical diagnosis by endoscopic capsule: Whipple's disease

Whipple's disease is a chronic systemic infection produced by the actinomycete Tropheryma whipplei. Endoscopic tests are key in the diagnosis as they allow biopsy and histopathological examination for definitive diagnosis of this entity. We present a case of Whipple's disease where capsule endoscopy, uncommon for the diagnosis of this condition, was essential for it and its performance before and after antibiotic treatment allows to describe the macroscopic evolution of the findings in the small bowel. This case illustrates the usefulness of capsule endoscopy to allow complete examination of the small bowel disease in which up to 30% of patients may present with normal endoscopy.

Management of the clinical issue of constipation with abdominal complaints in adults: a national survey of Primary Care physicians and gastroenterologists

Irritable bowel syndrome and functional constipation represent a relevant and common health issue. However, real-world clinical practice includes patients with constipation who may or may not have other abdominal complaints (pain, bloating, abdominal discomfort) with variable frequency. The goal of the present study was to obtain information on the workload entailed by patients with constipation and associated abdominal complaints, predominant clinical behaviors, education needs, and potential daily practice aids both in Primary Care and gastroenterology settings. The clinical behavior of doctors is generally similar at both levels, despite differences in healthcare approach: use of empiric therapies and clinically guided diagnostic tests, with some differences in colonoscopy use (not always directly accessible from Primary Care). Regarding perceptions, general support and osmotic laxatives are most valued by PC doctors, whereas osmotic laxatives, combined laxatives, and linaclotide are most valued by GE specialists. Furthermore, over half of respondents considered differentiating both diagnoses as challenging. Finally, considerable education needs are self-acknowledged at both levels, as is a demand for guidelines and protocols to help in managing this issue in clinical practice. A strength of this study is its providing a joint photograph of the medical approach and the perceptions of constipation with abdominal discomfort from a medical standpoint. Weaknesses include self-declaration (no formal validation) and a response rate potentially biased by professional motivation.

Vasculites cerebrais na doença inflamatória intestinal

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Evaluation of the Correlation Between tTG-IgA Titer and Duodenal Biopsy Findings in Children With Suspected Celiac Disease

Background: Celiac disease is an immune-mediated inflammation of the small intestine caused by sensitivity to dietary gluten in genetically sensitive individuals. Objectives: In this study, we aimed to evaluate the predictive value of tissue transglutaminase (tTG) antibodies for the diagnosis of celiac disease in a pediatric population in order to determine if duodenal biopsy can be avoided. Patients and Methods: The subjects were selected among individuals with probable celiac disease, referring to a gastrointestinal clinic. After physical examinations and performing tissue transglutaminase-immunoglobulin A (tTG-IgA) tests, upper endoscopy was performed if serological titer was higher than 18 IU/mL. Therapy started according to pathologic results. Results: The sample size was calculated to be 121 subjects (69 female and 52 male subjects); the average age of subjects was 8.4 years. A significant association was found between serological titer and pathologic results; in other words, subjects with high serological titer had more positive pathologic results for celiac disease, compared to others (P < 0.001). Maximum sensitivity (65%) and specificity (65.4%) were achieved at a serological titer of 81.95 IU/ml; the calculated accuracy was lower in comparison with other studies. As the results indicated, lower antibody titer was observed in patients with failure to gain weight and higher antibody titer was reported in diabetic patients. Conclusions: As the results indicated, a single serological test (tTg-IgA test) was not sufficient for avoiding intestinal biopsy.