Azathioprine in the therapy of paediatric inflammatory bowel disease – part II: pharmacodynamics, pharmacokinetics, and the possibilities of measuring its metabolites in clinical practice

Summary Background: Thiopurines (predominantly azathioprine and mercaptopurine) are widely used in paediatrics to maintain remission in the treatment of inflammatory bowel disease. After its absorption from the gastrointestinal tract, azathioprine is converted into 6 mercaptopurine in approximately 90%. Several enzymes (such as thiopurine methyltransferase, xanthine oxidase and hypoxanthine-guanine phosphoribosyl transferase) participate in its further metabolism, producing non-active methylated metabolites (6 methylmercaptopurine) and thiouric acid and active 6-thioguanine nucleotide. The concentration of these metabolites can be measured in red blood cells. Aim: To map the benefits and possibilities of thiopurine metabolites measurements in patients suffering from inflammatory bowel disease. Conclusion: The measurement of active and non-active metabolites can help evaluate the bioavailability of those drugs, identify some causes of adverse effects and reveal non-adherence. Keywords Crohn’s disease, merkaptopurin, pediatrie, thiopuriny, ulcerative colitis

Azathioprine in the therapy of paediatric inflammatory bowel disease – part I: treatment indications, dosing and thiopurine-related adverse events

Background: Thiopurines (in Europe mainly azathioprine) are widely used in the treatment of inflammatory bowel diseases in children. Due to a prolonged time until the onset of therapeutic effect, those drugs are aimed to be used in the maintenance phase of the therapy rather than for induction of remission. Thiopurines are sometimes used in combination therapy (with aminosalicylates or biological treatment agents). The adverse events of these drugs occur as often as in 15–40% cases and may lead to treatment cessation in a significant number of patients. Aims: To overview available information on (mainly) children suffering from inflammatory bowel disease. Conclusion: Genetic examination accompanied with laboratory monitoring of blood count parameters (specifically at the beginning of therapy) and biochemistry can help prevent some of the severe adverse events. Keywords Crohn’s disease, ulcerative colitis, pediatrie, merkaptopurin, thiopuriny

Crohn's disease in Kazakhstan: epidemiological aspects of incidence

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract with an increasing incidence worldwide and widespread in industrialized countries, while the incidence is also increasing in Asia and the Middle East. Purpose of the study. To study the epidemiological aspects of the incidence of CD in Kazakhstan. Material and methods. The study for 2013-2018, analyzed the registration and reporting forms of the Ministry of Health of the Republic of Kazakhstan on new cases of CD (ICD: K50) using descriptive and analytical methods of biomedical statistics. Results. During the study period, 4,671 new cases of CD were registered in Kazakhstan, of which 341 (7.9%) in children under 15 years old, 84 (2.0%) in adolescents (15-17 years old) and adults (18 years old and older) – 4,226 cases (90.9%). The incidence of CD in Kazakhstan was 4.5 per 100,000 of the total population, while in children – 1.210/0000 (95% CI=1.09-1.32), in adolescents – 2.120/0000 (95% CI=1.47-2.77) and the adult population – 5.860/0000 (95% CI=3.20-8.53). The trends in the CD incidence as a whole in the entire population had a pronounced tendency to decrease (Тde=−30.3%), a slight increase was observed only in the child population (Тin=+1.1%), and in other studied groups they decreased: in adolescents – Тde=−11.9% and in the adult population – Тde=−33.8%. Conclusion. The study has revealed some aspects of incidence in different age groups and the established trends require further study of this pathology. Keywords: Crohn's disease, incidence, trends, Kazakhstan.

TRANSPLANTATION OF ADIPOSE-DERIVED MESENCHYMAL STEM CELLS IN REFRACTORY CROHN’S DISEASE: SYSTEMATIC REVIEW

ABSTRACT Background: Crohn’s disease is a pathological condition that has different options of treatment, but there are patients who need other therapeutic approach, such as the use of adipose-derived mesenchymal stem cells. Aim: Systematic literature review to determine the different ways of adipose-derived mesenchymal stem cells administration in humans with luminal refractory and perianal fistulizing Crohn’s disease. Methods: It was conducted a search for articles (from 2008 to 2018) on PubMed and ScienceDirect databases using the keywords Crohn’s disease, fistulizing Crohn’s disease, luminal Crohn’s disease and transplantation of mesenchymal stem cells or mesenchymal stem cells or stromal cells. Thirteen publications were selected for analysis. Results: Only one study referred to the luminal Crohn´s disease. The number of cells administered was variable, occurring mainly through subcutaneous adipose tissue by liposuction. It could be highlighted the autologous transplant with exclusive infusion of mesenchymal stem cells. The procedures involved in pre-transplant were mainly curettage, setons placement and stitching with absorbable suture, and conducting tests and drug treatment for luminal Crohn´s disease. During transplant, the injection of mesenchymal stem cells across the fistula path during the transplant was mainly on the intestinal tract wall. Conclusion: Although the use of mesenchymal stem cells is promising, the transplant on the luminal region should be more investigated. The injection of mesenchymal stem cells, exclusively, is more explored when compared to treatment with other products. The preparation of the fistulizing tract and the location of cell transplantation involve standardized health care in most studies.

DOENÇA DE CROHN

INTRODUÇÃO: A doença de Crohn é qualificada como uma doença inflamatória intestinal, de caráter crônico, recidivante, transmural e que pode afetar qualquer parte do trato digestivo, desde a boca até o ânus, mas, principalmente, o intestino delgado e o cólon. São de cunho multifatorial, com prevalência e incidência variando de acordo com a genética, meio ambiente, microbiota intestinal e até mesmo um possível agente entérico infeccioso. É uma doença que afeta pessoas de várias idades, sexos e raças, apesar de se verificar maior incidência em jovens do sexo feminino e em regiões urbanas. METODOLOGIA: Trata-se de um artigo de revisão no qual, a partir das palavras “doença de Crohn” e “doença inflamatórias intestinais”, foi realizado busca por periódicos nos bancos de dados: PubMed, Scielo, Portal Periódicos CAPES e Google acadêmico. CONCLUSÃO: A doença de Crohn apresenta uma importante taxa de morbimortalidade no mundo, principalmente em regiões em franca urbanização e industrialização. O diagnóstico é um procedimento extremamente complicado devido a sua clínica inespecífica e pelos vários aspetos em comum com outras patologias. Dessa forma, ainda se faz necessário uma melhor investigação científica na área, com intuito de se desenvolver melhores técnicas diagnosticas e condutas a serem tomadas no seguimento e cura dessa patologia.Palavras-chave: Doença de Crohn, Doença inflamatórias intestinais, Diarreia. ABSTRACT INTRODUCTION: Crohn's disease is described as an inflammatory, chronic, recurrent, transmural inflammatory disease that can affect any part of the digestive tract, from the mouth to the anus, but especially the small intestine and colon. They are multifactorial, with prevalence and incidence varying according to genetics, environment, intestinal microbiota and even a possible infectious enteric agent. It is a disease that affects people of various ages, sexes and races, although there is a greater incidence in young women and in urban areas. METHODOLOGY: This is a review article in which, from the words "Crohn's disease" and "inflammatory bowel disease", a search was made for journals in the databases: PubMed, Scielo, Portal Periódicos CAPES and Google academic. CONCLUSION: Crohn's disease presents an important morbidity and mortality rate in the world, especially in regions where there is rapid urbanization and industrialization. Diagnosis is an extremely complicated procedure due to its nonspecific clinical and various aspects in common with other pathologies. Thus, a better scientific investigation in the area is still necessary, in order to develop better diagnostic techniques and behaviors to be taken in the follow-up and cure of this pathology. Keywords: Crohn's disease, Inflammatory bowel disease, Diarrhea.

PERFIL EPIDEMIOLÓGICO DOS ACIDENTES POR ANIMAIS PEÇONHENTOS NA REGIÃO NORTE ENTRE OS ANOS DE 2012 E 2015

O envenenamento causado por animais peçonhentos é considerado um importante problema de saúde pública, especialmente em países tropicais ou subtropicais, sendo incluídos pela Organização Mundial da Saúde (OMS) na lista de Doenças Tropicais Negligenciadas. Descrever o perfil epidemiológico dos acidentes por animais peçonhentos ocorridos na região Norte do Brasil entre 2012 e 2015, buscando subsidiar o entendimento da dinâmica deste agravo e analisar comparativamente os valores obtidos em estudos de outras regiões do país. Realizou-se estudo transversal descritivo, retrospectivo, clínico e epidemiológico dos acidentes por animais peçonhentos notificados entre 2012 e 2015 ao Sistema de Informação de Agravos de Notificação (SINAN). Observaram-se 58.432 casos de acidentes por animais peçonhentos na região Norte durante o período analisado, sendo a maioria causada por serpentes (34.801), seguido por escorpiões (13.040) e aranhas (3.109). Entre os acidentados, constatou-se o predomínio do sexo masculino (72,58%), com idade entre 20-39 anos (37%). Na região Norte, o Pará apresentou o maior número de casos registrados (7122 casos/ano), enquanto Roraima apresentou o menor (528 casos/ano). A letalidade observada nos acidentes peçonhentos foi de 0,37%, sendo maior em acidentes por abelhas (0,59%) e por serpentes (0,47%). O tempo médio entre a picada e o atendimento foi entre 0-3 horas, com uma evolução clínica para a cura em 85,9% dos casos. A região Norte registrou um número importante de acidentes com animais peçonhentos e a vigilância epidemiológica torna-se essencial na construção de estratégias em saúde para controle desse agravo.Palavras chave: epidemiologia, acidentes peçonhentos, envenenamento, Norte. ABSTRACT INTRODUCTION: Crohn's disease is described as an inflammatory, chronic, recurrent, transmural inflammatory disease that can affect any part of the digestive tract, from the mouth to the anus, but especially the small intestine and colon. They are multifactorial, with prevalence and incidence varying according to genetics, environment, intestinal microbiota and even a possible infectious enteric agent. It is a disease that affects people of various ages, sexes and races, although there is a greater incidence in young women and in urban areas. METHODOLOGY: This is a review article in which, from the words "Crohn's disease" and "inflammatory bowel disease", a search was made for journals in the databases: PubMed, Scielo, Portal Periódicos CAPES and Google academic. CONCLUSION: Crohn's disease presents an important morbidity and mortality rate in the world, especially in regions where there is rapid urbanization and industrialization. Diagnosis is an extremely complicated procedure due to its nonspecific clinical and various aspects in common with other pathologies. Thus, a better scientific investigation in the area is still necessary, in order to develop better diagnostic techniques and behaviors to be taken in the follow-up and cure of this pathology. Keywords: Crohn's disease, Inflammatory bowel disease, Diarrhea.