A restrição de alimentos lácteos é obrigatória para pacientes com doença inflamatória intestinal? Estudo transversal multinacional / Is dairy foods restriction mandatory for inflammatory bowel disease patients: a multinational cross-sectional study

ABSTRACT Background: The role of dairy foods in inflammatory bowel disease (IBD) has been controversial and it is debatable if patients with IBD should avoid milk and dairy products or not, as well as the relationship between these foods and symptoms among those population. Objective: This multi centric cross-sectional study designed to evaluate if it is really necessary to deprive IBD patients from consumption of dairy foods. Methods: A multicenter study with 12 gastroenterology referral centers in four countries was designed to evaluate gastrointestinal (GI) symptoms after consumption of dairy foods from all outpatients with IBD during 6 months and to compare patients treated at the same centers without IBD (non IBD cases). Results: Overall 1888 cases included (872 IBD patients and 1016 non IBD cases). 56.6% of participants were female with average age of 40.1 years. Racially 79.8% participants were Caucasians and originally they were citizens of 10 countries. Relative prevalence of IBD was higher in Africans and Indians and the most frequent prevalence of dairy foods intolerance was seen in Asians. Among IBD patients, 571 cases diagnosed as ulcerative colitis and 189 participants as Crohn's disease. Average duration of diagnosis as IBD was 6.8 years (from 2 months to 35 years). The most prevalent GI symptoms after consumption of all the dairy foods were bloating and abdominal pain. Totally, intolerance of dairy foods and lactase deficiency was more prevalent among IBD patients in comparison with non IBD cases (65.5% vs 46.1%, P=0.0001). But the rate of GI complains among IBD patients who had not any family history of lactase deficiency, history of food sensitivity or both were 59.91%, 52.87% & 50.33% respectively and similar to non IBD cases (P=0.68, 0.98 & 0.99 respectively). Conclusion: The rate of dairy foods intolerance among IBD patients without family history of lactase deficiency or history of food sensitivity is similar to non IBD cases and probably there is no reason to deprive them from this important source of dietary calcium, vitamin D and other nutrients.

RESUMO Contexto: O papel dos alimentos lácteos na doença inflamatória intestinal (DII) tem sido controverso e é discutível se os pacientes com DII devem ou não evitar leite e laticínios, bem como a relação entre esses alimentos e sintomas nesta população. Objetivo: Estudo transversal multicêntrico foi projetado para avaliar se é realmente necessário privar os pacientes com DII do consumo desta classe de alimentos. Métodos: Um estudo multicêntrico com 12 centros de referência em gastroenterologia de quatro países foi projetado para avaliar sintomas gastrointestinais após o consumo de alimentos lácteos em todos os ambulatórios de DII durante seis meses e comparar pacientes tratados nos mesmos centros sem DII. Resultados: No total, foram incluídos 1888 casos (872 pacientes com DII e 1016 casos sem DII. 56,6% dos participantes eram do sexo feminino com idade média de 40,1 anos. 79,8% dos participantes eram caucasianos e originalmente eram cidadãos de 10 países. A prevalência relativa de DII foi maior em africanos e indianos e a prevalência mais frequente de intolerância a alimentos lácteos observada nos asiáticos. Entre os pacientes com DII, 571 casos foram diagnosticados como colite ulcerativa e 189 participantes como doença de Crohn. A duração média do diagnóstico como DII foi de 6,8 anos (de 2 meses a 35 anos). Os sintomas de gastrointestinais mais prevalentes após o consumo de todos os alimentos lácteos foram inchaço e dor abdominal. No total, a intolerância aos alimentos lácteos e a deficiência de lactase foi mais prevalente entre os pacientes com DII em comparação com os casos sem DII (65,5% vs 46,1%, P=0,0001). A taxa de queixas gastrointestinais entre os pacientes com DII que não tinham histórico familiar de deficiência de lactase, histórico de sensibilidade alimentar ou ambos foram de 59,91%, 52,87% e 50,33% respectivamente e semelhantes aos casos sem DII (P=0,68, 0,98 e 0,99, respectivamente). Conclusão: A taxa de intolerância de alimentos lácteos entre pacientes com DII sem histórico familiar de deficiência de lactase ou histórico de sensibilidade alimentar é semelhante aos casos sem DII e provavelmente não há razão para privá-los dessa importante fonte de cálcio dietético, vitamina D e outros nutrientes.

Leche materna deslactosada con la enzima beta galactosidasa para lactantes intolerantes / Leite materno sem lactose com a enzima beta-galactosidase para lactentes intolerantes / Lactose-free breast milk with the enzyme beta galactosidase for intolerant infants

Introducción: los bebés deben beneficiarse de la leche materna, incluso cuando presentan intolerancia a la lactosa. Por esto, se debe recurrir a la obtención de leche materna deslactosada. Objetivo: analizar el efecto de la enzima beta galactosidasa en la hidrólisis de la lactosa de leche materna madura para bebés clínicamente diagnosticados con intolerancia a la lactosa. Materiales y método: estudio exploratorio, descriptivo y explicativo. El contenido de lactosa se cuantificó desde el inicio hasta el final del tratamiento, controlando temperatura, tiempos y cantidad de enzima ß-galactosidasa adicionada en la leche materna. Se recolectaron 1000 ml de leche materna, obtenidos del Banco de Leche del Hospital General de Medellín (Antioquia, Colombia). Resultados: las muestras donadas se encontraban pasteurizadas y posteriormente fueron sometidas a la acción de la enzima lactasa. Se cuantificó el contenido de lactosa sin la enzima, reportando en promedio 6,34 mg/100 ml ± 0,23. El mayor aporte de lactosa obtenido posterior a la exposición a la enzima (30 minutos) fue de 6,07 mg/ml ± 0,35 (correspondiente a 95 % del contenido inicial), finalizando con un aporte de 0,35 % a una concentración de 0,4 % tras 24 horas, porcentaje que representa 95 % de la hidrólisis total en la leche materna. Conclusiones: en todas las muestras analizadas de diferentes madres se pudo obtener leche materna con bajas concentraciones de lactosa tras 24 horas de haber sido sometidas a la acción de ß-galactosidasa. Lo anterior se establece como una alternativa para los bebés intolerantes a la lactosa, que permitiría no privarlos de todos los beneficios que ofrece este alimento.

Introduction: Babies should benefit from breast milk, even when they are lactose intolerant. For this reason, parents should resort to obtaining lactose-free breast milk. Objective: To examine the effect of the enzyme ß-galactosidase on the hydrolysis of lactose in mature breast milk for babies clinically diagnosed with lactose intolerance. Materials and method: Exploratory, descriptive, and explanatory study. The lactose content was quantified from the beginning to the end of the treatment, controlling variables such as temperature, times, and the amount of ß-galactosidase enzyme added in breast milk. A total of 1000 ml of breast milk were obtained from the milk bank at Hospital General de Medellín (Antioquia, Colombia). Results: Donated samples were first pasteurized and subsequently subjected to the action of the enzyme lactase. The lactose content without the enzyme was quantified, reporting an average of 6.34 mg/100 mL±0.23. The highest contribution of lactose obtained after exposure to the enzyme was 6.07 mg/mL±0.35 (corresponding to 95% of the initial content), at 30 minutes, ending with a contribution of 0.35% at a concentration of 0.4% in 24 hours, percentage that represents 95% of total hydrolysis in breast milk. Conclusions: In all the examined samples from different mothers, it was possible to obtain breast milk with low concentrations of lactose 24 hours after these were exposed to the action of ß-galactosidase. This becomes an alternative for feeding lactose intolerant babies and not deprive them from all the benefits offered by breast milk.

Introdução: os bebês se devem beneficiar do leite materno, mesmo quando tenham intolerância à lactose, razão pela qual se deve recorrer à obtenção de leite materno sem lactose. Objetivo: analisar o efeito da enzima beta-galactosidase na hidrólise da lactose no leite materno maduro para bebês diagnosticados clinicamente com intolerância à lactose. Materiais e método: estudo exploratório, descritivo, explicativo. O teor de lactose foi quantificado do início ao fim do tratamento; temperatura, tempos e quantidade de enzima beta-galactosidase adicionada no leite materno foram controlados; foram coletados 1000ml de leite materno, obtidos no Banco de Leite do Hospital General de Medellín (Antioquia, Colômbia). VResultados: as amostras doadas foram pasteurizadas e posteriormente submetidas à ação da enzima lactase. O teor de lactose sem a enzima foi quantificado, relatando uma média de 6,34mg/100ml±0,23. A maior contribuição de lactose obtida após a exposição à enzima foi de 6,07mg/ml±0,35 (correspondendo a 95% do conteúdo inicial) em 30 minutos, finalizando com uma contribuição de 0,35% na concentração de 0,4% em 24 horas, percentual que representa 95% da hidrólise total no leite materno. Conclusões: em todas as amostras analisadas de diferentes mães, foi possível obter leite materno com baixas concentrações de lactose 24 horas após ser submetido à ação da beta galactosidase, como alternativa para bebês intolerantes à lactose e não os privar de todos os outros benefícios oferecidos por esse alimento ideal.

Intolerancia a la lactosa: mitos y verdades. Actualización / Lactose intolerance: myths and facts. An update

La lactosa es el principal carbohidrato de la leche materna. Es un disacárido conformado por glucosa y galactosa. Su producción en la glándula mamaria es independiente de la dieta materna. Además de proveer energía, es la única fuente de galactosa de la dieta, necesaria para la síntesis de macromoléculas como oligosacáridos, glicoproteínas y glicolípidos. Favorece la absorción y retención de calcio, magnesio y cinc. Su digestión por la enzima lactasa y posterior absorción tienen lugar en intestino delgado. El déficit de lactasa, que puede ser primario congénito (muy infrecuente), primario tardío o secundario por lesión intestinal, puede generar intolerancia con síntomas como dolor, distensión abdominal, flatulencia y diarrea. En el colon, bifidobacterias y lactobacilos pueden hidrolizarla. El manejo nutricional de la intolerancia deberá hacerse siempre preservando la lactancia materna. La reducción o suspensión de la lactosa deberá ser transitoria y se reemplazarán alimentos suspendidos por otros con adecuados aportes calóricos, proteicos y de minerales y vitaminas.

Lactose is the main carbohydrate present in humanmilk. It is a disaccharide made up of glucoseand galactose. It is produced in the mammaryglands, regardless of maternal diet. In addition toproviding energy, it is the only source of dietarygalactose, necessary for macromolecule synthesis,including oligosaccharides, glycoproteins, andglycolipids. It favors calcium, magnesium, andzinc absorption and retention. Its digestion bylactase and subsequent absorption occurs inthe small intestine. Lactase deficiency may beclassified into congenital primary (very rare),late-onset primary or secondary due to an injuryof the intestine; it may cause intolerance withpain, abdominal distension, abdominal gas, anddiarrhea. In the colon, it may be hydrolyzed bybifidobacteria and lactobacilli. The nutritionalmanagement of intolerance should alwayspreserve breastfeeding. Lactose reduction orelimination should be transient, and eliminatedfood should be replaced with other similar incalorie, protein, mineral, and vitamin content.

Progress in neonatal lactose intolerance / 国际儿科学杂志

Lactose intolerance(LI)refers to the poor absorption of lactose, which caused by insufficient lactase or low activity.LI can leads to a series of symptoms of gastrointestinal symptom and seriously affects the growth and development of children.The symptoms of LI are similar to gastrointestinal diseases.Due to the lack of simple and effective detection method, neonatal LI is often ignored or confused with other gastrointestinal diseases, leading to excessive use of antibiotics and amino acid formula.Therefore, early identification, diagnosis and treatment of neonatal LI are very important.This article reviews the development characteristics, etiology, clinical manifestations, diagnosis, antidiastole and treatment of neonatal LI.

Immobilization of lactase on magnetic chitosan microspheres and its effect on enzymatic properties / 中国组织工程研究

BACKGROUND: The free enzyme has the problems of poor stability and inability to be reused during application. Using magnetic polymer microspheres as the carrier of the binding enzyme to prepare immobilized enzyme can maintain the natural activity of the enzyme, and can be reused, but also provide convenient conditions for automatic production management. OBJECTIVE: Magnetic chitosan microspheres as carrier of binding enzyme were used to prepare the immobilized lactase, which is easy to recycle, can be reused, and has high enzyme activity and stability. METHODS: By inputting a certain amount of magnetic chitosan microspheres into the phosphoric acid buffer for swelling for 2 hours, the swelling magnetic chitosan microspheres were collected with a magnet and added to a certain concentration of lactase phosphate buffer. They were shocked in a constant temperature shaker for 1 hour and preserved in refrigerator at 4 °C. The microspheres were precipitated with a magnet to pour out the supernatant. After full washing with buffer solution, the immobilized lactase was obtained. The properties of the magnetic microspheres (the amount of glutaraldehyde used in the preparation of microspheres was 2, 4, 6, 8, 10, 12, 14 mL), the amount of enzymes (0.5, 1, 1.5, 2 g/L) added, the pH (6.4, 6.8, 7.0, 7.2) of the buffer, and the immobilization time (1, 2, 5, 10, 15, 20 hours) were tested to determine the optimal immobilization conditions. RESULTS AND CONCLUSION: (1) The optimum conditions for immobilized lactose with magnetic chitosan microspheres were as follows: magnetic chitosan microspheres prepared with 10 mL of glutaraldehyde were selected as the immobilized carrier of lactase. The amount of enzyme added was 0.3 g/L, pH 7.0 and the immobilization time was 5 hours. (2) Compared with the free enzyme, immobilized lactase showed a wider range of reaction temperature and pH value. (3) The ability of immobilized enzyme binding substrate was enhanced. (4) After repeated use of the immobilized enzyme five times, the enzyme activity remained 65%. (5) The storage stability of lactase was also improved after immobilization.

Evaluation of lactase activity in probiotic cultures containing inulin rich plant extracts as prebiotic sources

@#Aims: The present study deals with the isolation and identification of lactase producing probiotic strains from camel and sheep milk, determination of the enzyme activity by β-galactosidase assay (Miller Assay) in the presence of garlic, peas, onion and leeks extracts containing inulin as a prebiotic component. Methodology and results: The two isolates were screened for lactase producing ability to degrade lactose on MRS agar at 37 °C. These were identified as Lactococcus lactis from camel (Marecha) milk and Lactobacillus casei from sheep (Kajli) milk through morphological and biochemical tests using MRS medium. The optimized pH and temperature of both strains were 6 and 35 °C, respectively. Among the three concentrations used (0.2%, 0.4%, 0.8%), the optimal concentration of inulin rich onion and leeks extracts was 0.8% for maximum growth of L. casei and of the peas extract for L. lactis growth. 0.2% garlic extract was more effective prebiotic source for L. lactis growth. 0.8% commercial inulin used as a positive control was less effective as compared to plant extracts used in the study. With o-nitrophenyl-β-Dgalactoside) used as a substrate in the enzyme assay, maximum lactase activity obtained with 0.8% concentration of garlic extract is 7.10 Miller Units as compared to the peas extract with 6.17 Miller Units from L. lactis. Lactobacillus casei has produced more lactase, 6.85 Miller units with onion extract than with leeks extract, 6.43 Miller Units. Pure commercial inulin used as a control has given maximum enzyme activity as 9.14 Miller Units at 0.2% concentration. Conclusion, significance and impact of the study: It is concluded that the extracted prebiotic may enhance lactase activity of the probiotics to supplement the development of food products for lactose intolerant patients.

Karyotyping and population genetics in Cold War Mexico: Armendares's and Lisker's characterization of child and indigenous populations, 1960s-1980s / Cariotipia e genética de populações no México da Guerra Fria: as caracterizações de Armendares e Lisker sobre as populações infantil e indígena, 1960-1980

Abstract This paper focuses on geneticists Salvador Armendares's and Rubén Lisker's studies from the 1960s to the 1980s, to explore how their work fits into the post-1945 human biological studies, and also how the populations they studied, child and indigenous, can be considered laboratories of knowledge production. This paper describes how populations were considered for different purposes: scientific inquiry, standardization of medical practices, and production or application of medicines. Through the narrative of the different trajectories and collaborations between Armendares and Lisker, this paper also attempts to show the contact of their scientific practices, which brought cytogenetics and population genetics together at the local and global levels from a transnational perspective.

Resumo Aborda o trabalho dos geneticistas Salvador Armendares e Rubén Lisker, entre 1960 e 1980, para analisar como se insere nos estudos biológicos humanos do pós-1945, e demonstra como as populações estudadas por eles, a infantil e a indígena, podem ser consideradas laboratórios de produção de conhecimento. O artigo revela como as populações foram consideradas para diversos propósitos: investigação científica, padronização das práticas médicas e produção ou aplicação de suas medicinas. Por meio da narrativa das diferentes trajetórias e colaborações entre Armendares e Lisker, também procura discutir o contato de suas práticas científicas, que colocaram a citogenética e a genética de populações lado a lado nos níveis local e global a partir de uma perspectiva transnacional.

Lactose intolerance: what is a correct management?

SUMMARY Individuals with Lactose Intolerance (LI) tend to exclude milk from their diet since this behavior seems to relieve the symptoms caused by the disease. However, milk is a food of high nutritional value, and complete exclusion of dairy products may favor the development of bone diseases such as osteopenia and osteoporosis. The objective of this review was to evaluate the scientific evidence on the adequate management of patients with LI. This study was carried out from the review of the scientific literature in PubMed and SciELO databases. Complete exclusion of conventional dairy products is not necessary since most individuals with LI can tolerate up to 12 grams of lactose daily in a single dose. Yogurts and cheeses matured for having low amounts of lactose are part of the strategy that allows consumption of dairy products by patients with LI. Currently, there is a diversity of products considered as "milk substitutes" and supplements aimed at individuals with LI. However, these strategies still require better-designed studies.

RESUMO Os indivíduos com Intolerância à Lactose (IL) tendem a excluir o leite da alimentação, uma vez que essa conduta parece aliviar os sintomas ocasionados pela doença. Entretanto, o leite é um alimento de alto valor nutricional e a exclusão completa dos laticínios pode favorecer o desenvolvimento de doenças ósseas como osteopenia e osteoporose. O objetivo desta revisão foi avaliar as evidências científicas sobre o manejo adequado de pacientes com IL. Este estudo foi realizado a partir da revisão da literatura científica nas bases de dados PubMed e SciELO. A exclusão completa dos produtos lácteos convencionais não é necessária, pois a maior parte dos indivíduos com IL consegue tolerar diariamente até 12 g de lactose em uma única dose. Os iogurtes e queijos maturados, por terem baixa quantidade de lactose, fazem parte da estratégia que garante consumo de produtos lácteos por pacientes com IL. Atualmente existe uma diversidade de produtos considerados "substitutos do leite" e suplementos voltados para os indivíduos com IL, no entanto, essas estratégias ainda requerem estudos mais bem desenhados.

Efecto de los residuos fibrosos de avena ( Avena sativa ) y caraotas ( Phaseolus vulgaris ) sobre la actividad in vitro de las disacaridasas intestinales en ratas / Effect of the Fibrous Residues of Avena (Avena sativa) and Black Beans (Phaseolus vulgaris) on the in vitro Activity of Intestinal Disacaridases in Rats

Resumen Antecedentes: las disacaridasas intestinales pueden ser inhibidas o estimuladas parcialmente en presencia de fibra. Objetivo: evaluar el efecto de los residuos fibrosos de avena (Avena sativa) y caraotas (Phaseolus vulgaris) sobre la actividad in vitro de las disacaridasas intestinales. Materiales y métodos: 15 ratas Sprague Dawley se dividieron en tres grupos: un grupo control, un grupo alimentado con harina de caraota y un grupo alimentado con harina de avena, durante 21 días. Se obtuvo un homogeneizado de la mucosa intestinal que fue utilizado para la determinación de la actividad de las disacaridasas por un método enzimático, en presencia de sustrato natural y con la adición de residuos fibrosos de harina de avena y caraotas en concentración de 2,5 % (P/V). Resultados: la mayor actividad enzimática se registró en la región intestinal media para cada enzima (p<0,05). El orden de actividad enzimática en mg glucosa/mg proteína/min fue maltasa (0,149) sacarasa (0,096) y lactasa (0,014) (p<0,05). La maltasa fue inhibida en mayor medida por el residuo de caraota; la sacarasa, por el residuo de avena; y la lactasa, por ambos. Conclusiones: la adición de fibra purificada de avena y caraota produjo una disminución significativa de la actividad in vitro de las disacaridasas intestinales, especialmente en presencia del residuo de caraota.

Abstract Background: Intestinal disaccharidases can be partially inhibited or stimulated in the presence of fiber. Objective: To evaluate the effect of fibrous residues of oats (Avena sativa) and black beans (Phaseolus vulgaris) on the "in vitro" activity of the intestinal disaccharidases. Materials and Methods: 15 Sprague Dawley rats, were divided into three groups: control, fed with bean flour, and fed with oatmeal flour for 21 days. Homogenate was obtained by scraping the mucosa. The determination of enzymatic activity of the disaccharidases was measured by the enzymatic method, in the presence of its natural substrate and with addition of the fibrous residues obtained from the oatmeal and black beans, in concentration of 2.5 % (W/V). Results: The highest enzymatic activity was recorded in the middle intestinal region for each enzyme (p <0.05). The order of enzymatic activity in mg glucose / mg protein / min was maltase (0.149) sucrase (0.096) and lactase (0.014) (p<0.05). Maltase was inhibited to a greater extent by bean residue; sucrase by oat residue and lactase by both. Conclusion: The addition of purified fiber of oats and bean produced a significant decrease in the in vitro activity of the intestinal disaccharidases, especially in the presence of the bean residue.

Infantile Colic: An Update

Context: Infantile colic is self-limiting condition but it can be a cause of anxiety for parents and challenge for doctors. The challenge for thedoctors lies in correct identification of the condition and appropriate management. The objective of this review article is to summarize thepathophysiology, treatment options and outcome in infantile colic so that clinicians can have a fair idea about the condition, recentupdates and future prospects.Evidence: A search of the Cochrane Library, PubMed, and Google Scholar was made using the key words “Infant colic”, Infantile colic”,“excessive crying in infants”. All the materials were analyzed and summarized.Results: At present, infantile colic is an area of clinical research both in terms of etiology and treatment. Various etiological theories havebeen proposed but none of them are strong enough to completely describe the condition. Various treatment agents are being tried forcolic like counseling and behavioral modification, dietary modification, lactase and probiotic supplementation, pain relieving agents, andchiropathy. Proper counseling of the parents is the first line of management at present. Simethicone has no role in decreasing thesymptoms of colic and Dicyclomine is not recommended in children younger than six months. No specific recommendations have beenmade on the use of pain relieving agents and manipulative therapies in colic. At present strong evidence is lacking regarding the use ofprobiotics, lactase supplementation and dietary modification.Conclusion: Counseling of parents about the benign nature of the condition is considered first line for now until an effective treatment isestablished. Other treatment options are prescribed on a case-based manner, and based on the parental perception of the condition.

The study on the incidence and risk factors of lactase deficiency in newborns / 中国新生儿科杂志

Objective To study the incidence of lactase deficiency and the risk factors affecting intestinal lactase secretion in newborns with lactase deficiency.Method From February to December 2016,newborns admitted to the neonatal ward of the Affiliated Hospital of Hangzhou Normal University were enrolled in this prospective study.Urine samples were taken within one to two hours after feeding for galactose qualitative tests,and the related clinical data were recorded.The newborns were assigned into lactase deficient group and non-lactase deficient group according to the test results.Then the risk factors of lactase deficiency were analyzed comparing the clinical data between the two groups.Result A total of 1 022 newborns were hospitalized during the research period,of whom 213 were enrolled in this study according to the inclusion criteria.154 cases had positive results in the urine galactose qualitative tests,yielding the incidence of lactase deficiency of 72.3 ％.42 cases had lactose intolerance symptoms,and the incidence of lactose intolerance was 27.3 ％ (42/154).Age and positive family history in lactase deficient group were higher than non-lactase deficient group (10.3 ±6.4 d vs.8.1 ±5.8 d and 23.4％ vs.10.2％),while the gestational age of lactase deficient group was lower than non-lactase deficient group (37.8 ±2.9 weeks vs.39.0 ± 1.7 weeks),and the differences between the two groups were statistically significant (P ＜ 0.05).No significant differences existed in gender,birth weight,antibiotics use and feeding volumes between the two groups (P ＞ 0.05).Multivariate Logistic regression analysis showed that age (OR =1.065,95％CI 1.007 ～ 1.127) and positive family history (OR =2.912,95％ CI 1.053 ～ 8.056) were the risk factors of lactase deficiency.Gestational age (OR =0.747,95％ CI 0.617 ～ 0.904) was the protective factor of lactase deficiency in newborns.Conclusion The incidence of lactase deficiency in newborns is high,but not all the newborns manifest lactose intolerance symptoms.Age and positive family history were the risk factors while gestational age was the protective factor for lactase deficiency in newborns.

Progress in infants lactose intolerance / 国际儿科学杂志

The infants lactose intolerance is the incomplete hydrolysis of lactose due to lactase deficiency,which may lead to non-infectious diarrhea,even chronic,persistent diarrhea.It may impair their health and growth severly,such as malnutrition and growth restriction.The early diagnosis and treatment is important.This review summarizes the progress of Lactose Intolerance in infants in aspects of pathogenesis,genetic,clinical manifestations,diagnosis,treatment as well as prognosis.

Classificação da intolerância à lactose: uma visão geral sobre causas e tratamentos / Classification of lactose intolerance: An overview of causes and treatments

A deficiência total ou parcial da enzima denominada lactase, responsável por hidrolisar em glicose e galactose a lactose presente no leite, é popularmente conhecida como intolerância à lactose. No presente trabalho foram revisadas as causas e tratamentos para intolerância à lactose. Foi realizada uma revisão retrospectiva e integrativa da literatura nas bases SciELO, MedLine e PubMed. A intolerância possui três classificações: primária, secundária e congênita. A intolerância ontogenética à lactose ou hipolactasia primária adulta é a forma mais comum. Já a deficiência secundária consiste em um quadro fisiopatológico que tem como consequência a má absorção de lactose. Por fim, a intolerância congênita à lactose é uma deficiência de herança genética, que acomete recém-nascidos nos primeiros dias de vida. Na hipolactasia, o agravamento surge na vida adulta, justamente com perda da função gradativa da enzima que degrada a lactose. Isso ocorre pelo fato de essa enzima, presente e ativa durante a amamentação em mamífero, perder sua função no início do desmame. Em pacientes não intolerantes, essa mesma enzima passa por um processo de mutação, permanecendo ativa ao longo da vida adulta. O tratamento mais comum para pacientes com intolerância à lactose envolve a retirada total ou parcial do leite e seus derivados, já que a supressão total causa alguns danos à nutrição e à manutenção do organismo.

The total or partial deficiency of lactase, responsible for hydrolyzing lactose into glucose and galactose, is popularly known as lactose intolerance. In this work we reviewed the causes and treatments for lactose intolerance. An integrative and retrospective literature review was carried out at the SciELO, MedLine and PubMed databases. Intolerance has three classifications: primary, secondary and congenital. The ontogenetic lactose intolerance or adult primary hypolactasia is the most common form. The secondary deficiency consists of a pathophysiological which results in the absorption of lactose. Congenital lactose intolerance is a genetic inheritance disability that affects infants in the first days of life. In the hypolactasia, aggravation arises in adulthood, just with gradual loss of function of the enzyme that breaks down lactose. This enzyme, present and active during breastfeeding in mammalian, starts losing its function at the weaning. In non intolerant patients this same enzyme passes through a changing process which remains active throughout adult life. The most common treatment for patients with lactose intolerance involves partial or total removal of the milk and its products since the total withdrawal causes some damage to nutrition and maintenance of body.

Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in the Czech/Slav and Czech Roma/Gypsy populations

Abstract Lactase non-persistence (leading to primary lactose intolerance) is a genetically dependent inability to digest lactose in adulthood. As part of the human adaptation to dairying, the human lactase LCT-13910C/T mutation (which propagates adult expression of lactase) developed, spread and participated in the adaptation to dairying. This variant is associated with lactase activity persistence, and its carriers are able to digest lactose. We compared the frequencies of lactase 13910C/T (rs4988235) genotypes in Czechs/Slavs (N = 288) and Czech Gypsies/Roma (N = 300), two ethnically different groups where this polymorphism has not yet been analysed. Allelic frequencies significantly differed between the populations (p < 0.0001). In Czechs/Slavs, the lactase persistence T allele was present in 76% of the individuals, which is in agreement with frequencies among geographically neighbouring populations. In the Czech Gypsy/Roma population, only 27% of the adults were carriers of at least one lactase persistence allele, similar to the Indian population. In agreement with this result, dairy product consumption was reported by 70.5% of Czechs/Slavs and 39.0% of the Czech Gypsy/Roma population. Both in the Czech Gypsy/Roma and in the Czech/Slavs populations, the presence of carriers of the lactase persistence allele was similar in subjects self-reporting the consumption of unfermented/fresh milk, in comparison to the others.

Oral administration of exogenous lactase in tablets for patients diagnosed with lactose intolerance due to primary hypolactasia / Administração oral de lactase exógena em comprimidos em pacientes portadores de intolerância à lactose devido à hipolactasia primária

ABSTRACT Background Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. , Objective Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Methods Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r) - Eurofarma Laboratórios S.A.) or the reference product (Lactaid(r) - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days. Results Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. Conclusion The experimental product was non-inferior to the reference product, indicating that it was an effective replacement therapy for endogenous lactase in lactose intolerance patients.

RESUMO Contexto A hipolactasia primária é uma condição muito frequente na qual há redução da atividade da lactase na mucosa intestinal.A presença de sintomas abdominais devidos à má absorção da lactose presente em alguns casos caracteriza a intolerância à lactose. Objetivo Avaliar a eficácia de um produto contendo lactase exógena em comprimidos comparativamente a de um produto comparador com eficácia comprovada em pacientes portadores de intolerância à lactose. Métodos Estudo multicêntrico, randomizado, de grupos paralelos, com investigador cego, comparativo de não-inferioridade. Cento e vinte e nove (129) pacientes adultos portadores de intolerância à lactose e teste do hidrogênio no ar expirado compatível com o diagnóstico de hipolactasia foram randomizados para receber o produto experimental (Perlatte(r) - Eurofarma Laboratórios S.A.) ou o produto comparador (Lactaid(r) - McNeil Nutritionals, EUA), por via oral (um comprimido, três vezes ao dia), durante 42 dias consecutivos. Resultados Os dados dos 128 pacientes que efetivamente receberam o tratamento do estudo foram avaliados (66 tratados com o produto experimental e 62 com o produto comparador). Os dois grupos se mostraram homogêneos quanto aos dados demográficos e clínicos basais. A média da concentração do hidrogênio expirado aos 90 minutos no teste realizado ao final do tratamento (Dia 42) foi significativamente menor no grupo tratado com o produto experimental (17±18 ppm versus 34±47 ppm na população por protocolo). A diferença entre as médias dos dois grupos foi de -17 ppm (intervalo de confiança de 95% [IC95%]: -31,03; -3,17). O limite superior do IC95% não ultrapassou a margem de não-inferioridade estipulada a priori (7,5 ppm). As análises secundárias de eficácia confirmaram a semelhança entre os tratamentos (populações por protocolo e com intenção de tratamento). A tolerabilidade foi excelente em ambos os grupos e não houve relato de eventos adversos graves relacionados ao produto. Conclusão O produto experimental se mostrou não-inferior ao produto comparador, indicando sua eficácia no tratamento substitutivo da lactase endógena em pacientes portadores de intolerância à lactose.

Enzyme activity of ß-galactosidase from Kluyveromyces lactis and Aspergillus oryzae on simulated conditions of human gastrointestinal system / Atividade de ß-galactosidase de Kluyveromyces lactis e Aspergillus oryzae, em condições simuladas do sistema gastrintestinal humano

An alternative to relieve the symptoms of lactose intolerance is the intake of the enzyme ?-galactosidase in pharmaceutical dosage forms. The ability of ?-galactosidase produced by Kluyveromyces lactis and Aspergillus oryzae to hydrolyze lactose in simulated conditions of the human gastrointestinal tract was investigated. The experiment was carried out in the optimum temperature for each enzyme activity, 40 and 55°C, respectively, and at the normal human body temperature (37°C) at concentrations of 1.5, 3.0, and 5.0 g/L (enzyme from A. oryzae) or mL/L (enzyme from K. lactis). Both enzymes were completely inactivated under simulated gastric conditions (pH 2). When the enzymes were subjected to simulated small intestine conditions (pH 7.4), lactose hydrolysis has occurred, but at 37°C the percentage was lower than that under the optimal temperatures. At concentrations of 1.5, 3.0, and 5.0 mL/L the enzyme from K. lactis hydrolyzed 76.63%, 88.91% and 94.80% of lactose at 40°C, and 55.99%, 80.91% and 81.53% at 37°C, respectively. In contrast, the enzyme from A. oryzae hydrolyzed 7.11%, 16.18% and 21.29% at 55°C, and 8.4%, 11.85% and 16.43% at 37°C. It was observed that under simulated intestinal conditions, the enzyme from K. lactis was more effective on lactose hydrolysis as compared to the enzyme from A. oryzae. Considering the findings of this study, it is extremely necessary to use an enteric coating on ?-galactosidase capsules so that this enzyme is released only in the small intestine, which is its site of action, thus not suffering the action of the stomach pH.(AU)

Uma das alternativas para amenizar os sintomas da intolerância à lactose é a ingestão de ?-galactosidase em formas farmacêuticas. Neste trabalho avaliou-se a capacidade de hidrólise de ?-galactosidase produzida por Kluyveromyces lactis e Aspergillus oryzae simulando as condições do trato gastrintestinal humano. O teste foi realizado nas temperaturas ótimas de ação para cada enzima, 40 e 55°C, respectivamente, e na temperatura corpórea humana (37°C), nas concentrações de 1,5; 3,0 e 5,0 g/L para a enzima de Aspergillus oryzae ou mL/L para a de Kluyveromyces lactis. Na simulação da condição estomacal humana (pH 2), ambas enzimas foram totalmente inativadas. Quando as enzimas foram submetidas às condições simuladas do intestino delgado (pH 7,4), observou-se hidrólise da lactose, porém, a 37°C, a porcentagem foi menor do que a observada nas temperaturas ótimas de cada enzima. A enzima de K. lactis nas concentrações de 1,5; 3,0 e 5,0 mL/L apresentou hidrólise de 76,63%, 88,91% e 94,80% a 40°C e 55,99%, 80,91% e 81,53%, a 37°C, respectivamente. Nas concentrações 1,5; 3,0 e 5,0 g/L, a porcentagem de hidrólise pela enzima de A. oryzae a 55°C foi de 7,11%, 16,18% e 21,29%. Para esta enzima, nessas concentrações, a hidrólise obtida a 37°C foi 8,4%, 11,85% e de 16,43%. Sob condições intestinais simuladas, a enzima de K. lactis apresentou maior eficiência na hidrólise da lactose quando comparada à enzima de A. oryzae. Considerando-se as etapas avaliadas neste estudo, observa-se que é extremamente necessário o uso de um revestimento entérico em cápsulas de ?-galactosidase, para que esta enzima seja liberada somente no intestino delgado, seu local de ação, não sofrendo, portanto, a ação do pH estomacal.(AU)

Bases conceptuales del diagnóstico de intolerancia a lactosa, hipolactasia y mala digestión de lactosa / Conceptual basis of the diagnosis of lactose intolerance, hypolactasia and lactose maldigestion

Se revisa la fisiopatología de hipolactasia, mala digestión de lactosa e intolerancia a lactosa para aclarar confusiones conceptuales y puntualizar diagnósticos. La lactasa es la enzima que digiere la lactosa de la leche, liberando galactosa y glucosa. En adultos con fenotipo Hipolactasia Primaria Tipo Adulto (No persistencia de Lactasa), la actividad enzimática es el 10 % de la máxima, propia de la infancia; en los de fenotipo Persistencia de Lactasa se mantiene elevada. En europeos, los fenotipos están estrechamente asociados al polimorfismo C/T-13910; por consiguiente, su genotipificación constituye prueba diagnóstica; no así en caribeños colombianos por presentar moderada asociación. El diagnóstico directo de hipo-lactasia/persistencia es el enzimático; un índice lactasa/sacarasa< 0,3 indica hipolactasia. Mala digestión de lactosa, la incapacidad de digerir cierta cantidad, se evalúa con la prueba de hidrógeno en el aliento o con la de tolerancia a lactosa, las cuales permiten inferir si el sujeto es probable persistente (digestor) o probable hipolactásico (mal digestor). Intolerancia a lactosa es el síndrome clínico digestivo que, tras ingerirla, puede sobrevenir por causa de hipolactasia o de mala absorción de glucosa-galactosa; se diagnostica si al excluir la leche de la dieta durante dos semanas el cuadro desaparece y luego, al restituirla, reaparece. Mala absorción de lactosa es una irrealidad fisiológica porque la lactosa no se absorbe. No existe sinonimia entre hipolactasia, mala digestión de lactosa e intolerancia a lactosa. Son estados fisiopatológicos diferentes, no siempre asociados entre sí. La comprensión de la identidad conceptual de cada uno es fundamental para diagnosticarlos acertadamente.

The pathophysiology of hypolactasia, lactose maldigestion and lactose intolerance are reviewed to clarify conceptual confusions and convey precise diagnoses. Lactase is the enzyme that helps to digest milk lactose, releasing galactose and glucose. While in adults with primary adult-type hypolactasia phenotype, the enzyme activity reaches 10% of the maximum observed in childhood, in individuals with lactase persistence phenotype, the activity remains high. In Europeans, phenotypes are closely associated with C/T-13910polymorphism; therefore, genotyping may be used as a diagnostic test. However, this is not possible in Colombian Caribbean population due to the existence of moderate association genotype-phenotype. The direct diagnosis ofhypolactasia/persistence consists of an enzymatic method; a lactase/sacarase index<0.3 indicates hypolactasia. Lactose maldigestion, the inability to digest a certain amount of lactose, is evaluated through application of either breath hydrogen or a lactose intolerance test, which allow to infer whether the individual might be a lactase persistent (digester) or hypolactasic (maldigester). Lactose intolerance is the clinical digestive syndrome that may appear following ingestion of lactose, due to hypolactasia or to glucose-galactose malabsorption. A subject is considered to be intolerant to lactose when symptoms disappear as milk is excluded from the diet for two weeks, and reappear upon its restoration as part of his diet. "Lactose malabsorption" is a physiological misnomer because lactose is not absorbed as such. Hypolactasia, lactose maldigestion and lactose intolerance are not synonyms. They involve different pathophysiological states, which are not always associated with each other. Understanding each of these three concepts is critical for a correct diagnosis.

Análisis de los polimorfismos europeos en el gen lactasa entre grupos étnicos del Caribe Colombiano / Analysis of the european polymorphisms in lactase gene between ethnic groups in the Colombian Caribbean / Análise dos polimorfismos europeus no gene lactasa entre os grupos etnicos do Caribe Colombiano

La prevalencia de hipolactasia tipo adulto está influenciada por la etnicidad y la geografía. Los genotipos CC y GG, de los SNPs C/T-13910 y G/A-22018, respectivamente determinan hipolactasia en ciertos grupos étnicos y países del mundo. El objetivo de este estudio fue analizar estos SNPs en muestras de los tres grupos étnicos que habitan el Caribe Colombiano. Trescientos sesenta y un sujetos, agrupados como afrodescendientes, indígenas y mestizos, fueron genotipificados usando PCR/RFLP. El análisis genético se hizo mediante Arlequin 3.11 y las frecuencias genotípicas fueron comparadas con Statgraphics Centurion XVI. Solamente el SNP C/T-13910 mostró equilibrio de Hardy- Weinberg y no hubo desequilibrio de ligamiento entre los SNPs estudiados. La frecuencia del genotipo CC-13910 fue 90% en afrodescendientes, 95% en indígenas y 80% en mestizos. En indígenas la frecuencia de GG-22018 fue 23% pero dicho genotipo no se halló en afrodescendientes y mestizos. El genotipo AA-22018 no se halló en indígenas. Ningún grupo presentó el genotipo TT-13910. Las frecuencias genotípicas fueron estadísticamente diferentes entre los grupos estudiados y las de los genotipos CC-13910 y GG-22018 no concordaron con las frecuencias fenotípicas reportadas en otros estudios. Los resultados sugieren que la posibilidad diagnóstica de hipolactasia mediante genotipificación de estos polimorfismos es escasa en el Caribe Colombiano.

The prevalence of adult-type hypolactasia is influenced by ethnicity and geography. The CC and GG genotypes of the SNPs C/T-13910 and G/A-22018, respectively indicate hypolactasia in certain ethnic groups worldwide. The aim of this study was to analyse these SNPs in samples of the three ethnic groups that inhabit the Colombian Caribbean. Three hundred and sixty-one subjects were genotyped using PCR/RFLP. These subjects were grouped as being of African descent, Indigenous and Mestizo. The genetic analysis was performed through Arlequin 3.11 and genotype frequencies were compared with Statgraphics Centurion XVI. Only SNP C/T-13910 showed Hardy-Weinberg equilibrium and there was no linkage disequilibrium between the SNPs. The frequency of CC-13910 was 90% in Afro-descendant, 95% in indigenous people and 80% in mestizos.The frequency of GG-22018 was 23% in indigenous people, but this genotype was not present in afro-descendants and Mestizos. The indigenous people did not have AA-22018, and none of the groups had TT-13910. The genotype frequencies were statistically different among the groups studied and the frequencies of CC-13910 and GG-22018 were not in concordance with the phenotype frequencies reported in other papers. The results suggest that diagnostic possibility of hypolactasia by genotyping of those polymorphisms in the Colombian Caribbean population is scarce.

A prevalência da hipolactasia primária tipo adulto é influenciada pela etnicidade e a geografia. Os genótipos CC e GG, dos SNPs C/T-13910 e G/A-22018, respectivamente, são determinantes da hipolactasia em alguns grupos étnicos e países do mundo. O objetivo do presente estudo foi analisar estes SNPs em amostras dos três grupos étnicos do Caribe Colombiano. Trezentas e sessenta e uma pessoas reunidas como afrodescendentes, indígenas e mestiços foram genotipificadas utilizando PCR/RFLP. A análise genética foi realizada usando o software Arlequin 3.11 e as frequências genotípicas foram comparadas com o Statgraphics Centurion XVI. Somente o SNP C/T-13910 mostrou equilíbrio de Hardy-Weinberg e não houve desequilíbrio de ligamento entre os SNPs estudados. A frequência do genótipo CC-13910 foi de 90% para afrodescendentes, 95% para indígenas e 80% em mestiços. Nos indígenas a frequência de GG-22018 foi de 23% mas tal genótipo não esteve presente na população de afrodescendentes e mestiços. O genótipo AA-22018 não foi encontrado em indígenas. Nenhum grupo apresentou o genótipo TT-13910. As frequências genotípicas foram estatisticamente diferentes entre os grupos avaliados e as dos genótipos CC-13910 e GG-22018, não concordaram com as frequências fenotípicas relatados em outros estudos. Os resultados sugerem que a possibilidade diagnóstica de hipolactasia através de genotipificação destes polimorfismos é escassa em populações do Caribe Colombiano.

Proper understanding of the infant formula foods for special medical purposes / 临床儿科杂志

General rules for infant formula for special medical purposes were published by National Health and Family Planning Commission of the People’s Republic of China in 2010. Lactose-free or low lactose formula is suggested to be a part of treatment in bottle-fed infants with acute diarrhea. Lactase is suggested to be taken before each feeding in breastfeeding infants with acute diarrhea. Partial hydrolyzed formula (pHF) can be added when the breast milk is insufifcient and it is mainly used during the transition from extensively hydrolyzed formula to standard formula during allergy treatment. Extensively hydrolyzed formula should be suggested as the nutritional support during milk avoidance for most of cow’s milk allergy infants. Amino acid formula is the clinical tool to diagnose the cow’s milk allergy and provides the nutritional support to severe cow’s milk allergy infants. Although preterm/low birth weight formula can decrease the rate of the extrauterine growth retardation and sustain the fast growth of preterm babies with insufifcient breast milk, Breast-milk with fortiifer is strongly recommended as the main nutritional support to keep preterm and low birth weight infants’ growth. Infants with disorders of amino acid catabolism should choose speciifc formula.

The basic research of primary lactase deficiency / 国际儿科学杂志

Lactose is one of the important nutrients in milk.It is decomposed by the lactase enzyme and plays an important role in the life activities of cells in human health.Due to the lack of lactase,the symptoms of lactose intolerance occur highly in Chinese population,thus limiting the large part of the people to drink milk.Milk is a good source of high-quality protein,minerals and vitamins for the human,so the problem of lactase deficiency also seems particularly severe.