Dietary fiber and the microbiota: A narrative review by a group of experts from the Asociación Mexicana de Gastroenterología.

Dietary fiber intake is one of the most influential and efficacious strategies for modulating the gut microbiota. Said fiber can be digested by the microbiota itself, producing numerous metabolites, which include the short-chain fatty acids (SCFAs). SCFAs have local and systemic functions that impact the composition and function of the gut microbiota, and consequently, human health. The aim of the present narrative review was to provide a document that serves as a frame of reference for a clear understanding of dietary fiber and its direct and indirect effects on health. The direct benefits of dietary fiber intake can be dependent on or independent of the gut microbiota. The use of dietary fiber by the gut microbiota involves several factors, including the fiber's physiochemical characteristics. Dietary fiber type influences the gut microbiota because not all bacterial species have the same capacity to produce the enzymes needed for its degradation. A low-fiber diet can affect the balance of the SCFAs produced. Dietary fiber indirectly benefits cardiometabolic health, digestive health, certain functional gastrointestinal disorders, and different diseases.

Technical opinion of the Asociación Mexicana de Gastroenterología on soy plant-based beverages. / Posición técnica de la Asociación Mexicana de Gastroenterología sobre las bebidas vegetales a base de soya.

There has been a recent increase in the consumption of cow's milk substitutes, specifically plant-based beverages, which have erroneously been named "plant milks". Plant-based beverages do not have a standard of identity, and so their nutritional composition can vary from one brand to another, even within the same category. The aim of the present narrative review was to produce a technical opinion to serve as a frame of reference for sustaining the recommendation of soy plant-based beverages. Nutrition and gastroenterology experts that belong to the Asociación Mexicana de Gastroenterología jointly commented on and analyzed themes on plant-based beverages, and on soy drinks in particular, including their nutritional characteristics, consumption in children, and potential growth and development alterations, as well as soy drink consumption in adults and its association with gastrointestinal alterations and other conditions. Plant-based beverages, including those made from soy, are not a replacement for breastmilk or breastmilk substitutes. Soy beverages are considered safe and can enrich the varied diet of its consumers, as long as they are considered an additional liquid portion of the diet. They can be ingested by adults and children above two years of age that present with cow's milk protein allergy or lactose intolerance.

Review of the scientific evidence and technical opinion on noncaloric sweetener consumption in gastrointestinal diseases. / Revisión de la evidencia científica y opinión técnica sobre el consumo de edulcorantes no calóricos en enfermedades gastrointestinales.

The present review of noncaloric sweeteners (NCSs) by the Asociación Mexicana de Gastroenterología was carried out to analyze and answer some of the most frequent questions and concerns about NCS consumption in patients with gastrointestinal disorders, through a thorough review of the medical literature. A group of gastroenterologists and experts on nutrition, toxicology, microbiology, and endocrinology reviewed and analyzed the published literature on the topic. The working group formulated conclusions, based on the scientific evidence published, to give an opinion with respect to NCS ingestion. Current evidence does not confirm the carcinogenic potential of NCSs. However, the studies analyzed showed that saccharin could have a proinflammatory effect and that polyols can cause gastrointestinal symptoms and manifestations, depending on the dose and type of compound. The ingestion of xylitol, erythritol, sucralose, aspartame, acesulfame K, and saccharin could increase the secretion of the gastrointestinal hormones that regulate intestinal motility, and stevia and its derivatives could have a favorable effect on the percentage of liver fat. Caution should be taken in recommending aspartame consumption in patients with chronic liver disease because it reduces the ratio of branched-chain amino acids to aromatic amino acids. In addition, NCS ingestion could modify the composition of the intestinal microbiota, having an effect on gastrointestinal symptoms and manifestations. It is important to continue conducting causality studies on humans to be able to establish recommendations on NSC consumption.

The Mexican consensus on non-cardiac chest pain. / Consenso mexicano sobre dolor torácico no cardiaco.

INTRODUCTION: Non-cardiac chest pain is defined as a clinical syndrome characterized by retrosternal pain similar to that of angina pectoris, but of non-cardiac origin and produced by esophageal, musculoskeletal, pulmonary, or psychiatric diseases. AIM: To present a consensus review based on evidence regarding the definition, epidemiology, pathophysiology, and diagnosis of non-cardiac chest pain, as well as the therapeutic options for those patients. METHODS: Three general coordinators carried out a literature review of all articles published in English and Spanish on the theme and formulated 38 initial statements, dividing them into 3 main categories: (i)definitions, epidemiology, and pathophysiology; (ii)diagnosis, and (iii)treatment. The statements underwent 3rounds of voting, utilizing the Delphi system. The final statements were those that reached >75% agreement, and they were rated utilizing the GRADE system. RESULTS AND CONCLUSIONS: The final consensus included 29 statements. All patients presenting with chest pain should initially be evaluated by a cardiologist. The most common cause of non-cardiac chest pain is gastroesophageal reflux disease. If there are no alarm symptoms, the initial approach should be a therapeutic trial with a proton pump inhibitor for 2-4weeks. If dysphagia or alarm symptoms are present, endoscopy is recommended. High-resolution manometry is the best method for ruling out spastic motor disorders and achalasia and pH monitoring aids in demonstrating abnormal esophageal acid exposure. Treatment should be directed at the pathophysiologic mechanism. It can include proton pump inhibitors, neuromodulators and/or smooth muscle relaxants, psychologic intervention and/or cognitive therapy, and occasionally surgery or endoscopic therapy.

Technical position on milk and its derivatives in adult health and disease from the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Gerontología y Geriatría. / Posición técnica sobre la leche y derivados lácteos en la salud y en la enfermedad del adulto de la Asociación Mexicana de Gastroenterología y la Asociación Mexicana de Gerontología y Geriatría.

Milk is a liquid food that possesses an important quantity of highly bioavailable macronutrients. In addition, it is readily accessible, as well as relatively inexpensive. Given that the knowledge of physicians about nutrition and food composition is deficient, in general, many of the dietary interventions recommended in diverse clinical settings lack a scientific basis. The aim of the present review was to produce a technical opinion that serves as a frame of reference to best sustain recommendations for consuming milk and dairy products as daily nutrition in the adult and older adult. The effects of milk and dairy products during the pediatric stage are not addressed in the present work. The Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Gerontología y Geriatría jointly discussed and analyzed topics dealing with the legal designation of milk, the classification and nutritional profile of cow's milk, its nutritional characteristics, its consumption in the adult, intolerance to cow's milk, and associations of milk consumption with digestive tract alterations and other conditions. Finally, certain aspects of milk consumption in the older adult and its relation to overall health are briefly discussed.

Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection. / Consenso sobre prevención, diagnóstico y tratamiento de la infección por Clostridium difficile.

In recent decades, Clostridium difficile infection (CDI) has become a worldwide health problem. Mexico is no exception, and therefore the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, endoscopists, internists, infectious disease specialists, and microbiologists) to carry out the "Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection", establishing useful recommendations (in relation to the adult population) for the medical community. Said recommendations are presented herein. Among them, it was recognized that CDI should be suspected in subjects with diarrhea that have a history of antibiotic and/or immunosuppressant use, but that it can also be a community-acquired infection. A 2-step diagnostic algorithm was proposed, in which a highly sensitive test, such as glutamate dehydrogenase (GDH), is first utilized, and if positive, confirmed by the detection of toxins through immunoassay or nucleic acid detection tests. Another recommendation was that CDI based on clinical evaluation be categorized as mild-moderate, severe, and complicated severe, given that such a classification enables better therapeutic decisions to be made. In mild-moderate CDI, oral vancomycin is the medication of choice, and metronidazole is recommended as an alternative treatment. In addition, fecal microbiota transplantation was recognized as an efficacious option in patients with recurrence or in the more severe cases of infection, and surgery should be reserved for patients with severe colitis (toxic megacolon), in whom all medical treatment has failed.

Clinical guidelines on the diagnosis and treatment of celiac disease in Mexico. / Guía clínica para diagnóstico y tratamiento de la enfermedad celíaca en México.

Celiac disease, celiac sprue, or gluten-sensitive enteropathy, is a generalized autoimmune disease characterized by chronic inflammation and atrophy of the small bowel mucosa. It is caused by dietary exposure to gluten and affects genetically predisposed individuals. In Mexico, at least 800,000 are estimated to possibly have the disease, prompting the Asociación Mexicana de Gastroenterología to summon a multidisciplinary group of experts to develop the "Clinical guidelines on the diagnosis and treatment of celiac disease in Mexico" and establish recommendations for the medical community, its patients, and the general population. The participating medical professionals were divided into three working groups and were given the selected bibliographic material by the coordinators (ART, LUD, JMRT), who proposed the statements that were discussed and voted upon in three sessions: two voting rounds were carried out electronically and one at a face-to-face meeting. Thirty-nine statements were accepted, and once approved, were developed and revised by the coordinators, and their final version was approved by all the participants. It was emphasized in the document that epidemiology and risk factors associated with celiac disease (first-degree relatives, autoimmune diseases, high-risk populations) in Mexico are similar to those described in other parts of the world. Standards for diagnosing the disease and its appropriate treatment in the Mexican patient were established. The guidelines also highlighted the fact that a strict gluten-free diet is essential only in persons with confirmed celiac disease, and that the role of gluten is still a subject of debate in relation to nonceliac, gluten-sensitive patients.

[The Mexican consensus on gastroesophageal reflux disease. Part I]. / Consenso Mexicano de enfermedad por relujo gastroesofágico. Parte I.

BACKGROUND: The changes, advances, and new discoveries regarding different aspects of gastroesophageal reflux disease (GERD) have made it necessary to update the Mexican Consensus published in 2002. AIMS: To elaborate a new Mexican Consensus on GERD. METHODS: The general project coordinators selected six GERD experts to carry out an extensive review of the literature for the purpose of elaborating statements on the principal aspects of GERD. These were then placed under the consideration of specialists in the study of this disease. Definitive approval by all participants was reached using the modified Delphi method with three rounds of anonymous and iterative voting. The following scale was employed: A- in complete agreement; B- in agreement, but with minor concerns; C- in agreement, but with major concerns; D- in disagreement, but with major concerns; E- in disagreement, but with minor concerns; or F- in complete disagreement. Consensus was declared when 67.00% or more of the participants concurred on a category of agreement (A, B, or C). RESULTS: A consensus was reached on 160 of the statements upon completion of the voting rounds, with 90.00% concurrence for the majority of them. CONCLUSIONS: The 2011 Mexican Consensus on Gastroesophageal Disease is a practical and up-to-date consultation tool, providing the opinion of Mexican experts on all the new information available about this disease. It allows there to be homogeneity in diagnostic and therapeutic criteria, all of which serves to benefit our patients.

The effects of steroidal estrogens in ACI rat mammary carcinogenesis: 17beta-estradiol, 2-hydroxyestradiol, 4-hydroxyestradiol, 16alpha-hydroxyestradiol, and 4-hydroxyestrone.

Several investigators have suggested that certain hydroxylated metabolites of 17beta-estradiol (E2) are the proximate carcinogens that induce mammary carcinomas in estrogen-sensitive rodent models. The studies reported here were designed to examine the carcinogenic potential of different levels of E2 and the effects of genotoxic metabolites of E2 in an in vivo model sensitive to E2-induced mammary cancer. The potential induction of mammary tumors was determined in female ACI rats subcutaneously implanted with cholesterol pellets containing E2 (1, 2, or 3 mg), or 2-hydroxyestradiol (2-OH E2), 4-hydroxyestradiol (4-OH E2), 16alpha-hydroxyestradiol (16alpha-OH E2), or 4-hydoxyestrone (4-OH E1) (equimolar to 2 mg E2). Treatment with 1, 2, or 3 mg E2 resulted in the first appearance of a mammary tumor between 12 and 17 weeks, and a 50% incidence of mammary tumors was observed at 36, 19, and 18 weeks respectively. The final cumulative mammary tumor incidence in rats treated with 1, 2, or 3 mg E2 for 36 weeks was 50%, 73%, and 100% respectively. Treatment of rats with pellets containing 2-OH E2, 4-OH E2, 16alpha-OH E2, or 4-OH E1 did not induce any detectable mammary tumors. The serum levels of E2 in rats treated with a 1 or 3 mg E2 pellet for 12 weeks was increased 2- to 6-fold above control values (approximately 30 pg/ml). Treatment of rats with E2 enhanced the hepatic microsomal metabolism of E2 to E1, but did not influence the 2- or 4-hydroxylation of E2). In summary, we observed a dose-dependent induction of mammary tumors in female ACI rats treated continuously with E2; however, under these conditions 2-OH E2, 4-OH E2, 16alpha-OH E2, and 4-OH E1 were inactive in inducing mammary tumors.

Causas y asociaciones de la diarrea en la alimentación enteral / Causes and associations of the diarrhea in the enteral feeding

Siendo la diarrea una de las complicaciones más frecuentes de los pacientes alimentados con sonda, se intenta evaluar la frecuencia de episodios diarreicos y sus posibles asociaciones. Se estudiaron parámetros nutricionales, tipos de fórmulas, administración, ubicación de la sonda y asociación con fármacos

Causas y asociaciones de la diarrea en la alimentación enteral / Causes and associations of the diarrhea in the enteral feeding

Siendo la diarrea una de las complicaciones más frecuentes de los pacientes alimentados con sonda, se intenta evaluar la frecuencia de episodios diarreicos y sus posibles asociaciones. Se estudiaron parámetros nutricionales, tipos de fórmulas, administración, ubicación de la sonda y asociación con fármacos

Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1.

Calophyllum brasiliense, Lonchocarpus oaxacensis, and Lonchocarpus guatemalensis are used in Latin American folk medicine. Four natural xanthones, an acetylated derivative, and two coumarins were obtained from C. brasiliense. Two flavanones were extracted from L. oaxacensis and one chalcone from L guatemalensis. These compounds were tested as substrates and inhibitors for two recombinant sulfotransferases (SULTs) involved in the metabolism of many endogenous compounds and foreign chemicals. Assays were performed using recombinant phenolsulfotransferase (SULT1A1) and hydroxysteroidsulfotransferase (SULT2A1). Three of the five xanthones, one of the flavonoids and the coumarins tested were substrates for SULT1A1. None of the xanthones or the flavonoids were sulfonated by SULT2A1, whereas the coumarin mammea A/BA was a substrate for this enzyme. The natural xanthones reversibly inhibited SULT1A1 with IC50 values ranging from 1.6 to 7 microM whereas much higher amounts of these compounds were required to inhibit SULT2A1 (IC50 values of 26-204 microM). The flavonoids inhibited SULT1A1 with IC50 values ranging from 9.5 to 101 microM, which compared with amounts needed to inhibit SULT2A1 (IC50 values of 11 to 101 microM). Both coumarins inhibited SULT1A1 with IC50 values of 47 and 185 pM, and SULT2A1 with IC50 values of 16 and 31 microM. The acetylated xanthone did not inhibit either SULT1AI or SULT2A1 activity. Rotenone from a commercial source had potency comparable to that of the flavonoids isolated from Lonchocarpus for inhibiting both SULTs. The potency of this inhibition depends on the position and number of hydroxyls. The results indicate that SULT1A1, but not SULT2A1, is highly sensitive to inhibition by xanthones. Conversely, SULT2A1 is 3-6 times more sensitive to coumarins than SULT1A1. The flavonoids are non-specific inhibitors of the two SULTs. Collectively, the results suggest that these types of natural products have the potential for important pharmacological and toxicological interactions at the level of phase-II metabolism via sulfotransferases.

Challenges of cancer drug design: a drug metabolism perspective.

The time course and duration of action of drugs used in cancer chemotherapy are greatly influenced by the molecular and biochemical properties of enzymes associated with their metabolism. Variation in the response of individual patients to cancer chemotherapeutic agents is in large measure due to genetic and environmental factors that impinge on specific enzymes belonging to the two major classes of drug metabolizing enzymes. Current knowledge of the molecular biology and biochemistry of phase I drug metabolizing enzymes (cytochrome P450, flavin-containing and xanthine oxidases, NADPH quinone reductase, and aldehyde and dihydropyridine dehydrogenases), and phase II enzymes (glucuronosyl-, sulfo-, N-acetyl-, and glutathione transferases, and hydrolases) is reviewed briefly. Advances in understanding genetic and environmental factors that influence activities of phase I and phase II pathways of drug metabolism are discussed in the first sections of this review followed by a consideration of the influence of drug metabolism on the actions of agents currently used in the treatment of cancer. Emphasis is given to drugs that have recently been introduced into the armamentarium of cancer chemotherapy including: inhibitors of chromatin function, target-based inhibitors of signal transduction and cyclin-dependent kinases, and angiogenesis inhibitors acting on metalloproteinases, epithelial cell growth, angiogenesis stimulation, and endothelial-specific integrins.

Electrochemiluminescence-based detection of beta-lactam antibiotics and beta-lactamases.

Bacterial resistance to clinically administered beta-lactam antibiotics is usually caused by beta-lactamases, enzymes that hydrolytically inactivate the antibiotics. This paper describes the use of electrogenerated chemiluminescence (ECL) to detect beta-lactam antibiotics and their hydrolysis by beta-lactamases. All 10 tested antibiotics were detected on the basis of their ability to participate in an ECL reaction with ruthenium(II) tris(bipyridine). In every case, antibiotic-promoted ECL changed when the antibiotic was hydrolyzed by beta-lactamases or NaOH. Standard curves of antibiotic concentration versus ECL intensity showed that antibiotics could be quantitated to low micromolar concentrations. Substrate profiles were generated for four beta-lactamases using six structurally diverse beta-lactam antibiotics. ECL-based antibiotic detection was accomplished in untreated whole milk, and beta-lactamases were detected in crude bacterial broth culture. Because several structurally diverse antibiotics were detectable by ECL, this method may become valuable for the detection of many or all beta-lactam antibiotics and their inactivation by beta-lactamases.

Spectrophotometric quantitation of silver in X-ray film images and silver-stained electrophoresis gel bands.

This paper describes a novel spectrophotometric method for quantitating the silver in silver-stained electrophoresis gel bands and X-ray film images. Silver in excised areas is quantitated by (i) oxidation/solubilization of Ag0 to Ag+ with nitric acid, (ii) neutralization followed by extraction into an organic solution of dithizone (diphenylthiocarbazone), and (iii) visible absorbance measurement at 600 nm. Spectrophotometric quantitation is possible because dithizone undergoes a dramatic color change from blue-green to yellow upon binding Ag+ (delta epsilon 600 = 3.28 x 10(4) M-1 cm-1). Experiments with silver-stained gels and with X-ray film images obtained by chemiluminescence and autoradiography demonstrated that the color change relates to the amount of silver present and hence to the amount of material represented by the band or image. This method is a convenient, inexpensive alternative to the use of a densitometer to quantitate silver-containing images.

Accurate and efficient cleavage of the human insulin proreceptor by the human proprotein-processing protease furin. Characterization and kinetic parameters using the purified, secreted soluble protease expressed by a recombinant baculovirus.

Maturation of the insulin proreceptor in a late Golgi compartment requires cleavage at an Arg-Lys-Arg-Arg processing site, suggesting involvement of furin, a transmembrane serine protease of the Kex2 family of processing enzymes. A genetically engineered secreted, soluble form of human furin (ss-furin), expressed by infection of insect cells with a recombinant baculovirus, was purified to near homogeneity. ss-Furin exhibited rapid and efficient cleavage of both isoforms of the human insulin proreceptor in solubilized extracts of cultured mammalian cells expressing preproreceptor cDNA. Proreceptor cleavage occurred at the physiological processing site as judged by the effects of mutations in this site on cleavage by purified ss-furin. Moreover, purified ss-furin exhibited specificity for proreceptor cleavage identical to that of the endogenous insulin proreceptor-processing enzyme. Furin thus displays the properties expected of an insulin proreceptor-processing enzyme in that it (i) cleaves the proreceptor efficiently and at the correct site; (ii) exhibits the same specificity in processing variant proreceptors as the endogenous enzyme; (iii) appears to be localized in the correct secretory compartment; and (iv) has the same broad pattern of tissue distribution as the insulin proreceptor.

Isoabzymes: structurally and mechanistically similar catalytic antibodies from the same immunization.

Mechanistic and structural comparisons of five catalytic monoclonal antibodies generated from the same hybridoma fusion indicated that all five hydrolyze phenyl acetate by subtle variations of the same mechanism. All of the antibodies showed a pre-steady-state multi-turnover burst in which kcat and Km declined but kcat/Km did not change. The burst of one of the antibodies, 20G9, has previously been found to result from inhibition by the product, phenol. Although all of the antibodies showed the burst, their individual values for kcat, Km, and hapten Ki differed substantially. Three of the antibodies that were investigated for the effect of pH on kcat showed an acid limb pK of 9.5-9.6. Substrate inhibition was seen in four of the five antibodies. Variable region nucleotide sequencing of the heavy and light chains confirmed that all five antibodies were structurally similar and also revealed several potentially critical tyrosines. Despite their structural similarities, analysis of their sequences suggested that the antibodies are products of distinct, independent rearrangements of immunoglobulin gene segments that took place in different progenitor B cells. A plot of Ki for hapten inhibition vs Km/kcat for substrate hydrolysis for the mechanistically related antibodies ("isoabzymes") gave a linear relationship suggesting a catalytic role for transition-state complementarity. Taken together with previous work [Martin et al. (1991) Biochemistry 30, 9757-9761], the data conform to a mechanism in which the antibodies exploit both transition-state complementarity and an acyl-tyrosyl intermediate during phenyl acetate hydrolysis.