First Mexican Consensus on Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a subtype of chronic and incurable inflammatory bowel disease. It can affect the entire gastrointestinal tract and its etiology is unknown. OBJECTIVE: The aim of this consensus was to establish the most relevant aspects related to definitions, diagnosis, follow-up, medical treatment, and surgical treatment of Crohn's disease in Mexico. MATERIAL AND METHODS: Mexican specialists in the areas of gastroenterology and inflammatory bowel disease were summoned. The consensus was divided into five modules, with 69 statements. Applying the Delphi panel method, the pre-meeting questions were sent to the participants, to be edited and weighted. At the face-to-face meeting, all the selected articles were shown, underlining their level of clinical evidence; all the statements were discussed, and a final vote was carried out, determining the percentage of agreement for each statement. RESULTS: The first Mexican consensus on Crohn's disease was produced, in which recommendations for definitions, classifications, diagnostic aspects, follow-up, medical treatment, and surgical treatment were established. CONCLUSIONS: Updated recommendations are provided that focus on definitions, classifications, diagnostic criteria, follow-up, and guidelines for conventional medical treatment, biologic therapy, and small molecule treatment, as well as surgical management.

Antibacterial properties of phenothiazine derivatives against multidrug-resistant Acinetobacter baumannii strains.

AIM: As options to treat recalcitrant bacterial infections which are increasingly limited due to multidrug-resistant strains, searching for new, effective antibacterial compounds is necessary. One strategy is to generate treatment alternatives by drug repurposing. METHODS AND RESULTS: In this work, phenotypic microarrays were used for the screening of miscellaneous compounds against the growth and biofilm formation of Acinetobacter baumannii, an important emergent multidrug-resistant opportunistic pathogen. The results showed that the phenothiazine derivatives, such as promethazine, trifluoperazine, thioridazine, and chlorpromazine, inhibited the growth of antibiotic-sensitive and multidrug-resistant strains (showing minimal inhibitory concentrations ranging from 0·05 to 0·6 g l-1 and minimal bactericidal concentrations ranging from 0·1 to 2·5 g l-1 ). All phenothiazine derivatives were active against biofilm cells (with minimal biofilm eradication concentrations ranging from 0·5 to >3 g l-1 ). Chlorpromazine promoted reactive oxigen species (ROS) production, and cell membrane and DNA damage. Chlorpromazine showed synergy with antibiotics such as ceftazidime, meropenem, and colistin and was an effective treatment for experimentally infected Galleria mellonella when combined with ceftazidime. CONCLUSIONS: It was demonstrated that phenothiazine derivatives, especially chlorpromazine, are drugs with attractive antibacterial properties against nosocomial MDR strains of A. baumannii, by generating ROS and cell membrane and DNA damage. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study indicates that repurposing phenothiazine derivatives for treating recalcitrant infections by A. baumannii could be promising.

Second Mexican consensus on biologic therapy and small-molecule inhibitors in inflammatory bowel disease. / Segundo Consenso Mexicano de terapia biológica y moléculas pequeñas en enfermedad inflamatoria intestinal.

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic and incurable entity. Therapy with anti-TNF-α agents was the first biologic therapy approved in Mexico for IBD. New biologic agents, such as vedolizumab and ustekinumab, have recently been added, as have small-molecule inhibitors. AIM: To update the biologic therapeutic approach to IBD in Mexico with new anti-TNF-α agents and novel biologics whose mechanisms of action induce and maintain remission of Crohn's disease and ulcerative colitis (UC). MATERIALS AND METHODS: Mexican specialists in the areas of gastroenterology and inflammatory bowel disease were summoned to participate. The consensus was divided into 3 modules, with 49 statements. The Delphi method was applied, sending the statements to all participants to be analyzed and edited, before the face-to-face meeting. During said meeting, the clinical studies were shown, emphasizing the level of clinical evidence, and the final discussion and voting round on the level of agreement of all the statements was conducted. RESULTS: In this second Mexican consensus, recommendations are made for new anti-TNF-α agents, such as golimumab, new biologics with other mechanisms of action, such as vedolizumab and ustekinumab, as well as for the small-molecule inhibitor, tofacitinib. CONCLUSIONS: The updated recommendations focus on patient-reported outcomes, biologic therapy, small-molecule inhibitors, and the safety aspects of each of the drugs.

Anti-inflammatory and antiproliferative evaluation of 4ß-cinnamoyloxy,1ß,3α-dihydroxyeudesm-7,8-ene from Verbesina persicifolia and derivatives.

The anti-inflammatory and antiproliferative activities of 4ß-cinnamoyloxy,1ß,3α-dihydroxyeudesm-7,8-ene (1) and of three derivatives, namely diacetate (2), hydrogenate (3) and diacetate hydrogenate (4) were evaluated. All derivatives exert an anti-inflammatory effect significantly lower than that exerted by 1. Otherwise, both the lead compound and 2-4 showed a comparable antiproliferative activity on human tumor cell lines. The investigation of the mechanism of action accountable for cytotoxicity highlighted the capacity to impair mitochondrial functions through two different pathways, depending on chemical structure. In particular, the lead compound 1 and derivative 3 are able to induce mitochondrial permeability transition, while derivatives 2 and 4 inhibit Complex II in the respiratory chain.

Vasodilation and radical-scavenging activity of imperatorin and selected coumarinic and flavonoid compounds from genus Casimiroa.

Hypertension is a very widespread condition which is not strictly considered as an illness but if not countered, progressively causes damage to all tissues and loss in their functionality. For this reason the find of new antihypertensive agents is prominent and medicinal plants and their derivatives are valuable for the purpose. The genus Casimiroa (Rutaceae) includes plants from Central America and Mexico; among these, Casimiroa edulis Llave et Lex. and Casimiroa pubescens Ramirez are the most relevant species, even for their medicinal uses. The decoction of leaves and seeds is traditionally taken as a tea mainly to lower blood pressure. The object of this research was the study of vascular activity of coumarinic and flavonoid compounds isolated from seeds of Casimiroa spp. in comparison with Casimiroa edulis and Casimiroa pubescens extracts. The phenolic compounds isolated from Casimiroa were herniarin (Her), imperatorin (Imp), 8-geranyloxypsoralen (GOP) and 5,6,2',3',4'-pentamethoxyflavone (PMF). All these compounds induced vasorelaxation on rat arterial tissues although with different effectiveness. To study the cellular mechanisms of the vasorelaxation exhibited by imperatorin, we used selective inhibitors of different receptors and enzymes, such as atropine, pyrilamine, nifedipine, L-NAME and DETC. In a further step of this research, we evaluated the radical-scavenging activity of Casimiroa extracts and isolated compounds by means of DPPH assay. In general, we observed that the scavenging activities increased in a concentration-dependent manner for all substances. The phenolic compounds highlight a synergism of vasodilation and antioxidant activity which may be very useful in the management of cardiovascular diseases. Among the evaluated compounds, imperatorin shows a significant vasorelaxant activity even higher than acetylcholine and similar to nitrite, and also useful antiradical capabilities. All these properties suggest its possible role against hypertension and vasculopathies, even if in vivo studies are needed to determine the actual applications.

[Clinical characteristics of acute pancreatitis in Mexico]. / Características clínicas de la pancreatitis aguda en México.

BACKGROUND: Acute pancreatitis (AP) etiology and frequency vary in relation to geographic region. AIMS: To determine the etiology, frequency, and mortality of AP in a Mexican population. PATIENTS AND METHODS: We carried out a prospective study of first episode AP patients over a period of 6 years. RESULTS: A total of 605 patients with a mean age of 40 years were included in the study. Sixty-four percent of them presented with overweight and/or obesity determined through BMI. Etiology was biliary in 66.60%, it was due to alcohol consumption in 15.90%, hypertriglyceridemia in 7.80%, it was post-endoscopic retrograde cholangiopancreatography (ERCP) in 2.10%, and was undetermined in 7.20%. Pancreatic infection was suspected in 70 patients and they underwent CT-guided fine needle aspiration. Thirty-two of those patients were diagnosed with pancreatic infection in which Staphylococcus spp was the most common microorganism. Overall mortality was 5.00% (2.60% < 30 years and 10.00% > 70 years). Necrosis, pancreatic infection, and mortality were more frequent in the cases in which etiology was due to alcohol ingestion. CONCLUSIONS: The most frequent AP etiology was biliary, but that caused by alcohol presented with more complications. Overall mortality was 5.00% and was higher in the elderly patients.

Effect of antispasmodic agents, alone or in combination, in the treatment of Irritable Bowel Syndrome: systematic review and meta-analysis.

INTRODUCTION: Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain, bloating, and changes in bowel habit. AIMS: To determine the clinical effectiveness of the antispasmodic agents available in Mexico for the treatment of IBS. METHODS: We carried out a systematic review and meta-analysis of randomized controlled clinical trials on antispasmodic agents for IBS treatment. Clinical trials identified from January 1960 to May 2011 were searched for in MEDLINE, the Cochrane Library, and in the ClinicalTrials.gov registry. Treatment response was evaluated by global improvement of symptoms or abdominal pain, abdominal distention/bloating, and frequency of adverse events. The effect of antispasmodics vs placebo was expressed in OR and 95% CI. RESULTS: Twenty-seven studies were identified, 23 of which fulfilled inclusion criteria. The studied agents were pinaverium bromide, mebeverine, otilonium, trimebutine, alverine, hyoscine, alverine/simethicone, pinaverium/simethicone, fenoverine, and dicyclomine. A total of 2585 patients were included in the meta-analysis. Global improvement was 1.55 (CI 95%: 1.33 to 1.83). Otilonium and the alverine/simethicone combination produced significant values in global improvement while the pinaverium/simethicone combination showed improvement in bloating. As for pain, 2394 patients were included with an OR of 1.52 (IC 95%: 1.28 a 1.80), favoring antispasmodics. CONCLUSIONS: Antispasmodics were more effective than placebo in IBS, without any significant adverse events. The addition of simethicone improved the properties of the antispasmodic agents, as seen with the alverine/simethicone and pinaverium/simethicone combinations.

Neuropharmacological study of Dracocephalum moldavica L. (Lamiaceae) in mice: sedative effect and chemical analysis of an aqueous extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Dracocephalum moldavica is used as a tranquilizer and as remedy for nervous conditions relief in the Mexican traditional medicine. Despite its intensive use no literature reported neuropharmacological studies on Dracocephalum moldavica as yet. AIM OF THE STUDY: The sedative, anxiolytic-like and antidepressant-like effects of the aqueous extract of aerial parts of Dracocephalum moldavica (Lamiaceae) (DM) were evaluated in behavioral models in mice. The general toxic effects of DM were evaluated as well as their chemical analysis was performed. MATERIALS AND METHODS: DM effects were evaluated on pentobarbital-induced sleeping time (SPT), the hole-board (HBT), and the avoidance exploratory behavior (AEBT) tests and on the forced swimming test (FST). General activity and motor coordination were evaluated in the open field (OFT) and Rota-rod tests, respectively. The acute toxicity of DM was determinate by its LD(50) dose. The chemical analyses DM were performed by chromatographic and HPLC-ESI-MS techniques. RESULTS: DM prolonged the pentobarbital-induced sleeping time, induced sedation in the HBT, decreased spontaneous activity and produced motor coordination impairment in mice. However, DM did not show anxiolytic effects in the AEBT or HBT and it was not effective in FST. The DM-treatment produced mortalities with LD(50)=470 mg/kg body weight. The HPLC-ESI-MS analysis of DM revealed that (acacetin, apigenin and luteolin)-7-O-ß-D-(6″-O-malonyl)-glucoside derivates are the main compounds of DM. CONCLUSIONS: DM induced sedative actions and a general inhibition of CNS activity observed by the decrease of animals' general activity, motor coordination and exploration.

Antidepressant-like effects of an alkaloid extract of the aerial parts of Annona cherimolia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Several species of Annona (Annonaceae) are used in traditional Mexican medicine by their anti-anxiety, anticonvulsant and tranquilizing properties. It has been reported that the alkaloids isolated from some species of the Annona have affinity to serotonergic 5-HT(1A) receptors and modulate dopaminergic transmission, which is involved in depressive disorders. AIM OF THE STUDY: To investigate the antidepressant-like effect of an alkaloid extract from the aerial parts of Annona cherimola (TA) in mice. MATERIALS AND METHODS: The antidepressant-like effect was evaluated in the forced swimming test. To elucidate a possible mechanism of action, experiments of synergism with antidepressant drugs, such as imipramine (IMI), clomipramine (CLIMI), and fluoxetine (FLX), were carried out. The neurotransmitter content (DA: dopamine, 5HT: serotonin and its metabolites, HVA: homovanillic acid and 5HIAA: 5-hydroxyindoleacetic) in the whole brain of mice were also determined by HPLC method. TA chemical composition was determined using high performance liquid chromatography-electrospray mass spectrometry. RESULTS: The results showed that repeated treatment with TA produced antidepressant-like effects in mice. This effect was not related to an increase in locomotor activity. Administration of TA facilitated the antidepressant effect of IMI and CLIMI as well as increased the turnover of DA and 5-HT. The alkaloids: 1,2-dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzoquinoline-3,8,9,10-tetraol, anonaine, liriodenine, and nornuciferine were the main constituents of TA. CONCLUSIONS: Results showed that TA produces an antidepressant-like action from a generalized increase in monominergic turnover, supporting the use in tradicional medicine of Annona cherimolia, and strongly suggest its therapeutic potency as an antidepressant agent.

[Epidemiology and clinical characteristics of ulcerative colitis in north-eastern Mexico]. / Epidemiología y características clínicas de la colitis ulcerosa crónica idiopática en el noreste de México.

BACKGROUND: Inflammatory Bowel Disease (IBD) compromises two entities: Ulcerative Colitis (UC) and Crohn Disease (CD). The incidence and prevalence vary widely in relation to ethnicity and demographic localization. Historically it has been considered a rare disease in Mexico. OBJECTIVE: To determine the frequency of new UC cases and their clinical characteristics in a referral hospital of North-Eastern Mexico. METHODS: An epidemiological, descriptive and retrospective study was made which included newly diagnosed patients with UC in a five years period. RESULTS: The adjusted rate of patients diagnosed with UC to the number of admissions for year was 2.3, 2.6, 3.0, 3.6 and 4.1/1000 admissions between 2004 and 2008. The rate of newly diagnosed patients with UC has doubled in the year 2008 compared with the year 2004 (p < 0.05). Fifty five percent of the patients showed mild disease, 30% showed moderate disease and 15% showed severe disease. Fifty percent of the patients had pancolitis, left sided colitis was present in 21% and 29% of the patients just had proctitis. Other clinical aspects of UC corresponded to those previously described. CONCLUSION: The frequency of new patients diagnosed with UC has significantly increased in this tertiary-care referral hospital for the last five years.

[Hepatic actinomycosis ; presentation a case in a diabetic patient]. / Actinomicosis hepática; presentación de un caso en un paciente diabético.

We report the case of an Hispanic female diabetic patient admitted to our hospital complaining of progressive abdominal pain, weight loss, nausea and vomiting. Work-up included an abdominal computed tomography (CT) scan which reported a large liver mass consistent with atypical abscess. Serum alpha-fetoprotein value was normal, so a fine needle aspiration biopsy of the liver was performed and the report was consistent with an actinomycosis-induced abscess. Patient was treated with intravenous and oral amoxicillin with satisfactory clinical response.

Isolation of (-)(2S)-5,6,7,3',5'-pentahydroxyflavanone-7-O-ß-D-glucopyranoside, from Lippia graveolens H.B.K. var. berlandieri Schauer, a new anti-inflammatory and cytotoxic flavanone.

A new flavanone glycoside, (-)(2S)-5,6,7,3',5'-pentahydroxyflavanone-7-O-ß-D-glucopyranoside (1), was isolated from the stems of Lippia graveolens H.B.K. (Verbenaceae). The structure of 1 was elucidated based on spectral analysis and chemical transformations. The treatment of 1 with acetic anhydride and pyridine afforded the corresponding per-acetylated derivative 2, while an acid hydrolysis reaction of 1 afforded a 5,6,7,3',5'-pentahydroxy flavanone (3). Additionally, the anti-inflammatory and cytotoxic activities of 1, 2 and 3 were determined.

Depressant effects of Clinopodium mexicanum Benth. Govaerts (Lamiaceae) on the central nervous system.

ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of leaves of Clinopodium mexicanum Benth. Goaverts (Lamiaceae), commonly known as "Toronjil de Monte", is used in the Mexican traditional medicine to induce sleep, as well as sedative and analgesic remedy. AIM OF THE STUDY: To evaluate the putative depressant effects of an aqueous extract of the medicinal plant Clinopodium mexicanum on the central nervous system (CNS). MATERIALS AND METHODS: The effects of the extract (AECM) on mice were tested in several animal paradigms, including sodium pentobarbital-induced sleep, open field tests, and hole-board tests. The effects of AECM on pentylenetetrazole- and picrotoxin-induced convulsions in mice and on the antithermonociceptive response in the hot-plate paradigm were also tested. Additionally, the active extract (AECM) was analyzed with HPLC-ESI-MS techniques. RESULTS: Mice acutely treated with AECM at 100, 200, 500 and 1000mg/kg doses prolonged the sleeping time induced by sodium pentobarbital (42mg/kg). This extract, at 100 and 200mg/kg doses, showed a sedative effect in the hole-board paradigm and decreased spontaneous activity in mice. AECM at 10, 100 and 200mg/kg prolonged the onset of seizures induced by pentylenetetrazole (90mg/kg) and antagonized tonic convulsions induced by picrotoxin (10mg/kg). Additionally, AECM inhibited the response to a thermonociceptive stimulus. The intraperitoneal AECM treatment produced mortality with an LD(50)=2154mg/kg. Chemical analysis showed that the flavanone glycosides neoponcirin, poncirin, and isonaringenin are the main compounds of the active extract. CONCLUSIONS: This study demonstrates that an acutely administered single dose of an aqueous extract of Clinopodium mexicanum can exert depressant effects on the CNS. These findings are in agreement with the traditional use of Clinopodium mexicanum to induce sleep as well as sedative and analgesic remedy. The chemical analysis of AECM revealed the presence of the flavanone glycosides neoponcirin, poncirin, and isonaringin.

[Considerations in evaluating the quality of life of patients with digestive, liver and bile disorders in Mexico]. / Consideraciones en la evaluación de la calidad de vida de enfermos con afecciones digestivas, hepáticas y biliares en México.

BACKGROUND: In Mexico, there are few reviews of life quality related to health. These reviews do not substitute symptom, analytic and morphologic evaluations by physicians. They only complement them, by introducing the patient;s vision about his perception of his own health. They also intent to reflect the impact of disease on the patient and on his general health. Besides, they also recognize the influence of health on a daily living basis. Objetive: To analyze the nowadays literature existing in Mexico, with regard to the instruments to evaluate the quality of life within patients with gastrointestinal diseases. METHODS: Search of instruments for measuring the status of life related to health in the mexican population in the MEDLINE database, with emphasis on gastrointestinal and hepatobiliar diseases. RESULTS: One hundred references had been found, but only 10 correspond to studies that use different instruments of evaluation of life status related to gastrointestinal diseases in Mexico. Five of these studies are specific questionnaires and five are generic. CONCLUSION: Actually there are few investigations about evaluation of quality of life in Mexican patients, because of the cultural differences within the Hispano-American countries. All of the questionnaires must be evaluated before using them in our population.

[Helicobacter pylori erradication and its relation to antibiotic resistance and CYP2C19 status]. / Erradicación de H. pylori y su relación con la resistencia a los antibióticos y el estatus de CYP2C19.

OBJECTIVE: to assess the efficacy of rabeprazole (RPZ), amoxicillin (Am), and clarithromycin (Cla) (7 vs. 14 days) in the eradication of H. pylori, and to determine the effect of strain-specific antibiotic resistance and host CYP2C19 status. MATERIAL AND METHODS: first, we determined the CYP2C19 status of 100 healthy subjects to establish a sample size for the clinical trial. Then, 59 H. pylori-infected patients were randomized to receive RPZ (20 mg daily) plus Cla (500 mg b.d.) and Am (1,000 mg b.d.) for 7 vs. 14 days. The MIC for Am and Cla were determined using the agar dilution method. The CYP2C19 genotype was determined by the PCR-RFLP method. RESULTS: In the per-protocol analysis (PP) eradication rates were 89.7 and 72% for the 7- and 14-day groups (p = 0.159). In the intention to-treat analysis (ITT) eradication rates were 86.7 and 62.1% in the 7- and 14-day groups, respectively (p = 0.06). None of the strains was resistant to Am, and 4 strains were resistant to Cla: 3 (11.1%) in the 14-day group and 1 (4%) in the 7-day group. Neither strain-specific antibiotic resistance nor host CYP2C19 status influenced eradication rates. CONCLUSIONS: both 7- and 14-day therapies were effective for H. pylori eradication. Strain resistance and CYP2C19 status do not seem to influence eradication rates in the studied population.