Introducing the NUATEI Consortium: A Mexican Research Program for the Identification of Natural and Synthetic Antimicrobial Compounds for Prevalent Infectious Diseases.

The need for new drugs to treat human infections is a global health concern. Diseases like tuberculosis, trypanosomiasis, amoebiasis, and AIDS remain significant problems, especially in developing countries like Mexico. Despite existing treatments, issues such as resistance and adverse effects drive the search for new alternatives. Herein, we introduce the NUATEI research consortium, made up of experts from the Institute of Biomedical Research at UNAM, who identify and obtain natural and synthetic compounds and test their effects against human pathogens using in vitro and in vivo models. The consortium has evaluated hundreds of natural extracts and compounds against the pathogens causing tuberculosis, trypanosomiasis, amoebiasis, and AIDS, rendering promising results, including a patent with potential for preclinical studies. This paper presents the rationale behind the formation of this consortium, as well as its objectives and strategies, emphasizing the importance of natural and synthetic products as sources of antimicrobial compounds and the relevance of the diseases studied. Finally, we briefly describe the methods of the evaluation of the compounds in each biological model and the main achievements. The potential of the consortium to screen numerous compounds and identify new therapeutic agents is highlighted, demonstrating its significant contribution to addressing these infectious diseases.

Epidemiología y prevalencia de Mycoplasma genitalium y resistencia a azitromicina en el Área Norte de Tenerife, Islas Canarias / Epidemiology and prevalence of Mycoplasma genitalium and resistance to azithromycin in the North Area of Tenerife, Canary Islands

INTRODUCCIÓN: La infección y resistencia antimicrobiana de Mycoplasma genitalium está infradiagnósticada en nuestra comunidad ya que no es una Enfermedad de Declaración Obligatoria y requiere técnicas de biología molecular, no siempre disponibles. OBJETIVO: Estudiar la epidemiología y prevalencia de M. genitalium y la tasa de resistencia frente a azitromicina en nuestra Área de Salud. MÉTODOS: Estudio retrospectivo, desde abril de 2019 a julio de 2020, realizado en el Área de Salud del Norte de Tenerife, la cual atiende el Hospital Universitario Canarias. Para el diagnóstico de las infecciones de transmisión sexual (ITS) se utilizó la RT-PCR Allplex™ STI Essential Assay (Seegene, South Korea). Las muestras en las que se detectó M. genitalium fueron congeladas a −80°C para posteriormente realizar estudio de resistencia a azitromicina con la RT-PCR Allplex™ MG y AziR Assay (Seegene, South Korea). RESULTADOS: Se identificaron 111/3.849 (prevalencia de 2,8%) pacientes con M. genitalium, de los cuales la mayoría, 59(53,1%) eran hombres con una mediana de 32 años (15-74) y cuyas muestras procedían principalmente de Atención Primaria: 55 (49,5%). Para la detección de resistencia a azitromicina, de los 111 pacientes solo se pudo analizar las muestras de 79, detectándose resistencia in vitro en 15(18,3%): 10 con A2059G, 4 con A2058G y 1 con ambas. La resistencia a azitromicina fue más frecuente en hombres 12 (15,8%). DISCUSIÓN Y CONCLUSIONES: Con este estudio se pone de manifiesto la importancia de la prevalencia de M. genitalium en nuestro entorno, así como su alta tasa de resistencia a azitromicina por lo que se hace necesario vigilar dicha resistencia en nuestro Área de Salud para su adecuado tratamiento.

BACKGROUND: Infection and antimicrobial resistance of Mycoplasma genitalium is under-diagnosed in our community as it is not a Notifiable Infectious Disease and requires for its detection molecular biology techniques, which are not always available. AIM: To study the epidemiology and prevalence of M. genitalium and the rate of resistance to azithromycin in our Health Care Area. METHODS: We conducted a retrospective study from April 2019 to July 2020 in the Northern Health Care Area of Tenerife, which is attended to the Universitary Hospital Complex of the Canary Islands. The RT-PCR Allplex™ STI Essential Assay (Seegene, South Korea) to diagnose Sexually Transmitted Infections (STI) was used. Samples in which M. genitalium was detected were stored at −80°C for subsequent diagnosis of resistance to azithromycin with the RT-PCR Allplex™ MG and AziR Assay (Seegene, South Korea). RESULTS: Of a total of 111/3,849 (2.8% prevalence) patients diagnosed with M. genitalium, 59 (53.1%) were male with a mean age of 30 (19-61) years and mainly from Primary Care 55 (49.5%). Only 79 samples of the 111 patients could be tested to detect azithromycin resistance, of which 15 (18.3%) were resistant in vitro: 10 with A2059G, 4 with A2058G and 1 with both. Azithromycin resistance was more frequent in men 12 (15.8%) and detected mainly in urine samples 6 (60%). Discussion and CONCLUSIONS: This study highlights the prevalence of M. genitalium in our setting as well as the high rate of resistance to azithromycin, making it necessary to detect resistance to azithromycin in M. genitalium for its appropriate treatment in our Health Care Area.

Synergy of Plant Essential Oils in Antibiotic Therapy to Combat Klebsiella pneumoniae Infections.

Increased antibiotic resistance presents a health problem worldwide. The World Health Organization published a list of pathogens considered a priority for designing new treatments. Klebsiella pneumoniae (Kp) is a top-priority microorganism, highlighting the strains that produce carbapenemases. Developing new efficient therapies or complementing existing treatments is a priority, and essential oils (EOs) provide an alternative. EOs could act as antibiotic adjuvants and enhance antibiotic activity. Employing standard methodologies, the antibacterial activity of the EOs and their synergic effect with antibiotics were detected. A string test was used to identify the impact of the EOs over the hypermucoviscosity phenotype presented by Kp strains, and Gas Chromatography-Mass Spectrometry analysis identified EOs and the composition of EOs. The potential of EOs for designing synergistic therapies with antibiotics to combat the infection of KPC diseases was demonstrated. In addition, the alteration of the hypermucoviscosity phenotype was shown as the principal mechanism of a synergic action between EOs and antibiotics. The differential composition of the EOs lets us identify some molecules that will be analyzed. Synergic activity of EOs and antibiotics can provide a solid platform for combating multiresistant pathogens that represent a severe health sector problem, such as Kp infections.

Five centuries of Cirsium ehrenbergii Sch. Bip. (Asteraceae) in Mexico, from Huitzquilitl to Cardo Santo: History, ethnomedicine, pharmacology and chemistry.

ETHNOPHARMACOLOGICAL RELEVANCE: Several medicinal plants, including the endemic herb Cirsum ehrenbergii (Asteraceae), have been documented in manuscripts, medical and botanical books written in Mexico since the XVI century until the present. This unique circumstance is a real window in the time that allows to investigate historical and contemporary ethnopharmacological knowledge. AIM OF THE STUDY: To examine the persistence, disappearance, and transformation of ethnomedicinal knowledge of C. ehrenbergii along time. Also, to investigate the chemistry and pharmacology of this species in relation to its historical and present day main ethnomedical applications related to Central Nervous System and inflammation. MATERIALS AND METHODS: A thorough review was performed of written sources of medicinal plants from XVI and onwards. For the pharmacological studies, the organic extracts were tested in mice models to assess its antidepressant and anti-inflammatory properties. The active extracts were studied chemically. The isolated compounds were identified by 1H, 13C NMR, or characterized by GC-MS. RESULTS: Cirsum ehrenbergii was illustrated for the first time (1552) in the Libellus de Medicinalibus Indorum Herbis (Booklet of Medicinal Plants of the Indians) and named in the Nahuatl native language as huitzquilitl (edible thistle). It was there recommended as nigris sanguinis remedium (remedy for black blood), and for the treatment of illnesses with an inflammatory component. Nigris sanguinis was well known in the European medicine of that time and currently it has been interpreted as "depression". At the present time, peasants and native population in Mexico mainly name C. ehrenbergii in Spanish as cardo Santo (holy thistle). Its original Nahuatl name has been almost forgotten. However, these communities use this species, among other maladies, to heal "nervios" (anxiety and/or depression) and for anti-inflammatory purposes. These ailments and treatments resemble those recorded in the Libellus and in several medicinal plant books along centuries. The ethanol extract of C. ehrenbergii roots showed antidepressant-like activity in mice administered at 300 mg/kg, as indicated by the forced swim test (FST). The glycosylated flavonoid linarin was identified as antidepressant principle and was active at the doses of 30 and 60 mg/kg in the FST. Regarding to anti-inflammatory activity, the most active was the methylene chloride extract of the aerial parts, which contains taraxasterol, pseudotaraxasterol, ß-sitosterol and stigmasterol. CONCLUSIONS: Cirsium ehrenbergii extracts possess antidepressant-like (roots, EtOH) and anti-inflammatory (aerial parts, CH2Cl2) properties, containing active compounds. Our results sustain historical and present day ethnomedical applications of this species documented along five centuries.

New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis.

In recent years, knowledge of the role that protein methylation is playing on the physiopathogenesis of bacteria has grown. In Mycobacterium tuberculosis, methylation of the heparin binding hemagglutinin adhesin modulates the immune response, making this protein a subunit vaccine candidate. Through its C-terminal lysine-rich domain, this surface antigen interacts with heparan sulfate proteoglycans present in non-phagocytic cells, leading to extrapulmonary dissemination of the pathogen. In this study, the adhesin was expressed as a recombinant methylated protein in Rhodococcus erythropolis L88 and it was found associated to lipid droplets when bacteria were grown under nitrogen limitation. In order to delve into the role methylation could have in host-pathogen interactions, a comparative analysis was carried out between methylated and unmethylated protein produced in Escherichia coli. We found that methylation had an impact on lowering protein isoelectric point, but no differences between the proteins were found in their capacity to interact with heparin and A549 epithelial cells. An important finding was that HbhA is a Fatty Acid Binding Protein and differences in the conformational stability of the protein in complex with the fatty acid were observed between methylated and unmethylated protein. Together, these results suggest that the described role for this mycobacteria protein in lipid bodies formation could be related to its capacity to transport fatty acids. Obtained results also provide new clues about the role HbhA methylation could have in tuberculosis and point out the importance of having heterologous expression systems to obtain modified proteins.

Sobre el primer libro de plantas medicinales escrito en el Continente Americano: El Libellus Medicinalibus Indorum Herbis de México, 1552. Una revisión / On the first book of medicinal plants written in the American Continent: The Libellus Medicinalibus Indorum Herbis from Mexico, 1552. A review

Resumen: El "Libellus de Medicinalibus Indorum Herbis" (Librito de las Hierbas Medicinales de los Indios) fue elaborado por los sabios indígenas Martín De la Cruz y Juan Badiano, 31 años después de la caída del imperio azteca. El primero es su autor, el segundo tradujo el manuscrito del Náhuatl al latín. Contiene numerosas recetas para tratar enfermedades humanas y 185 dibujos a color de las plantas utilizadas. En 1939 se publicó por primera vez como "Un Herbario Azteca". Empero, también contiene enfermedades y prácticas médicas europeas del siglo XVI. Presentamos una revisión actualizada de este hermoso códice, su historia, concepción, creadores y botánica; además, la química y farmacología de cinco plantas ahí citadas. El Libellus es una ventana en el tiempo que permite la investigación científica del antiguo conocimiento etnofarmacológico en Mesoamérica y documentar su persistencia, desaparición o transformación. Sin embargo, esto requiere superar desafíos lingüísticos, pero también derivados de su contexto histórico, antropológico, cultural, botánico y médico.

Abstract: The "Libellus de Medicinalibus Indorum Herbis" (Little Book of Indian Medicinal Plants) was composed by the indigenous sages Martín De la Cruz and Juan Badiano, 31 years after the Aztec Empire fall. The former was the author, and the latter translated the manuscript from the Nahuatl language to Latin. It contains numerous recipes for treating human diseases and 185 colored drawings of the prescribed plants. In 1939 it was first published as "An Aztec Herbarium". However, it also contains XVI century European diseases and medical practices. We present an updated review of this beautiful codex, its history, conception, creators, and botany; as well as, the chemistry and pharmacology of five plants therein cited. The Libellus is a window in the time that allows the scientific research of ancient ethnopharmacological knowledge in Mesoamerica and document its persistence, disappearance, or transformation. However, this requires overcoming linguistic defies, but also derived from its historical, anthropological, cultural, botanical, and medical context.

Multi-walled carbon nanotubes functionalized with bathocuproinedisulfonic acid: analytical applications for the quantification of Cu(II).

This work reports the successful non-covalent functionalization of multi-walled carbon nanotubes (MWCNTs) with bathocuproinedisulfonic acid (BCS) and the analytical application of the resulting dispersion (MWCNTs-BCS) to develop an electrochemical sensor for Cu(II) quantification. The sensor was obtained by casting glassy carbon electrodes (GCEs) with MWCNTs-BCS. The sensing mechanism was based on the open circuit preconcentration of Cu(II) at the electrode surface by complexation of Cu(II) through the phenanthroline ring nitrogen of the BCS that supports the MWCNTs, the reduction of the preconcentrated Cu(II), and final differential pulse voltammetry-anodic stripping in 0.020 M acetate buffer, pH 5.00. The sensitivity of the sensor was (2.73 ± 0.08) µA µM-1, with a linear range between 5.0 × 10-7 M and 6.0 × 10-6 M, a detection limit of 0.15 µM (9.5 µg L-1), and reproducibility of 6.2% using the same dispersion and 7.1% using three different MWCNTs-BCS dispersions. The quantification of Cu(II) was highly selective even in the presence of As3+, Cr3+, Cd2+, Ni2+, Pb2+, Co2+, Zn2+, Fe2+, Hg2+, Rh, Ir, and Ru. The proposed sensor was successfully used for quantifying Cu(II) in tap water. Graphical abstract.

Diacetylcurcumin: Its Potential Antiarthritic Effect on a Freund's Complete Adjuvant-Induced Murine Model.

The present study aims to evaluate the antiarthritic activity of diacetylcurcumin (DAC), a synthetic derivative where the free phenolic groups of curcumin are derivatized by acetylation, thereby conferring greater lipophilicity to the parent molecule and partially overcoming the limited systemic bioavailability of curcumin. Antiarthritic activity was evaluated on a Freund's complete adjuvant (FCA)-induced murine model of arthritis. Oral administration of DAC (60 and 120 mg/kg) resulted in a significant inhibition of inflammation in the acute and chronic phases, respectively, demonstrating an improved and sustained anti-inflammatory effect, comparable to that of curcumin (150 mg/kg) in the chronic stage at a lower dose. Phenylbutazone (80 mg/kg) was used as a reference drug. The pharmacological consequence of DAC or curcumin treatment is the prevention of secondary lesions commonly associated with this biological model.

Antinociceptive, anti-inflammatory, and central nervous system (CNS) effects of the natural coumarin soulattrolide.

Soulattrolide is a natural coumarin synthesized by the leaves of species of Calophyllum (Calophyllaceae) rain forest trees, including the American C. brasiliense, and the Asian C. teysmanii. Soulattrolide is a potent inhibitor of the reverse transcriptase from HIV-1 (RT-HIV-1), and active against Mycobacterium tuberculosis. However, the effects of this coumarins on other systems, remains to be evaluated. C. brasiliense is used in traditional medicine for the treatment of pain and inflammation. Therefore, we decided to explore the antinociceptive, anti-inflammatory activity of soulattrolide in mice, as well as, some of its possible effects on the CNS. Soulattrolide showed antinociceptive effects in the writhing test (ED50 = 33.8 mg/kg), as well as, in the formalin test with an ED50 = 7.9, and 22.1 mg/kg for Phases 1 and 2, respectively. The highest dose of soulattrolide (50 mg/kg) induced 40% of antinociception in the hot plate test. Regarding to anti-inflammatory activity, in the 12-O-Tetradecanoylphorbol-13-acetate (TPA) test, soulattrolide showed an IC50 = 1.81 µmol/ear, whereas in the myeloperoxidase assay, it showed an inhibition of 87% (1 µmol/ear). Soulattrolide showed sedative effects on the pentobarbital-induced sleeping time test, and the rotarod test, but lacked antidepressant activity on the tail suspension test. In conclusion, we report for the first time, the antinociceptive effects of soulattrolide in mice, like those of naproxen; soulattrolide also showed mild anti-inflammatory activity, as well as mild sedative and anxiolytic properties, therefore, it has also activity on the CNS.

Mexican Propolis: A Source of Antioxidants and Anti-Inflammatory Compounds, and Isolation of a Novel Chalcone and ε-Caprolactone Derivative.

The propolis produced by bees are used in alternative medicine for treating inflammation, and infections, presumably due to its antioxidant properties. In this context, five propolis from México were investigated to determine their inhibitory lipid peroxidation properties. The ethyl acetate extract from a red propolis from Chiapas State (4-EAEP) was the most potent (IC50 = 1.42 ± 0.07 µg/mL) in the TBARS assay, and selected for further studies. This extract afforded two new compounds, epoxypinocembrin chalcone (6), and an ε-caprolactone derivative (10), as well as pinostrobin (1), izalpinin (2), cinnamic acid (3), pinocembrin (4), kaempherol (5), 3,3-dimethylallyl caffeate in mixture with isopent-3-enyl caffeate (7a + 7b), 3,4-dimethoxycinnamic acid (8), rhamnetin (9) and caffeic acid (11). The HPLC profile, anti-mycobacterial, and antioxidant properties of this extract was also determined. Most of the isolated compounds were also tested by inhibition of reactive oxygen species (ROS) in challenged mouse bone marrow-derived mast cells (BMMCs), and DPPH. Their anti-inflammatory activity was evaluated by TPA, and MPO (myeloperoxidase) activity by ear edema test in mice. The most potent compounds were 7a + 7b in the TBARS assay (IC50 = 0.49 ± 0.06 µM), and 2 which restored the ROS baseline (3.5 µM). Our results indicate that 4-EAEP has anti-oxidant, and anti-inflammatory properties due to its active compounds, suggesting it has anti-allergy and anti-asthma potential.

Unique pharmacological properties of serotoninergic G-protein coupled receptors from cestodes.

BACKGROUND: Cestodes are a diverse group of parasites, some of them being agents of neglected diseases. In cestodes, little is known about the functional properties of G protein coupled receptors (GPCRs) which have proved to be highly druggable targets in other organisms. Notably, serotoninergic G-protein coupled receptors (5-HT GPCRs) play major roles in key functions like movement, development and reproduction in parasites. METHODOLOGY/PRINCIPAL FINDINGS: Three 5-HT GPCRs from Echinococcus granulosus and Mesocestoides corti were cloned, sequenced, bioinformatically analyzed and functionally characterized. Multiple sequence alignment with other GPCRs showed the presence of seven transmembrane segments and conserved motifs but interesting differences were also observed. Phylogenetic analysis grouped these new sequences within the 5-HT7 clade of GPCRs. Molecular modeling showed a striking resemblance in the spatial localization of key residues with their mammalian counterparts. Expression analysis using available RNAseq data showed that both E. granulosus sequences are expressed in larval and adult stages. Localization studies performed in E. granulosus larvae with a fluorescent probe produced a punctiform pattern concentrated in suckers. E. granulosus and M. corti larvae showed an increase in motility in response to serotonin. Heterologous expression revealed elevated levels of cAMP production in response to 5-HT and two of the GPCRs showed extremely high sensitivity to 5-HT (picomolar range). While each of these GPCRs was activated by 5-HT, they exhibit distinct pharmacological properties (5-HT sensitivity, differential responsiveness to ligands). CONCLUSIONS/SIGNIFICANCE: These data provide the first functional report of GPCRs in parasitic cestodes. The serotoninergic GPCRs characterized here may represent novel druggable targets for antiparasitic intervention.

Heliopsis longipes: anti-arthritic activity evaluated in a Freund's adjuvant-induced model in rodents

ABSTRACT This study assesses the anti-arthritic effect of the affinin-enriched (spilanthol, main alkamide) hexane extract from the roots of Heliopsis longipes (A. Gray) S.F. Blake, Asteraceae, on a Freund adjuvant-induced arthritis model in rodents. The extract was orally administered at a dose of 2, 6.6, or 20 mg/kg; a significant edema-inhibitory activity in the acute and chronic phases was observed with a dose of 2 and 20 mg/kg, respectively. The extract showed higher anti-inflammatory and anti-arthritic effects than the reference drug phenylbutazone (80 mg/kg). Moreover, the extract prevented the occurrence of secondary lesions associated to this pharmacological model.

Natural Compounds from Mexican Medicinal Plants as Potential Drug Leads for Anti-Tuberculosis Drugs

ABSTRACT In Mexican Traditional Medicine 187 plant species are used in the treatment of respiratory conditions that may be associated with tuberculosis. In this contribution, we review the ethnobotany, chemistry and pharmacology of 63 species whose extracts have been assayed for antimycobacterial activity in vitro. Among these, the most potent is Aristolochia brevipes (MIC= 12.5 µg/mL), followed by Aristolochia taliscana, Citrus sinensis, Chrysactinia mexicana, Persea americana, and Olea europaea (MIC<64 µg/mL). Other potent extracts (inhibition > 95%, 50 µg/mL) include: Amphipterygium adstringens, Larrea divaricata, and Phoradendron robinsoni. Several active compounds have been identified, the most potent are: Licarin A (isolated from A. taliscana), and 9-amino-9-methoxy-3,4-dihydro-2H-benzo[h]-chromen-2-one (transformation product of 9-methoxytariacuripyrone isolated from Aristolochia brevipes), both with MIC= 3.125 µg/mL, that is 8-fold less potent than the reference drug Rifampicin (MIC= 0.5 µg/mL). Any of the compounds or extracts here reviewed has been studied in clinical trials or with animal models; however, these should be accomplished since several are active against strains resistant to common drugs.

Natural Compounds from Mexican Medicinal Plants as Potential Drug Leads for Anti-Tuberculosis Drugs.

In Mexican Traditional Medicine 187 plant species are used in the treatment of respiratory conditions that may be associated with tuberculosis. In this contribution, we review the ethnobotany, chemistry and pharmacology of 63 species whose extracts have been assayed for antimycobacterial activity in vitro. Among these, the most potent is Aristolochia brevipes (MIC= 12.5 µg/mL), followed by Aristolochia taliscana, Citrus sinensis, Chrysactinia mexicana, Persea americana, and Olea europaea (MIC<64 µg/mL). Other potent extracts (inhibition > 95%, 50 µg/mL) include: Amphipterygium adstringens, Larrea divaricata, and Phoradendron robinsoni. Several active compounds have been identified, the most potent are: Licarin A (isolated from A. taliscana), and 9-amino-9-methoxy-3,4-dihydro-2H-benzo[h]-chromen-2-one (transformation product of 9-methoxytariacuripyrone isolated from Aristolochia brevipes), both with MIC= 3.125 µg/mL, that is 8-fold less potent than the reference drug Rifampicin (MIC= 0.5 µg/mL). Any of the compounds or extracts here reviewed has been studied in clinical trials or with animal models; however, these should be accomplished since several are active against strains resistant to common drugs.

Arsenic and fluoride removal from groundwater by electrocoagulation using a continuous filter-press reactor.

We investigated simultaneous arsenic and fluoride removal from ground water by electrocoagulation (EC) using aluminum as the sacrificial anode in a continuous filter-press reactor. The groundwater was collected at a depth of 320 m in the Bajío region in Guanajuato Mexico (arsenic 43 µg L(-1), fluoride 2.5 mg L(-1), sulfate 89.6 mg L(-1), phosphate 1.8 mg L(-1), hydrated silica 112.4 mg L(-1), hardness 9.8 mg L(-1), alkalinity 31.3 mg L(-1), pH 7.6 and conductivity 993 µS cm(-1)). EC was performed after arsenite was oxidized to arsenate by addition of 1 mg L(-1) hypochlorite. The EC tests revealed that at current densities of 4, 5 and 6 mA cm(-2) and flow velocities of 0.91 and 1.82 cm s(-1), arsenate was abated and residual fluoride concentration satisfies the WHO standard (CF < 1.5 mg L(-1)). Spectrometric analyses performed on aluminum flocs indicated that these are mainly composed of aluminum-silicates of calcium and magnesium. Arsenate removal by EC involves adsorption on aluminum flocs, while fluoride replaces a hydroxyl group from aluminum aggregates. The best EC was obtained at 4 mA cm(-2) and 1.82 cm s(-1) with electrolytic energy consumption of 0.34 KWh m(-3).

[Hemobilia secondary to hepatic artery pseudoaneurysm]. / Hemobilia secundaria a pseudoaneurisma de la arteria hepática.

Hemobilia is defined as the presence of blood in the biliary tree characterized by the triad: jaundice, right hypochondrium pain (RH) and upper gastrointestinal bleeding (UGB). Among the etiologies highlighted in order of frequency there are: liver trauma (accidental and iatrogenic), inflammatory causes (acute and chronic cholecystitis), infections (cholangitis, liver abscesses, parasitic infections) and vascular diseases (aneurysms, vasculitis, arteriovenous malformations). There exist many complementary tests for the diagnosis of hemobilia, such as imaging (abdominal ultrasound, CT scan, angio CT), videoendoscopy, endoscopic retrograde cholangiopancreatography and angiography, the latter being considered the diagnostic tool and therapeutic modality of choice. We report the case of a 52-year-old male patient with hemobilia secondary to apseudoaneurysm ofthe hepatic artery, along with a review of the existing literature.

Antimycobacterial and HIV-1 Reverse Transcriptase Activity of Julianaceae and Clusiaceae Plant Species from Mexico.

The extracts of 14 Julianaceae and 5 Clusiaceae species growing in Mexico were tested in vitro (50 µg/mL) against Mycobacterium tuberculosis H37Rv and HIV reverse transcriptase (HIV-RT). The Julianaceae bark and leaf extracts inhibited M. tuberculosis (>84.67%) and HIV-RT (<49.89%). The Clusiaceae leaves extracts also inhibited both targets (>58.3% and >67.6%), respectively. The IC50 values for six selected extracts and their cytotoxicity (50 µg/mL) to human macrophages were then determined. Amphipterygium glaucum, A. molle, and A. simplicifolium fairly inhibited M. tuberculosis with IC50 of 1.87-2.35 µg/mL; but their IC50 against HIV-RT was 59.25-97.83 µg/mL. Calophyllum brasiliense, Vismia baccifera, and Vismia mexicana effect on M. tuberculosis was noteworthy (IC50 3.02-3.64 µg/mL) and also inhibited RT-HIV (IC50 26.24-35.17 µg/mL). These 6 extracts (50 µg/mL) presented low toxicity to macrophages (<23.8%). The HPLC profiles of A. glaucum, A. molle, and A. simplicifolium indicated that their antimycobacterial activity cannot be related to masticadienonic, 3α, or 3ß-hydromasticadienonic acids, suggesting that other compounds may be responsible for the observed activity or this might be a synergy result. The anti-HIV-RT and antimycobacterial activities induced by C. brasiliense can be attributed to the content of calanolides A, B, as well as soulatrolide.

Diagnóstico y tratamiento de la pancreatitis aguda en la Argentina. Resultados de un estudio prospectivo en 23 centros.

In Argentina there are no multicenter studies evaluating the management of patients with acute pancreatitis (AP) nationwide. OBJECTIVES: The main objective of this study is to know how the patients with AP are treated in Argentina. The secondary objective is to assess whether the results comply with the recommendation of the American College of Gastroenterology Guide. MATERIAL AND METHODS: Twenty three center participated in the study. They include in a database hosted online consecutive patients with acute pancreatitis from june 2010 to june 2013. RESULTS: 854 patients entered the study. The average age was 46.6 years and 495 (58%) belonged to the female sex. The most common cause (88.2%) of AP was biliary. Some prognostic system was used in 99 % of patients and the most used was Ranson (74.5%). Were classified as mild 714 (83.6%) patients and severe 140 (16.4%). Systemic complications occurred in 43 patients and local complications in 21. 86 patients underwent dynamic CT scans and 73 patients had pancreatic and / or peripancreatic necrosis. Mortality was 1.5%. There was no difference in mortality in relation to the size, complexity or affiliation of the center. The comply of key recommendations of the American College of Gastroenterology Guide was over 80%. CONCLUSIONS: The diagnosis and treatment of patients with AP in 23 health centers located throughout the country was optimal. The management complied with most of the recommendations of the American College of Gastroenterology Guide.

Diagnóstico y tratamiento de la pancreatitis aguda en la Argentina. Resultados de un estudio prospectivo en 23 centros.

In Argentina there are no multicenter studies evaluating the management of patients with acute pancreatitis (AP) nationwide. OBJECTIVES: The main objective of this study is to know how the patients with AP are treated in Argentina. The secondary objective is to assess whether the results comply with the recommendation of the American College of Gastroenterology Guide. MATERIAL AND METHODS: Twenty three center participated in the study. They include in a database hosted online consecutive patients with acute pancreatitis from june 2010 to june 2013. RESULTS: 854 patients entered the study. The average age was 46.6 years and 495 (58%) belonged to the female sex. The most common cause (88.2%) of AP was biliary. Some prognostic system was used in 99 % of patients and the most used was Ranson (74.5%). Were classified as mild 714 (83.6%) patients and severe 140 (16.4%). Systemic complications occurred in 43 patients and local complications in 21. 86 patients underwent dynamic CT scans and 73 patients had pancreatic and / or peripancreatic necrosis. Mortality was 1.5%. There was no difference in mortality in relation to the size, complexity or affiliation of the center. The comply of key recommendations of the American College of Gastroenterology Guide was over 80%. CONCLUSIONS: The diagnosis and treatment of patients with AP in 23 health centers located throughout the country was optimal. The management complied with most of the recommendations of the American College of Gastroenterology Guide.