Efficacy of Omalizumab for the treatment of Bullous Pemphigoid. Spanish multicenter real-world experience.

BACKGROUND: Bullous Pemphigoid (BP) is the most common autoimmune blistering disease. Most patients are elderly and associate multiple comorbidities. Topical and systemic corticosteroids are considered as the first-line treatment for BP and immunosuppressors are used as steroid-sparing treatments but both have side effects and contraindications which are even more common in this elderly population. New treatments targeting interleukins and receptors related to BP pathogenesis have been proposed to decrease this side effects while achieving equal or better effectiveness response rates.Omalizumab is a monoclonal antibody that targets IgE that has been proposed for the treatment of BP due to the evidence that IgE autoantibodies play an essential role in BP pathogenesis. OBJECTIVES AND METHODOLOGY: To assess the efficacy and security of Omalizumab for the treatment of BP, we carried out a multicenter, retrospective, observational study including patients diagnosed of BP who received omalizumab for at least 3 months from 15 tertiary hospitals in Spain. IgE levels prior to treatment was measured and we evaluate the possible correlation with clinical response. We excluded patients treated with Omalizumab for less than 3 months as we consider this duration is insufficient for a comprehensive assessment of its efficacy. To evaluate the effectiveness of the treatment we used the percentage of BSA improvement. RESULTS: We included 36 patients. The vast majority associate multiple comorbidities and all patients had used other systemic therapies apart from corticoids before Omalizumab.83% experienced some kind of treatment response and 42% of all patient treated achieved complete response.We did not find any correlation between higher levels and a better response (p=0,1791).All patients tolerated Omalizumab without reported side-effects. CONCLUSIONS: Omalizumab is a good therapeutic alternative for BP as it obtained clinical response in most patients and nearly half of the cases achieving complete response. It showed no side effects which is crucial in elderly patients suffering from BP.

New Insights into the Chemical Composition of Ayahuasca.

Ayahuasca is a psychedelic beverage originally from the Amazon rainforest used in different shamanic settings for medicinal, spiritual, and cultural purposes. It is prepared by boiling in water an admixture of the Amazonian vine Banisteriopsis caapi, which is a source of ß-carboline alkaloids, with plants containing N,N-dimethyltryptamine, usually Psychotria viridis. While previous studies have focused on the detection and quantification of the alkaloids present in the drink, less attention has been given to other nonalkaloid components or the composition of the solids suspended in the beverage, which may also affect its psychoactive properties. In this study, we used nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) to study the composition of ayahuasca samples, to determine their alkaloid qualitative and quantitative profiles, as well as other major soluble and nonsoluble components. For the first time, fructose was detected as a major component of the samples, while harmine (a ß-carboline previously described as an abundant alkaloid in ayahuasca) was found to be present in the solids suspended in the beverage. In addition, N,N-dimethyltryptamine (DMT), harmine, tetrahydroharmine, harmaline, and harmol were identified as the major alkaloids present in extracts of all samples. Finally, a novel, easy, and fast method using quantitative NMR was developed and validated to simultaneously quantify the content of these alkaloids found in each ayahuasca sample.

Bioprospecting the Antibiofilm and Antimicrobial Activity of Soil and Insect Gut Bacteria.

Antimicrobial resistance is a growing concern in public health and current research shows an important role for bacterial biofilms in recurrent or chronic infections. New strategies, therefore, are necessary to overcome antimicrobial resistance, through the development of new therapies that could alter or inhibit biofilm formation. In this sense, antibiofilm natural products are very promising. In this work, a bioprospection of antimicrobial and antibiofilm extracts from Uruguayan soil bacteria and insect gut bacteria was carried out. Extracts from extracellular broths were tested for their ability to inhibit planktonic cell growth and biofilm formation. Genomic analysis of Bacillus cereus ILBB55 was carried out. All extracts were able to inhibit the growth of, at least, one microorganism and several extracts showed MICs lower than 500 µg mL-1 against microorganisms of clinical relevance (Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter cloacae). Among the extracts evaluated for biofilm inhibition only ILBB55, from B. cereus, was able to inhibit, S. aureus (99%) and P. aeruginosa (62%) biofilms. Genomic analysis of this strain showed gene clusters similar to other clusters that code for known antimicrobial compounds. Our study revealed that extracts from soil bacteria and insect gut bacteria, especially from B. cereus ILBB55, could be potential candidates for drug discovery to treat infectious diseases and inhibit S. aureus and P. aeruginosa biofilms.

Effects of Culture Conditions on Antimicrobial Activity of Ganoderma resinaceum (Agaricomycetes) Extracts.

Among many sources of natural bioactive substances, mushrooms constitute a huge and mostly unexplored group. Biologically active secondary metabolites of Ganoderma, a group of wood-degrading mushrooms, have recently been reviewed. Our previous study revealed the antimicrobial activity of extracts from G. resinaceum grown in submerged culture against phytopathogens. Different factors can influence the production of secondary metabolites, including nutritional factors. In this study we evaluated the influence of different culture conditions on the antimicrobial activity of extracts from liquid cultures of G. resinaceum, through use of a factorial design. Minimum inhibitory concentrations for extracts produced under different culture conditions were determined against Staphylococcus aureus and Xanthomonas vesicatoria. Based on the results of these assays, larger-scale cultures in malt extract broth supplemented with 20 g/L glucose and a 15-day incubation time should be performed in order to isolate from G. resinaceum antibiotic compound(s) that are potentially useful against S. aureus. In addition, pH 5 should be considered for the production of antimicrobial metabolites against X. vesicatoria from supernatant broths or extracts from G. resinaceum.

Anti-MRSA Activity of Fruiting Body Extracts of Spectacular Rustgill Mushroom, Gymnopilus junonius (Agaricomycetes).

Despite the great advances in chemotherapeutics, infectious diseases are still one of the leading causes of death worldwide. Among some of the clinically relevant pathogens, methicillin-resistant Staphylococcus aureus (MRSA) ranks as one of the most difficult bacteria to treat. It is a common cause of skin, soft-tissue, and endovascular infections, as well as pneumonia, septic arthritis, endocarditis, osteomyelitis, and sepsis. The research on Basidiomycota is extensive; many species show a broad spectrum of pharmacological activities, including antimicrobial activity. The vast majority of the literature to date generally focuses on screening the antibacterial properties of mushroom extracts. A gap still exists in the identification of the individual compounds responsible for these properties, and few low molecular weight compounds have been described. Gymnopilus junonius, the big laughter mushroom, grows wild in Uruguay, especially on Eucalyptus spp. plantations; it is known as the "eucalyptus fungus." In this work, we report the bioguided isolation, structural elucidation, and antistaphylococcal activity of the main antimicrobial components of fresh basidiocarps of G. junonius.

Screening for Antimicrobial Activity of Wood Rotting Higher Basidiomycetes Mushrooms from Uruguay against Phytopathogens.

In this work, the antimicrobial activity of extracts of wood rotting higher Basidiomycetes mushrooms isolated from Eucalyptus plantations in Uruguay was studied using bacterial and fungal phytopathogens as targets. Fifty-one extracts from mycelia and growth broth were prepared from higher Basidiomycetes mushrooms, from which eight extracts (from Ganoderma resinaceum, Laetiporus sulphureus, Dictyopanus pusillus, and Bjerkandera adusta) showed antimicrobial activity against Xanthomonas vesicatoria, Aspergillus oryzae, Penicillium expansum, Botrytis cinerea, and Rhizopus stolonifer as assayed in the qualitative test. The minimum inhibitory concentration (MIC) for those fungal extracts was determined and the results showed that L. sulphureus deserved further study, with low MIC values against X. vesicatoria. The antimicrobial activity of L. sulphureus culture broth extracts grown under different culture conditions was evaluated against X. vesicatoria. From the results of these assays, larger-scale cultures for the production of the compound(s) with antimicrobial activity should be performed using malt extract broth, at pH 5, at 20°C and static culture conditions.

Mate and Tea Intake, Dietary Antioxidants and Risk of Breast Cancer: a Case-Control Study.

Recently, we reported an inverse association between high 'mate' intake (infusion of Ilex paraguariensis herb, a staple beverage in temperate South America) and breast cancer (BC) risk. Stronger inverse associations were found in high strata of tea, vegetable, fruit and energy intakes, and in overweight/obese women, suggesting possible roles for 'mate' mainly from its antioxidant contribution. The present study attempted to thoroughly explore possible associations among 'mate' and tea intake, dietary antioxidants and BC risk. Combining two databases of previous studies, 572 BC incident cases and 889 controls were interviewed with a specific questionnaire featuring socio-demographic, reproductive and lifestyle variables, and a food frequency questionnaire (64 items), focusing on 'mate' intake (consumer status, daily intake, age at start, age at quit, duration of habit). Food-derived nutrients were calculated from available databases. Odds ratios (OR) and their 95% confidence intervals were calculated through unconditional logistic regression, adjusting for relevant potential confounders. The highest 'mate' intake was significantly inversely associated with BC risk for both low and high carotenoids (OR=0.40 vs. 0.41), vitamin C (OR=0.33 vs. 0.50), vitamin E (OR=0.37 vs. 0.45), flavonols (OR=0.38 vs. 0.48) and reduced glutathione (OR=0.48 vs. 0.46) strata. High tea intake showed significant inverse risk associations only with high carotenoids (OR=0.41), vitamin E (OR=0.48) and reduced glutathione (OR=0.43) strata. In conclusion, a strong and inverse association for 'mate' intake and BC was found, independent of dietary antioxidant levels. Also strong inverse associations with tea intake were more evident only at high levels of certain dietary antioxidants.

Mate Intake and Risk of Breast Cancer in Uruguay: a Case- Control Study.

Regarding 'mate' intake (infusion of Ilex paraguariensis herb, a staple beverage in temperate South American regions), most epidemiologic studies showed positive associations with risk of some cancers, (e.g. upper aerodigestive tract), but evidence on breast cancer (BC) risk is limited to a previous multi-site study, which reported a non significant odds ratio [OR]=0.85, 95% confidence interval [95% CI] 0.67-1.09, p for trend=0.31) for the highest quartile of intake. The present study was conducted in order to further assess associations of 'mate' intake with BC risk. We combined two databases of women belonging to public and private healthcare hospitals. The sample included 572 BC incident cases and 889 controls interviewed with a specific questionnaire featured by socio-demographic, reproductive and lifestyle variables, and a food frequency questionnaire of 64 items, also analyzing 'mate' intake (consumer status, daily intake, age at start, age at quit, duration of habit, intensity of intake). ORs and their 95%CI were calculated through unconditional logistic regression, adjusting for relevant potential confounders. The highest quartile of 'mate' intake was inversely associated with BC risk (OR=0.40, 95%CI 0.26-0.57, p for trend <0.001). Stratified analyses also displayed strong significant inverse associations for 'mate' in frequent tea drinkers (OR=0.22), high energy intake (OR=0.23), high body mass index (OR=0.29) and in postmenopausal women (OR=0.36), among other results. As conclusions, we found evidence of a significant inverse association for 'mate' intake and BC risk.

Xanthane sesquiterpenoids from the roots and flowers of Xanthium cavanillesii.

The sesquiterpene lactones xanthanodiene, 4-epi-xanthanol, 4-epi-isoxanthanol, and 4-epi-xanthinin, as well as the xanthanolide derivative 4-oxo-bedfordia acid were isolated from the chloroform extracts of roots and flowers of Xanthium cavanillesii Schouw. The identities of these compounds were corroborated through comparison of their spectroscopic data, including IR, MS, and (1)H and (13)C NMR assignments, with literature reports. In addition, the structural characterization of 4-oxo-bedfordia acid was revisited and a comprehensive spectroscopic study of the compound is presented. This is to our knowledge the first phytochemical investigation of the roots of X. cavanillesii, and of flowers in the whole Xanthium genus.

Cardiotoxicidad inducida por Trastuzumab en pacientes uruguayas portadoras de cáncer de mama HER positivo / Trastuzumab-induced cardiotoxicity in uruguayan patients with HER positive breast cancer

RESUMEN: Objetivo: Valorar la frecuencia y severidad de la cardiotoxicidad inducida por Trastuzumab (TTZ) en pacientes portadoras de cáncer de mama (CM) HER 2 positivo, asistidas en los Servicios de Oncología del Hospital de Clínicas y de la Asociación Española Primera en Salud. Métodos: Estudio observacional retrospectivo, que incluyó pacientes del Hospital de Clínicas y de la Asociación Española diagnosticadas de CM HER 2 positivo, que recibieron tratamiento con TTZ entre enero de 2007 y diciembre de 2013. Resultados: Se incluyeron 69 pacientes, la mayoría de las cuales tuvieron CM localizado, y cuya media de edad fue 50,1 años. 27% de las pacientes presentó cardiotoxicidad, y el 26% de éstas desarrolló insuficiencia cardíaca sintomática; todas recibieron tratamiento médico adecuado, siendo la insuficiencia cardíaca reversible en la mayoría de los casos. Conclusiones: La frecuencia de cardiotoxicidad observada en el estudio fue del 27 % (IC 95 %: 16,27; 38,8). Con las limitaciones propias del estudio, éste permite verificar similitudes con otras poblaciones reportadas, variando la frecuencia entre 3,7 y 34 %. Sin embargo, la proporción de pacientes que presentaron insuficiencia cardíaca sintomática (7%) fue algo superior a la reportada en la literatura, que es del 4%. La cardiotoxicidad fue reversible en la mayoría de las pacientes.

ABSTRACT: Objective: To evaluate the frequency and severity of Trastuzumab-induced cardiotoxicity in HER2 positive breast cancer (BC) patients assisted in Oncologic Services of the Hospital de Clínicas and Asociación Española Primera en Salud. Methods: Retrospective observational study of HER2 positive BC patients from Hospital de Clínicas and Asociación Española under systemic therapy with Trastuzumab (TTZ) from January 2007 to December 2013. Results: The study included 69 patients, most were early BC, mean age was 50,1 years . 27% of the patients developed cardiotoxicity and 26 % of them developed symptomatic heart failure. All patients received adequate medical treatment and the most instances were reversible Conclusions: The frequency of cardiotoxicity observed in the study was 27% (IC 95 %: 16,27; 38,8). With the limitations of the study, it can verify reported similarities with other populations, oscillating frequency between 3.7 and 34%. However, the proportion of patients who had symptomatic heart failure (7%) was higher than that reported in the literatura wich is 4%. Cardiotoxicity was reversible in most patients.

Synthesis and antifungal activities of natural and synthetic biflavonoids.

The synthesis of some natural and synthetic biflavonoids was performed in good overall yields starting from readily available materials via high yielding aldol and Ullmann condensations. Some of these compounds, especially bichalcones, display an interesting activity against fungi, higher than that of the corresponding monomers.

Prospección química y microbiológica del bosque de galería del Río Uruguay / Chemical and microbiological prospecting woodland along the Uruguay River / Prospecção química e microbiológica do bosque de galeria do Rio Uruguai

La bioprospección es la búsqueda de información a partir de especies biológicas para su uso posterior en procesos de producción en diversos sectores. Ejemplos de esa información es la contenida en el material genético de todos los seres vivos, en los compuestos químicos que producen, en sus interacciones o en el conocimiento de las personas que de una manera u otra han estudiado a esos seres vivos. En este trabajo se presentan los resultados de la prospección botánica, química y microbiológica del bosque de galería del río Uruguay en la zona del rio Queguay, ecosistema con gran biodiversidad (comprende unas 200 especies) y de características poco comunes en el país dado su carácter subtropical. Se estudiaron 75 extractos provenientes de 31 especies pertenecientes a quince familias cubriendo de esa forma una gran biodiversidad.

Bioprospecting is the search for information from biological species for later use in production processes in various sectors. Examples of this information is contained in the genetic material of all living beings in the chemicals they produce, in their interactions or the knowledge of people who in one way or another, have studied these living beings. This paper presents the results of botanical, chemical and microbiological study of the gallery forest of the Uruguay River in the area of the Queguay river. This ecosystem presents great biodiversity (comprising about 200 species) and unusual features in the country given its subtropical character. We studied 75 extracts from 31 species belonging to fifteen families covering therefore a large biodiversity.

A bioprospecção é a bisca de informações a partir de espécies biológicas para seu uso posterior em processos de produção em diversos setores. Exemplos dessa informação está contida no material genético de todos os seres vivos, nas substâncias químicas que produzem, nas suas interações ou n o conhecimento das pessoas que, de uma maneira ou de outra, estudam os seres vivos. Neste trabalho é apresentado os resultados da prospecção botânica, química e microbiológica do bosque de galeria do Rio Uruguai na zona do Rio Queguay, ecosistema com grande biodiversidade, com cerca de duzentas espécies, e de características pouco comum no país dado seu caráter subtropical. Foram estudados 75 extratos provenientes de 31 espécies pertencentes a quinze famílias, cobrindo, assim, uma grande biodiversidade.

[Pendred's syndrome: a cause of goiter associated with deafness]. / Síndrome de Pendred: una causa de bocio relacionada con sordera.

Pendred's syndrome is an autosomal recessive disorder leading to congenital sensorineural hearing loss and a variable degree of goiter due to reduced iodine organification. The cause of this disease is dysfunction of an anion transporter protein located on the apical membrane of thyrocytes, called pendrin, which is also found in the kidney and cochlea. Molecular analysis of the gene is useful to identify other affected family members and provide proper genetic advice and early diagnosis in descendants. We present the cases of two siblings with sensorineural deafness who were diagnosed with Pendred's syndrome as adults because one of them consulted for goiter.

A new bioactive xanthanolide from Xanthium cavanillesii.

Development of new antimicrobial compounds against different microorganisms is becoming critically important, as infectious diseases are still one of the leading causes of death in the world. The pharmaceutical industry is searching for new lead compounds with novel chemical structures to overcome the increasing resistance to known antibiotics. Plants can be a useful source of these lead compounds. Xanthium cavanillesii Schouw, Asteraceae, grows wild in Uruguay and its infusion is used in traditional medicine as a skin antiseptic. We have previously reported studies on the antimicrobial activity of several extracts of X. cavanillesii against different microorganisms. In this work, we present the isolation and structural elucidation by spectroscopical methods of a sesquiterpene lactone with a new xanthanolide derived skeleton.

Initial antimicrobial activity studies of plants of the riverside forests of the southern Uruguay River / Estudos antimicrobianos preliminares de plantas da floresta ribeirinha do sul do rio Uruguai

Development of new antimicrobial compounds against different microorganisms is becoming critically important, as infectious diseases are still one of the leading causes of death in the world. Plants can be a useful source of these lead compounds. In this study, 66 extracts of 25 plants of the riverside forest of southern Uruguay River were studied for antimicrobial activity against Staphylococcus aureus, Listeria inocua, Escherichia coli, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Aspergillus niger and Candida albicans. Fifty-three of these extracts showed some kind of antimicrobial activity. Six of these (Eugenia mansoni, Eugenia repanda, Myrcianthes cisplatensis, Paullinia ellegans, Petunia sp and Ruprechtia laxiflora) presented activity against Mycobacterium tuberculosis with MIC values as low as 50 μg/mL.

As doenças infecciosas ainda são uma das principais causas de morte no mundo, sendo de significativa importância o desenvolvimento de novos compostos antimicrobianos contra diferentes microrganismos. As plantas podem ser uma boa fonte para direcionar a busca destes compostos. Neste estudo, 66 extratos de 25 plantas da floresta ribeirinha do sul do Rio Uruguai foram estudados para a atividade antimicrobiana contra o Staphylococcus aureus, Listeria inocua, Escherichia coli, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Aspergillus niger e Candida albicans. Cinqüenta e três destes extratos apresentaram algum tipo de atividade antimicrobiana. Seis (Eugenia mansoni, Eugenia repanda, Myrcianthes cisplatensis, Paullinia ellegans, Petunia sp e Ruprechtia laxiflora) apresentaram atividade contra o Mycobacterium tuberculosis com CIM de 50 μg/mL.

Prospección química del bosque de galería del río Uruguay / Triagem fitoquímica de plantas nativas do rio Uruguai / Phytochemical screening of the native forest of Uruguay River

Prospecção da biodiversidade é a exploração de um ecossistema para se obter informações sobre possíveis utilizações inovadoras em diferentes processos de produção humanos. Exemplos do tipo de informação pretendida são os dados científicos contidos no material genético dos organismos vivos, os compostos químicos produzidos por eles e suas interações ou no conhecimento das pessoas que já interagiram com eles de várias maneiras. Uma das ferramentas de prospecção da biodiversidade é a procura por informações químicas. Esta informação está contida nos compostos produzidos por muitos seres vivos para comunicar-se, defender-se e trocar informações, e eles são conhecidos como metabólitos secundários. Neste projeto, nós propomos a prospecção botânica, química e biológica da biodiversidade da mata ciliar da Bacia do Rio Uruguay próxima ao riacho Guaviyú. Este ecossistema particular apresenta uma substancial biodiversidade de aproximadamente 200 espécies com um perfil subtropical incomum.

Biodiversity prospecting is the exploration of an ecosystem for information regarding possible innovative uses in different human production processes. Examples of the kind of information sought are the scientific data contained in the genetic material of living organisms, the chemical compounds they produce and their interactions or in the knowledge of people that have interacted with them in various ways. One of the tools of biodiversity prospecting is searching for chemical information. This information is contained in the compounds produced by many living beings to communicate, to defend themselves and exchange information, and they are known as secondary metabolites. In this project, we propose the botanical, chemical and biological biodiversity prospecting of the gallery forest of the Uruguay River Basin near the Guaviyú stream. This particular ecosystem presents a substantial biodiversity of approximately 200 species with an unusual subtropical profile.