Myo-Inositol Levels Measured with MR Spectroscopy Can Help Predict Failure of Antiangiogenic Treatment in Recurrent Glioblastoma.

Background Patients with recurrent glioblastoma (GBM) are often treated with antiangiogenic agents, such as bevacizumab (BEV). Despite therapeutic promise, conventional MRI methods fail to help determine which patients may not benefit from this treatment. Purpose To use MR spectroscopic imaging (MRSI) with intermediate and short echo time to measure corrected myo-inositol (mI)normalized by contralateral creatine (hereafter, mI/c-Cr) in participants with recurrent GBM treated with BEV and to investigate whether such measurements can help predict survivorship before BEV initiation (baseline) and at 1 day, 4 weeks, and 8 weeks thereafter. Materials and Methods In this prospective longitudinal study (2016-2020), spectroscopic data on mI-a glial marker and osmoregulator within the brain-normalized by contralateral creatine in the intratumoral, contralateral, and peritumoral volumes of patients with recurrent GBM were evaluated. Area under the receiver operating characteristic curve (AUC) was calculated for all volumes at baseline and 1 day, 4 weeks, and 8 weeks after treatment to determine the ability of mI/c-Cr to help predict survivorship. Results Twenty-one participants (median age ± standard deviation, 62 years ± 12; 15 men) were evaluated. Lower mI/c-Cr in the tumor before and during BEV treatment was predictive of poor survivorship, with receiver operating characteristic analyses showing an AUC of 0.75 at baseline, 0.87 at 1 day after treatment, and 1 at 8 weeks after. A similar result was observed in contralateral normal-appearing tissue and the peritumoral volume, with shorter-term survivors having lower levels of mI/c-Cr. In the contralateral volume, a lower ratio of mI to creatine (hereafter, mI/Cr) predicted shorter-term survival at baseline and all other time points. Within the peritumoral volume, lower mI/c-Cr levels were predictive of shorter-term survival at baseline (AUC, 0.80), at 1 day after treatment (AUC, 0.93), and at 4 weeks after treatment (AUC, 0.68). Conclusion Lower levels of myo-inositol normalized by contralateral creatine within intratumoral, contralateral, and peritumoral volumes were predictive of poor survivorship and antiangiogenic treatment failure as early as before bevacizumab treatment. Adapting MR spectroscopic imaging alongside conventional MRI modalities conveys critical information regarding the biologic characteristics of tumors to help better treat individuals with recurrent glioblastoma. Clinical trial registration no. NCT02843230 © RSNA, 2021 Online supplemental material is available for this article.

Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring / Potencial antiproliferativo, genotóxico e mutagênico do aroma de chocolate sintético para alimentos

Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.

Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring / Potencial antiproliferativo, genotóxico e mutagênico do aroma de chocolate sintético para alimentos

Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.

Vitamina d: su implicancia en la infección por SARS-CoV-2 y su rol en el desarrollo y prevención de la enfermedad / Vitamin d: the implications in SARS-CoV-2 infection and its role in the development and prevention of the disease

Introducción: La pandemia del SARS-CoV-2 ha sido un desafío para la medicina en estos últimos años por su alta tasa de contagios y muertes asociadas. Progresivamente los investigadores han ido dilucidando vías de transmisión y manifestaciones clínicas más frecuentes, que han facilitado la detección el virus. Con el objetivo de optimizar la prevención y tratamiento en pacientes infectados, investigadores de todo el mundo han evaluado la importancia de la respuesta inmune frente al virus, destacando la acción de algunos inmunomoduladores, como por ejemplo, la vitamina D. Desarrollo: Tras invadir el organismo, el SARS-CoV-2 se une a receptores de las células epiteliales del tracto respiratorio, específicamente en el neumocito tipo II, disminuyendo la producción de surfactante y provocando una producción desregulada de citocinas proinflamatorias, principal responsable de los casos más severos. Se ha demostrado que la Vitamina D puede modular la respuesta inmune tras unirse a su receptor VDR, disminuyendo la liberación de citocinas proinflamatorias. Algunos estudios han determinado que el uso de suplementos de vitamina D en dosis altas pudieran producir efectos protectores frente a infecciones respiratorias agudas. Conclusión: Finalmente, pese a los estudios realizados que relacionan el déficit de vitamina D con casos más severos de COVID-19, aún se requiere más evidencia para recomendar suplementación.

Introduction: The SARS-CoV-2 pandemic has been a challenge for medicine in recent years, due to its high contagion rate and associated deaths. Researchers have progressively elucidated transmission methods and most frequent clinical manifestations, that helps the virus detection. With the objective of optimizing prevention and treatment of infected patients, researchers all over the world have evaluated the importance of the immune system response against the virus, highlighting some immunomodulators, such as vitamin D. Body: After SARS-CoV-2 invades the organism, it binds to the receptor located on the respiratory tract epithelial cells, specifically type 2 pneumocyte, decreasing surfactant production and increasing the production of pro inflammatory cytokines, being the main reason for severe cases. Vitamin D has been shown to modulate the immune response after binding to its receptor, decreasing the release of proinflammatory cytokines. Some studies have shown that vitamin D supplementation in high doses may produce protective effects against acute respiratory infections. Conclusion: Finally, even the studies that correlate vitamin D deficiency and COVID-19 severe cases, we still need more evidence to recommend Vitamin D supplementation.

Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring.

Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

Evaluación del efecto acaricida de Momordica charantia, Megaskepasma erythrochlamys y Gliricidia sepium sobre Rhipicephalus microplus / Acaricidal effect of Momordica charantia, Megaskepasma erythrochlamys and Gliricidia sepiumon the Rhipicephalus microplus

RESUMEN Objetivo. Se evaluó la actividad acaricida de Momordica charantia (Mc), Megaskepasma erythrochlamys (Me) y Gliricidia sepium (Gs) sobre Rhipicephalus microplus (Rm). Materiales y métodos. Se realizó la marcha fitoquímica preliminar de hojas del extracto metanólico de Mc (EMc), del extracto etanólico de Me (EMe) y del extracto acetónico de Gs (EGs) a través de la técnica de colorimetría y cromatografía en capa delgada (CCD). La actividad acaricida se realizó a través de pruebas in-vitro utilizando la prueba de inmersión de larvas (LIT) y la prueba de inmersión de adultos (AIT). Para las pruebas in-situ se usaron bovinos en pastoreo infestados naturalmente con garrapatas, utilizando las CL50 obtenidas en las pruebas in-vitro AIT; posteriormente las teleoginas se llevaron a incubación para evaluar su capacidad reproductiva. Resultados. Se determinó la presencia de varios grupos de metabolitos secundarios de interés acaricida. Se demostró el efecto acaricida de los extractos de las plantas sobre teleoginas; aunque sólo EGs mostró actividad larvicida. Los extractos a 160 mg/mL afectaron el ciclo de vida de Rm inhibiendo la ovoposición en un 46.9%, 66.1% y 84.03% (p<0.05) para EGs, EMc y EMe, respectivamente. Por otro lado, en las pruebas in situ se observó diferencia significativa (p<0.05) entre el tratamiento de EMc y EMe respecto a los grupos controles. Conclusiones. Los resultados obtenidos son prometedores para fortalecer la posibilidad de vinculación de los extractos de estas plantas dentro de planes integrados de control de garrapatas en sistemas de producción de bovinos.

ABSTRACT Objective. The acaricidal activity of Momordica charantia (Mc), Megaskepasma erythrochlamys (Me) and Gliricidia sepium (Gs) on Rhipicephalus microplus (Rm) was evaluated. Materials and methods. Preliminary phytochemical analysis of leaves of the methanolic extract of Mc (EMc), the ethanolic extract of Me (EMe) and the acetone extract of Gs (EGs) were carried out through the technique of colorimetry and thin layer chromatography (CCD). The acaricidal activity was performed through in-vitro tests using the larval immersion test (LIT) and the adult immersion test (AIT). For in-situ tests, grazing cattle naturally infested with ticks were used, using the LC50 obtained from the in-vitro AIT tests; later the teleogines were taken to incubation to evaluate their reproductive capacity. Results. The presence of several groups of secondary metabolites of acaricidal interest was determined. The acaricidal effect of the extracts of the plants on teleogines was demonstrated; although only EGs showed larvicidal activity. Extracts at 160 mg/mL affected the life cycle of Rm by inhibiting ovoposition in 46.9%, 66.1% and 84.03% (p<0.05) for EGs, EMc and EMe, respectively. On the other hand, the in-situ tests showed a significant difference (p<0.05) between the treatment of EMc and EMe with respect to the control groups. Conclusions. The results obtained are promising to strengthen the possibility of linking the extracts of these plants into integrated plans for the control of ticks in cattle systems.

Suplementación nutricional con omega 3 en retina: relación entre volumen y concentración en productos comerciales / Nutritional supplements with omega 3 in retinal disease: Relationship between volume and concentration in commercial products

OBJETIVO: Comparar las características morfométricas y la concentración de ácido docosahexaenoico (DHA) y ácido eicosapentanoico (EPA) de los diferentes suplementos nutricionales con omega 3 disponibles en el mercado para las dolencias de la retina. MATERIAL Y MÉTODOS: Estudio doble ciego, con observador único, de una muestra de diferentes comprimidos de suplementación de omega 3 comercializados en España. Se estudió tanto la longitud del comprimido como la concentración de omega 3 en total y de DHA y EPA por separado, utilizando para ello la cantidad proporcionada por el fabricante y el volumen de la cápsula calculado a partir del desarrollo de una fórmula específica para ello. RESULTADOS: Se incluyeron un total de 10 suplementos nutricionales diferentes. La media de omega 3 total, DHA y EPA fue de 383,10 ± 160,90; 210,72 ± 93,3 y 112,34 ± 140,98 mg, respectivamente. El tamaño medio de las cápsulas fue de 14,77 ± 0,19×8,13 ± 0,09 mm. La cápsula de menor tamaño fue la de Oftan mácula omega(R) (Esteve, Barcelona, España). Brudymacula(R) (Brudylab, Barcelona, España) y Brudyretina 1.5 g(R) (Brudylab, Barcelona, España) son las cápsulas con mayor cantidad de DHA. Nutrof omega(R) (Laboratorios Thea, Barcelona, España) es la que presenta menor concentración de omega 3, DHA y EPA por cápsula. CONCLUSIÓN: Existen diferencias importantes en cuanto a tamaño, volumen, cantidad y concentración de omega 3 y sus derivados entre los diferentes preparados comerciales. Solo el conocimiento de las características de los suplementos nutricionales nos permitirá la personalización de su indicación a nuestros pacientes

OBJECTIVE: To analyse the morphometric characteristics and the concentration of (docosahexaenoic acid) DHA and eicosapentaenoic acid (EPA) of the different nutritional supplements with omega 3 available on the market for retinal disease. MATERIAL AND METHODS: A double-blind study was conducted with a single observer, of the different omega 3 supplementation tablets sample marketed in Spain. The length of the tablet, the concentration of omega 3 in total, as well as DHA and EPA were studied separately using the amount provided by the manufacturer and the volume of the capsule calculated from the development of a specific formula for it. RESULTS: A total of 10 different nutritional supplements were included. The mean of total omega 3, DHA and EPA was 383.10 ± 160.90, 210.72 ± 93.3, and 112.34 ± 140.98 mg, respectively. The mean size of the capsules was 14.77 ± 0.19×8.13 ± 0.09 mm The smallest sized capsule was that of Oftan macula omega(R) (Esteve, Barcelona, Spain). Brudymacula(R) (Brudylab, Barcelona, Spain) and Brudyretina 1.5 g(R) (Brudylab, Barcelona, Spain) tablets contained more DHA, with Nutrof omega(R) (Thea Laboratories, Barcelona, Spain) having the lowest concentration of omega 3, DHA and EPA, per tablet. CONCLUSION: There are significant differences in size, volume, quantity, and concentration of omega 3 and its derivatives, between different commercial preparations. Only the knowledge of the characteristics of the nutritional supplements will enable us to provide a more personalised indication of their use for our patients

Nutritional supplements with omega 3 in retinal disease: Relationship between volume and concentration in commercial products. / Suplementación nutricional con omega 3 en retina: relación entre volumen y concentración en productos comerciales.

OBJECTIVE: To analyse the morphometric characteristics and the concentration of (docosahexaenoic acid) DHA and eicosapentaenoic acid (EPA) of the different nutritional supplements with omega 3 available on the market for retinal disease. MATERIAL AND METHODS: A double-blind study was conducted with a single observer, of the different omega 3 supplementation tablets sample marketed in Spain. The length of the tablet, the concentration of omega 3 in total, as well as DHA and EPA were studied separately using the amount provided by the manufacturer and the volume of the capsule calculated from the development of a specific formula for it. RESULTS: A total of 10 different nutritional supplements were included. The mean of total omega 3, DHA and EPA was 383.10±160.90, 210.72±93.3, and 112.34±140.98mg, respectively. The mean size of the capsules was 14.77±0.19×8.13±0.09mm The smallest sized capsule was that of Oftan macula omega® (Esteve, Barcelona, Spain). Brudymacula® (Brudylab, Barcelona, Spain) and Brudyretina 1.5 g® (Brudylab, Barcelona, Spain) tablets contained more DHA, with Nutrof omega® (Thea Laboratories, Barcelona, Spain) having the lowest concentration of omega 3, DHA and EPA, per tablet. CONCLUSION: There are significant differences in size, volume, quantity, and concentration of omega 3 and its derivatives, between different commercial preparations. Only the knowledge of the characteristics of the nutritional supplements will enable us to provide a more personalised indication of their use for our patients.

Impacto de la implantación de un Código Sepsis intrahospitalario en la prescripción de antibióticos y los resultados clínicos en una unidad de cuidados intensivos / Impact of the implementation of a Sepsis Code hospital protocol in antibiotic prescription and clinical outcomes in an intensive care unit

INTRODUCCIÓN: Se analiza el impacto de un Código Sepsis intrahospitalario sobre el uso y consumo de antibióticos, la estancia hospitalaria y la mortalidad. DISEÑO: Estudio retrospectivo cuasiexperimental observacional. Ámbitos: UCI polivalente de 11 camas en un hospital de tercer nivel. PACIENTES: Pacientes ingresados en UCI con diagnóstico de sepsis grave o shock séptico. INTERVENCIONES: Un grupo postintervención (POST-CS) (septiembre 2012-agosto 2013) se comparó con un grupo histórico (PRE-CS) control (enero-diciembre 2010). VARIABLES: Tipo de tratamiento antibiótico, estrategia terapéutica antibiótica y resultados clínicos. El consumo de antibióticos fue expresado en dosis diarias definidas/100 estancias. RESULTADOS: Se incluyeron 42 pacientes con sepsis grave/shock séptico en el grupo POST-CS y 50 en el grupo PRE-CS. El consumo total de antibióticos (dosis diarias definidas) fue similar en ambos grupos. En el grupo POST-CS la tasa de desescalamiento fue significativamente mayor (75 vs. 30,8%, p < 0,005), mientras que la prescripción de antibióticos de uso restringido fue significativamente menor (74 vs. 52%, p = 0,031). Finalmente, el grupo de pacientes POST-CS presentó una mortalidad intrahospitalaria y a 28 días significativamente menor (23 vs. 44% [p = 0,035] y 31 vs. 56% [p = 0,01]), así como una disminución de la estancia en UCI en el límite de la significación estadística (5 vs. 10,5 días, p = 0,05). CONCLUSIÓN: La implantación de un programa de Código Sepsis intrahospitalario se asoció a una mejor utilización del tratamiento antibiótico, incrementándose significativamente el desescalamiento terapéutico y disminuyendo el uso de antibióticos de uso restringido, así como a una significativa disminución de la mortalidad y una tendencia hacia una menor estancia en UCI

INTRODUCTION: A study was performed to analyze the impact of an in-hospital Sepsis Code (SC) program on use of antibiotic and clinical outcomes. DESIGN: Quasi-experimental observational retrospective study. SETTING: Polyvalent 11 beds ICU belonging to a tertiary Universitary hospital. PATIENTS: Patients admitted consecutively to the ICU with diagnosis of severe sepsis or septic shock. INTERVENTIONS: A post intervention group (POST-SC) (September 2012-August 2013) was compared with a historical group (PRE-SC) used as control (January-December 2010). VARIABLES: Antibiotic treatment, therapeutic antibiotic strategy, mortality and length of stay. Antibiotic consumption was expressed as defined daily doses (DDD)/ 100 stays. RESULTS: 42 patients with SS/SS in POST-SC group and 50 patients in PRE-SC group were consecutively recluted and further analyzed. Total antibiotic consumption (DDD) was similar in both groups. Rate of de-escalation therapy was significantly higher in POST-SC group (75% vs 30,8%, p < 0,005) while prescription of restricted antibiotics was significantly lower (74% vs 52%, p = 0,031). Finally POST-SC patients showed a significantly decrease in hospital and 28 days mortality rates [23% vs 44%, (p = 0,035) and 31% vs 56% (p = 0,014) respectively] as well as a reduction in ICU length of stay compared to PRE-SC cohort (5 days vs 10,5 days, p = 0,05). CONCLUSION: The implementation of a Sepsis Code-hospital protocol is associated to an improvement in the management of antibiotic therapy with a significant increase in de-escalation therapy and lesser utilization of restricted use antibiotics, as well as a significant reduction in mortality, and a tendency towards shorter ICU length stay

Antitumoral gene-based strategy involving nitric oxide synthase type III overexpression in hepatocellular carcinoma.

Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoblastoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. The first-generation adenoviruses were designed to overexpress NOS-3 or green fluorescent protein, and luciferase complementary DNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenovirus and Hepa 1-6 cells were used for in vitro and in vivo experiments. Adenoviruses were administered through the tail vein 2 weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8, -9 and -3 activities in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by Nω-nitro-l-arginine methyl ester hydrochloride, p53 and CD95 small interfering RNA. AFP-NOS-3/RSV-luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

Essential oils from clove affect growth of Penicillium species obtained from lemons.

Continuous use of fungicides to control citrus postharvest diseases has led to increasing resistant strains of pathogens. Since the appearance of fungicide resistance has become an important factor in limiting the efficacy fungicide treatments, new studies have been needed in order to improve control methods. There is a growing consumer's concern about the possible harmful effects of synthetic fungicides on the human health and the environment. Alternatives to synthetic fungicides for citrus decay control include essential oils. These compounds are known for their natural components and they are searched for potential bioactive plant extracts against fungi. In this study, two isolates of P. digitatum and P. italicum each were collected from lemon fruits affected by green and blue mould, respectively. Isolates were purified in potato dextrose agar (PDA) in order to separate the two species which we are demonstrated that they commonly grow together in nature. In vitro assays, in which isolates were grown at 26 degrees C on Petri dishes containing PDA for up to 17 days, were carried out by pouring several doses of essential oils from clove (Syzygium aromaticum L.) on PDA to obtain the following concentrations (v/v): 1.6; 8, 40, 200 and 500 microL L(-1) + tween 80 (0.1 mL L(-1)). Mycelial growth curves and growth, conidiation, mass of aerial mycelium and conidial size were measured. Penicillium isolates showed a slight degree of variability in their growth kinetics, depending on the isolate. 500 microL L(-1) inhibited the growth of all the isolates, whereas concentrations lower than 40 microL L(-1) slightly increased the growth. 200 microL L(-1) reduced both growth and conidiation in all isolates. Aerial mycelium of P. digitatum was not affected by clove, whereas reduced the mass of mycelium of P. italicum at concentrations higher than 8 microL L(-1). In vivo experiment was carried out inoculating a drop of an extract of conidia with a hypodermal syringe though a puncture reaching the albedo. Fruits inoculated were stored at 23 degrees C and 74% RH for 25 days. Imazalil was used as a fungicide control. The treatment composed by 25% of commercial dose of imazalil plus 200 microL L(-1) of clove was the best to reduce decay until 10% of commercial dose of imazalil. In addition, this experimental treatment significantly reduced conidiation, therefore could inhibit the decay dispersion during storage. This suggests that treatments based on both imazalil and clove essential oils may have potential effect in controlling both green and blue mould.

Antiangiogenic agents and endothelin antagonists in advanced castration resistant prostate cancer.

Despite multiple advances in prostate cancer therapy, treatment options for castration resistant disease are very limited. While data from recent studies are encouraging, there is no drug that has significantly improved results of standard chemotherapy. Some of the most consistent results are provided by antiangiogenic agents, showing high response rates and manageable toxicity. We describe some of the main therapeutic angiogenesis inhibitors in metastatic castration resistant prostate cancer. These agents include vascular endothelial growth factor inhibitors, tyrosine kinase inhibitors, antiangiogenic and inmunomodulatory agents and endothelin receptor antagonists.

Alterations in brain metabolism during the first year of HIV infection.

Migration of both uninfected and infected monocytes into the brain during acute HIV infection likely initiates metabolic changes that can be observed with magnetic resonance spectroscopy (MRS). Herein, we measured changes in brain metabolism during the first year of HIV infection and examined the relationship of these metabolite levels to CD16+ monocyte populations measured in the blood. MRS was performed on nine HIV+ subjects identified during acute HIV infection and nine seronegative control subjects. HIV+ subjects were examined within 90 days of an indeterminate Western blot, then again 2 and 6 months later, during early infection. Blood samples were collected for plasma viral RNA and monocyte subset quantification. HIV+ subjects were identified with acute viral ailment and did not display severe cognitive deficits such as dementia or minor cognitive motor disorder. Changes in lipid membrane metabolism (choline levels) in the frontal cortex and white matter were observed during the initial year of HIV infection. Greater numbers of CD16+ monocytes were associated with lower N-acetylaspartate levels and higher choline levels in the brain. These results suggest that HIV infection induces metabolic changes in the brain early during infection and that these changes may be related to monocyte dynamics in the periphery.

[Antimicrobial susceptibility, capsular serotypes and clonal relationship of invasive streptococcus pneumoniae isolates in adult population of the Bio-Bio region, Chile. 2005-2006]. / Susceptibilidad antimicrobiana, serotipos capsulares y relación clonal entre cepas invasoras de streptococcus pneumoniae aisladas de pacientes adultos de la Región del Bío-Bío, Chile. Periodo 2005-2006.

Streptococcus pneumoniae infections constitute a public health problem. In our country there is scarce information regarding isolates from bacteraemic episodes in adult population. The antibiotic susceptibility, serotypes and clonal relationship of 56 isolates of S. pneumoniae from adult patients with bacteraemic infections in Concepcion-Talcahuano, Bio-Bio Region, Chile, were studied. Resistance to tetracycline (21.4%), trimethoprim/ sulfamethoxazole (18%), erythromycin (18%), chloramphenicol (7%) and 1 penicillin resistant isolate from a meningeal focus (2%) was found. Also, all the isolates were susceptible to cefotaxime, levofloxacin, moxifloxacin and vancomycin. A wide variety of capsular serotypes was demonstrated, with predominance of serotypes 1, 5, 23F, 7F and 3. The macrorestriction analysis by pulse field electrophoresis revealed 31 electrophoretic patterns and 12 clonal groups, discarding a predominant clone. According to the results, at least, 80% of the S. pneumoniae serotypes isolated from bacteraemic adult patients are included in the available commercial vaccine.

Estudio comparativo entre la ecografía y la neuroestimulación en el aprendizaje del bloqueo ciático poplíteo posterior / No disponible

Introducción: La anestesia regional guiada mediante ecografía es un campo en rápido crecimiento y su docencia está siendo objeto de estudio. Este trabajo compara la realización del bloqueociático-poplíteo posterior mediante ecografía (ECO) o neuroestimulación (NE) por médicos especialistas en formación. Material y método: Se realizó un estudio prospectivo aleatorizado, con los pacientes distribuidos en dos grupos: el grupo ECO mediante técnica guiada con ecografía; el grupo NE empleó referencias de anatomía de superficie más neuroestimulación, considerando válida una respuesta muscular entre 0.2-0.5 mA. Las variables registradas fueron: tiempo de ejecución, número de intentos, número de punciones vasculares y de parestesias, así como éxito del bloqueo. Las técnicas fueron realizadas por un único especialista en formación, sin experiencia previa en anestesia regional ni ecografía, bajo la supervisión de un anestesiólogo experto. Resultados: Se obtuvieron 19 casos (ECO: 10; NE: 9). El grupo ECO requirió menos tiempo que el NE (108,5-338,6 sg, IC95%; p < 0,005) y menor número de intentos, 1,6 ± 0,7 para ECO, frente 9,5 ± 3,8 para NE (media ± ds; p < 0,05), obteniendo éxito en primera punción en un 80% para ECO frente a al11,1% para NE (p < 0,05). El grupo ECO asoció una menor incidencia de punciones vasculares y de parestesias. La tasa de éxito de la técnica fue del 100% en el grupo ECO, frente al 67,7% en NE. Conclusiones: Estos resultados sugieren que el empleo de ecografía en el aprendizaje del bloqueo poplíteo posterior por especialistas en formación, pudiera facilitar la ejecución de la técnica, asociar menor morbilidad y proporcionar mayor éxito del bloqueo nervioso periférico (AU)

Background: The ultrasound-guided regional anesthesia is a rapidly growing field and its teaching is being studied. This paper compares the performance of the posterior popliteal sciatic blockadeby ultrasound (ECO) with that of neurostimulation (NS) carried out by specialist doctors in training. Material and method: A prospective randomized trial was conducted with patients divided into two groups: group ECO treated with ultrasound-guided technique, and group NE in which surface anatomy and neurostimulation references were used, considering valid a muscle response between 0.2 and 0.5 mA. The variables recorded were run time, number of attempts, number of vascular punctures and paresthesias, and success of the blockade. The techniques were performed by a single training specialist without prior experience in regional anesthesia and ultrasound, under the supervision of an expert anaesthesiologist. Results: 19 cases were obteined (ECO: 10, NE 9), the ECO required less time than NE (108,5-338,6 sg, 95%, p < 0.005)and fewer attempts, 1.6 ± 0.7 for ECO, versus 9.5 ± 3.8 for NE(mean ± sd, p < 0.05), and success was achieved on first puncture on 80% of attempts in ECO group, versus 11.1% in NE group (p< 0.05). The ECO group associated a lower incidence of vascular puncture and paresthesia. The success rate of the technique was 100% in the ECO group, versus 67,7% in NE group. Conclusions: These results suggest that the use of ultrasound in the posterior popliteal block learning by training specialists could facilitate the implementation of the technique, and provideless morbidity associated with more successful peripheral nerveblock (AU)

[Pentosan polysulfate sodium prevents kidney morphological changes and albuminuria in rats with type 1 diabetes]. / El pentosán polisulfato de sodio previene las alteraciones morfológicas renales y la albuminuria en ratas con diabetes tipo 1.

Decreased levels of glycosaminoglycans (GAGs) have been observed in the kidney and other organs, in human and animal models of diabetes. Long-term administration of heparins and other glycosaminoglycans has demonstrated a beneficial effect on morphological and functional kidney abnormalities in diabetic rats. We assessed the effect of pentosan polysulfate sodium (PPS), a semi-synthetic glycosaminoglycan with low anticoagulant activity, on kidney involvement in streptozotocin diabetic rats. Diabetes was induced in male Sprague-Dawley rats by i.v. administration of streptozotocin (STZ). Animals were randomly allocated to three groups: C = control, STZ and STZ + PPS = pretreated with PPS (15 mg/kg, s.c.). After three months of follow-up, blood and 24 h-urine samples were obtained, the animals were sacrificed and the kidney microdissected for morphometric analysis. Urinary albumin excretion was markedly increased in untreated diabetic rats (C = 0.26 ± 0.03 vs STZ = 7.75 ± 1.8 mg/24 h) and PPS treatment partially prevented the albumin rise (3.7 ± 0.7 mg/24 h), without affecting the metabolic control HbA1c (C = 3.6 ± 1.7; STZ = 8.82 ± 0.47; STZ + PPS = 8.63 ± 0.54). Electron microscope observation revealed typical renal lesions described in experimental diabetes (STZ group). PPS administration prevents the tubular basement membrane thickening and the loss of cytoarchitecture induced by experimental diabetes. Our data demonstrate that long-term administration of PPS has a favourable effect on morphological and functional abnormalities in kidneys of diabetic rats and suggests a potential therapeutic use for this compound.

Susceptibilidad antimicrobiana, serotipos capsulares y relación clonal entre cepas invasoras de Streptococcus pneumoniae aisladas de pacientes adultos de la Región del Bío-Bío, Chile: Período 2005-2006 / Antimicrobial susceptibility, capsular serotypes and clonal relationship of invasive Streptococcus pneumoniae isolates in adult population of the Bio-Bio Region, Chile: 2005-2006

Las infecciones ocasionadas por Streptococcus pneumoniae constituyen un problema de salud pública. En nuestro país existe escasa información sobre aislados de procesos bacteriémicos en población adulta. Se estudió la susceptibilidad, serotipos y relación clonal de 56 aislados de S. pneumoniae desde hemocultivos, entre enero 2005 y agosto 2006, de pacientes adultos de la intercomuna Concepción-Talcahuano, Región del Bío-Bío, Chile. Se encontró resistencia a tetraciclina (21,4 por ciento), cotrimoxazol (18 por ciento), eritromicina (18 por ciento), cloranfenicol (7 por ciento) y a penicilina en un solo aislado procedente de un foco meníngeo (2 por ciento). La totalidad mostró susceptibilidad a cefotaxima, levofloxacina, moxifloxacina y vancomicina. Se demostró una amplia variedad de serotipos capsulares, con predominio de los serotipos 1, 5, 23F, 7F y 3. El análisis de macrorestricción y electroforesis en campo pulsado reveló 31 patrones electroforéticos con 12 grupos clona-les, descartando un clon predominante. De acuerdo a los resultados, al menos 80 por ciento de los serotipos de aislados de S. pneumoniae de procesos bacteriémicos están incluidos en la vacuna comercial disponible.

Streptococcus pneumoniae infections constitute a public health problem. In our country there is scarce information regarding isolates from bacteraemic episodes in adult population. The antibiotic susceptibility, sero-types and clonal relationship of 56 isolates of S. pneumoniae from adult patients with bacteraemic infections in Concepcion-Talcahuano, Bio-Bio Region, Chile, were studied. Resistance to tetracycline (21.4 percent), trimethoprim/ sulfamethoxazole (18 percent), erythromycin (18 percent), chloramphenicol (7 percent) and 1 penicillin resistant isolate from a meningeal focus (2 percent) was found. Also, all the isolates were susceptible to cefotaxime, levofloxacin, moxifloxacin and vancomycin. A wide variety of capsular serotypes was demonstrated, with predominance of serotypes 1, 5, 23F, 7F and 3. The macrorestriction analysis by pulse field electrophoresis revealed 31 electrophoretic patterns and 12 clonal groups, discarding a predominant clone. According to the results, at least, 80 percent of the S. pneumoniae serotypes isolated from bacteraemic adult patients are included in the available commercial vaccine.

[An analysis of the value of bowel preparation for preventing postoperative complications in endoscopic surgery]. / Análisis de la utilidad de la preparación intestinal en la prevención de complicaciones postoperatorias en cirugía endoscópica.

OBJECTIVES: To assess the relationship between mechanical preparation of the bowel before endourological surgery and the occurrence of postoperative complications. MATERIALS AND METHODS: A prospective, randomized study was conducted in 162 patients undergoing TUR of the bladder, TURP, and lase adenomectomy from October 2008 to February 2009. No patient was excluded. An enema was administered before surgery to 66 patients, but not to the remaining patients. Variables analyzed included occurrence of urinary tract infection (UTI), fever, acute urinary retention (AUR), postoperative need for enemas or laxatives, surgical field contamination, and mean hospital stay. A descriptive analysis, a means comparison (t test), and a Chi-square test were performed. RESULTS: Mean patient age was 70.5 years (SD+/-10.62), and mean hospital stay 4.8 days (SD+/-3.9). UTI occurred in 6.2% of patients, fever in 3.1%, and AUR in 1.2%, and 15.4% of patients required enemas or laxatives. Fecal contamination of the surgical field was found in one patient (0.6%). There were no statistically significant differences between the study groups in the variables analyzed. CONCLUSIONS: In our series, bowel preparation using enema has shown no value for decreasing postoperative complications of endourological surgery.

Chronic fluoxetine treatment induces structural plasticity and selective changes in glutamate receptor subunits in the rat cerebral cortex.

It has been postulated that chronic administration of antidepressant drugs induces delayed structural and molecular adaptations at glutamatergic forebrain synapses that might underlie mood improvement. To gain further insight into these changes in the cerebral cortex, rats were treated with fluoxetine (flx) for 4 weeks. These animals showed decreased anxiety and learned helplessness. N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit levels (NR1, NR2A, NR2B, GluR1 and GluR2) were analysed in the forebrain by both western blot of homogenates and immunohistochemistry. Both methods demonstrated an upregulation of NR2A, GluR1 and GluR2 that was especially significant in the retrosplenial granular b cortex (RSGb). However, when analysing subunit content in postsynaptic densities and synaptic membranes, we found increases of NR2A and GluR2 but not GluR1. Instead, GluR1 was augmented in a microsomal fraction containing intracellular membranes. NR1 and GluR2 were co-immunoprecipitated from postsynaptic densities and synaptic membranes. In the immunoprecipitates, NR2A was increased while GluR1 was decreased supporting a change in receptor stoichiometry. The changes of subunit levels were associated with an upregulation of dendritic spine density and of large, mushroom-type spines. These molecular and structural adaptations might be involved in neuronal network stabilization following long-term flx treatment.