Transcriptomic analysis of primary nasal epithelial cells reveals altered interferon signalling in preterm birth survivors at one year of age.

Introduction: Many survivors of preterm birth (<37 weeks gestation) have lifelong respiratory deficits, the drivers of which remain unknown. Influencers of pathophysiological outcomes are often detectable at the gene level and pinpointing these differences can help guide targeted research and interventions. This study provides the first transcriptomic analysis of primary nasal airway epithelial cells in survivors of preterm birth at approximately 1 year of age. Methods: Nasal airway epithelial brushings were collected, and primary cell cultures established from term (>37 weeks gestation) and very preterm participants (≤32 weeks gestation). Ex vivo RNA was collected from brushings with sufficient cell numbers and in vitro RNA was extracted from cultured cells, with bulk RNA sequencing performed on both the sample types. Differential gene expression was assessed using the limma-trend pipeline and pathway enrichment identified using Reactome and GO analysis. To corroborate gene expression data, cytokine concentrations were measured in cell culture supernatant. Results: Transcriptomic analysis to compare term and preterm cells revealed 2,321 genes differentially expressed in ex vivo samples and 865 genes differentially expressed in cultured basal cell samples. Over one third of differentially expressed genes were related to host immunity, with interferon signalling pathways dominating the pathway enrichment analysis and IRF1 identified as a hub gene. Corroboration of disrupted interferon release showed that concentrations of IFN-α2 were below measurable limits in term samples but elevated in preterm samples [19.4 (76.7) pg/ml/µg protein, p = 0.03]. IFN-γ production was significantly higher in preterm samples [3.3 (1.5) vs. 9.4 (17.7) pg/ml/µg protein; p = 0.01] as was IFN-ß [7.8 (2.5) vs. 13.6 (19.5) pg/ml/µg protein, p = 0.01]. Conclusion: Host immunity may be compromised in the preterm nasal airway epithelium in early life. Altered immune responses may lead to cycles of repeated infections, causing persistent inflammation and tissue damage which can have significant impacts on long-term respiratory function.

Trasplante cardíaco por hemocromatosis. Caso pediátrico / Cardiac transplantation due to hemochromatosis. A pediatric case report

La hemocromatosis es una enfermedad caracterizada por el excesivo depósito de hierro en múltiples órganos, entre ellos hígado, páncreas, piel y corazón. La infiltración de este último es un importante factor en morbilidad y mortalidad. Presentamos un caso de un paciente pediátrico con insuficiencia cardíaca terminal que ameritó trasplante cardíaco, que resultó sin complicaciones. Posterior a la cirugía, mostró mejoría bioquímica y clínica, lo que influyó positivamente en su calidad de vida y prolongó su supervivencia.

Hemochromatosis is a disease characterized by excess iron stores in multiple organs, including the liver, pancreas, skin, and heart. The infiltration of the heart is an important factor in morbidity and mortality. Here we describe the case of a pediatric patient with end-stage heart failure who required a heart transplantation, with no complications. After the surgery, she showed biochemical and clinical improvement, with a positive impact on her quality of life and a prolonged survival.

Cardiac transplantation due to hemochromatosis. A pediatric case report. / Trasplante cardíaco por hemocromatosis. Caso pediátrico.

Hemochromatosis is a disease characterized by excess iron stores in multiple organs, including the liver, pancreas, skin, and heart. The infiltration of the heart is an important factor in morbidity and mortality. Here we describe the case of a pediatric patient with end-stage heart failure who required a heart transplantation, with no complications. After the surgery, she showed biochemical and clinical improvement, with a positive impact on her quality of life and a prolonged survival.

La hemocromatosis es una enfermedad caracterizada por el excesivo depósito de hierro en múltiples órganos, entre ellos hígado, páncreas, piel y corazón. La infiltración de este último es un importante factor en morbilidad y mortalidad. Presentamos un caso de un paciente pediátrico con insuficiencia cardíaca terminal que ameritó trasplante cardíaco, que resultó sin complicaciones. Posterior a la cirugía, mostró mejoría bioquímica y clínica, lo que influyó positivamente en su calidad de vida y prolongó su supervivencia.

[Ovarian reserve and premature ovarian failure in girls and adolescents after hematopoietic stem cell transplantation]. / Reserva ovárica y falla ovárica prematura en niñas y adolescentes postrasplante de progenitores hematopoyéticos.

INTRODUCTION: The increased survival of children and adolescents after Stem Cell Transplantation (SCT) has allowed us to gain a better understanding of the late effects that this procedure might have. OBJECTIVE: to measure ovarian function and reserve after SCT. PATIENTS AND METHOD: A descriptive, observatio nal, and cross-sectional study of girls and adolescents with SCT between 1999 and 2011. External gynecologic examination, hormone tests, and abdominal gynecologic ultrasound were performed, observing pubertal development pre-SCT. The following data from the clinical record were recorded: baseline pathology, type of conditioning, use of radiotherapy in conditioning, age at the time of SCT, and history of acute or chronic graft-versus-host disease (GVHD). Hormonal tests included follicle- stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin (PRL), thyroid-stimula ting hormone (TSH), free thyroxine, total testosterone, sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH). Statistical analysis included the chi-square or Fisher's Exact test with a p-value < 0.05. RESULTS: 41 patients were evaluated. The median age at the time of SCT was 6.8 years (1.5-14.1) and the median age at evaluation was 14.8 years (range: 4-25.4 years). 93% of the transplants were in patients with oncological disease and with myeloablative conditioning regimens. All patients presented decreased ovarian reserve, and 72% showed Premature Ovarian Failure (POF). CONCLUSIONS: All patients had decreased ovarian reserve and most of them had a high prevalence of POF. Before SCT, a gynecological evaluation and subsequent follow-up for hormone monitoring and initiation of hormone replacement are essential.

Pseudomonas aeruginosa modulates neutrophil granule exocytosis in an in vitro model of airway infection.

A population of neutrophils recruited into cystic fibrosis (CF) airways is associated with proteolytic lung damage, exhibiting high expression of primary granule exocytosis marker CD63 and reduced phagocytic receptor CD16. Causative factors for this population are unknown, limiting intervention. Here we present a laboratory model to characterize responses of differentiated airway epithelium and neutrophils following respiratory infection. Pediatric primary airway epithelial cells were cultured at the air-liquid interface, challenged individually or in combination with rhinovirus (RV) and Pseudomonas aeruginosa, then apically washed with medical saline to sample epithelial infection milieus. Cytokine multiplex analysis revealed epithelial antiviral signals, including IP-10 and RANTES, increased with exclusive RV infection but were diminished if P. aeruginosa was also present. Proinflammatory signals interleukin-1α and ß were dominant in P. aeruginosa infection milieus. Infection washes were also applied to a published model of neutrophil transmigration into the airways. Neutrophils migrating into bacterial and viral-bacterial co-infection milieus exhibited the in vivo CF phenotype of increased CD63 expression and reduced CD16 expression, while neutrophils migrating into milieus of RV-infected or uninfected cultures did not. Individually, bacterial products lipopolysaccharide and N-formylmethionyl-leucyl-phenylalanine and isolated cytokine signals only partially activated this phenotype, suggesting that additional soluble factors in the infection microenvironment trigger primary granule release. Findings identify P. aeruginosa as a trigger of acute airway inflammation and neutrophil primary granule exocytosis, underscoring potential roles of airway microbes in prompting this neutrophil subset. Further studies are required to characterize microbes implicated in primary granule release, and identify potential therapeutic targets.

Chromosome Number, Ploidy Level, and Nuclear DNA Content in 23 Species of Echeveria (Crassulaceae).

Echeveria is a polyploid genus with a wide diversity of species and morphologies. The number of species registered for Echeveria is approximately 170; many of them are native to Mexico. This genus is of special interest in cytogenetic research because it has a variety of chromosome numbers and ploidy levels. Additionally, there are no studies concerning nuclear DNA content and the extent of endopolyploidy. This work aims to investigate the cytogenetic characteristics of 23 species of Echeveria collected in 9 states of Mexico, analyzing 2n chromosome numbers, ploidy level, nuclear DNA content, and endopolyploidy levels. Chromosome numbers were obtained from root tips. DNA content was obtained from the leaf parenchyma, which was processed according to the two-step protocol with Otto solutions and propidium iodide as fluorochrome, and then analyzed by flow cytometry. From the 23 species of Echeveria analyzed, 16 species lacked previous reports of 2n chromosome numbers. The 2n chromosome numbers found and analyzed in this research for Echeveria species ranged from 24 to 270. The range of 2C nuclear DNA amounts ranged from 1.26 pg in E. catorce to 7.70 pg in E. roseiflora, while the 1C values were 616 Mbp and 753 Mbp, respectively, for the same species. However, differences in the level of endopolyploidy nuclei were found, corresponding to 4 endocycles (8C, 16C, 32C and 64C) in E. olivacea, E. catorce, E. juarezensis and E. perezcalixii. In contrast, E. longiflora presented 3 endocycles (8C, 16C and 32C) and E. roseiflora presented 2 endocycles (8C and 16C). It has been suggested that polyploidization and diploidization processes, together with the presence of endopolyploidy, allowed Echeveria species to adapt and colonize new adverse environments.

Seasonal evidences of microplastics in environmental matrices of a tourist dominated urban estuary in Gulf of Mexico, Mexico.

The study evaluated the spatial and seasonal variations of microplastic abundances in water, sediments, and commercial fishes of a semi-urban tourist impacted estuary in the Gulf of Mexico, Mexico. The prevalence of microplastics (MPs) elucidated diffuse sources namely long-range transport, domestic, agricultural, fishing, industrial and recreational activities and the local climatic conditions. Seasonally, the mean abundances of MPs in both water and sediments were high during Nortes (strong winds) followed by the dry and rainy seasons. Overall, black and blue colored MPs dominated the region and all the recovered plastics were fibers. The commercial fishes (n = 187) contained 881 MPs in their gastrointestinal tracts, suggesting that the food web of the estuary is highly prone to microplastic contamination. SEM images of extracted plastic fibers presented surface morphologies that are impacted by physical strains. Further, the elemental characterization of fibers using EDX displayed significant peaks of Al, As, Cl, Cr, Cu, Pb, and Zn that were used as additives during the production of plastics. The main types of polymers included low-density polyethylene, polyester, polypropylene, polycarbonate, rayon, polyvinyl chloride, polyacrylonitrile, polyamide, nylon and polyethylene terephthalate. MP abundances demonstrated in this study elucidate that estuaries are a major conduit for land-derived plastics to the ocean and the results will aid in implementing remedial/clean up actions of the estuary for better conservation of the ecosystem.

Microbiomic Analysis on Low Abundant Respiratory Biomass Samples; Improved Recovery of Microbial DNA From Bronchoalveolar Lavage Fluid.

In recent years the study of the commensal microbiota is driving a remarkable paradigm shift in our understanding of human physiology. However, intrinsic technical difficulties associated with investigating the Microbiomics of some body niches are hampering the development of new knowledge. This is particularly the case when investigating the functional role played by the human microbiota in modulating the physiology of key organ systems. A major hurdle in investigating specific Microbiome communities is linked to low bacterial density and susceptibility to bias caused by environmental contamination. To prevent such inaccuracies due to background processing noise, harmonized tools for Microbiomic and bioinformatics practices have been recommended globally. The fact that the impact of this undesirable variability is negatively correlated with the DNA concentration in the sample highlights the necessity to improve existing DNA isolation protocols. In this report, we developed and tested a protocol to more efficiently recover bacterial DNA from low volumes of bronchoalveolar lavage fluid obtained from infants and adults. We have compared the efficiency of the described method with that of a commercially available kit for microbiome analysis in body fluids. We show that this new methodological approach performs better in terms of extraction efficiency. As opposed to commercial kits, the DNA extracts obtained with this new protocol were clearly distinguishable from the negative extraction controls in terms of 16S copy number and Microbiome community profiles. Altogether, we described a cost-efficient protocol that can facilitate microbiome research in low-biomass human niches.

Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis.

Early-life viral infections are responsible for pulmonary exacerbations that can contribute to disease progression in young children with cystic fibrosis (CF). The most common respiratory viruses detected in the CF airway are human rhinoviruses (RV), and augmented airway inflammation in CF has been attributed to dysregulated airway epithelial responses although evidence has been conflicting. Here, we exposed airway epithelial cells from children with and without CF to RV in vitro. Using RNA-Seq, we profiled the transcriptomic differences of CF and non-CF airway epithelial cells at baseline and in response to RV. There were only modest differences between CF and non-CF cells at baseline. In response to RV, there were 1,442 and 896 differentially expressed genes in CF and non-CF airway epithelial cells, respectively. The core antiviral responses in CF and non-CF airway epithelial cells were mediated through interferon signaling although type 1 and 3 interferon signaling, when measured, were reduced in CF airway epithelial cells following viral challenge consistent with previous reports. The transcriptional responses in CF airway epithelial cells were more complex than in non-CF airway epithelial cells with diverse over-represented biological pathways, such as cytokine signaling and metabolic and biosynthetic pathways. Network analysis highlighted that the differentially expressed genes of CF airway epithelial cells' transcriptional responses were highly interconnected and formed a more complex network than observed in non-CF airway epithelial cells. We corroborate observations in fully differentiated air-liquid interface (ALI) cultures, identifying genes involved in IL-1 signaling and mucin glycosylation that are only dysregulated in the CF airway epithelial response to RV infection. These data provide novel insights into the CF airway epithelial cells' responses to RV infection and highlight potential pathways that could be targeted to improve antiviral and anti-inflammatory responses in CF.

The Detection of Bile Acids in the Lungs of Paediatric Cystic Fibrosis Patients Is Associated with Altered Inflammatory Patterns.

Background: Cystic fibrosis (CF) is a hereditary disorder in which persistent unresolved inflammation and recurrent airway infections play major roles in the initiation and progression of the disease. Little is known about triggering factors modulating the transition to chronic microbial infection and inflammation particularly in young children. Cystic fibrosis respiratory disease starts early in life, with the detection of inflammatory markers and infection evident even before respiratory symptoms arise. Thus, identifying factors that dysregulate immune responsiveness at the earliest stages of the disease will provide novel targets for early therapeutic intervention. Methods: We evaluated the clinical significance of bile acid detection in the bronchoalveolar lavage fluid of clinically stable preschool-aged children diagnosed with CF. Results: We applied an unbiased classification strategy to categorize these specimens based on bile acid profiles. We provide clear associations linking the presence of bile acids in the lungs with alterations in the expression of inflammatory markers. Using multiple regression analysis, we also demonstrate that clustering based on bile acid profiles is a meaningful predictor of the progression of structural lung disease. Conclusions: Altogether, our work has identified a clinically relevant host-derived factor that may participate in shaping early events in the aetiology of CF respiratory disease.

Quistes de inclusión epitelial, una extraña causa de aumento de volumen vulvar en niñas y adolescentes: un caso clínico / Cysts of epithelial inclusion, a strange cause of increased vulvar volume in girls and teens: a clinical case

Los tumores vulvares son un desafío diagnóstico en la práctica clínica por las múltiples etiologías subyacentes. CASO CLÍNICO: Adolescente de 13 años que presentó dos nódulos vulvares de un mes de evolución, asociados a leve dolor. Ecografía preoperatoria sospecha un quiste de inclusión epidérmica, el que se confirmó con biopsia excisional.

Vulvar tumors are a diagnostic challenge in clinical practice due to the multiple underlying etiologies. CLINICAL CASE: A 13-year-old adolescent who presented two vulvar nodules of one month of evolution, associated with mild pain. Preoperative ultrasound suspected an epidermal inclusion cyst, which was confirmed with excisional biopsy.

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry.

BACKGROUND: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. METHODS: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. RESULTS: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. CONCLUSIONS: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

Developmental control of hypoxia during bud burst in grapevine.

Dormant or quiescent buds of woody perennials are often dense and in the case of grapevine (Vitis vinifera L.) have a low tissue oxygen status. The precise timing of the decision to resume growth is difficult to predict, but once committed, the increase in tissue oxygen status is rapid and developmentally regulated. Here, we show that more than a third of the grapevine homologues of widely conserved hypoxia-responsive genes and nearly a fifth of all grapevine genes possessing a plant hypoxia-responsive promoter element were differentially regulated during bud burst, in apparent harmony with resumption of meristem identity and cell-cycle gene regulation. We then investigated the molecular and biochemical properties of the grapevine ERF-VII homologues, which in other species are oxygen labile and function in transcriptional regulation of hypoxia-responsive genes. Each of the 3 VvERF-VIIs were substrates for oxygen-dependent proteolysis in vitro, as a function of the N-terminal cysteine. Collectively, these data support an important developmental function of oxygen-dependent signalling in determining the timing and effective coordination bud burst in grapevine. In addition, novel regulators, including GASA-, TCP-, MYB3R-, PLT-, and WUS-like transcription factors, were identified as hallmarks of the orderly and functional resumption of growth following quiescence in buds.

Consumo de lácteos y adecuación del aporte de calcio en estudiantes de la Facultad de Medicina de laUniversidad Nacional del Nordeste / Dairy consumption and adequacy of calcium intake in students of the Faculty of Medicine of the National University of the Northeast

Los lácteos constituyen un grupo alimentariode gran relevancia para el ser humano, se consideran como tales a la leche y sus derivados, por ser los alimentos fuente de calcio por excelencia su ingesta adecuada garantiza cubrir la Ingesta Recomendada del mineral. El objetivo general del trabajo fue determinar la adecuación de la Ingesta recomendada de calcio, para ello se realizó un estudio de enfoque cuantitativo de carácter descriptivo. La población de estudio fueron los estudiantes de Licenciatura en Enfermería de la Facultad de Medicina de la Universidad de Nacional del Nordeste. Sobre ella se tomó una muestra no probabilística accidental conformada por 100 unidades muestrales. Tras el análisis de datos se observó que el 22% de los encuestados no cubre la IR de calcio mientras que el 58% lo hace en exceso y solo el 20% cumple la media de 1000 mg/día. Como conclusión se destaca la necesidad de implementar estrategias de educación nutricional a fin de mejorar el patrón de consumo de lácteos y la consecuente ingesta de calcio

Trastuzumab emtansine in locally advanced or metastatic HER2 positive breast cancer; GENESIS-SEFH drug evaluation report.

Trastuzumab emtansina (T-DM1) is an antibody-drug conjugate directed against the HER2 for the treatment of HER2+ mestastatic breast cancer (MBC), who has previously received trastuzumab plus a taxane. According to the results of the EMILIA trial versus lapatinib plus capecitabine T-DM1 shows an improvement in progression-free survival (PFS) and the overall survival (OS). It has a favorable profile reducing the incidence of grade 3-4 adverse reactions such as hand-foot syndrome and diarrhea. On the contrary increases significantly severe thrombocytopenia; bleeding risk and liver function should also be monitored. With the current import price T-DM1 has a cost per QALY of over 120,000 €. The price of the drug for the Spanish NHS has not yet been established. Drug cost would be the key factor in the sensitivity analysis and a 50% reduction in the price of the drug would place it close to the threshold of cost-effectiveness usually considered in our midst. According to the budget impact model used, a maximum of 1,218 patients / year and the budgetary impact throughout the Spanish state would be at € 70,490,850. In the initial analysis no advantage was found for T-DM1 in those patients without visceral involvement. Although a subsequent re-analysis of the results of PFS in which the definition of visceral involvement was specified a significant benefit was shown in this subgroup. We believe that this approach introduces a high degree of uncertainty, which does not guarantee the benefit achieved for this subgroup of patients.

T-DM1 es un conjugado anticuerpo-farmaco dirigido contra el HER2 para el tratamiento del cancer de mama metastasico (CMM) HER2 +, que ha recibido previamente trastuzumab mas un taxano. De acuerdo con los resultados del ensayo EMILIA frente a lapatinib mas capecitabina T-DM1 muestra una mejora en la supervivencia libre de progresion (SLP) y la supervivencia global (SG). Tiene un perfil favorable reducir la incidencia de reacciones adversas grado 3-4 tales como el sindrome mano- pie y la diarrea. Sin embargo, aumenta significativamente el riesgo de trombocitopenia grave y debe monitorizarse el riesgo de hemorragia y la funcion hepatica. Con el precio de importacion actual T-DM1 tiene un coste por AVAC de mas de 120.000 €. El precio del farmaco para el Sistema Nacional de Salud en Espana aun no ha sido establecido. El precio del farmaco seria el factor clave en el analisis de sensibilidad y una reduccion del 50% en el precio lo situaria cerca del umbral de coste-efectividad generalmente considerada en nuestro medio como aceptable. De acuerdo con el modelo de impacto presupuestario utilizado, se trataria un maximo de 1.218 pacientes / ano y el impacto presupuestario de todo el estado espanol estaria entorno a 70.490.850 € para este volumen de pacientes. En el analisis inicial no se encontro ninguna ventaja para T-DM1 en aquellos pacientes sin afectacion visceral. Aunque un re-analisis posterior de los resultados de SLP en el que se especifica la definicion de la afectacion visceral se muestra un beneficio significativo en este subgrupo. Creemos que este enfoque presenta un alto grado de incertidumbre, y no garantiza el beneficio logrado para este subgrupo de pacientes.

The effect of nopal (Opuntia ficus indica) on postprandial blood glucose, incretins, and antioxidant activity in Mexican patients with type 2 diabetes after consumption of two different composition breakfasts.

Nopal is a plant used in traditional Mexican medicine to treat diabetes. However, there is insufficient scientific evidence to demonstrate whether nopal can regulate postprandial glucose. The purpose for conducting this study was to evaluate the glycemic index, insulinemic index, glucose-dependent insulinotropic peptide (GIP) index, and the glucagon-like peptide 1 (GLP-1) index, and the effect of nopal on patients with type 2 diabetes after consumption of a high-carbohydrate breakfast (HCB) or high-soy-protein breakfast (HSPB) on the postprandial response of glucose, insulin, GIP, GLP-1, and antioxidant activity. In study 1, the glycemic index, insulinemic index, GIP index, and GLP-1 index were calculated for seven healthy participants who consumed 50 g of available carbohydrates from glucose or dehydrated nopal. In study 2, 14 patients with type 2 diabetes consumed nopal in HCB or HSPB with or without 300 g steamed nopal. The glycemic index of nopal was 32.5±4, insulinemic index was 36.1±6, GIP index was 6.5±3.0, and GLP-1 index was 25.9±18. For those patients with type 2 diabetes who consumed the HCB+nopal, there was significantly lower area under the curve for glucose (287±30) than for those who consumed the HCB only (443±49), and lower incremental area under the curve for insulin (5,952±833 vs 7,313±1,090), and those patients with type 2 diabetes who consumed the HSPB avoided postprandial blood glucose peaks. Consumption of the HSPB+nopal significantly reduced the postprandial peaks of GIP concentration at 30 and 45 minutes and increased the antioxidant activity after 2 hours measured by the 2,2-diphenyl-1-picrilhidracyl method. These findings suggest that nopal could reduce postprandial blood glucose, serum insulin, and plasma GIP peaks, as well as increase antioxidant activity in healthy people and patients with type 2 diabetes.

Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma

Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50%) in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma.

Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50%) in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

Perturbation of polyamine catabolism affects grape ripening of Vitis vinifera cv. Trincadeira.

Grapes are economically the most important fruit worldwide. However, the complexity of biological events that lead to ripening of nonclimacteric fruits is not fully understood, particularly the role of polyamines' catabolism. The transcriptional and metabolic profilings complemented with biochemical data were studied during ripening of Trincadeira grapes submitted to guazatine treatment, a potent inhibitor of polyamine oxidase activity. The mRNA expression profiles of one time point (EL 38) corresponding to harvest stage was compared between mock and guazatine treatments using Affymetrix GrapeGen(®) genome array. A total of 2113 probesets (1880 unigenes) were differentially expressed between these samples. Quantitative RT-PCR validated microarrays results being carried out for EL 35 (véraison berries), EL 36 (ripe berries) and EL 38 (harvest stage berries). Metabolic profiling using HPLC and (1)H NMR spectroscopy showed increase of putrescine, proline, threonine and 1-O-ethyl-ß-glucoside in guazatine treated samples. Genes involved in amino acid, carbohydrate and water transport were down-regulated in guazatine treated samples suggesting that the strong dehydrated phenotype obtained in guazatine treated samples may be due to impaired transport mechanisms. Genes involved in terpenes' metabolism were differentially expressed between guazatine and mock treated samples. Altogether, results support an important role of polyamine catabolism in grape ripening namely in cell expansion and aroma development.