Immunological mechanisms involved in the human response to a dog dander allergoid.

BACKGROUND: Dog allergens are a common cause of allergic sensitisation and trigger respiratory symptoms worldwide. However, clinical evidence regarding dog immunotherapy is limited. Therefore, the aim of this study was to analyse the immunomodulatory properties of a new allergoid from dog dander, thereby deepening the understanding of the molecular mechanisms involved in the reestablishment of the tolerogenic response. METHODS: Three independent batches of dog dander native and allergoid allergen extracts were manufactured and characterised. Allergenic profiles were analysed by the identification of all dog allergens and quantification of the major allergens Can f 1 and Can f 5. The allergenicity profile of the allergoid was studied using biological potency and basophil activation tests. In vitro immunomodulatory parameters was evaluated as the capacity of the allergoid to induce IgG antibodies that block IgE binding to the allergen and cytokine promotion (IFN-γ, IL-4, IL-6, IL-10, IL-13, and TNF-α) in PBMCs from allergic donors. RESULTS: The presence of all dog allergens, including Can f 1 and Can f 5, was confirmed in both types of extracts. The new allergoid showed a low IgE binding capacity, which significantly affected the activation of effector cells, such as basophils. The IgG antibodies induced by the allergoid in rabbits blocked human IgE binding epitopes on the dog native extract and induced Th1 and Treg responses by increasing IFN-γ and IL-10 levels in PBMCs from allergic donors. CONCLUSION: This new dog dander allergoid containing Can f 1 and Can f 5 showed a low capacity to bind IgE and to activate basophils in dog allergic patients. Furthermore, it showed potent activation of Th1 mediators and induction of tolerance through Treg activation. This allergoid could offer a safer profile than the native extract and could be an effective immunotherapy treatment for dog allergic patients.

Evaluación de los desenlaces posoperatorios de los pacientes sometidos a septoplastia y turbinoplastia entre los años 2016 a 2018 de la Fundación Santa Fe de Bogotá / Evaluation of postoperative outcomes of septoplasty and septoturbinoplasty patients of Fundación Santa Fe de Bogota between the years 2016 to 2018

Introducción: La tasa de infección después de la cirugía nasal electiva es muy baja, lo que hace que la profilaxis antibiótica de rutina sea redundante. En Colombia no disponemos de información acerca de la tasa de infección de septoplastia; por esta razón, en este artículo se busca describir la tasa de infección posquirúrgica en los pacientes llevados a septoplastia o septoplastia y turbinoplastia de la Fundación Santa Fe de Bogotá, entre los años 2016-2018. Metodología: se realizó un estudio observacional, descriptivo y retrospectivo mediante la revisión de la base de datos del servicio. Se calculó la proporción de infección para todos los individuos participantes del estudio de manera general y estratificada por el uso de antibiótico profiláctico y posoperatorio, y se describió la frecuencia de las complicaciones. Resultados: encontramos 255 pacientes en la base de datos de la sección de otorrinolaringología, de los cuales 206 cumplieron con los criterios de inclusión. El 23,3 % de los pacientes recibió un antibiótico profiláctico y el 24,76 % recibió un antibiótico postoperatorio. La tasa de infección posoperatoria fue de 2,91 % (intervalo de confianza [IC] del 95 %: 1,07-6,23). El 96,6 % de los pacientes no presentaron complicaciones. Conclusiones: nuestros hallazgos se correlacionan con la literatura global

Introduction: infection rate after elective nasal surgery is very low which makes routine antibiotic prophylaxis redundant. In Colombia we do not have information about postoperative infection in septoplasty. A study was designed to determine the postoperative infection rate in patients undergoing septoplasty or septoplasty and turbinoplasty at Fundación Santa Fe de Bogotá between 2016 to 2018. Methods: an observational, descriptive and retrospective study was conducted. The database of the Otolaryngology Section was reviewed. The proportion of infection for all individuals participating in the study was calculated in a general and stratified manner by use of prophylactic and postoperative antibiotic and the frequency of complications was described. Results: we found 255 patients in the patient database of which 206 patients met the inclusion criteria. 23.3 % of patients received prophylactic antibiotic and 24.76 % received postoperative antibiotic. The percentage of postoperative infection was 2.91 % (95 % CI: 1.07-6.23). 96.6 % of the patients did not present any complications. Conclusion: septoplasty has a low risk of infection which was in accordance to the findings found in the present study.

Carers' preferences for the delivery of therapy services for people with disability in rural Australia: evidence from a discrete choice experiment.

BACKGROUND: The implementation of the Australian National Disability Insurance Scheme is expected to generate a responsive, person-centred system that will empower people with disability to choose the services and support they receive. However, little attention has been paid to examine how users of the National Disability Insurance Scheme will choose and spend their individual budgets. This study aimed to determine quantitatively the relative importance that carers of people with a disability living in rural Australia place on different therapy service delivery characteristics. METHODS: A stated preference discrete choice experiment was incorporated into a survey of carers of people with disability living in rural Australia. Carers chose between therapy delivery services differing in attributes such as travel time to receive therapy, sector providing the service (i.e. Government, not-for-profit and private), out-of-pocket costs, person who delivers the therapy (therapist or other staff) and waiting time. RESULTS: A total of 133 carers completed the discrete choice experiment. The majority of respondents cared for a child with a disability (84%); the average age of the person they cared for was 17 years (SD 14.25). Participants expressed strong preferences for a short waiting time (0-3 months) to receive therapy services; services delivered by a therapist, no out-of-pocket cost and travelling up to 4 h to receive a therapy session (P < 0.05). Sector providing the service was not statistically significant. CONCLUSION: Carers of people with a disability in rural Australia exhibited strongest preferences for short waiting times (0-3 months). Therapy services that are delivered by therapy assistants or support workers will require careful introduction to achieve uptake and acceptability.

Network-analysis-guided synthesis of weisaconitine D and liljestrandinine.

General strategies for the chemical synthesis of organic compounds, especially of architecturally complex natural products, are not easily identified. Here we present a method to establish a strategy for such syntheses, which uses network analysis. This approach has led to the identification of a versatile synthetic intermediate that facilitated syntheses of the diterpenoid alkaloids weisaconitine D and liljestrandinine, and the core of gomandonine. We also developed a web-based graphing program that allows network analysis to be easily performed on molecules with complex frameworks. The diterpenoid alkaloids comprise some of the most architecturally complex and functional-group-dense secondary metabolites isolated. Consequently, they present a substantial challenge for chemical synthesis. The synthesis approach described here is a notable departure from other single-target-focused strategies adopted for the syntheses of related structures. Specifically, it affords not only the targeted natural products, but also intermediates and derivatives in the three families of diterpenoid alkaloids (C-18, C-19 and C-20), and so provides a unified synthetic strategy for these natural products. This work validates the utility of network analysis as a starting point for identifying strategies for the syntheses of architecturally complex secondary metabolites.

Inhibitory effects of curcumin on dengue virus type 2-infected cells in vitro.

Curcumin, a traditional Chinese and Indian treatment for many diseases, has recently been found to alter the in vitro infection processes of various viruses, including hepatitis C virus, human immunodeficiency virus, coxsackievirus, and Japanese encephalitis virus. The present study evaluated the cellular effects of curcumin in an in vitro (cellular) infection model of dengue virus. Within a dose range of 10 to 30 µM and a treatment period of 24 hours, the cytotoxicity of curcumin was low, as determined by MTT assays. Cells infected with dengue virus type 2 at a multiplicity of infection of 5 were treated with various concentrations of curcumin or the proteasome inhibitor MG132. Plaque assays, immunofluorescence analysis, western blots, and in-cell western assays were then performed. Treatment with 10, 15, and 20 µM curcumin decreased the number of plaques produced, caused an intracellular accumulation of viral proteins, and increased the level of Lys48 ubiquitin-conjugated proteins. At 20 µM curcumin, changes in cell and nuclear morphology and alterations in the actin cytoskeleton were also observed. Treatment with MG132 also reduced plaque production. These results show that curcumin can interfere with the infection processes of dengue virus and that this interference may not occur through direct effects on viral particle production but may result from curcumin's effects on various cellular systems such as the cytoskeleton, the ubiquitin-proteasome system, or the apoptosis process.

Test de Parche como método diagnóstico de las reacciones adversas a medicamentos / Patch test as a diagnostic method for adverse drug reactions

Las reacciones adversas a medicamentos (RAM) son un motivo frecuente de consulta en la práctica dermatológica. La hipersensibilidad a fármacos es una causa común de RAM, y es de gran relevancia confirmar este mecanismo para que el paciente evite futuras exposiciones. El test de parche tiene un rol relevante en el proceso diagnóstico de las reacciones de hipersensibilidad no inmediatas, otros test como la intradermorreacción o el test de provocación son más invasivos o de alto riesgo, y los exámenes in vitro para reacciones tardías no se encuentran fácilmente disponibles. El problema es que existe escasa estandarización del procedimiento y el valor predictivo del examen es incierto. En esta revisión exponemos la mejor evidencia disponible, lo que permitirá al especialista decidir cuándo hacer este examen y cómo interpretar sus resultados.

Adverse drugs reactions (ADR) are a frequent diagnosis in dermatological practice. Drug hypersensitivity is a common ADR etiology, and it is greatly relevant to confirm this mechanism to avoid future exposures of the patient to the culprit drug. Patch test has an outstanding role in non-immediate hypersensitivity reactions diagnosis process, other tests like intradermal reaction or provocation test are more aggressive or implies more risk, and in-vitro test for non-inmediate reactions are not easily available. One of the main problems of patch test is the lack of standarization of the procedure and the uncertain predictive value. In this review is exposed the best evidence available, so the specialist could decide when to do the test and how interpret its results.

Discapacidad visual; otra forma de verla / Visual impairment; another way of see it

La discapacidad visual es un problema de salud pública que afecta a más de doscientos ochenta y cinco millones de personas alrededor del mundo, dentro de los cuales doscientos cuarenta y seis millones sufren baja visión y treinta y nueve millones ceguera primaria. Es una entidad altamente relacionada con las condiciones socioeconómicas y las posibilidades de acceder a los servicios de salud, esto explica que entre el 80 y el 90 por ciento de las personas con alteraciones visuales sean de países en vía de desarrollo, principalmente en zonas rurales. Una infinidad de casos de ceguera y baja visión son consecuencia de eventos prevenibles, entre los cuales sobresalen los defectos refractivos no corregidos tales como astigmatismo, miopía, hipermetropía y presbicia. Es por esto que la discapacidad visual se ha convertido en una prioridad para múltiples entidades a nivel mundial, que buscan disminuir la presentación de ceguera prevenible a través de una simple corrección visual bien diagnosticada...

Visual impairment is a public health problem that affects more than two hundred eighty-five million people around the world, among them two hundred forty-six million suffer low vision and thirty-nine million primary blindness. It is highly related to socio-economic conditions and the possibilities to access to health services, explained that between 80 and 90 percent of persons with visual impairments from countries developing, mainly in rural areas. An infinite number of cases of blindness and low vision are the result of events preventable, among which stand out the uncorrected refractive errors such as myopia, hyperopia, astigmatism and presbyopia. It is for this reason that visual impairment has become a priority for many organizations around the world, seeking to reduce the presentation of preventable blindness through a simple visual correction well diagnosed...

Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

Multiple biomarker tissue arrays: A computational approach to identifying protein-protein interactions in the EGFR/ERK signalling pathway.

BACKGROUND: Many studies have demonstrated genetic and environmental factors that lead to renal cell carcinoma (RCC) and that occur during a protracted period of tumourigenesis. It appears suitable to identify and characterise potential molecular markers that appear during tumourigenesis and that might provide rapid and effective possibilities for the early detection of RCC. EGFR activation induces cell cycle progression, inhibition of apoptosis and angiogenesis, promotion of invasion/metastasis, and other tumour promoting activities. Over-expression of EGFR is thought to play an important role in tumour initiation and progression of RCC because up-regulation of EGFR has been associated with high grade cancers and a worse prognosis. METHODS: Characterisation of the protein profile interacting with EGFR was performed using the following: an immunohistochemical (IHC) study of EGFR, a comprehensive computational study of EGFR protein-protein interactions, an analysis correlating the expression levels of EGFR with other significant markers in the tumourigenicity of RCC, and finally, an analysis of the utility of EGFR for prognosis in a cohort of patients with renal cell carcinoma. RESULTS: The cases that showed a higher level of this protein fell within the clear cell histological subtype (p = 0.001). The EGFR significance statistic was found with respect to a worse prognosis. In vivo significant correlations were found with PDGFR-ß, Flk-1, Hif1-α, proteins related to differentiation (such as DLL3 and DLL4 ligands), and certain metabolic proteins such as Glut5. In silico significant associations gave us a panel of 32 EGFR-interacting proteins (EIP) using the APID and STRING databases. CONCLUSIONS: This work summarises the multifaceted role of EGFR in the pathology of RCC, and it identifies EIPs that could help to provide mechanistic explanations for the different behaviours observed in tumours.

Searching for Hif1-alpha interacting proteins in renal cell carcinoma

INTRODUCTION: Kidney tumours are frequently characterised by hypoxic conditions due to a local imbalance between oxygen (O2) supply and consumption. Hif1-α regulates angiogenesis, tumour growth, tumour progression, metastatic spread, and glucose metabolism by acting as a transcription factor for relevant genes. Here, we describe an immunohistochemical study of Hif1-α, a comprehensive computational study of Hif1-α interacting proteins (HIPs), an analysis correlating expression levels of Hif1-α with upstream and downstream proteins, and an analysis of the utility of Hif1-α for prognosis in a cohort of patients with renal cell carcinoma. MATERIALS AND METHODS: The patient cohort included 80 patients. For immunohistochemistry evaluation, tissue microarrays were constructed. The IntAct, MINT, and BOND databases were used for the HIP approach. The Kruskal-Wallis test was used for comparing protein expression with pathology measurements. Correlation was expressed as the Pearson coefficient. RESULTS: Hif1-α expression correlates significantly with the "clear" histological subtype of renal cell carcinoma (p < 0.01). The samples with the worst prognoses related to the pathological variables analysed showed the highest levels of Hif1-α expression. Significant correlations were found with Bcl-2, CAIX, C-kit, EGFR, TGF-β, proteins of the VEGF family, proteins related to differentiation (such as Notch1 and Notch3) and certain metabolic enzymes. Bioinformatic analysis suggested 45 evidence-based HIPs and 4 complexes involving protein Hif1-α. CONCLUSIONS: This work summarises the multifaceted role of Hif1-α in the pathology of renal cell carcinomas, and it identifies HIPs that could help provide mechanistic explanations for the different behaviours seen in tumours (AU)

Searching for Hif1-α interacting proteins in renal cell carcinoma.

INTRODUCTION: Kidney tumours are frequently characterised by hypoxic conditions due to a local imbalance between oxygen (O2) supply and consumption. Hif1-α regulates angiogenesis, tumour growth, tumour progression, metastatic spread, and glucose metabolism by acting as a transcription factor for relevant genes. Here, we describe an immunohistochemical study of Hif1-α, a comprehensive computational study of Hif1-α interacting proteins (HIPs), an analysis correlating expression levels of Hif1-α with upstream and downstream proteins, and an analysis of the utility of Hif1-α for prognosis in a cohort of patients with renal cell carcinoma. MATERIALS AND METHODS: The patient cohort included 80 patients. For immunohistochemistry evaluation, tissue microarrays were constructed. The IntAct, MINT, and BOND databases were used for the HIP approach. The Kruskal-Wallis test was used for comparing protein expression with pathology measurements. Correlation was expressed as the Pearson coefficient. RESULTS: Hif1-α expression correlates significantly with the "clear" histological subtype of renal cell carcinoma (p < 0.01). The samples with the worst prognoses related to the pathological variables analysed showed the highest levels of Hif1-α expression. Significant correlations were found with Bcl-2, CAIX, C-kit, EGFR, TGF-ß, proteins of the VEGF family, proteins related to differentiation (such as Notch1 and Notch3) and certain metabolic enzymes. Bioinformatic analysis suggested 45 evidence-based HIPs and 4 complexes involving protein Hif1-α. CONCLUSIONS: This work summarises the multifaceted role of Hif1-α in the pathology of renal cell carcinomas, and it identifies HIPs that could help provide mechanistic explanations for the different behaviours seen in tumours.

Treatment of dry age-related macular degeneration with dobesilate.

The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture.

Crecimiento en pastoreo rotacional de toretes de razas criollas Romosinuano y Blanco Orejinegro en Colombia / Growth in rotational grazing of young bulls from Romosinuano and Blanco Orejinegro creole breeds in Colombia

Objetivo. Evaluar el crecimiento de toretes de las razas Romosinuno (ROMO) y Blanco Orejinegro (BON) en una prueba de comportamiento en pastoreo rotacional. Materiales y métodos. La prueba fue desarrollada en la Estación Experimental El Nus, en la Región Andina Colombiana, donde se evaluaron 20 toretes BON y 16 ROMO provenientes de quince ganaderías comerciales, los cuales fueron mantenidos en un solo grupo durante 221 días en pastoreo rotacional en franjas con periodos cortos de ocupación, de los cuales 56 días fueron en pastoreo no suplementado y 165 días bajo tres diferentes fases de pastoreo suplementado en el potrero. Se realizaron pesajes cada 28 días y se evaluaron variables como: la evolución en peso, la ganancia total y diaria, la diferencia entre pesajes, la relación consumo peso vivo y la tasa de consumo. Resultados. El peso inicial en la raza BON fue 180.4±36.9 kilos con 9.6±1.74 meses de edad y en la raza ROMO fue de 171.8±32.6 kilos con 10.1±3.2 meses de edad. El incremento general de los individuos entre pesajes fue 0.497 kilos por día para los individuos de raza BON, y 0.366 kilos por día para la raza ROMO. En la prueba de eficiencia la tasa de consumo de suplemento alcanzada fue 64.8% y 71% para BON y ROMO respectivamente, equivalentes a una ingestión de materia seca de 0.47% y 0.53% con relación al peso vivo. Conclusiones. Este trabajo evidencia un mayor desempeño de los individuos de la raza BON comparados con los animales de la raza ROMO e indica una alta variabilidad en la respuesta a un manejo semi-intensivo en las poblaciones en evaluación.

Topical treatment of actinic keratoses with potassium dobesilate 5% cream. a preliminary open-label study.

BACKGROUND: Fibroblast growth factor (FGF) is involved in skin tumorigenesis: it promotes cell viability, induces angiogenesis and stimulates invasiveness. Dobesilate is a drug that blocks the activity of FGF. The primary objective was to evaluate the efficacy and tolerability of potassium dobesilate 5% cream in the treatment of actinic keratoses. METHODS: Potassium dobesilate 5% cream was applied twice daily for 16 weeks to actinic keratosis lesions in 30 patients. The lesions were evaluated clinically at an initial baseline visit, at intermediate visits, and at 16 weeks of treatment. - RESULTS: The use of potassium dobesilate 5% cream for 16 weeks induced complete regression in 70% of evaluated actinic keratoses, corresponding to grade I, II and III clinical variants, and a partial response (at least 75% reduction of lesions) in 20% of the cases. CONCLUSION: Our preliminary trial shows that potassium dobesilate exerts anti-tumorigenic effects and may play a useful role in the chemoprevention of skin cancers.

Expression of Notch1 to -4 and their ligands in renal cell carcinoma: a tissue microarray study.

BACKGROUND: Mutations in signalling pathways essential for embryonic development often lead to tumourigenesis, as is also true for Notch. The aim of this study was to assess the relationship between Notch1 to -4 and their ligands with anatomopathological features of the patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: This study investigated the pattern of protein expression in RCC specimens using tissue microarray technology. A total of 80 paraffin-embedded RCC samples were retrospectively analysed together with ACHN and A.704 cell lines. RESULTS: Notch1 showed significant positive correlation with chromophobe RCC, no broken capsule, Furhman grade I and when the number of nodes involved was small [(N=1); p=0.039, 0.016, 0.037 and 0.001, respectively)]. Notch3 showed higher expression when the tumour was located in the right kidney (p=0.048). CONCLUSION: Notch1 may be useful in the future as a biomarker for the differential diagnosis of different RCC histological subtypes. Notch1 to -3 may also have potential use as a strong prognostic factor.

Tissue array analysis for the differentiation of gliosis from gliomas.

The aim of this study was to provide a methodology to make a clear distinction between malignant tumors and morphologically similar benign processes, by examining the expression of EGFR, VEGF, HIF1-α, survivin, Bcl-2 and p53 proteins. Four groups of patient samples were studied: group 1, low-grade astrocytomas (WHO grades I-II) (n=6); group 2, peripheral area of high-grade astrocytomas (WHO grades III-IV) (n=5); group 3, gliomatosis cerebri (n=11); and group 4, reactive gliosis (n=6). Tissue arrays (TAs) were designed to study apoptosis, angiogenesis and invasion-related proteins by immunohistochemistry (IHC). By means of non-parametric analysis (Mann-Whitney U test), EGFR staining was shown to be significantly lower in reactive gliosis than in the low- and high-grade astrocytomas (p=0.015 and p=0.030, respectively); Bcl-2 immunoreactivity was significantly higher in the gliomatosis cerebri samples than in the reactive processes (p=0.005); and finally, Bcl-2 presented significantly lower expression levels in reactive gliosis compared to the peripheral areas of high-grade astrocytomas (p=0.004). The results indicate that Bcl-2 and EGFR may be useful in conducting differential diagnosis between the above groups, while the expression of the remaining antibodies does not appear to aid in distinguishing between the samples analyzed. The use of TAs to identify the protein expression profiles of biological markers related to different pathways was verified, and its potential as a discriminatory technique for everyday pathology procedures was demonstrated.

Stem cell and lung cancer development: blaming the Wnt, Hh and Notch signalling pathway

Primary lung cancer may arise from the central (bronchial) or peripheral (bronchiolo-alveolar) compartments. However the origins of the different histological types of primary lung cancer are not well understood. Stem cells are believed to be crucial players in tumour development and there is much interest in identifying those compartments that harbour stem cells involved in lung cancer. Although the role of stem cells in carcinogenesis is not well characterised, emerging evidence is providing new insights into this process. Numerous studies have indicated that lung cancer is not a result of a sudden transforming event but a multistep process in which a sequence of molecular changes result in genetic and morphological aberrations. The exact sequence of molecular events involved in lung carcinogenesis is not yet well understood, therefore deeper knowledge of the aberrant stem cell fate signalling pathway could be crucial in the development of new drugs against the advanced setting (AU)

Relevant Networks involving the p53 Signalling Pathway in Renal Cell Carcinoma.

INTRODUCTION: Renal cell carcinoma is the most common type of kidney cancer. A better understanding of the critical pathways and interactions associated with alterations in renal function and renal tumour properties is required. Our final goal is to combine the knowledge provided by a regulatory network with experimental observations provided by the dataset. METHODS: In this study, a systems biology approach was used, integrating immunohistochemistry protein expression profiles and protein interaction information with the STRING and MeV bioinformatics tools. A group consisting of 80 patients with renal cell carcinoma was studied. The expression of selected markers was assessed using tissue microarray technology on immunohistochemically stained slides. The immunohistochemical data of the molecular factors studied were analysed using a parametric statistical test, Pearson's correlation coefficient test. RESULTS: Bioinformatics analysis of tumour samples resulted in 2 protein networks. The first network consists of proteins involved in the angiogenesis pathway and the apoptosis suppressor, BCL2, and includes both positive and negative correlations. The second network shows a negative interaction between the p53 tumour suppressor protein and the glucose transporter type 4. CONCLUSION: The comprehensive pathway network will help us to realise the cooperative behaviours among pathways. Regulation of metabolic pathways is an important role of p53. The pathway involving the tumour suppressor gene p53 could regulate tumour angiogenesis. Further investigation of the proteins that interact with this pathway in this type of tumour may provide new strategies for cancer therapies to specifically inhibit the molecules that play crucial roles in tumour progression.