Association of Circulating Markers of Microbial Translocation and Hepatic Inflammation with Liver Injury in Patients with Type 2 Diabetes.

BACKGROUND: Virtually the entire spectrum of liver disease is observed in association with type 2 diabetes mellitus (T2DM); indeed, T2DM is now the most common cause of liver disease in the U.S. We conducted a pilot study to investigate the relevance of increased microbial translocation and systemic inflammation in the development of liver injury in patients with T2DM. METHODS: Patients with T2DM (n = 17) and non-diabetic controls (NDC; n = 11) aged 25-80 yrs. participated in this study. Serum levels of endotoxin, calprotectin, soluble CD14 and CD163, and several inflammatory cytokines were measured. In addition to standard liver injury markers, ALT and AST, novel serum markers of liver injury, keratin 18 (K-18) M30 (apoptosis-associated caspase-cleaved keratin 18), and M65 (soluble keratin 18) were evaluated. Statistical analyses were performed using the Mann-Whitney test to assess differences between study groups. Pearson's correlation analysis was performed to determine the strength of association between two variables using GraphPad Prism 9.5.0 software. RESULTS: Patients with T2DM had significantly higher levels of sCD14 in comparison to NDC, suggesting an increase in gut permeability, microbial translocation, and monocyte/macrophage activation. Importantly, relevant to the ensuing inflammatory responses, the increase in sCD14 in patients with T2DM was accompanied by a significant increase in sCD163, a marker of hepatic Kupffer cell activation and inflammation. Further, a positive correlation was observed between sCD163 and endotoxin and sCD14 in T2DM patients but not in NDC. In association with these changes, keratin 18 (K-18)-based serum markers (M65 and M30) that reflect hepatocyte death were significantly higher in the T2DM group indicating ongoing liver injury. Notably, both M65 and M30 levels correlated with sCD14 and sCD163, suggesting that immune cell activation and hepatic inflammation may be linked to the development of liver injury in T2DM. CONCLUSIONS: These findings suggest that the pathogenic changes in the gut-liver axis, marked by increased microbial translocation, may be a major component in the etiology of hepatocyte inflammation and injury in patients with T2DM. However, larger longitudinal studies, including histological evidence, are needed to confirm these observations.

Curcumin Sensitizes 4T1 Murine Breast Cancer Cells to Cisplatin Through PAR4 Secretion.

BACKGROUND/AIM: Prostate apoptosis response 4 (PAR4), a tumour-suppressor protein, selectively induces apoptosis of cancer cells without affecting normal cells. Its soluble form is induced by secretagogues (e.g., chloroquine), and it induces apoptosis by interacting with the receptor of glucose-regulated protein 78, which is overexpressed in cancer cells. In this study, curcumin was analyzed as an inducer of PAR4 expression in 4T1 murine breast cancer cell. and its ability to induce PAR4 secretion in Balb/c mice. In addition, the cisplatin sensitizing effect of soluble PAR4 was analyzed. MATERIAL AND METHODS: The 4T1 cell line was treated in vitro using different concentrations of curcumin; cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and PAR4 expression by western blotting. The expression of soluble PAR4 in the serum of mice treated with intraperitoneal curcumin was analyzed using the dot-blot method. Moreover, MTT assay was used to analyze the effects of serum from curcumin-treated mice on cell viability. Tumor size was analyzed in mice treated with curcumin alone and in combination with cisplatin. RESULTS: Curcumin showed a dose- and time-dependent effects on cell viability on 4T1 cells, as well as increasing PAR4 expression. Compared with the control group (phosphate-buffered saline), mice treated with curcumin showed an increase in plasma PAR4. In the Balb/C tumor model, mice treated with curcumin and cisplatin showed greater tumor shrinkage than the control group. CONCLUSION: These results indicate that curcumin induces expression of soluble PAR4 and sensitizes tumor cells to cisplatin.

Distribution of M1 and M2 macrophages in cerebral granulomas caused by Encephalitozoon cuniculi.

Encephalitozoon cuniculi spores cause severe granulomatous inflammation in the brain where mononuclear cells and macrophages infiltrate. Here, we orally infected New Zealand white rabbits with 1 × 106E. cuniculi viable spores to study the recruitment and localization of macrophages in brain granulomas. At day 30 post-infection, the positive phenotype markers iNOS (M1) and Arg-1 (M2) were located in the periphery and center of granulomas, respectively. Live intracytoplasmic spores were found only in positive Arg-1 cells. This is the first work to describe the recruitment and distribution of M1 and M2 macrophages in the brain granulomas of rabbits infected with E. cuniculi.

Rheumatology Training in Latin America: A Collaborative Study by the Pan American League of Associations for Rheumatology.

BACKGROUND/OBJECTIVE: Demand for rheumatology care has steadily increased in recent years. The number of specialists in this field, however, seems insufficient. No recent studies have diagnosed the attributes of rheumatology training in Latin America. METHODS: This is a descriptive cross-sectional study. We obtained data on each country through local rheumatologists of the Pan-American League Against Rheumatism, who acted as principal investigators for participating countries. Our sample was analyzed and described through means and standard deviations or through frequencies and percentages, depending on the variable. RESULTS: Countries with the most rheumatology-training programs were Brazil (n = 50), Argentina (n = 18), and Mexico (n = 15). Ecuador, Honduras, and Nicaragua do not have rheumatology-training programs. The countries with the most available slots for rheumatology residents were Brazil (n = 126) and Argentina (n = 36). To be admitted into rheumatology training, candidates were required to have completed graduate studies in internal medicine in 42.1% of the programs. In 8 countries (42.1%), residents are not required to pay tuition; the median cost of tuition in the remaining countries is US $528 (interquartile range, US $2153). CONCLUSIONS: Conditions associated with rheumatology training in Latin America vary. Significant differences exist in income and tuition fees for residents, for example, and 4 countries in Latin America do not currently offer programs. Information collected in this study will be useful when comparing the status of rheumatology services offered in Latin America with those in other countries. Most countries require a wider offering of rheumatology-training programs, as well as more available slots.

Estrés, ansiedad y consumo de drogas legales en trabajadores de la industria / Stress, anxiety and consumption of legal drugs in industry workers

INTRODUCCIÓN. El estrés y la ansiedad provienen de diferentes situaciones, pudiendo generar un aumento en el consumo de drogas lícitas. OBJETIVO. Valorar el estrés percibido, ansiedad, consumo de alcohol y tabaco en trabajadores operativos de una empresa de metal mecánica de la ciudad de Querétaro. MATERIALES Y MÉTODOS. Estudio transversal, descriptivo. Se aplicaron 4 formatos a través del uso de una plataforma digital, obteniendo la participación de 46 trabajadores. Se consideraron a trabajadores de ambos sexos, con una antigüedad mínima de 1 año. Se implementó una escala de estrés percibido, la escala de ansiedad de Hamilton, el Test Audit y una encuesta de consumo de tabaco. El análisis de los datos se llevó a cabo por en los programas SPSS versión 25 y Excel para Windows. El protocolo fue evaluado y aprobado por el Sub-Comité de Investigación y Bioética de la Facultad de Enfermería de la Universidad Autónoma de Querétaro. RESULTADOS. El promedio de edad fue de 33.48 años y 55.3% fueron varones. 28% sobresalieron de resto en el estrés percibido. 2% de los participantes manifestó una ansiedad muy severa y 7% moderada.15% se encuentra en la zona II de consumo de alcohol y han sido fumadores el 28.3% de los trabajadores. CONCLUSIÓN: Es necesario poder abordar al total de trabajadores y valorar de manera más cercana las variables estudiadas. Se identificaron casos de personas con situaciones de estrés y ansiedad que es necesario regular. Una vinculación con el departamento de salud sería la más conveniente.

INTRODUCTION: Stress and anxiety come from different situations, and can generate an increase in the consumption of legal drugs, especially in the work-industrial environment. OBJECTIVE: To determine the relationship between stress and anxiety with the consumption of legal substances in industry workers. METHODS: Several forms were applied through a digital platform, obtaining the participation of 47 workers of a company in Querétaro, where the frequency of consumption of legal drugs was evaluated, the data collection was carried out by the SPSS program version 14, the study lasted 6 months. RESULTS. Age average was 33.48 years and 55.3% were male. 28% obtained outstanding results in stress. 2% of participants had a very severe anxiety and 7% moderate. 15% is on zone two of alcohol consumption and have been smokers 28.3% of workers. CONCLUSION. It is necessary to address with all workers and value in a close way all studied variables. Some cases of stress and anxiety were identified, and it is necessary to approach. It is necessary a bonding with health department of the company.

Mixed Pneumoconiosis Associated with Diffuse Pulmonary Ossification in Wild Coyotes (Canis latrans).

Mixed pneumoconiosis is a pulmonary disease associated with several inhaled mineral irritants. Dust was found in the alveolar macrophages, alveolar and bronchial walls and pulmonary interstitial tissue of two female coyotes (Canis latrans). The dust contained large amounts of silica, coal, iron and copper particles, which were associated with severe pulmonary disease. Lung injury in the animals was characterized by pulmonary nodules, severe interstitial fibrosis, alveolar hyperplasia and bone formation within alveolar spaces. Coyotes inhaled mineral dust while roaming a field close to three mineral extraction zones. To our knowledge, this is the first report of the concomitant inhalation of multiple minerals in association with diffuse pulmonary ossification in the pulmonary parenchyma of two wild canine animals.

Analysis of the Anti-Inflammatory Capacity of Bone Broth in a Murine Model of Ulcerative Colitis.

Background and Objectives: Nutritional deficiencies are one of the main triggers for the development of gastrointestinal diseases, such as ulcerative colitis (UC). Therefore, the objective of the present work consisted of determining the nutrients present in the bone broth (BB) and evaluating their anti-inflammatory properties in a murine model of UC, induced by intrarectal administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS), and acetic acid (AcOH). The BB was prepared from the femur of bovine cattle and cooked in distilled water for 8 h at 100 ± 2 °C. Materials and Methods: The BB was administered ad libitum to BALB/c mice for 10 days before the induction of UC. Colon samples were collected for histological analysis and determination of cytokine expression levels by qPCR. Results: It was found that amino acids (AA) are the main nutritional contribution of BB, 54.56% of these correspond to essential AA. The prophylactic administration of BB in the murine model of UC reduced histological damage, decreased the expression of IL-1ß (61.12%), IL-6 (94.70%), and TNF-α (68.88%), and increased the expression of INF-γ (177.06%), IL-4 (541.36%), and IL-10 (531.97%). Conclusions: This study shows that BB has anti-inflammatory properties, and its consumption can decrease the symptoms of UC.

Cytotoxic Effect In Vitro of Acalypha monostachya Extracts over Human Tumor Cell Lines.

Acalypha monostachya (A. monostachya) is a plant that is used in traditional medicine as a cancer treatment; however, its effect has not been validated. In this study, the potential cytotoxic effects and morphological changes of A. monostachya were evaluated in human tumor cell lines. The aqueous (AE), methanolic (ME), and hexane (HE) extracts were obtained, and flavonoid-type phenolic compounds were detected, which indicates an antineoplastic effect. We observed a time-dependent and concentration-selective toxicity in human tumor cells. Additionally, the ME and HE showed the greatest cytotoxic effect at minimum concentrations compared to the AE, which showed this effect at the highest concentrations. All extracts induced significant morphological changes in tumor cells. The HeLa (cervix carcinoma) cells were more sensitive compared to the MDA-MB-231 (triple-negative breast cancer) cells. In conclusion, we demonstrated a cytotoxic in vitro effect of A. monostachya extracts in tumoral human cell lines. These results show the potential antineoplastic effects of A. monostachya in vitro. Hereafter, our lab team will continue working to usefully isolate and obtain the specific compounds of A. monostachya extracts with cytotoxic effects on tumor cells to find more alternatives for cancer treatment.

Effects of Transportation Stress on Complete Blood Count, Blood Chemistry, and Cytokine Gene Expression in Heifers.

Blood samples were obtained from 16 high-risk heifers; eight were newly arrived from a 40 h road trip (0 days post-arrival (DPA)), whereas the other eight heifers had been in the feedlot at 25 DPA. Both groups were transported from the southeast tropical region of Mexico to a feedlot in the northeast and were sampled on the same day. The complete blood count, blood chemistry, and cytokine gene expression were analyzed. Gene expression was analyzed using specific primers to amplify and quantify the cDNA reverse transcribed from the mRNA transcripts for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2. Higher values for hematocrit (p = 0.029), hemoglobin (p = 0.002), eosinophils (0.029), albumin (p = 0.014), alanine aminotransferase (p = 0.004), bilirubin (p = 0.003), cholesterol (p = 0.014), and cortisol (p = 0.051) were observed in the 0 DPA group than the 25 DPA group. In the electrophoresis of TNF-α amplification products, two non-specific bands were observed in the 0 DPA group. These bands were sequenced, and BLAST analysis suggested that they corresponded to bovine lymphotoxin and have not been reported previously related to stress. The TNF-α expression level was higher (p = 0.001) in the 25 DPA group than the 0 DPA group according to the semi-quantitative expression analysis. This may indicate a persistent inflammatory process that could be related to trauma and disease, which can negatively impact their subsequent health and growth performance. In conclusion, homeostatic disruption was apparent in the 0 DPA heifers, which showed higher cortisol and reductions in TNF-α levels and stress-induced bovine lymphotoxin (SIBL) co-expression.

Paro cardiaco extrahospitalario: conocimientos en una comunidad universitaria / Out-of-hospital cardiac arrest: knowledge in a university community

Objetivo: determinar el nivel de conocimiento de una comunidad universitaria en Bogotá, para actuar como primer respondiente ante situaciones de emergencia como el paro cardiorrespiratorio y sus principales causas. Metodología: estudio cuantitativo, descriptivo y transversal. Muestra: 1.294 integrantes de una comunidad universitaria, margen de error 3,0 %; nivel de confianza 97,0 %. Muestreo por conveniencia. La información se recolectó a través de la plataforma Google Forms®, por medio de un cuestionario de catorce preguntas, distribuidas en tres categorías: reconocimiento del evento, activación de sistema de emergencias y atención inicial. Se cumplieron los requisitos éticos para la investigación en salud en Colombia. Resultados: el 62,7 % de los participantes identificó las acciones para reconocer un paro cardiorrespiratorio y, aunque el 83,6 % ante estas situaciones llamaría a emergencias, solo el 37,0 % afirmó conocer el número telefónico. La sospecha de síndrome coronario agudo es un evento considerado por un 68,2 % como una emergencia; no sucede lo mismo con el accidente cerebrovascular, donde solo el 52,1 %, tenía esta claridad. El 81, 4 % describió acciones correctas frente a una víctima con obstrucción grave de la vía aérea por cuerpo extraño y el 50,6 % si la obstrucción es leve. Conclusión: el nivel de conocimiento de la comunidad universitaria en materia de atención del paro cardiorrespiratorio extrahospitalario es bajo predominantemente relacionado con las maniobras de reanimación cardiopulmonar y la operación del desfibrilador externo automático. Resulta necesario implementar estrategias educativas dirigidas a todas las comunidades, y esto podría ser una oportunidad de desarrollo para el profesional de enfermería en los diferentes ámbitos de acción.

Objective: To determine the level of knowledge of a university community in Bogotá to act as first responders in emergencies like cardiopulmonary arrests and their main causes. Methods: Quantitative, descriptive, and cross-sectional study. Sample: 1294 members of a university community, 3% error, 97% confidence level. Convenience sampling method was used. Data were collected through the Google Forms® platform using a 14-item questionnaire, addressing three categories: event recognition, emergency system activation, and initial assistance. The ethical requirements for health research in Colombia were met. Results: More than half of the participants (62.7%) identified the actions to recognize cardiopulmonary arrest and, although 83.6% would call the emergency services in such situations, only 37.0% said they knew the telephone number. Suspected acute coronary syndrome is considered by 68.2% as an emergency; this is not the case of strokes, which only 52.1% considered them emergencies. Correct actions were described by 81.4% of the participants for severe foreign body airway obstruction and by 50.6% for mild airway obstruction. Conclusion: The university community's knowledge level about out-of-hospital cardiopulmonary arrest assistance is low, especially regarding cardiopulmonary resuscitation and use of an automated external defibrillator. Implementing educational strategies aimed at all communities is necessary, and it could mean a development opportunity for nursing professionals in different fields of action.

Objetivo: determinar o nível de conhecimento de uma comunidade universitária de Bogotá, para atuar como o primeiro respondente em situações de emergência como parada cardiorrespiratória e suas principais causas. Metodologia: estudo quantitativo, descritivo e transversal. Amostra: 1.294 membros de uma comunidade universitária, margem de erro de 3,0%; nível de confiança de 97,0%. Amostragem por conveniência. As informações foram coletadas por meio da plataforma Google Forms®, mediante um questionário de quatorze perguntas, distribuídas em três categorias: reconhecimento do evento, acionamento do sistema de emergência e atendimento inicial. Cumpriram-se os requisitos éticos para a pesquisa em saúde na Colômbia. Resultados: 62,7% dos participantes identificaram as ações para reconhecer uma parada cardiorrespiratória e, embora 83,6% ligassem para o pronto-socorro nessas situações, apenas 37,0% afirmaram conhecer o número de telefone. A suspeita de síndrome coronariana aguda é um evento considerado por 68,2% como uma emergência; o mesmo não acontece com o acidente vascular cerebral, onde apenas 52,1% tinham essa clareza. 81,4% descreveram ações corretas diante de uma vítima com obstrução grave de via aérea por corpo estranho e 50,6% se a obstrução for leve. Conclusão: o nível de conhecimento da comunidade universitária quanto ao atendimento à parada cardíaca extra-hospitalar é baixo, predominantemente relacionado às manobras de reanimação cardiopulmonar e ao funcionamento do desfibrilador externo automático. É necessária a implementação de estratégias educacionais voltadas para todas as comunidades, e esta pode ser uma oportunidade de desenvolvimento para o profissional de enfermagem nos diferentes campos de atuação.

Expression of the Wilms' tumour gene and its association with PPARß/δ in healthy skin and melanoma of horses.

The Wilms' tumour gene (WT1) has previously been described as an oncogene in several neoplasms of humans, including melanoma, and its expression increases cancer cell proliferation. Recent reports associate the expression of the PPARß/δ gene (peroxisome proliferator-activated receptor beta/delta) with the downregulation of WT1 in human melanoma and murine melanoma cell lines. The aim of this work was to analyse the expression of WT1 and its association with PPARß/δ in samples of healthy and melanoma-affected skin of horses by immunohistochemistry. WT1 protein expression was detected in healthy skin, mainly in the epidermis, hair follicle, sebaceous gland and sweat gland, while no expression was observed in equine melanoma tissues. Moreover, it was observed that PPARß/δ has a basal expression in healthy skin and that it is overexpressed in melanoma. These results were confirmed by a densitometric analysis, where a significant increase of the WT1-positive area was observed in healthy skin (128.66 ± 19.84 pixels 106) compared with that observed in melanoma (1.94 ± 0.04 pixels 106). On the other hand, a positive area with an expression of PPARß/δ in healthy skin (214.94 ± 11.85 pixels 106) was significantly decreased compared to melanoma (624.86 ± 181.93 pixels 106). These data suggest that there could be a regulation between WT1 and PPARß/δ in this disease in horses.

Current status of the rheumatologists' workforce in Latin America: a PANLAR collaborative study.

INTRODUCTION: Studies conducted by various scientific societies have shown that the demand for specialized rheumatology care is greater than the projected growth of the workforce. Our research aims to assess the current status of the rheumatology workforce in Latin America. METHOD: This is a descriptive, cross-sectional study. A survey was created on the RedCap platform. Data were analyzed with STATA 15® Software. We present descriptive analyses. The rate of inhabitants per rheumatologist was calculated using the number of rheumatologists practicing in each country and the inhabitants for year 2020. RESULTS: Our sample was composed by 19 PANLAR member countries in Latin America. Latin America has one rheumatologist per 106,838 inhabitants. The highest rate of rheumatologist per inhabitants was found in Uruguay (1 per 27,426 inhabitants), and the lowest was found in Nicaragua (1 per 640,648 inhabitants). Mean age was 51.59 (SD12.70), ranging between 28 and 96 years of age. Mean monthly compensation was USD $2382.6 (SD$1462.5). The country with lowest salary was Venezuela ($197), whereas the highest was Costa Rica ($4500). CONCLUSIONS: There is a high variability in rheumatologists' workforce characteristics in Latin America. These results could lead to policies aiming to increase the availability and income of rheumatologists, in order to increase opportunity and quality of care of patients living with rheumatic diseases. Key Points • The rheumatologists' workforce varies significantly among Latin American countries. • The supply of rheumatologists is insufficient for meeting the increasing need for specialists in this field.

Inhibitory Effect of Cuphea aequipetala Extracts on Murine B16F10 Melanoma In Vitro and In Vivo.

Cuphea aequipetala (C. aequipetala) has been used in Mexican traditional medicine since prehispanic times to treat tumors. In this paper, we evaluated the antiproliferative and apoptotic effect of the methanolic and aqueous extracts of C. aequipetala on several cancer cell lines including the B16F10 cell line of murine melanoma and carried a murine model assay. In vitro assay analyzed the effect in the cellular cycle and several indicators of apoptosis, such as the caspase-3 activity, DNA fragmentation, phosphatidylserine exposure (Annexin-V), and induction of cell membrane permeabilization (propidium iodide) in the B16F10 cells. In vivo, groups of C57BL/6 female mice were subcutaneously injected with 5x105 B16F10 cells and treated with 25 mg/mL of C. aequipetala extracts via oral. Aqueous and methanolic extracts showed a cytotoxic effect in MCF-7, HepG2, and B16F10 cell lines. The methanolic extract showed more antiproliferative effect with less concentration, and for this reason, the in vitro experiments were only continued with it. This extract was able to induce accumulation of cells on G1 phase of the cell cycle; moreover, it was able to induce DNA fragmentation and increase the activity of caspase-3 in B16F10 cells. On the other hand, in the murine model of melanoma, the aqueous extract showed a greater reduction of tumor size in comparison with the methanolic extract, showing an 80% reduction versus one of around 31%, both compared with the untreated control, indicating a better antitumor effect of C. aequipetala aqueous extract via oral administration. In conclusion, the in vitro data showed that both C. aequipetala extracts were able to induce cytotoxicity through the apoptosis pathway in B16F10 cells, and in vivo, the oral administration of aqueous extract reduces the melanoma tumoral mass, suggesting an important antitumoral effect and the perspective to search for effector molecules involved in it.

WT1 expression as a potential biomarker of malignancy in canine breast tumor / La expresión de WT1 como un biomarcador potencial maligno en un tumor de mama canino

SUMMARY: Veterinary oncology is very important nowadays to get a better understanding of human carcinogenesis. Estrogen receptor, progesterone receptor and Human Epidermal Growth Factor receptor 2 are frequently evaluated by immunohistochemistry (HIC) in human breast tumor. WT1 is an oncogene, its overexpression has been detected in leukemia and diverse solid tumors like breast cancer, lung cancer and mesothelioma in humans. WT1 expression was evaluated in 15 canine breast tumors (CBT) diagnosed by histopathological analysis to find its relationship with neoplasia and malignancy. IHC and RT-PCR were performed in CBT tissues. Fisher´s test was used to analyze WT1 relationship with malignancy. Of the 15 tumors, 9 (60 %) were diagnosed as benign and 6 (40 %) were malignant. With IHC, WT1 expression was positive only in biopsies diagnosed as malignant. Expression of WT1 by RT-PCR was detected in 14 of the 15 tumors (93.33 %) as well as in control healthy mammary gland. Clinical significance: This study describes for the first time a close correlation between CBT and a positive result for WT1 expression with IHC; hence, it can be used as a biomarker for this neoplasia and as an indicator of malignancy. RT-PCR analysis also showed to be good option to detect WT1 expression. These results will be useful to further investigations to elucidate WT1-related signaling pathways in CBT. Also to know molecules that regulate the translation of this protein as a marker for tumor progression.

RESUMEN: La oncología veterinaria es muy importante hoy en día para comprender mejor la carcinogénesis humana. El receptor de estrógeno, el receptor de progesterona y el receptor 2 del factor de crecimiento epidérmico humano se evalúan con frecuencia mediante inmunohistoquímica (HIC) en tumores de mama humanos. WT1 es un oncogén, su sobreexpresión se ha detectado en leucemia y en diversos tumores sólidos como el cáncer de mama, cáncer de pulmón y mesotelioma en humanos. La expresión de WT1 se evaluó en 15 tumores de mama caninos (TCC) diagnosticados mediante análisis histopatológico para encontrar su relación con la neoplasia y la malignidad. IHC y RT-PCR se realizaron en tejidos CBT. La prueba de Fisher se utilizó para analizar la relación de WT1 con la malignidad. De los 15 tumores, 9 (60 %) fueron diagnosticados como benignos y 6 (40 %) fueron malignos. Con IHC, la expresión de WT1 fue positiva solo en biopsias diagnosticadas como malignas. La expresión de WT1 por RT-PCR se detectó en 14 de los 15 tumores (93,33 %), así como en el control de la glándula mamaria sana. Importancia clínica: este estudio describe por primera vez una estrecha correlación entre la TCC y un resultado positivo para la expresión de WT1 con IHC; por lo tanto, se puede utilizar como un biomarcador para esta neoplasia y como un indicador de malignidad. El análisis por RT-PCR también demostró ser una buena opción para detectar la expresión de WT1. Estos resultados serán útiles para futuras investigaciones para dilucidar las vías de señalización relacionadas con WT1 en la TCC. También para conocer moléculas que regulan la traducción de esta proteína como marcador de progresión tumoral.

Rubens y la artritis reumatoidea / Rubens and rheumatoid arthritis

El estudio de las pinturas barrocas, especialmente las de origen flamenco, permiten evidenciar en algunas de sus figuras signos físicos sugestivos de enfermedad. Peter Paul Rubens constituye uno de los máximos representantes de esta corriente artística. Se cree que Rubens padeció artritis reumatoidea (AR) y que retrató el desarrollo y progresión de su propia enfermedad en varias obras de arte. Este artículo relata brevemente la vida de Rubens y describe algunos de sus trabajos centrados en la figura humana con alteraciones articulares que podrían corresponder a una AR

The study of baroque paintings, especially those of Flemish origin, makes it possible to show in some of their figures physical signs suggestive of disease. Peter Paul Rubens constitutes one of the maximum representatives of this artistic current. It is believed that Rubens suffered from rheumatoid arthritis (RA) and that he portrayed the development and progression of his own disease in several works of art. This article briefly recounts Rubens' life and describes some of his works focused on the human figure with joint alterations that could correspond to an AR

Renoir y la artritis reumatoidea / Renoir and rheumatoid arthritis

Renoir constituye uno de los pintores más representativos del movimiento impresionista. Su amplia producción artística centrada en la figura humana muestra su habilidad con el pincel que no se vio limitada por el desarrollo de la Artritis Reumatoide (AR) que lo aquejaba. En esta reseña histórica se repasan aspectos de la vida de Renoir relacionados con la historia natural de la enfermedad y sus estrategias para mitigar el dolor y la limitación funcional que le permitieron continuar produciendo importantes obras de arte

Renoir is one of the most representative painters of the impressionist movement. His extensive artistic production centered on the human figure shows his ability with the brush that was not limited by the development of Rheumatoid Arthritis (RA) that afflicted him. In this historical review, we inspect aspects of Renoir's life related to the natural history of the disease and its strategies to mitigate pain and functional limitation, which allowed him to continue producing important works of art

Quantitative analysis of TNF-α, IL-4, and IL-10 expression, nitric oxide response, and apoptosis in Encephalitozoon cuniculi-infected rabbits.

The expression of tumor necrosis factor (TNF) -α, interleukin (IL) -4 and IL-10, as well as apoptosis and nitric oxide (NO) levels were measured in the brain and kidneys of immunocompetent and immunosuppressed New Zealand White rabbits infected with Encephalitozoon cuniculi. All of the animals had clinical signs histopathological lesions compatible with encephalitozoonosis and were E. cuniculi-positive by using a carbon immunoassay test. Encephalitozoon cuniculi infection promoted the expression of TNF-α and NO production in the kidneys of infected rabbits, and a synergic effect was observed in animal treated with dexamethasone. The IL-4 expression was similar in the brain and kidneys of infected rabbits, regardless of their immunologic status. The IL-10 mRNA expression in the brain of infected immunosuppressed rabbits was elevated when compared with positive controls. Apoptosis of granuloma mononuclear-like cells was detected in immunocompetent E. cuniculi-infected rabbits, but it was more evident in infected-immunosuppressed animals. Nitric oxide levels were elevated both in immunocompetent and immunosuppressed infected animals, but it was more apparent in the kidneys. These data suggest that modulation of the immune response by E. cuniculi could contribute to the survival of the parasite within phagocytic cells in granulomas via an as yet undetermined mechanism.

Phosphodiesterase 4b expression plays a major role in alcohol-induced neuro-inflammation.

It is increasingly evident that alcohol-induced, gut-mediated peripheral endotoxemia plays a significant role in glial cell activation and neuro-inflammation. Using a mouse model of chronic alcohol feeding, we examined the causal role of endotoxin- and cytokine-responsive Pde4 subfamily b (Pde4b) expression in alcohol-induced neuro-inflammation. Both pharmacologic and genetic approaches were used to determine the regulatory role of Pde4b. In C57Bl/6 wild type (WT) alcohol fed (WT-AF) animals, alcohol significantly induced peripheral endotoxemia and Pde4b expression in brain tissue, accompanied by a decrease in cAMP levels. Further, along with Pde4b, there was a robust activation of astrocytes and microglia accompanied by significant increases in the inflammatory cytokines (Tnfα, Il-1ß, Mcp-1 and Il-17) and the generalized inflammatory marker Cox-2. At the cellular level, alcohol and inflammatory mediators, particularly LPS, Tnfα and Hmgb1 significantly activated microglial cells (Iba-1 expression) and selectively induced Pde4b expression with a minimal to no change in Pde4a and d isoforms. In comparison, the alcohol-induced decrease in brain cAMP levels was completely inhibited in WT mice treated with the Pde4 specific pharmacologic inhibitor rolipram and in Pde4b-/- mice. Moreover, all the observed markers of alcohol-induced brain inflammation were markedly attenuated. Importantly, glial cell activation induced by systemic endotoxemia (LPS administration) was also markedly decreased in Pde4b-/- mice. Taken together, these findings strongly support the notion that Pde4b plays a critical role in coordinating alcohol-induced, peripheral endotoxemia mediated neuro-inflammation and could serve as a significant therapeutic target.

Dysregulation of hepatic cAMP levels via altered Pde4b expression plays a critical role in alcohol-induced steatosis.

Alcohol-induced hepatic steatosis is a significant risk factor for progressive liver disease. Cyclic adenosine monophosphate (cAMP) signalling has been shown to significantly regulate lipid metabolism; however, the role of altered cAMP homeostasis in alcohol-mediated hepatic steatosis has never been studied. Our previous work demonstrated that increased expression of hepatic phosphodiesterase 4 (Pde4), which specifically hydrolyses and decreases cAMP levels, plays a pathogenic role in the development of liver inflammation/injury. The aim of this study was to examine the role of PDE4 in alcohol-induced hepatic steatosis. C57BL/6 wild-type and Pde4b knockout (Pde4b(-/-) ) mice were pair-fed control or ethanol liquid diets. One group of wild-type mice received rolipram, a PDE4-specific inhibitor, during alcohol feeding. We demonstrate for the first time that an early increase in PDE4 enzyme expression and a resultant decrease in hepatic cAMP levels are associated with the significant reduction in carnitine palmitoyltransferase 1A (Cpt1a) expression. Notably, alcohol-fed (AF) Pde4b(-/-) mice and AF wild-type mice treated with rolipram had significantly lower hepatic free fatty acid content compared with AF wild-type mice. Importantly, PDE4 inhibition in alcohol-fed mice prevented the decrease in hepatic Cpt1a expression via the Pparα/Sirt1/Pgc1α pathway. These results demonstrate that the alcohol- induced increase in hepatic Pde4, specifically Pde4b expression, and compromised cAMP signalling predispose the liver to impaired fatty acid oxidation and the development of steatosis. Moreover, these data also suggest that hepatic PDE4 may be a clinically relevant therapeutic target for the treatment of alcohol-induced hepatic steatosis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Liver Injury Assessment by Vetscan VS2 Analyzer and Most Frequently Used ALT/GTP Reagent.

BACKGROUND AND AIM: Liver injury is estimated by serum alanine aminotransferases (ALT) levels in experimental animal models. Laboratories use various techniques to measure ALT levels including assay reagents and chemistry analyzers. VetScan VS2 (VS2) is widely used in veterinary clinics and research laboratories for highly reproducible, convenient and effective testing. Alternatively, ALT liquid reagent is used by laboratories to estimate liver injury in animal studies. The aim of this study was to perform comparative analyses of data obtained from these two assays in two different animal models. METHODS: In this study, we used two different mouse models and compared the ALT levels measured using VetScan VS2 chemistry analyzer and ALT liquid reagent. Immunohistochemical analysis of hepatic tissue was also performed to document liver pathology. The first model is a high fat diet feeding model that results in a mild hepatic steatosis (fat accumulation in the liver) without elevation of ALT levels. For a severe liver injury model, we employed a hepatotoxin-induced liver injury model (carbon tetrachloride, CCl4), which leads to the development of hepatic fibrosis and very high ALT levels. RESULTS: VetScan VS2 and ALT reagent gave different values of ALT for all animal groups. However, linear regression analysis showed a significantly high association between ALT levels obtained by VS2 and ALT liquid reagent in a high-fat feeding model with no liver injury. For the CCl4 induced liver injury model, serum dilution (5 and 10 times) was performed to obtain accurate results with ALT reagent. ALT levels acquired from both techniques showed a close association. Interestingly, this correlation was closer when serum was diluted 5 fold. CONCLUSION: This study demonstrates that both methods give similar results when evaluating liver injury in animal studies. However, the serum dilution factor is critical for severe liver injury assessment when using ALT reagent and requires some optimization. In this regard, VetScan VS2 is easier to use and gives comparable results.