Long chain capsaicin analogues synthetized by CALB-CLEAs show cytotoxicity on glioblastoma cell lines.

Glioblastoma is one of the most lethal tumors, displaying striking cellular heterogeneity and drug resistance. The prognosis of patients suffering from glioblastoma after 5 years is only 5%. In the present work, capsaicin analogues bearing modifications on the acyl chain with long-chain fatty acids showed promising anti-tumoral activity by its cytotoxicity on U-87 and U-138 glioblastoma multiforme cells. The capsaicin analogues were enzymatically synthetized with cross-linked enzyme aggregates of lipase B from Candida antarctica (CALB). The catalytic performance of recombinant CALB-CLEAs was compared to their immobilized form on a hydrophobic support. After 72 h of reaction, the synthesis of capsaicin analogues from linoleic acid, docosahexaenoic acid, and punicic acid achieved a maximum conversion of 69.7, 8.3 and 30.3% with CALB-CLEAs, respectively. Similar values were obtained with commercial CALB, with conversion yields of 58.3, 24.2 and 22% for capsaicin analogues from linoleic acid, DHA and punicic acid, respectively. Olvanil and dohevanil had a significant cytotoxic effect on both U-87 and U-138 glioblastoma cells. Irrespective of the immobilization form, CALB is an efficient biocatalyst for the synthesis of anti-tumoral capsaicin derivatives. KEY POINTS: • This is the first report concerning the enzymatic synthesis of capsaicin analogues from docosahexaenoic acid and punicic acid with CALB-CLEAs. • The viability U-87 and U-138 glioblastoma cells was significantly affected after incubation with olvanil and dohevanil. • Capsaicin analogues from fatty acids obtained by CALB-CLEAs are promising candidates for therapeutic use as cytotoxic agents in glioblastoma cancer cells.

Bioactividad e identificación de los ácidos grasos de la esponja marina Tetilla rodriguesi (Tetractinellida: Tetillidae) en el Caribe colombiano / Bioactivity and identification of fatty acids of the marine sponge Tetilla rodriguesi (Tetractinellida: Tetillidae) in the Colombian Caribbean

Resumen Introducción: Durante millones de años, los organismos marinos han venido desarrollando estrategias para adaptarse a los cambios ambientales y con esto, sintetizando una gran variedad de metabolitos secundarios con actividades biológicas. Objetivo: Evaluar las actividades antimicrobiana y antioxidante e identificar los ácidos grasos del extracto metanólico de la esponja marina Tetilla rodriguesi recolectada en la bahía de Cispatá. Métodos: Los especímenes de T. rodriguesi se sometieron a extracción para obtener el extracto metanólico, del cual se obtuvieron los ácidos grasos que fueron esterificados e identificados haciendo uso de técnicas cromatográficas. Con el extracto metanólico se realizó la actividad antioxidante frente a los radicales ABTS+• y DPPH• y la actividad antimicrobiana por el método de microdilución frente a cepas de referencia de Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis y Candida albicans; además de aislados clínicos de Candida albicans (obtenida en sangre) y Candida krusei (obtenida en catéter). Resultados: Los resultados arrojaron la identificación de 19 ácidos grasos de diferente naturaleza. En el análisis de la actividad antioxidante se pudo encontrar, que la inhibición de los radicales evaluados fue moderada (296.98 ppm para ABTS+• y 3 523.62 ppm para DPPH•). La evaluación de la actividad antimicrobiana mostró, que el extracto metanólico de T. rodriguesi logró reducir en gran medida el crecimiento de todos los microorganismos evaluados. Conclusión: A pesar de que los poríferos tienden a poseer ácidos grasos de gran tamaño, en este trabajó no se encontró la presencia de ácidos grasos de cadena carbonada mayor a 20 miembros. Los resultados de la actividad antioxidante, se asemejan en gran medida al encontrado en otras especies del mismo phylum. En esta investigación, se pudo establecer que el extracto metanólico de T. rodriguesi logró disminuir en gran medida el crecimiento de todas las cepas bacterianas y fúngicas utilizadas.

Abstract Introduction: For millions of years, organisms that inhabit the marine environment have been developing strategies to adapt to environmental changes and with this, synthesizing a great variety of secondary metabolites with biological activities. Objective: Evaluate the antimicrobial and antioxidant activities and identify the fatty acids of the methanolic extract of the marine sponge Tetilla rodriguesi collected in Cispatá bay, Colombian Caribbean. Methods: T. rodriguesi specimens were subjected to extraction to obtain the methanolic extract, of which the fatty acids were obtained, esterified and identified it using chromatographic techniques. With the methanolic extract, the antioxidant activity was carried out against the radicals ABTS+• and DPPH•, and the antimicrobial activity by the microdilution method against reference strains of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis and Candida albicans; in addition to clinical isolates of Candida albicans (obtained in blood) and Candida krusei (obtained in catheter). Result: The results yielded the identification of 19 fatty acids of different nature. In the analysis of the antioxidant activity could be found that inhibition of radical evaluated was moderate (296.98 ppm for ABTS+• and 3 523.62 ppm for DPPH•). The evaluation of antimicrobial activity showed that the methanol extract of T. rodriguesi managed to greatly reduce the growth of all microorganisms tested. Conclusions: Despite the fact that porifers tend to have large fatty acids, in this study the presence of fatty acids with a carbon chain greater than 20 members was not found. The result of antioxidant activity is largely resembled that found in other species of the same phylum. In this research, it was established that the methanolic extract of T. rodriguesi managed to greatly reduce the growth of all the bacterial and fungal strains used.

The Association of the First Surge of the COVID-19 Pandemic with the High- and Low-Value Outpatient Care Delivered to Adults in the USA.

BACKGROUND: The first surge of the COVID-19 pandemic entirely altered healthcare delivery. Whether this also altered the receipt of high- and low-value care is unknown. OBJECTIVE: To test the association between the April through June 2020 surge of COVID-19 and various high- and low-value care measures to determine how the delivery of care changed. DESIGN: Difference in differences analysis, examining the difference in quality measures between the April through June 2020 surge quarter and the January through March 2020 quarter with the same 2 quarters' difference the year prior. PARTICIPANTS: Adults in the MarketScan® Commercial Database and Medicare Supplemental Database. MAIN MEASURES: Fifteen low-value and 16 high-value quality measures aggregated into 8 clinical quality composites (4 of these low-value). KEY RESULTS: We analyzed 9,352,569 adults. Mean age was 44 years (SD, 15.03), 52% were female, and 75% were employed. Receipt of nearly every type of low-value care decreased during the surge. For example, low-value cancer screening decreased 0.86% (95% CI, -1.03 to -0.69). Use of opioid medications for back and neck pain (DiD +0.94 [95% CI, +0.82 to +1.07]) and use of opioid medications for headache (DiD +0.38 [95% CI, 0.07 to 0.69]) were the only two measures to increase. Nearly all high-value care measures also decreased. For example, high-value diabetes care decreased 9.75% (95% CI, -10.79 to -8.71). CONCLUSIONS: The first COVID-19 surge was associated with receipt of less low-value care and substantially less high-value care for most measures, with the notable exception of increases in low-value opioid use.

Leveraging Digital Technology to Reduce Cancer Care Inequities.

The rise of digital technologies such as telehealth, mobile apps, electronic medical records, and telementoring for rural primary care providers could provide opportunities for improving equity in cancer care delivery and outcomes. Benefitting from new technologies requires access to broadband internet, appropriate devices (smartphones, computers, etc.) along with basic digital literacy skills to use the devices. When these requirements are not met, the likelihood of widening existing inequities in access to care increases. This article introduces opportunities for improving cancer care using health informatics systems for engaging patients and flagging bias and existing videoconferencing technology to build workforce capacity. Policy recommendations for expanding evidence-based interventions are also highlighted, with the aim of mitigating the effects of workforce shortages and reducing persistent inequities in access to and quality of care.

Factors associated with the desire to undergo post-mastectomy breast reconstruction in a Mexican breast cancer center.

PURPOSE: To assess the proportion of breast cancer patients treated with total mastectomy who are interested in undergoing breast reconstruction, the factors associated with their desire to undergo this procedure, and the motives stated for their decision. METHODS: Women with stage I-III breast cancer, public health insurance, and history of total mastectomy treated at a center in Monterrey, Mexico, were invited to answer a series of questionnaires regarding their clinical and demographic characteristics, information received about breast reconstruction, body image, and relationship satisfaction. RESULTS: A total of 100 patients were interviewed, of which 68% desired to undergo breast reconstruction. Only 35% recalled talking about this procedure with a physician and 85% claimed not to have enough information to make an informed decision. Those who desired breast reconstruction were younger (p < 0.001), more likely to be in a relationship (p = 0.025), and had a higher probability of having talked to a physician about the procedure (p = 0.019). Furthermore, they felt less sexually attractive (p < 0.001), more deformed (p = 0.006), and less feminine (p = 0.005) since the mastectomy. The main motives to undergo this procedure were to have breast symmetry and greater freedom on which clothes to wear, while the main deterrent was the high economical cost. CONCLUSIONS: Insufficient information about the procedure and high economical cost were identified as potential barriers to undergo breast reconstruction. The findings of this study emphasize the pressing need to optimize patient care by providing information in a standardized manner and improving access to breast reconstruction within the Mexican public healthcare system.

Paragonimiasis pulmonar. Reporte de caso pediátrico / Pulmonary paragonimiasis. Pediatric case report

La paragonimiasis es una parasitosis provocada por varias especies de Paragonimus, un trematodo que se transmite a través del consumo de cangrejos poco cocidos o crudos y que se ha encontrado en áreas tropicales y subtropicales de América, Asia y África. Esta infección afecta, principalmente, los pulmones y provoca manifestaciones clínicas y radiológicas muy similares a la tuberculosis pulmonar, por lo cual siempre debe incluirse dentro del diagnóstico diferencial. Se presenta el caso de una niña escolar de 7 años de edad, hospitalizada con el diagnóstico de paragonimiasis pulmonar, quien presentó evolución favorable luego de recibir tratamiento con triclabendazol.

Paragonimiasis is a parasite infection caused by several species of Paragonimus, a trematode that is transmitted through the consumption of raw or undercooked crabs and that has been found in the subtropical areas of America, Asia and Africa. This infection mainly affects the lungs, causing clinical and radiological manifestations very similar to pulmonary tuberculosis, so it should always be included in the differential diagnosis. We present the case of a 7-year-old school patient, hospitalized with the diagnosis of pulmonary paragonimiasis, who had a favorable evolution after receiving treatment with triclabendazole.

Bioprospection of proteases from Halobacillus andaensis for bioactive peptide production from fish muscle protein

BACKGROUND: Biologically active peptides produced from fish wastes are gaining attention because their health benefits. Proteases produced by halophilic microorganisms are considered as a source of active enzymes in high salt systems like fish residues. Hence, the aim of this study was the bioprospection of halophilic microorganisms for the production of proteases to prove their application for peptide production. RESULTS: Halophilic microorganisms were isolated from saline soils of Mexico and Bolivia. An enzymatic screening was carried out for the detection of lipases, esterases, pHB depolymerases, chitinases, and proteases. Most of the strains were able to produce lipases, esterases, and proteases, and larger hydrolysis halos were detected for protease activity. Halobacillus andaensis was selected to be studied for proteolytic activity production; the microorganism was able to grow on gelatin, yeast extract, skim milk, casein, peptone, fish muscle (Cyprinus carpio), and soy flour as protein sources, and among these sources, fish muscle protein was the best inducer of proteolytic activity, achieving a protease production of 571 U/mL. The extracellular protease was active at 50°C, pH 8, and 1.4 M NaCl and was inhibited by phenylmethylsulfonyl fluoride. The proteolytic activity of H. andaensis was used to hydrolyze fish muscle protein for peptide production. The peptides obtained showed a MW of 5.3 kDa and a radical scavenging ability of 10 to 30% on 2,2-diphenyl-1-picrylhydrazyl and 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and a ferric reducing ability of plasma. Conclusion: The use of noncommercial extracellular protease produced by H. andaensis for biologically active peptide production using fish muscle as the protein source presents a great opportunity for high-value peptide production.

Pseudoscorpiones (arachnida) de isla fuerte y tortuguilla, caribe colombiano

En busca de contribuir al conocimiento de la fauna de invertebrados en la región Caribe de Colombia, se evaluó la fauna de pseudoescorpiones en dos zonas insulares continentales frente a la costa del departamento de Córdoba, la cual incluye a nueve especies, ocho géneros y seis familias. Se reporta por primera vez el género Solinus Chamberlin y se amplía la distribución conocida de Solinus corticola Chamberlin, 1923, hacia Colombia. Se efectúan consideraciones sobre las especies a los diferentes microhábitats (excepto Planctolpium arboreum Hoff, 1964). Se sugiere que el rafting y la foresia permitió la dispersión de estos géneros y especies desde el continente hacia las zonas insulares.

To contribute to the knowledge of the invertebrate fauna in the Caribbean region of Colombia, the pseudoscorpion fauna was evaluated in two continental islands zones in the coast of the department of Córdoba, which includes nine species distributed in eight genera and six families, the genus Solinus Chamberlin is reported for the first time and the known distribution of Solinus corticola Chamberlin, 1923 is extended to Colombia. Also, the adaptation of the species to the different microhabitats is considered (except for Planctolpium arboreum Hoff, 1964). It is suggested that the rafting and the phoresis allowed the dispersal of these genera and species from the mainland towards the insular zones.

Densidad poblacional y estructura de talla del pepino de mar Holothuria (Halodeima) grisea (Aspidochirotida: Holothuriidae) en aguas someras del sur del golfo de Morrosquillo, Caribe Colombiano / Density population and size structure of the sea cucumber Holothuria (Halodeima) grisea (Aspidochirotida: Holothuriidae) in shallow waters south of the gulf of Morrosquillo, Colombian Caribbean

Resumen Holothuria grisea, a pesar de no ser considerado un recurso comercial, ha sido objeto de extracciones ilegales en Colombia, hecho que se vuelve más grave debido al vació de información biológica de estos organismos. Por esta razón, se estimó la densidad poblacional y estructura de talla de H. grisea en tres sectores del sur del golfo de Morrosquillo de abril a noviembre 2015. Para ello, se ubicaron mensualmente tres transectos circulares en cada sector de muestreo abarcando un área de 300 m2, donde se contabilizaron y midieron in situ los individuos encontrados. La densidad media de H. grisea en el área estudiada fue 0.4 ind m-2, presentándose los mayores valores en el sector La Ahumadera (1.09 ± 0.11 ind m-2) y los menores valores en el Banco de Arena (0.02 ± 0.004 ind m-2). El análisis de varianza señalo una diferencia significativa en los valores de densidad y talla de H. grisea en los sectores estudiados. La especie presentó una distribución de tallas unimodal, registrándose una talla promedio de 13.5 ± 0.91 cm con una talla mínima de 2.5 y una máxima de 30 cm, en general las tallas intermedias presentaron una mayor representatividad a lo largo de este estudio (77.2 %). Los aspectos biológicos presentados en este documento son de gran importancia para la conservación de esta especie y corresponde a un avance en el conocimiento de la clase Holothuroidea en el Caribe Colombiano.

Abstract Holothuria grisea, despite not being considered a commercial resource has been the subject of illegal extractions in Colombia, a fact that becomes more serious due to the empty of biological information of these organisms. For this reason the density population and size structure of H. grisea were evaluated in three sectors south of the gulf of Morrosquillo from April to November 2015. To this end, three circular transects were located each month in each sampling site covering an area of 300 m2, where individuals were counted and measured in situ. The average density of H. grisea in the study area was 0.4 ind m-2, with the highest values in the La Ahumadera (1.09 ± 0.11 ind m-2) and the lowest values in Banco de Arena (0.02 ± 0.004 ind m-2). The analysis of variance showed a significance in the values of density and size of H. grisea in the studied sectors. The species presented a unimodal distribution of sizes with an average size of 13.5 ± 0.9 cm with a minimum size of 2.5 and a maximum of 30 cm, intermediate sizes generally showed a higher representativeness throughout this study (77.2 %). The biological aspects presented in this paper are of great importance for the conservation of this species and corresponds to an advance in the knowledge of the Holothuroidea class in the Colombian Caribbean. Rev. Biol. Trop. 66(2): 776-787. Epub 2018 June 01.

Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability.

INTRODUCTION: Colorectal medullary carcinoma (MC) is a rare subtype of poorly differentiated adenocarcinoma (PDA) with unclear prognostic significance. Microsatellite instable (MSI) colorectal carcinomas have demonstrated better prognosis in clinical stage II. AIM: To analyze the survival and clinicopathological characteristics of MCs versus PDAs with MSI in clinical stage III. MATERIAL AND METHODS: We studied 22 cases of PDAs with MSI versus 10 MCs. RESULTS: Of the 10 MCs, 7 patients were men; the mean age was 57.8 ±5.6 years. The mean tumor size was 9.6 ±4.1 cm, and the primary site was the right colon in 9; 7 patients showed lymph node metastases (LNM) and lymphovascular invasion (LVI). Of the 22 PDA cases, 12 (54.5%) were women with a mean age of 75 ±16.1 years. The mean tumor size was 6.4 ±3.2 cm. Twelve (54.5%) presented in the right colon, 21 (95.5%) showed LNM and 7 (31.8%) LVI. Follow-up was 32 ±8 months, with a 5-year overall survival of 42.9% for MCs and 76.6% for PDAs (p = 0.048). Univariate analysis found local recurrence (p = 0.001) and medullary subtype (p = 0.043) associated with lower survival. CONCLUSIONS: Medullary carcinomas were of greater tumor size and associated with more LVI and worse survival versus PDAs with MSI in stage III.

Satellitosis and CD117 immunohistochemical expression correlates with poor outcome in thick vulvar melanoma.

BACKGROUND: Melanoma of the vulva is the second most common vulvar cancer after epidermoid carcinoma. Patients suffering from this disease usually present with a late-stage disease with a poor prognosis. The prognostic factors reported in previous studies are not homogeneous and the clinical/pathogenic role of c-KIT expression is not clear. Breslow staging currently is the most accurate predictor factor. METHODS: A clinicopathological study with literature review was performed to identify predictors of prognosis and survival in melanoma of the vulva and investigated the expression of c-KIT (by immunohistochemistry) in 10 patients from the National Institute for Cancer Research (Mexico City). RESULTS: The 10 patients enrolled were all older women with delayed presentation, high-stage disease and limited response to treatment. Five patients (50%) were found to have c-KIT expression; 4 of them recurred (P=0.01), and ultimately 3 died (P=0.038). We identified satellitosis and c-KIT expression as prognostic predictors for death. CONCLUSIONS: We conclude that c-KIT expression is a valuable predictor of prognosis and survival, especially in thick (>4 mm) melanomas.

Mesorectal Invasion Depth in Rectal Carcinoma Is Associated With Low Survival.

BACKGROUND: Most cases of rectal cancer (RC) in our institution are in pathologic stage T3. They are a heterogeneous group but have been classified in a single-stage category. We performed the present study to validate the prognostic significance of the mesorectal extension depth (MED) in T3 RC measured in millimeters beyond the muscularis propria plane. MATERIALS AND METHODS: We performed a retrospective analysis of 104 patients with T3 RC who had undergone curative surgery after a course of preoperative chemoradiotherapy at a tertiary referral cancer hospital. The patients were grouped by MED (T3a, < 1 mm; T3b, 1-5 mm; T3c > 5-10 mm; and T3d > 10 mm). The clinicopathologic data and disease-free survival were analyzed. RESULTS: The 5-year disease-free survival rate according to the T3 subclassification was 87.5% for those with T3a, 57.9% for T3b, 38.7% for T3c, and 40.3% for those with T3d tumors (P = .050). On univariate and multivariate analysis, the prognostic factors affecting survival were overall recurrence (hazard ratio [HR], 3.670; 95% confidence interval [CI], 1.710-7.837; P = .001), histologic grade (HR, 2.204; 95% CI, 1.156-4.199; P = .016), mesorectal invasion depth (HR, 1.885; 95% CI, 1.164-3.052; P = .010), and lymph node metastasis (HR, 1.211; 95% CI, 1.015-1.444; P = .033). CONCLUSION: MED is a significant prognostic factor in patients with T3 RC who have undergone neoadjuvant chemoradiotherapy, especially when the MED is > 5 mm. The MED could be as important as other clinicopathologic factors in predicting disease-specific survival.

Melanoma in Mexico: Clinicopathologic Features in a Population with Predominance of Acral Lentiginous Subtype.

BACKGROUND: The aim of this study was to analyze the clinicopathologic features of melanoma in México as the demographics of melanoma are not well known in Mexican and Latin American people. MATERIALS AND METHODS: A total of 1219 patients with cutaneous melanoma were analyzed through a retrospective database collected from a cancer referral institute, and the results were compared with developed countries. RESULTS: Median age was 57 years, and 713 (58.5 %) were females. The most common melanoma subtype was acral lentiginous melanoma (ALM), which was observed in 538 (44.1 %) patients. Median Breslow thickness was 5.2 mm. Among 837 patients with complete data, the 5-year disease-specific survival (DSS) was 52.3 %. Factors associated with worse DSS on univariate analysis were Breslow thickness (p < 0.001), recurrence (p < 0.001), ulceration (p < 0.001), positive margin (p < 0.001), ALM (p = 0.001), and male sex (p = 0.001). Multivariate analysis demonstrated Breslow thickness [hazard ratio (HR) 1.45, 95 % confidence interval (CI) 1.27-1.65; p < 0.001], positive margin (HR 1.25, 95 % CI 1.03-1.57; p = 0.018), recurrence (HR 9.56, 95 % CI 6.89-9.87; p = 0.002), ALM (HR 8.07, 95 % CI 6.77-8.95; p = 0.004), and male sex (HR 1.33, 95 % CI 1.06-1.68; p = 0.013) as independent risk factors for DSS. CONCLUSION: Our patients had worse prognosis compared with data from the US Surveillance, Epidemiology, and End Results database. We found male sex and ALM as independent risk factors for worse survival, in addition to known risk factors.

Thyroid Transcription Factor-1 Expression in Adenocarcinomas of the Bile Duct.

BACKGROUND: The immunoreactivity of thyroid transcription factor-1 (TTF-1) is a very specific marker for lung and thyroid neoplasms; the expression of TTF-1 has also been demonstrated in extrapulmonary carcinomas. We examined the expression of TTF-1 in 15 intestinal-type adenocarcinomas of the extrahepatic bile duct. We then compared the expression to TTF-1 staining with other immunohistochemical markers including cytokeratin (CK) 7, CK20, caudal-type homeobox transcription factor 2 (CDX2), Napsin A, and MUC2. We additionally compared the clinicopathological prognostic factors with the TTF-1 expression status. RESULTS: Nuclear TTF-1 staining was detected in 2 cases (13.3%), and Napsin A was positive in the same 2 cases (13.3%). All cases were positive for CK20, CDX2, and MUC2; 5 cases were positive for CK7. There was no correlation between TTF-1 expression and the clinicopathological characteristics. CONCLUSIONS: To avoid potential pitfalls, TTF-1 should be interpreted in conjunction with the clinical setting, histology, and the results of markers such as CK7, CK20, Napsin A, and CDX2. This report is the first of TTF-1 positivity in adenocarcinomas from the extrahepatic biliary tract.

Diminished expression of CRHR2 in human colon cancer promotes tumor growth and EMT via persistent IL-6/Stat3 signaling.

BACKGROUND & AIMS: Chronic inflammation promotes development and progression of colorectal cancer (CRC). We explored the distribution of Corticotropin-Releasing-Hormone (CRH)-family of receptors and ligands in CRC and their contribution in tumor growth and oncogenic EMT. METHODS: mRNA expression of CRH-family members was analyzed in CRC (N=56) and control (N=46) samples, 7 CRC cell lines and normal NCM460 cells. Immunohistochemical detection of CRHR2 was performed in 20 CRC and 5 normal tissues. Cell proliferation, migration and invasion were compared between Urocortin-2 (Ucn2)-stimulated parental and CRHR2-overexpressing (CRHR2+) cells in absence or presence of IL-6. CRHR2/Ucn2-targeted effects on tumor growth and EMT were validated in SW620-xenograft mouse models. RESULTS: CRC tissues and cell lines showed decreased mRNA and protein CRHR2 expression compared to controls and NCM460, respectively. The opposite trend was shown for Ucn2. CRHR2/Ucn2 signaling inhibited cell proliferation, migration, invasion and colony formation in CRC-CRHR2+ cells. In vivo, SW620-CRHR2+ xenografts showed decreased growth, reduced expression of EMT-inducers and elevated levels of EMT-suppressors. IL-1b, IL-6 and IL-6R mRNAs where diminished in CRC-CRHR2+ cells, while CRHR2/Ucn2 signaling inhibited IL-6-mediated Stat3 activation, invasion, migration and expression of downstream targets acting as cell cycle- and EMT-inducers. Expression of cell cycle- and EMT-suppressors was augmented in IL-6/Ucn2-stimulated CRHR2+ cells. In patients, CRHR2 mRNA expression was inversely correlated with IL-6R and vimentin levels and metastasis occurrence, while positively associated with E-cadherin expression and overall survival. CONCLUSIONS: CRHR2 downregulation in CRC supports tumor expansion and spread through maintaining persistent inflammation and constitutive Stat3 activation. CRHR2low CRC phenotypes are associated with higher risk for distant metastases and poor clinical outcomes.

Mesorectal pathologic assessment in two grades predicts accurately recurrence, positive circumferential margin, and correlates with survival.

BACKGROUND AND OBJECTIVES: We aimed to determine the prognostic value of the mesorectum quality assessed in a two-grade system compared with a classic system. METHODS: Consecutive patients undergoing surgery for rectal cancer were included (n = 103). Mesorectum was assessed into three grades (classic system: complete, nearly complete, incomplete) and compared with a two-grade system (adequate, inadequate). RESULTS: Mesorectum was complete in 62 (60.25%) patients, nearly complete in 21, and incomplete in 20. Reassessment showed adequate mesorectum in 83 (80.5%) patients and inadequate in 20. A R0 resection was achieved in 90.4% of adequate mesorectum and in 65% of inadequate mesorectum (P = 0.006). Recurrence was present in 18% of adequate mesorectum patients as compared with 50% of inadequate mesorectum (P = 0.003). The classic system failed to accurately predict the 5-year survival rate between complete (78.9%) and nearly complete (86.2%) categories (P = 0.235); whereas a two grading system showed a 5-year survival rate of 80.8% for adequate versus 39.3% for inadequate (P = 0.034). CONCLUSION: High recurrence occurred in inadecuate mesorectum patients and was correlated with R1/R2 resections, positive margins, and decreased survival. We propose a simplified classification of mesorectum that correlates with survival and overall recurrence.

Hemangioma renal como causa de hematuria a propòsito de un caso / Renal hemangioma as a cause of hematuria in a 9 case

La pràctica ambulatoria asume hoy un papel protagònico en el sistema de salud.

Estado de la retina en pacientes miopes / State of retina in myopic patients

Se presenta el estudio descriptivo y lineal de 200 ojos correspondientes a 100 pacientes miopes en un periodo de 1 año atendidos en el Instituto Superior de Medicina Militar "Dr. Luis Díaz Soto". Se tuvieron en cuenta 4 grupos de edades, se dividieron en 3 grupos según grado de miopía y en 2 grupos relacionados con la frecuencia en que se revisaban la retina. Se obtuvieron que 154 ojos presentaban alteraciones: en retina periférica 40 ojos (25,97 %), en polo posterior 50 ojos (32,47 %) y ambas 64 ojos (41,56 %). Se encontró un predominio en el sexo femenino (95,22 %). El grupo de edad de 26 a 35 años tuvo el 100 % de sus pacientes afectados. Los que presentaron miopía alta fueron los de mayores alteraciones en retina periférica y polo posterior; la atrofia circumpapilar resultó la más encontrada. Solo e1 4 % de los pacientes estudiados se habían revisado la retina con anterioridad, el 1 % lo había realizado como establece la literatura médica. La crioterapia fue el tratamiento profiláctico más empleado en los 104 ojos con necesidad de este. La realización del examen de retina en los pacientes miopes de forma frecuente evita en gran porcentaje la aparición del desprendimiento de retina.

A descriptive and lineal study of 200 eyes corresponding to 100 myopic patients attended at "Dr. Luis Díaz Soto" Higher Military Medicine Institute in a year is presented. Four age groups were taken into account. They were divided into 3 groups according to the myopia degree, and into 2 groups regarding the frequency with which they checked their retinas. It was observed that 154 eyes presented alterations: 40 eyes (25.97 %), in peripheral retina; 50 eyes (32.47 %), in posterior pole; and 64 eyes (41.56 %) in both. It was observed a prevalence of females (95.22 %). 100 % of the patients included in the age group 26-35 were affected. The patients presenting high myopía had the greatest alterations in peripheral retina and posterior pole. Circumpapillary atrophy was the most found. Only 14 % of the studied patients had checked their retina before. 1 % had done it according to what is established by medical literature. Cryotherapy was the most used prophylactic treatment in the 104 eyes needing it. The frequent retina examination in myopic patients prevents in a great percent the appearance of retinal detachment.

Purification and biochemical characterization of the LIP2 lipase from Yarrowia lipolytica.

The LIP2 lipase from the yeast Yarrowia lipolytica (YLLIP2) was obtained from two genetically modified strains with multi-copies of the lip2 gene and further purified using gel filtration and cation exchange chromatography. Four YLLIP2 isoforms were identified and subjected to N-terminal amino-acid sequencing and mass spectrometry analysis. These isoforms differed in their glycosylation patterns and their molecular masses ranged from 36,874 to 38,481 Da, whereas the polypeptide mass was 33,385 Da. YLLIP2 substrate specificity was investigated using short (tributyrin), medium (trioctanoin) and long (olive oil) chain triglyceride substrates at various pH and bile salt concentrations, and compared with those of human gastric and pancreatic lipases. YLLIP2 was not inhibited by bile salts at micellar concentrations with any of the substrates tested, and maximum specific activities were found to be 10,760+/-115 U/mg on tributyrin, 16,920+/-480 U/mg on trioctanoin and 12,260+/-700 U/mg on olive oil at pH 6.0. YLLIP2 was found to be fairly stable and still active on long chain triglycerides (1590+/-430 U/mg) at pH 4.0, in the presence of bile salts. It is therefore a good candidate for use in enzyme replacement therapy as a means of treating pancreatic exocrine insufficiency.

Cyclooxygenase-2 induction by bradykinin in aortic vascular smooth muscle cells.

Vascular smooth muscle cell proliferation and migration play an important role in the pathophysiology of several vascular diseases, including atherosclerosis. Prostaglandins that have been implicated in this process are synthesized by two isoforms of cyclooxygenase (COX), with the expression of the regulated COX-2 isoform increased in atherosclerotic plaques. Bradykinin (BK), a vasoactive peptide increased in inflammation, induces the formation of prostaglandins through specific receptor activation. We hypothesized that BK plays an important role in the regulation of COX-2, contributing to the increase in production of prostaglandins in vascular smooth muscle cells. Herein we examined the signaling pathways that participate in the BK regulation of COX-2 protein levels in primary cultured aortic vascular smooth muscle cells. We observed an increase in COX-2 protein levels induced by BK that was maximal at 24 h. This increase was blocked by a B2 kinin receptor antagonist but not a B1 receptor antagonist, suggesting that the B2 receptor is involved in this pathway. In addition, we conclude that the activation of mitogen-activated protein kinases p42/p44, protein kinase C, and nitric oxide synthase is necessary for the increase in COX-2 levels induced by BK because either of the specific inhibitors for these enzymes blocked the effect of BK. Using a similar approach, we further demonstrated that reactive oxygen species and cAMP were not mediators on this pathway. These results suggest that BK activates several intracellular pathways that act in combination to increase COX-2 protein levels. This study suggests a role for BK on the evolution of the atheromatous plaque by virtue of controlling the levels of COX-2.