Endothelial ILK induces cardioprotection by preventing coronary microvascular dysfunction and endothelial-to-mesenchymal transition.

Endothelial dysfunction is an early event in coronary microvascular disease. Integrin-linked kinase (ILK) prevents endothelial nitric oxide synthase (eNOS) uncoupling and, thus, endothelial dysfunction. However, the specific role of endothelial ILK in cardiac function remains to be fully elucidated. We hypothesised that endothelial ILK plays a crucial role in maintaining coronary microvascular function and contractile performance in the heart. We generated an endothelial cell-specific ILK conditional knock-out mouse (ecILK cKO) and investigated cardiovascular function. Coronary endothelial ILK deletion significantly impaired cardiac function: ejection fraction, fractional shortening and cardiac output decreased, whilst left ventricle diastolic internal diameter decreased and E/A and E/E' ratios increased, indicating not only systolic but also diastolic dysfunction. The functional data correlated with extensive extracellular matrix remodelling and perivascular fibrosis, indicative of adverse cardiac remodelling. Mice with endothelial ILK deletion suffered early ischaemic-like events with ST elevation and transient increases in cardiac troponins, which correlated with fibrotic remodelling. In addition, ecILK cKO mice exhibited many features of coronary microvascular disease: reduced cardiac perfusion, impaired coronary flow reserve and arterial remodelling with patent epicardial coronary arteries. Moreover, endothelial ILK deletion induced a moderate increase in blood pressure, but the antihypertensive drug Losartan did not affect microvascular remodelling whilst only partially ameliorated fibrotic remodelling. The plasma miRNA profile reveals endothelial-to-mesenchymal transition (endMT) as an upregulated pathway in endothelial ILK conditional KO mice. Our results show that endothelial cells in the microvasculature in endothelial ILK conditional KO mice underwent endMT. Moreover, endothelial cells isolated from these mice and ILK-silenced human microvascular endothelial cells underwent endMT, indicating that decreased endothelial ILK contributes directly to this endothelial phenotype shift. Our results identify ILK as a crucial regulator of microvascular endothelial homeostasis. Endothelial ILK prevents microvascular dysfunction and cardiac remodelling, contributing to the maintenance of the endothelial cell phenotype.

Yersinia ruckeri infection activates local skin and gill B cell responses in rainbow trout.

Teleost fish lack organized structures in mucosal tissues such as those of mammals, but instead contain dispersed B and T cells with the capacity to respond to external stimuli. Nonetheless, there is still a great lack of knowledge regarding how B cells differentiate to plasmablasts/plasma cells in these mucosal surfaces. To contribute to a further understanding of the mechanisms through which fish mucosal B cells are activated, in the current study, we have studied the B cell responses in the skin and gills of rainbow trout (Oncorhynchus mykiss) exposed to Yersinia ruckeri. We have first analyzed the transcription levels of genes related to B cell function in both mucosal surfaces, and in spleen and kidney for comparative purposes. In a second experiment, we have evaluated how the infection affects the presence and size of B cells in both skin and gills, as well as the presence of plasmablasts secreting total or specific IgMs. The results obtained in both experiments support the local differentiation of B cells to plasmablasts/plasma cells in the skin and gills of rainbow trout in response to Y. ruckeri. Interestingly, these plasmablasts/plasma cells were shown to secrete specific IgMs as soon as 5 days after the exposure. These findings contribute to a further understanding of how B cells in the periphery respond to immune stimulation in teleost fish.

Accuracy of genomic within-family selection in aquaculture breeding programmes.

In aquaculture breeding programmes, selection within families cannot be applied for traits that cannot be recorded on the candidates (e.g., disease resistance or fillet quality). However, this problem can be overcome if genomic evaluation is used. Within-family genomic evaluation has been proposed for these programmes as large family sizes are available and substantial levels of linkage disequilibrium (LD) within families can be attained with a limited number of markers even in populations in global linkage equilibrium. Here, we compare by computer simulation: (i) within-family and population-wide LD; and (ii) the accuracy of within-family genomic selection when genomic evaluations are carried out either at the population level or within families. The population simulated was composed by a varying number of families of full-sibs (half for training and half for testing). The results indicate that, to practice within-family selection, performing the genomic evaluation separately for each family using only molecular information from the family could be recommended for populations either in linkage equilibrium or with a low level of disequilibrium.

Effect of pre-season and in-season training on anthropometric variables, somatotype, body composition and body proportion in elite basketball players.

The aims of the study were: 1) to evaluate the changes in anthropometric variables, body composition, somatotype and body proportions of elite basketball players throughout the pre-season period; 2) to evaluate the changes in anthropometric variables, body composition, somatotype and body proportions of elite basketball players throughout the in-season period; and 3) to observe if the age and position influenced the variables analyzed. A total of 17 players belonging to the men's ACB league team competing in the Euroleague (age = 23.42 ± 5.28 years-old) participated in the study. The players underwent an anthropometric measurement before and after the pre-season, as well as four evaluations throughout the in-season. Anthropometric indices, somatotype components according to Heath and Carter, and adiposity were calculated. The results show that during the pre-season, body mass, BMI, sum of 6 and 8 skinfolds, waist/hip ratio, adipose tissue (kg), adipose tissue percentage, and endomorphy decreased, while ectomorphy increased. However, no significant changes were found in the variables analyzed throughout the season; except for endomorphy, which increased along the in-season. Playing position and age did not have a significant influence on the changes in the anthropometric variables throughout the pre-season and the in-season. In conclusion, while changes in the anthropometric variables in the pre-season were observed, these remained the same during the in-season.

[Emergency detection of HIV infection in patients consulting for conditions potentially related to occult infection: Initial results of the "Urgències VIHgila" program]. / Detección en urgencias de infección por VIH en pacientes que consultan por condiciones potencialmente relacionadas con infección oculta: Resultados iniciales del programa "Urgències VIHgila".

OBJECTIVE: To estimate the prevalence of unknown HIV infection in patients who consulted in hospital emergency services (ED) for conditions defined in the SEMES-GESIDA Consensus Document (DC), evaluate the efficiency of its im-plementation and investigate the efficiency of HIV serology determination in other conditions. METHODS: Results were reviewed in 10 Catalan EDs for 12 months (July-21-June-22) after implementing CD recommendations: request HIV serology in case of suspected sexually transmitted infection, chemsex, post-exposure prophylaxis (PEP), mononucleosis syndrome, community pneumonia (18-65 y-o) or herpes zoster (18-65 y-o). Other reasons for request were included. Prevalence (%) of global seropositivity and for each circumstance was calculated, with a 95% confidence interval (95%CI). The efficient strategy was considered if the lower limit of the CI95%>0.1%. RESULTS: A total of5,107 HIV serologies were performed: 2,847(56%) in situations specified in CD, and 2,266 (44%) in other 138 circumstances. Forty-eight unknown HIV infections were detected (prevalence=0.94%;95%CI=0.69-1.24). The prevalence was somewhat higher in DC requests (30 cas-es 1.12%) than the rest (18 cases 0.71%; p=0.16). The individualized prevalence of CD reasons ranged between 7.41% (95%CI=0.91-24.3) in chemsex and 0.42% 95%CI=0.14-0.98) in PPE, always efficient except herpes zoster (0.76%; CI95%=0.02-4.18). In other reasons, cases were detected in 12 circumstances, and in four the determination could be efficient: lymphopenia (10%;CI95%=0.25-44.5), fever with polyarthralgia-polyarthritis (7.41%;CI95% =0.91-24.3), behavioral alteration-confusion-encephalopathy (3.45%;95%CI=0.42-11.9) and fever of unknown origin (2.50%;95%CI=0.82-5.74). CONCLUSIONS: The determination of HIV serology in HES in the processes defined by DC SEMES-GESIDA is efficient. Some circumstances are identified that could be added to those previously contemplated to increase efficiency.

Comparing three different methods to detect selective loci using dominant markers.

We carried out a simulation study to compare the efficiency of three alternative programs (DFDIST, DETSELD and BAYESCAN) to detect loci under directional selection from genome-wide scans using dominant markers. We also evaluated the efficiency of correcting for multiple testing those methods that use a classical probability approach. Under a wide range of scenarios, we conclude that BAYESCAN appears to be more efficient than the other methods, detecting a usually high percentage of true selective loci as well as less than 1% of outliers (false positives) under a fully neutral model. In addition, the percentage of outliers detected by this software is always correlated with the true percentage of selective loci in the genome. Our results show, nevertheless, that false positives are common even with a combination of methods and multitest correction, suggesting that conclusions obtained from this approach should be taken with extreme caution.

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway.

Epidemiological studies link long term exposure to xenoestrogen Bisphenol-A to adverse cardiovascular effects. Our previous results show that BPA induces hypertension by a mechanism involving CamKII activation and increased redox stress caused by eNOS uncoupling. Recently, CamKII sustained activation has been recognized as a central mediator of programmed cell death in cardiovascular diseases, including necroptosis. However, the role of necroptosis in cardiac response to BPA had not yet been explored. Mice exposed to BPA for 16 weeks showed altered heart function, electrical conduction, and increased blood pressure. Besides, a stress test showed ST-segment depression, indicative of cardiac ischemia. The hearts exhibited cardiac hypertrophy and reduced vascularization, interstitial edema, and large hemorrhagic foci accompanied by fibrinogen deposits. BPA initiated a cardiac inflammatory response, up-regulation of M1 macrophage polarization, and increased oxidative stress, coinciding with the increased expression of CamKII and the necroptotic effector RIP3. In addition, cell death was especially evident in coronary endothelial cells within hemorrhagic areas, and Evans blue extravasation indicated a vascular leak in response to Bisphenol-A. Consistent with the in vivo findings, BPA increased the necroptosis/apoptosis ratio, the expression of RIP3, and CamKII activation in endothelial cells. Necrostatin-1, an inhibitor of necroptosis, alleviated BPA induced cardiac dysfunction and prevented the inflammatory and hemorrhagic response in mice. Mechanistically, silencing of RIP3 reversed BPA-induced necroptosis and CamKII activation in endothelial cells, while inhibition of CamKII activation by KN-93 had no effect on RIP3 expression but decreased necroptotic cell death suggesting that BPA induced necroptosis is mediated by a RIP 3/CamKII dependent pathway. Our results reveal a novel pathogenic role of BPA on the coronary circulation. BPA induces endothelial cell necroptosis, promotes the weakening of coronary vascular wall, which caused internal ventricular hemorrhages, delaying the reparative process and ultimately leading to cardiac dysfunction.

Estabilidad fisicoquímica y microbiológica de un colirio de insulina 10 UI/mL / Physicochemical and microbiological stability of a 10 IU/mL insulin eye drop

Objetivo: Los pacientes con defectos epiteliales corneales persistentes son, a menudo, refractarios a los tratamientos convencionales. La insulina tópica surge como una posible alternativa, habiendo demostrado su efectividad y seguridad. Sin embargo, en la bibliografía actual disponible, hay una falta de estudios de estabilidad. El objetivo del presente trabajo fue evaluar la estabilidad fisicoquímica y microbiológica de un colirio de insulina 10 UI/ml durante 28 días. Método: Estudio de estabilidad fisicoquímica y microbiológica. Se elaboraron 2 lotes (A y B) de colirios de insulina 10 UI/ml, manteniendo el lote B cerrado hasta el día 15. Las variables fisicoquímicas analizadas fueron la concentración de insulina mediante inmunoanálisis quimioluminiscente, pH y osmolaridad. El estudio microbiológico se realizó mediante pruebas de esterilidad mientras que el estudio descriptivo se analizó mediante visualización directa. Resultados: No se observaron cambios significativos de concentración (±10%) en los colirios a excepción de 2 valores en una de las muestras del lote B. El pH y la osmolaridad se mantuvieron dentro de los rangos fisiológicos del ojo. No se observó crecimiento microbiano ni cambios en las características organolépticas. Conclusiones: Se puede considerar al colirio de insulina 10 UI/ml estable durante 28 días en refrigeración manteniendo el frasco abierto desde el día de su elaboración.(AU)

Objective: Patients with persistent corneal epithelial defects are often refractory to conventional treatments. Topical insulin emerges as a possible alternative of proven effectiveness and safety. However, in the current available literature, there is a lack of stability studies. The main objective of this study was to evaluate the physicochemical and microbiological stability of a 10 IU/ml insulin eye drop for 28 days. Methods: Physicochemical and microbiological stability study. Two batches (A and B) of 10 IU/ml insulin eye drops were prepared, keeping batch B closed until day 15. The physicochemical variables analysed were insulin concentration by chemiluminescent immunoassay, pH and osmolarity. The microbiological study was performed by sterility tests while the descriptive study was assessed by direct visualization. Results: No significant concentration changes (±10%) were observed in the eye drops except for 2 values in one of the samples from batch B. The pH and osmolarity remained within the physiological ranges of the eye. No microbiological growth or changes in organoleptic characteristics were observed. Conclusions: Insulin 10 UI/ml eye drops can be considered stable for 28 days under refrigeration if the bottle is kept open from the day of its preparation.(AU)

Highly dense linkage maps from 31 full-sibling families of turbot (Scophthalmus maximus) provide insights into recombination patterns and chromosome rearrangements throughout a newly refined genome assembly.

Highly dense linkage maps enable positioning thousands of landmarks useful for anchoring the whole genome and for analysing genome properties. Turbot is the most important cultured flatfish worldwide and breeding programs in the fifth generation of selection are targeted to improve growth rate, obtain disease resistant broodstock and understand sex determination to control sex ratio. Using a Restriction-site Associated DNA approach, we genotyped 18,214 single nucleotide polymorphism in 1,268 turbot individuals from 31 full-sibling families. Individual linkage maps were combined to obtain a male, female and species consensus maps. The turbot consensus map contained 11,845 markers distributed across 22 linkage groups representing a total normalised length of 3,753.9 cM. The turbot genome was anchored to this map, and scaffolds representing 96% of the assembly were ordered and oriented to obtain the expected 22 megascaffolds according to its karyotype. Recombination rate was lower in males, especially around centromeres, and pairwise comparison of 44 individual maps suggested chromosome polymorphism at specific genomic regions. Genome comparison across flatfish provided new evidence on karyotype reorganisations occurring across the evolution of this fish group.

Nitric oxide inhibition of coxsackievirus replication in vitro.

Nitric oxide is a radical molecule with antibacterial, -parasitic, and -viral properties. We investigated the mechanism of NO inhibition of Coxsackievirus B3 (CVB3) replication in vitro by determining the effect of NO upon a single replicative cycle of CVB3 grown in HeLa cells. Transfection of inducible NO synthase cDNA into HeLa cells reduces the number of viral particles produced during a single cycle of growth. Similarly, a noncytotoxic concentration of the NO donor S-nitroso-amino-penicillamine reduces the number of viral particles in a dose-dependent manner. To explore the mechanisms by which NO exerts its antiviral effect, we assayed the attachment, replication, and translation steps of the CVB3 life cycle. NO does not affect the attachment of CVB3 to HeLa cells. However, NO inhibits CVB3 RNA synthesis, as shown by a [3H]uridine incorporation assay, reverse transcription-PCR, and Northern analysis. In addition, NO inhibits CVB3 protein synthesis, as shown by [35S]methionine protein labeling and Western blot analysis of infected cells. Thus, NO inhibits CVB3 replication in part by inhibiting viral RNA synthesis by an unknown mechanism.

Efectividad y seguridad en vida real de nivolumab en el tratamiento del cáncer de pulmón no microcítico en segunda línea / Real-life efficacy and safety of nivolumab in the treatment of second-line non-small cell lung cáncer

Objetivo: Evaluar la efectividad y el perfil de seguridad de nivolumab utilizado en segunda línea en el tratamiento del cáncer de pulmón no microcítico en la práctica clínica real. Material y métodos: Estudio observacional retrospectivo en pacientes con cáncer de pulmón no microcítico en tratamiento con nivolumab en segunda línea entre diciembre-2015 y noviembre-2019. Se evaluó la respuesta mediante criterios RECIST v1.1 (Response Evaluation Criteria in Solid Tumors). Variables principales de efectividad: tasa de respuesta objetiva (TRO) y supervivencia global (SG); variables secundarias: supervivencia libre de progresión (SLP). Los posibles factores predictores de respuesta (edad, sexo, histología y ECOG-PS -Eastern Cooperative Oncology Gropup-Performance status-) se analizaron mediante un modelo de riesgos proporcionales de Cox para la SG Y SLP, y odds ratio para TRO. La seguridad se evaluó mediante la aparición de eventos adversos (EAs) y su grado según CTCEA v5.0 (Criterios Comunes de Terminología para Eventos Adversos).Resultados: Se incluyeron 48 pacientes, con una mediana de edad de 65,5 años (rango 46-83), mayoritariamente hombres (85,5%), ECOG-PS 0-1 (85%). En cuanto a la efectividad, TRO=27% (IC95% 14,04-40,12), mediana SG 13,01 meses (IC95% 7,67-18,36) y SLP 5,29 meses (IC95% 3,53-7,05). El sexo se identificó como factor predictor de mejor respuesta en términos de TRO. Un 10% de los pacientes presentaron al menos un EA G3-G4.Conclusiones: Nivolumab tuvo una efectividad ligeramente superior a la demostrada en ensayos clínicos. La seguridad del tratamiento fue aceptable, posicionando nivolumab como una alternativa válida en el tratamiento de cáncer de pulmón no microcítico en segunda línea. (AU)

Objective: To evaluate the effectiveness and safety profile of nivolumab used in second line for the treatment of non-small cell lung cancer in real clinical practice. Material and methods: Retrospective observational study was carried off in patients with non-small cell lung cancer treated with nivolumab in the second line between December 2015 and November 2019. The response was evaluated using RECIST v1.1 criteria. Main survival variables: objective response rate (ORR) and overall survival (OS); secondary variables: progression-free survival (PFS). The possible predictive response factors (age, sex, histology and ECOG-PS) were analyzed using a Cox proportional hazard model for survival, and odds ratio for the objective response rate. The safety was evaluated through the occurrence of adverse events (AD) and their degree according to CTCEA v5.Results: 48 patients were included, median age of 65.5 years (range 46-83), mostly men (85.5%), ECOG-PS 0-1 (85%). Regarding effectiveness, ORR=27% (95% CI 14.04-40.12), median SG 13.01 months (95% CI 7.67-18.36) and SLP 5.29 months (95% CI 3.53-7.05). Sex was identified as a predictor of better response in terms of ORR. EA G3-G4 appeared in 10% of patients.Conclusions: Nivolumab had a slightly higher effectiveness than demonstrated in clinical trials. The safety of the treatment was acceptable, positioning nivolumab as a valid alternative in the treatment of non-small cell lung cancer in second line. (AU)

Resultados en vida real de los antivirales de acción directa en el tratamiento de la hepatitis C crónica / Real life results of direct acting antiviral in hepatitis C treatment

Objetivo: Los antivirales de acción directa han logrado tasas de respuesta viral sostenida muy elevadas desde su comercialización. El objetivo de este trabajo fue el análisis de la efectividad y seguridad de los antivirales de acción directa en pacientes infectados por el virus de la hepatitis C crónica.Métodos: Se incluyeron pacientes infectados con el virus de la hepatitis C (VHC) y coinfectados por VHC y virus de la inmunodeficiencia humana (VIH) que iniciaron tratamiento con antivirales de acción directa entre 2015-2019. Como variable de efectividad se midió la respuesta viral sostenida.Resultados: Se incluyeron 303 pacientes, 235 (77,56%) monoinfectados y 68 (22,44%) coinfectados. El genotipo de virus más prevalente fue el 1 en ambos grupos. La proporción de cirróticos fue superior en la población monoinfectada 38,3% vs. 20,6%; p=0,047). De los 303 pacientes, a 279 se le analizó la carga viral a las 12 semanas de tratamiento; un 97,8% (273/279) alcanzaron respuesta viral sostenida, confirmándose 6 fracasos virológicos. En un análisis de subgrupos, en la mayoría de grupos según la presencia o no de cirrosis, la coinfección VIH y el genotipo, la efectividad se situó próxima o por encima del 90%. El tratamiento fue seguro, con toxicidad leve y sólo una suspensión de tratamiento. Se detectaron interacciones medicamentosas potenciales en un 20% de los pacientes.Conclusiones: Los antivirales de acción directa presentaron una efectividad elevada, igual e incluso superior a la descrita en los ensayos clínicos, e incluso en subpoblaciones difíciles de tratar. (AU)

Objetive: Direct-acting antivirals have achieved high sustained viral response rates since their commercialization. The main objective of this study was the analysis of the efficacy and safety of direct-acting antivirals in patients infected with the chronic hepatitis C virus.Methods: Patients infected with hepatitis C virus (HCV) and co-infected with HCV and human immunodeficiency virus (HIV) who started treatment with direct-acting antiviral drugs between 2015-2019 were included. The sustained viral response was measured as the effectivity variable.Results: 303 patients were included, 235 (77.56%) were monoinfected and 68 (22.44%) were co-infected. Genotype 1 virus was the most prevalent 1 in both groups. The proportion of cirrhotic was higher in the monoinfected population (38.3% vs. 20.6%; p=0.047). Of the 303 patients, 279 pacients had viral load analysis at 12 weeks of treatment, 97.8% (273/279) achieved sustained viral response and 6 virological failures were confirmed. In a subgroup analysis, the majority of the groups, regardless of the presence or not of cirrhosis, HIV coinfection or genotype, the efficacy was close to or above 90%. The treatment was safe, with mild toxicity and only one treatment suspension. Potential drug interactions were detected in 20% of patients.Conclusions: Direct-acting antivirals with a high efficacy, equal to or greater than that described in clinical trials, and even with subpopulations difficult to treat. (AU)

Interaction of interferon regulatory factor-1 and nuclear factor kappaB during activation of inducible nitric oxide synthase transcription.

We investigated the molecular mechanism for the synergistic induction of inducible nitric oxide synthase transcription by TNF-alpha and IFN-gamma. Since TNF-alpha and IFN-gamma stimulate cells in part by activating NF-kappaB and IRF-1, we hypothesized that these two transcription factors interact with each other. IRF-1 and NF-kappaB co-localize in the nucleus of stimulated macrophages. Co-immunoprecipitation experiments show that IRF-1 and NF-kappaB interact in stimulated but not resting cells. Super-shift experiments show that IRF-1 and NF-kappaB interact while binding to their respective DNA binding sites. These results demonstrate the existence of a physical interaction between IRF-1 and NF-kappaB proteins in vivo. We next suggested that this interaction between IRF-1 and NF-kappaB bends the DNA of the iNOS promoter region. Using a cyclization assay, we demonstrate that nuclear extracts from stimulated cells accelerate the rate of conversion of a linear to circular DNA, compared to extracts from resting cells. However, stimulated nuclear extracts cannot affect the rate of cyclization of a promoter with a mutant IRE or kappaB site. Furthermore, stimulated nuclear extracts depleted of IRF-1 and NF-kappaB cannot induce cyclization. We conclude that IRF-1 and NF-kappaB interact in vivo, and that this interaction physically bends the indicible nitric oxide synthase promoter DNA. This interaction may explain the mechanism by which IFN-gamma synergistically augments inducible nitric oxide synthase transcription.

[Medico-economic impact of an innovative management of CHF by HF unit]. / Analyse médico-économique de l'impact d'une prise en charge de l'insuffisance cardiaque chronique en unité thérapeutique d'insuffisance cardiaque versus prise en charge habituelle de ville.

Chronic heart failure remains a frequent, severe and costly disease. Despite encouraging data from different countries, heart failure clinics are scarce in France. We have analyzed the impact of a heart failure clinic (UTIC of Pontoise) in terms of reduction of rehospitalizations and in hospitalization costs in 4855 consecutive patients. In our study, heart failure clinic management dramatically reduces HF related hospitalizations (RRR: -28 %, P=0.001) and HF related costs (55% reduction, P<0.001) regardless of comorbidities or disease severity. HF clinics have to be developed in France in order to optimize management of CHF and reduce the HF related costs.

Hydrogen peroxide regulation of bovine endothelin-converting enzyme-1.

Vascular injury leads to the production of reactive oxygen species (ROS), but the mechanisms by which ROS contribute to vascular pathology are not completely understood. We hypothesized that ROS increase endothelin converting enzyme (ECE-1) expression. We found that glucose oxidase (GO) increases ECE-1 mRNA, protein, and activity in bovine aortic endothelial cells. Catalase abolishes this effect. Glucose oxidase treatment of endothelial cells transactivates the ECE-1 promoter. The ECE-1 promoter element that mediates this response to GO is located between -444 and -216 bp. This region contains a STAT response element, and GO activates STAT-3 binding to this STAT response element. Our data suggest that STAT3 mediates hydrogen peroxide induction of ECE-1 expression.

Computed tomography findings of peritoneal tuberculosis: systematic review of seven patients diagnosed in 6 years (1996-2001).

OBJECTIVE: The aim of this study was to describe the computed tomography (CT) findings in patients with demonstrated peritoneal tuberculosis (TB) and their concordance with the three types from the traditional classification (wet, fibrotic, and dry plastic). METHODS: We reviewed the CT images of all patients with microbiologically proven peritoneal tuberculosis over a 6-year period (1996-2001). RESULTS: Seven patients were included. Ascites was present in 5 patients (free ascites in 3 patients and loculated in 2). Involvement of the mesentery was found in 5 patients, the omentum in 4, and the parietal peritoneum in 3. Tuberculous lymphadenitis was the most common associated finding (6 patients). Two patients had hepatic lesions. The fibrotic type was found in all the patients, and 5 patients had an association of the fibrotic and wet types. None of the patients had lesions consistent with the dry plastic type. CONCLUSION: Peritoneal tuberculosis is best described as a combination of ascites, peritoneal lesions, and lymphadenopathy, rather than the three types from the traditional classification.

FT-IR spectroscopy of natural melanins isolated from Harding-Passey mouse melanoma.

The alterations caused on the structure of melanins by acid and alkaline extraction methods were studied by means of techniques such as Fourier Transform Infrared spectroscopy and thermogravimetry. Acid extraction results in the hydrolysis of aromatic monomers of the pigment, leading to uncyclicized residues and to a less conjugated polymer. Alkaline methods catalyse the covalent binding of proteins present in the melanin extract, thus leading to melanoprotein artifacts. A new method based on the delipidation with ether and deproteinization with SDS of previously isolated melanosomes is proposed. This method shows that melanins present in Harding-Passey mouse melanoma have a bound protein moiety, so that they should exist "in vivo" as melanoprotein complexes. Thermogravimetric data suggest that the chromogen moiety of the melanoproteins in Harding-Passey mouse melanoma is a mixture of eu- and pheomelanins.

[Treatment of neoplastic hypercalcemia]. / Tratamiento de la hipercalcemia neoplásica.

Hypercalcemia (HC) is a frequent complication of tumoral disease which should always be treated, tumor therapy being the best treatment. Occasionally, it can prove to be a medical emergency and should be treated without delay, especially where high risk patients are concerned. Sometimes, the treatment is not successful due to the fact that the drugs used in acute crises, although effective, have high toxicity; meanwhile, the drugs used for chronic HC lack the desired level of effectiveness and, in addition, tolerance problems are also implicated. In this paper, we consider the therapeutic schedule, based on physiopathologic mechanisms; and, the various drugs presently being used are reviewed. The therapeutic attitude to be followed during HC is indicated.

[The diagnostic and therapeutic outlooks in the diffuse pulmonary hemorrhage syndrome]. / Actitud diagnóstico terapéutica en el síndrome de hemorragia pulmonar difusa.

Diffuse pulmonary hemorrhage syndrome (DPHS) is reviewed and classified according to the international classification. We analyse the more characteristic features, as well as the most appropriate diagnosis methods which ensure early and effective treatment. We conclude by proposing the therapeutic attitude to be taken for DPHS.

The genome-wide structure of two economically important indigenous Sicilian cattle breeds.

Genomic technologies, such as high-throughput genotyping based on SNP arrays, provided background information concerning genome structure in domestic animals. The aim of this work was to investigate the genetic structure, the genome-wide estimates of inbreeding, coancestry, effective population size (Ne), and the patterns of linkage disequilibrium (LD) in 2 economically important Sicilian local cattle breeds, Cinisara (CIN) and Modicana (MOD), using the Illumina Bovine SNP50K v2 BeadChip. To understand the genetic relationship and to place both Sicilian breeds in a global context, genotypes from 134 other domesticated bovid breeds were used. Principal component analysis showed that the Sicilian cattle breeds were closer to individuals of Bos taurus taurus from Eurasia and formed nonoverlapping clusters with other breeds. Between the Sicilian cattle breeds, MOD was the most differentiated, whereas the animals belonging to the CIN breed showed a lower value of assignment, the presence of substructure, and genetic links with the MOD breed. The average molecular inbreeding and coancestry coefficients were moderately high, and the current estimates of Ne were low in both breeds. These values indicated a low genetic variability. Considering levels of LD between adjacent markers, the average r(2) in the MOD breed was comparable to those reported for others cattle breeds, whereas CIN showed a lower value. Therefore, these results support the need of more dense SNP arrays for a high-power association mapping and genomic selection efficiency, particularly for the CIN cattle breed. Controlling molecular inbreeding and coancestry would restrict inbreeding depression, the probability of losing beneficial rare alleles, and therefore the risk of extinction. The results generated from this study have important implications for the development of conservation and/or selection breeding programs in these 2 local cattle breeds.