Actividad de glutatión peroxidasa en bovinos lecheros a pastoreo correlacionada con la concentración sanguinea y plasmática de selenio

Con el objeto de validar una técnica para determinar la actividad sanguínea de glutatión peroxidasa (GSH-Px; EC 1.11.1.9) en el Laboratorio de Patología Clínica de la Universidad Austral de Chile y establecer la correlación entre su actividad y la concentración sanguínea y plasmática de selenio (Se) en bovinos a pastoreo en rebaños lecheros del sur de Chile, se tomaron 5-10 mL de sangre heparinizada a 112 vacas de ocho rebaños en la provincia de Valdivia. La actividad enzimática se analizó mediante una técnica cinética, y el Se por activación de neutrones. Fueron calculadas la inexactitud e imprecisión de la técnica cinética y se describen el rango, promedio y desviación estándar de la actividad enzimática. La correlación entre la actividad sanguínea de GSH-Px y la concentración de Se fue obtenida mediante el coeficiente de correlación simple. La inexactitud e imprecisión fueron 5,9% y 10%, respectivamente. La actividad de GSH-Px fue 89 ± 45 U/g de hemoglobina (Hb) y la correlación entre las variables señaladas fue r=0,97 (P<0,05). Según estos resultados, es posible recomendar el uso rutinario de la técnica descrita. La correlación señalada permite anotar que en bovinos a pastoreo la actividad de GSH-Px está relacionada con la concentración sanguínea de selenio.

Atividade do herbicida acetochlor em solo submetido à semeadura direta e ao preparo convencional

Com o objetivo de estudar a atividade do herbicida acetochlor em Argissolo Vermelho submetido à semeadura direta e ao preparo convencional, foram conduzidos experimentos no campo e em laboratório. O herbicida apresentou menor controle das plantas daninhas na semeadura direta do que sob preparo convencional. A redução de matéria seca de trigo na amostra de solo coletada na profundidade de 16-19 cm foi superior sob semeadura direta, indicando maior potencial de lixiviação do herbicida neste sistema de preparo. Os valores de coeficiente de partição do herbicida no solo (Kd) foram de 2,75 e 1,67 L kg-1 em relação ao solo sob semeadura direta e preparo convencional, respectivamente, indicando que o primeiro apresentou maior capacidade de sorver acetochlor. O coeficiente de partição em relação ao teor de carbono orgânico (Koc) foi de 166 e 126 L kg-1 no solo cultivado em semeadura direta e sob preparo convencional, respectivamente, sugerindo que o herbicida foi sorvido em maior intensidade pela matéria orgânica do solo sob semeadura direta.

Franceschetti hereditary recurrent corneal erosion.

PURPOSE: To describe new affected individuals of Franceschetti's original pedigree of hereditary recurrent erosion and to classify a unique entity called Franceschetti corneal dystrophy. DESIGN: Observational case series. METHODS: Slit-lamp examination of 10 affected individuals was conducted. Biomicroscopic examinations were supplemented by peripheral corneal biopsy in 1 affected patient with corneal haze. Tissue was processed for light and electron microscopy and immunohistochemistry was performed. DNA analysis was carried out in 12 affected and 3 nonaffected family members. RESULTS: All affected individuals suffered from severe ocular pain in the first decade of life, attributable to recurrent corneal erosions. Six adult patients developed bilateral diffuse subepithelial opacifications in the central and paracentral cornea. The remaining 4 affected individuals had clear corneas in the pain-free stage of the disorder. Histologic and immunohistochemical examination of the peripheral cornea in a single patient showed a subepithelial, avascular pannus. There was negative staining with Congo red. DNA analysis excluded mutations in the transforming growth factor beta-induced (TGFBI) gene and in the tumor-associated calcium signal transducer 2 (TACSTD2) gene. CONCLUSION: We have extended the pedigree of Franceschetti corneal dystrophy and elaborated its natural history on the basis of clinical examinations. A distinctive feature is the appearance of subepithelial opacities in adult life, accompanied by a decreased frequency of recurrent erosion attacks. Its clinical features appear to distinguish it from most other forms of dominantly inherited recurrent corneal erosion reported in the literature.

The Oncogene ATF3 Is Potentiated by Cyclosporine A and Ultraviolet Light A.

Cutaneous squamous cell carcinoma (SCC) represents the most important cutaneous complication following organ transplantation. It develops mostly on sun-exposed areas. A recent study showed the role of activating transcription factor 3 (ATF3) in SCC development following treatment with calcineurin inhibitors. It has been reported that ATF3, which may act as an oncogene, is under negative calcineurin/nuclear factor of activated T cells (NFAT) control and is upregulated by calcineurin inhibitors. Still, these findings do not fully explain the preferential appearance of SCC on chronically sun-damaged skin. We analyzed the influence of UV radiation on ATF3 expression and its potential role in SCC development. We found that ATF3 is a specifically induced AP1 member in SCC of transplanted patients. Its expression was strongly potentiated by combination of cyclosporine A and UVA treatment. UVA induced ATF3 expression through reactive oxygen species-mediated nuclear factor erythroid 2-related factor 2 (NRF2) activation independently of calcineurin/NFAT inhibition. Activated NRF2 directly binds to ATF3 promoter, thus inducing its expression. These results demonstrate two mechanisms that independently induce and, when combined together, potentiate the expression of ATF3, which may then force SCC development. Taking into account the previously defined role of ATF3 in the SCC development, these findings may provide an explanation and a mechanism for the frequently observed burden on SCCs on sun-exposed areas of the skin in organ transplant recipients treated by calcineurin inhibitors.

Complicated intra-abdominal infections in Europe: a comprehensive review of the CIAO study.

ABSTRACT: The CIAO Study ("Complicated Intra-Abdominal infection Observational" Study) is a multicenter investigation performed in 68 medical institutions throughout Europe over the course of a 6-month observational period (January-June 2012).Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.2,152 patients with a mean age of 53.8 years (range: 4-98 years) were enrolled in the study. 46.3% of the patients were women and 53.7% were men. Intraperitoneal specimens were collected from 62.2% of the enrolled patients, and from these samples, a variety of microorganisms were collectively identified.The overall mortality rate was 7.5% (163/2.152).According to multivariate analysis of the compiled data, several criteria were found to be independent variables predictive of patient mortality, including patient age, the presence of an intestinal non-appendicular source of infection (colonic non-diverticular perforation, complicated diverticulitis, small bowel perforation), a delayed initial intervention (a delay exceeding 24 hours), sepsis and septic shock in the immediate post-operative period, and ICU admission.Given the sweeping geographical distribution of the participating medical centers, the CIAO Study gives an accurate description of the epidemiological, clinical, microbiological, and treatment profiles of complicated intra-abdominal infections (IAIs) throughout Europe.

Cytotoxic T-cell and NK-cell Lymphomas: Current Questions and Controversies.

The cytotoxic T-cell and natural killer (NK)-cell lymphomas and related disorders are important but relatively rare lymphoid neoplasms that frequently are a challenge for practicing pathologists. This selective review, based on a meeting of the International Lymphoma Study Group, briefly reviews T-cell and NK-cell development and addresses questions related to the importance of precise cell lineage (αβ-type T cell, γδ T cell, or NK cell), the implications of Epstein-Barr virus infection, the significance of anatomic location including nodal disease, and the question of further categorization of enteropathy-associated T-cell lymphomas. Finally, developments subsequent to the 2008 World Health Organization Classification, including the recognition of indolent NK-cell and T-cell disorders of the gastrointestinal tract are presented.

Angiostatic kinase inhibitors to sustain photodynamic angio-occlusion.

Targeted angiostatic therapy receives major attention for the treatment of cancer and exudative age-related macular degeneration (AMD). Photodynamic therapy (PDT) has been used as an effective clinical approach for these diseases. As PDT can cause an angiogenic response in the treated tissue, combination of PDT with anti-angiogenic compounds should lead to improved therapy. This study was undertaken to test the clinically used small molecule kinase inhibitors Nexavar® (sorafenib), Tarceva® (erlotinib) and Sutent® (sunitinib) for this purpose, and to compare the results to the combination of Visudyne®-PDT with Avastin® (bevacizumab) treatment. When topically applied to the chicken chorioallantoic membrane at embryo development day (EDD) 7, a clear inhibition of blood vessel development was observed, with sorafenib being most efficient. To investigate the combination with phototherapy, Visudyne®-PDT was first applied on EDD11 to close all <100 μm vessels. Application of angiostatics after PDT resulted in a significant decrease in vessel regrowth in terms of reduced vessel density and number of branching points/mm(2) . As the 50% effective dose (ED50) for all compounds was approximately 10-fold lower, Sorafenib outperformed the other compounds. In vitro, all kinase inhibitors decreased the viability of human umbilical vein endothelial cells. Sunitinib convincingly inhibited the in vitro migration of endothelial cells. These results suggest the therapeutic potential of these compounds for application in combination with PDT in anti-cancer approaches, and possibly also in the treatment of other diseases where angiogenesis plays an important role.

Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart.

BACKGROUND: Stem cell labeling with iron oxide (ferumoxide) particles allows labeled cells to be detected by magnetic resonance imaging (MRI) and is commonly used to track stem cell engraftment. However, the validity of MRI for distinguishing surviving ferumoxide-labeled cells from other sources of MRI signal, for example, macrophages containing ferumoxides released from nonsurviving cells, has not been thoroughly investigated. We sought to determine the relationship between the persistence of iron-dependent MRI signals and cell survival 3 weeks after injection of syngeneic or xenogeneic ferumoxides-labeled stem cells (cardiac-derived stem cells) in rats. METHODS AND RESULTS: We studied nonimmunoprivileged human and rat cardiac-derived stem cells and human mesenchymal stem cells doubly labeled with ferumoxides and beta-galactosidase and injected intramyocardially into immunocompetent Wistar-Kyoto rats. Animals were imaged at 2 days and 3 weeks after stem cell injection in a clinical 3-T MRI scanner. At 2 days, injection sites of xenogeneic and syngeneic cells (cardiac-derived stem cells and mesenchymal stem cells) were identified by MRI as large intramyocardial signal voids that persisted at 3 weeks (50% to 90% of initial signal). Histology (at 3 weeks) revealed the presence of iron-containing macrophages at the injection site, identified by CD68 staining, but very few or no beta-galactosidase-positive stem cells in the animals transplanted with syngeneic or xenogeneic cells, respectively. CONCLUSIONS: The persistence of significant iron-dependent MRI signal derived from ferumoxide-containing macrophages despite few or no viable stem cells 3 weeks after transplantation indicates that MRI of ferumoxide-labeled cells does not reliably report long-term stem cell engraftment in the heart.

Extended access cocaine self-administration differentially activates dorsal raphe and amygdala corticotropin-releasing factor systems in rats.

Cocaine-induced neuroadaptation of stress-related circuitry and increased access to cocaine each putatively contribute to the transition from cocaine use to cocaine dependence. The present study tested the hypothesis that rats receiving extended versus brief daily access to cocaine would exhibit regional differences in levels of the stress-regulatory neuropeptide corticotropin-releasing factor (CRF). A secondary goal was to explore how CRF levels change in relation to the time since cocaine self-administration. Male Wistar rats acquired operant self-administration of cocaine and were assigned to receive daily long access (6 hours/day, LgA, n = 20) or short access (1 hour/day, ShA, n = 18) to intravenous cocaine self-administration (fixed ratio 1, ∼0.50 mg/kg/infusion). After at least 3 weeks, tissue CRF immunoreactivity was measured at one of three timepoints: pre-session, post-session or 3 hours post-session. LgA, but not ShA, rats showed increased total session and first-hour cocaine intake. CRF immunoreactivity increased within the dorsal raphe (DR) and basolateral, but not central, nucleus of the amygdala (BLA, CeA) of ShA rats from pre-session to 3 hours post-session. In LgA rats, CRF immunoreactivity increased from pre-session to 3 hours post-session within the CeA and DR but tended to decrease in the BLA. LgA rats showed higher CRF levels than ShA rats in the DR and, pre-session, in the BLA. Thus, voluntary cocaine intake engages stress-regulatory CRF systems of the DR and amygdala. Increased availability of cocaine promotes greater tissue CRF levels in these extrahypothalamic brain regions, changes associated here with a model of cocaine dependence.

Influence of infusion line compliance on drug delivery rate during acute line loop formation.

OBJECTIVE: To determine whether infusion line compliance contributes to irregular drug delivery during vertical displacement of syringe pumps. DESIGN: Five different commercially available infusion lines were studied at infusion rates of 0.5, 1.0, and 1.5 ml/h. Zero drug delivery time was measured after acute line loop formation (70 cm) using an electronic balance. Compliance of each infusion line was calculated using a pressure transducer and measurement of the occlusion release bolus at 300 mmHg occlusion pressure. Finally, the influence of infusion line compliance on drug delivery during acute lowering of the syringe pump was studied using low- and high-compliance infusion lines. RESULTS: Acute line loop formation resulted in zero drug delivery time from 5.1 +/- 1.5 to 44.0 +/- 6.8 s at flow rates of 0.5 ml/h. Increased flow rates significantly reduced loop-induced flow variability. A close correlation was found between zero drug delivery time and calculated infusion line compliance at 0.5 ml/h (linear regression R2 = 0.79). Lowering of the syringe pump 50 cm prolonged zero drug delivery time from 295.8 +/- 20.7 s with the low-compliance tube to 463.3 +/- 24.0 s with the high-compliance infusion line. CONCLUSIONS: Infusion line compliance contributes to irregular drug delivery associated with vertical displacement of syringe pumps. Siphoning of the infusion line during patient care should be avoided, and flow rates of 1 ml/h or higher are recommended. Low-compliance infusion lines are indicated whenever highly short-acting vasoactive drugs at low delivery rates are administered.