SKELETAL MUSCLE SENSITIVITY TO WASTING INDUCED BY UROTHELIAL CARCINOMA.

BACKGROUND: Skeletal muscle wasting is a common phenotypic feature of several types of cancer, and it is associated with functional impairment, respiratory complications, and fatigue. However, equivocal evidence remains regarding the impact of cancer-induced muscle wasting on the different fiber types. AIM: The aim of this study was to investigate the impact of urothelial carcinoma induced in mice on the histomorphometric features and collagen deposition in different skeletal muscles. MATERIALS AND METHODS: Thirteen ICR (CD1) male mice were randomly assigned into two groups: exposed to 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water for 12 weeks, plus 8 weeks of tap water (BBN, n = 8) or with access to tap water for 20 weeks (CONT, n = 5). Tibialis anterior, soleus, and diaphragm muscles were collected from all animals. For cross-sectional area and myonuclear domain analysis, muscle sections were stained with hematoxylin and eosin, and for collagen deposition assessment, muscle sections were stained with picrosirius red. RESULTS: All animals from the BBN group developed urothelial preneoplastic and neoplastic lesions, and the tibialis anterior from these animals presented a reduced cross-sectional area (p < 0.001), with a decreased proportion of fibers with a higher cross-sectional area, increased collagen deposition (p = 0.017), and higher myonuclear domain (p = 0.031). BBN mice also showed a higher myonuclear domain in the diaphragm (p = 0.015). CONCLUSION: Urothelial carcinoma induced muscle wasting of the tibialis anterior, expressed by a decreased cross-sectional area, higher infiltration of fibrotic tissue, and increased myonuclear domain, which also increased in the diaphragm, suggesting that fast glycolytic muscle fibers are more susceptible to be affected by cancer development.

Asymmetrical Brain Plasticity: Physiology and Pathology.

The brain is inherently asymmetrical. How that attribute, manifest both structurally (volumetric, cytological, molecular) as well as functionally, relates to cognitive function, is not fully understood. Since the early descriptions of Paul Broca and Marc Dax it has been known that the processing of language in the brain is fundamentally asymmetrical. Contemporary imaging studies have corroborated early observations, and have also revealed significant functional links to multiple other systems, such as those sub serving memory or emotion. Recent studies have demonstrated that laterality is both plastic and adaptive. Learning and training have shown to affect regional changes in asymmetry, such as that observed in the volume of the planum temporale associated with musical practice. Increasing task complexity has been demonstrated to induce recruitment of contralateral regions, suggesting that laterality is a manifestation of functional reserve. Indeed, in terms of cognitive function, successful aging is often associated with a reduction of asymmetrical activity. The goal of this review is to survey and critically appraise the current literature addressing brain laterality, both morphological and functional, with particular emphasis on the asymmetrical plasticity associated with environmental factors and training. The plastic recruitment of contralateral areas associated with aging and unilateral lesions will be discussed in the context of the loss of asymmetry as a compensatory mechanism, and specific instances of maladaptive plasticity will be explored.

Unilateral accumbal dopamine depletion affects decision-making in a side-specific manner.

Mechanisms underlying affective and cognitive deficits in Parkinson's disease (PD) remain less studied than motor symptoms. Nucleus accumbens (NAc) is affected in PD and due to its well-known involvement in motivation is an interesting target in this context. Furthermore, PD is frequently asymmetrical, with side-specific deficits aligning with evidences of accumbal laterality. We therefore used a 6-hydroxydopamine (6-OHDA) model to study the role of left and right NAc dopamine depletion in a battery of behavioral tasks. 2 months old male rats were used in all experiments. Habitual-based and goal-directed decision-making, impulsivity, anxiety- and depressive-like behavior and motor performance were tested 3 weeks after left (6-OHDA L) or right (6-OHDA R) NAc lesion was induced. Upon contingency degradation, 6-OHDA R decrease their lever press rate less than Sham and 6-OHDA L, indicating an impairment in the shift from habit-based to goal-directed strategies. On the other hand, 6-OHDA L lesions lead to increased rates of premature responding when delays where increased in the variable delay-to-signal test. Importantly, in both paradigms task acquisition was similar between groups. In the same line we found no differences in the amount of sugared pellets eaten when freely available as well as in both general and fine motor behaviors. In conclusion, left and right NAc play distinct roles in the contingency degradation and impulsivity. More studies are needed to understand the mechanisms behind this functional lateralization and its implications for PD patients.

Modulación de marcadores de inflamación y estrés oxidativo en pacientes con diabetes tipo 1 y sobrepeso que participan en un programa de cambio de estilo de vida / Modulation of Inflammatory and oxidative stress markers in overweight type 1 Diabetes patients participating in a lifestyle change program

Introduction: Reduction in the expression of inflammatory markers and oxidative stress associated with exercise will protect against cardiovascular complications in Diabetes Mellitus (DM). Aim: The aim of this study was evaluated cardiovascular fitness (VO2 Max), interleukin-6 (IL-6), monocyte chemo-attractant protein 1 (MCP-1) and serum lipid peroxidation (TBARS) in overweight patients with Type-1 diabetes (T1DM) participating in a lifestyle-change program. Results: 20 T1DM overweight patients (43.3 ± 13.8 years), with BMI= 29.6 ± 3.5 kg/m2 , initial HbA1c 7.9 ± 0.91% and treated with multiple insulin injections, were included in this work. The lifestyle-change program consisted of: a) walking 10,000 steps/day, b) sequence of exercises of 24 minutes, 3-5 times/week, c) ¨healthy-plate¨ (and counting carbohydrates, and d) prandial insulin as blood-glucose levels. VO2 max, HbA1c, TBARS, IL6, MCP-1 were determined before starting the lifestyle-change program. Six months of adherence later, participants showed an average number of steps of 8242 ± 1834, a significant increase in VO2 max, (33.4 ±1.3 vs 36.2 ±1.5 ml.Kg-1.min-1 p= 0.008), a significant decrease in serum MCP-1 (314 ±42 vs 235 ±43 MFI p= 0.02), and less TBARS (3.01 ±0.44 vs 2.12 ±0.22 µmol/mL p= 0.015). IL-6 and HbA1c showed no significant decrease. Conclusion: Our results showed that a 6-month systemized and simple exercise plan improves cardiorespiratory fitness (VO2 max), and reduces both circulating oxidative stress and inflammation markers in overweight patients with T1DM.

Introducción: La reducción en la expresión de marcadores inflamatorios y de estrés oxidativo asociado con el ejercicio podría proteger contra las complicaciones cardiovasculares de la diabetes mellitus (DM). Objetivo: El objetivo de este estudio fue evaluar en pacientes con DM tipo1 (DMT1) y sobrepeso, la capacidad cardiorespiratoria (VO2 Max), la expresión sérica de marcadores inflamatorios (IL-6 y MCP-1) y la peroxidación lipídica sérica (TBARS), luego de participar por 6 meses de un programa de cambios de estilo de vida. Resultados: Veinte pacientes adultos (43.3 ± 13.8 años), de ambos sexos, con un Índice de Masa Corporal de 29.6 ± 3.5 kg/m2 , HbA1c inicial de 7,9% ± 0,91, en tratamiento con inyecciones múltiples de insulina participaron del estudio. Se indicó: 1) caminar 10.000 pasos/día, 2) realizar en domicilio una secuencia de ejercicios de 20 minutos, 3-5 veces/semana, 3) plato saludable (consumo de 1 fruta antes de las 3 comidas principales), 4) Insulina prandial según glucemia y conteo de carbohidratos. Se registraron parámetros antropométricos, presión arterial, se determinó VO2 max, y se midieron los niveles séricos de HbA1c, IL6, MCP-1 y TBARs. Luego de seis meses, los participantes alcanzaron un número promedio de pasos de 8242 ± 1834 y mostraron un aumento significativo en VO2 max, (33.4 ±1.3 vs 36.2 ±1.5 ml.Kg-1.min-1 p= 0.008). Además, se encontró una disminución significativa de MCP-1 (314 ±42 vs 235 ±43 MFI p=0.02) y TBARs (3.01 ±0.44 vs 2.12 ±0.22 µmol/mL p= 0.015) en comparación con el día 0. No se observaron modificaciones en los niveles de IL-6 y HbA1c. Conclusión: Nuestros resultados demuestran que el ejercicio, implementado como un plan accesible y acompañado, es adecuado para reducir los riesgos de inflamación y estado pro-oxidativo en pacientes con DM tipo1.

Florid cutaneous papillomatosis as a marker of neoplastic recurrence.

Florid cutaneous papillomatosis is a rare paraneoplastic dermatosis, most commonly associated with gastric adenocarcinoma. It is characterized by a sudden onset of hyperkeratotic papules, clinically indistinguishable from viral warts. We report an 80-year-old man who presented to our department with a two-month history of multiple verrucous lesions affecting the face, perioral region, and hands. Two years before, he was treated for a gastric adenocarcinoma with a subtotal gastrectomy, but showed no evidence of residual disease or recurrence. Given the clinical background, a diagnosis of florid cutaneous papillomatosis was considered. Skin biopsy excluded a viral origin, and tumour recurrence was later identified through an abdominal ultrasound. The onset of this entity is typically prior or concurrent with the diagnosis of the internal malignancy, but it may also represent the first sign of recurrence of a previously treated neoplasm. Its early recognition is essential to ensure a thorough investigation and prompt treatment.

Información, percepción de riesgo y comportamientos en relación con las zoonosis en adultos de la ciudad de Córdoba / Information, risk perception and behaviors in relation to zoonoses in adults in the city of Córdoba

INTRODUCCIÓN Muchas de las actuales enfermedades emergentes y re-emergentes en seres humanos son transmitidas por animales. OBJETIVOS Analizar la información, percepción y comportamientos en relación con las zoonosis en adultos de 18 años o más en la ciudad de Córdoba. MÉTODOS Se realizó un estudio mixto cuanti-cualitativo. Para la etapa cuantitativa se diseñó un estudio transversal y correlacional, mediante la realización de una encuesta para recabar datos sociodemográficos, factores de riesgo, información y comportamientos en relación con las zoonosis. El muestreo fue aleatorio, polietápico y estratificado. El análisis de datos se realizó de forma descriptiva y mediante análisis bivariado. Para la etapa cualitativa se utilizó la teoría fundamentada, a los fines de indagar los argumentos que explican la percepción y/o comportamientos de riesgo de las enfermedades zoonóticas. Los datos fueron recabados mediante entrevista en profundidad y observación participante y para el análisis de datos se utilizó el Método Comparativo Constante. RESULTADOS Se observó que el 91% percibe que es riesgo para la salud la presencia de aguas estancadas y el 62% considera que es alto, presentando asociación significativa con NE alto; el 93% percibe como riesgo la presencia de basura acumulada y el 69% la considera de alto riesgo; el 59% declaró tener mascotas. La mayoría de los encuestados dijo tener conocimiento sobre las enfermedades zoonóticas, aunque, a excepción de rabia, no sabían explicar como ocurría el contagio. De los resultados cualitativos se puede observar que, si bien el nivel de información es importante ante comportamientos de cuidados preventivos para las zoonosis, existen otros factores ligados a los valores, nociones y creencias que influyen en ellos. Discusión El conocimiento sobre las enfermedades zoonóticas resulta fundamental, constituyendo la base de las medidas de intervención para la salud. Estos resultados constituyen un insumo para la formulación de acciones de promoción de la salud y prevención de enfermedades zoonóticas.

Extraspinal osteoarticular multidrug-resistant tuberculosis in children: A case series.

BACKGROUND: South Africa (SA) is known to have a high disease burden of tuberculosis (TB). Extraspinal osteoarticular multidrug-resistant tuberculosis (ESOA MDR-TB) in children has only been described in a few case reports worldwide. OBJECTIVES: To describe the epidemiology and highlight the potential problem of ESOA MDR-TB infections as seen in children from a single academic hospital in SA. METHODS: A retrospective record review was performed on all children diagnosed with ESOA TB infection at Chris Hani Baragwanath Academic Hospital, Johannesburg, between 1 January 2006 and 31 December 2015. All patients with a positive TB culture (fluid or tissue) from the surgical site of biopsy (bone or joint) and who were hospitalised were included. Organism culture and drug sensitivity testing were performed. RESULTS: Overall 19 cases of ESOA TB were identified. Areas involved included the shoulder (2 cases), elbow (2 cases), hip (7 cases), knee (4 cases), ankle (3 cases) and humerus (1 case). The mean age of the population was 7.7 (range 2.0 - 14.0) years. The mean white cell count was 11.3 (range 5 - 28.9) × 109/L, the mean C-reactive protein level 53.8 (range 1.0 - 364.0) mg/L and the mean erythrocyte sedimentation rate 35.5 (range 4.0 - 85.0) mm/h. Two cases (10.5%) were MDR, and a further case (5.3%) was resistant to isoniazid only. Four of 12 patients tested positive for HIV. One of the HIV-positive patients was isoniazid resistant. The two positive ESOA MDR-TB cases are discussed in detail. CONCLUSIONS: These findings indicate that ESOA MDR-TB is a reality in this paediatric population (10.5%) and a high index of suspicion should be maintained, especially when cultures are negative in children with signs and symptoms of ESOA TB. The effect of HIV infection on the incidence of ESOA MDR-TB requires further study.

Structural laterality is associated with cognitive and mood outcomes: An assessment of 105 healthy aged volunteers.

The human brain presents multiple asymmetries that dynamically change throughout life. These phenomena have been associated with cognitive impairments and psychiatric disorders although possible associations with specific patterns of cognitive aging are yet to be determined. We have therefore mapped and quantified morphological asymmetries in a heterogeneous and aged population (65.2±8.0 years old, 52 male and 53 female) to explore potential associations between the asymmetries in specific brain regions and cognitive performance. The sample was characterized in a battery of neuropsychological tests and in terms of brain structural asymmetries using a ROI-based approach. A substantial number of brain areas presented some degree of asymmetry. Such biases survived a stringent statistical correction and were largely confirmed in a voxel-based analysis. In specific brain areas, like the thalamus and insula, asymmetry was correlated with cognition and mood descriptors as the Stroop words/colors test or depressive mood scale, respectively. Curiously in the latter, the association was independent of its left/right direction. Altogether, results reveal that asymmetry is widespread in the aged brain and that area-specific biases (degree and direction) associate with the functional profile of the individual.

The influence of espresso coffee on neurocognitive function in HIV-infected patients.

The aim of our study was to evaluate the impact of coffee intake on cognitive function in persons living with HIV (PLWH). 130 PLWH with CD4 > 200 cells/mm(3), undetectable viral load, treated with HAART were included. A structured interview was applied and relevant clinical and laboratory data were assessed, including coffee intake. For neuropsychological assessment, the HIV Neurobehavioral Research Center Battery was chosen. Univariate nonparametric statistics and multivariate regression model were used. A significant association between espresso coffee use and a better cognitive function was verified in five of the eight psychometric measurements. In the multivariate analysis, after variable adjustment, linear regression analysis showed that coffee intake was a positive predictor for attention/working memory, executive functions and Global Deficit Score. Although the mechanisms behind the influence of caffeine on cognitive functioning are controversial, regular espresso coffee intake may have favourable effects on cognitive deterioration caused by HIV.

Lipid-based nanoformulations of trifluralin analogs in the management of Leishmania infantum infections.

AIM: To improve the potential of trifluralin (TFL) in the management of Leishmania infantum infections through the synthesis of analogs (TFLA) and incorporation in nanoparticulate drug delivery systems (NanoDDS), liposomes and solid lipid nanoparticles, for selective targeting to leishmania infection sites. MATERIAL & METHODS: In vitro screening of 18 TFLA was performed by flow cytometry. NanoDDS were loaded with active TFLA and evaluated for antileishmanial efficacy in mice through determination of parasite burden in liver and spleen. RESULTS: The in vitro testing revealed the most active and nontoxic TFLAs, which were selected for the in vivo studies based on high incorporation in liposomes and lipid nanoparticles (>90%). Selected TFLA nanoformulations showed superior antileishmanial activity in mice (parasite burden >80%), over free TFLA and Glucantime. CONCLUSION: The modification of TFL structure to obtain active TFLA, together with their incorporation in NanoDDS, improved their in vivo performance against L. infantum infection.

Interaction of Cytotoxic and Cytoprotective Bile Acids with Model Membranes: Influence of the Membrane Composition.

To understand the role of bile acids (BAs) in cell function, many authors have investigated their effect on biomembrane models which are less complex systems, but there are still many open questions. The present study aims to contribute for the deepening of the knowledge of the interaction between BAs and model membranes, in particular, focusing on the effect of BA mixtures. The cytotoxic deoxycholic acid (DCA), the cytoprotective ursodeoxycholic acid (UDCA), and the equimolar mixture (DCA + UDCA) were investigated. Monolayers and liposomes were taken as model membranes with two lipid compositions: an equimolar mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM), and cholesterol (Chol)) traditionally associated with the formation of lipid rafts and an equimolar POPC/SM binary mixture. The obtained results showed that DCA causes the fluidization of monolayers and bilayers, leading to the eventual rupture of POPC/SM liposomes at high concentration. UDCA may provide a stabilization of POPC/SM membranes but has a negligible effect on the Chol-containing liposomes. In the case of equimolar mixture DCA/UDCA, the interactions depend not only on the lipid composition but also on the design of the experiment. The BA mixture has a greater impact on the monolayers than do pure BAs, suggesting a cooperative DCA-UDCA interaction that enhances the penetration of UDCA in both POPC/SM and POPC/SM/Chol monolayers. For the bilayers, the presence of UDCA in the mixture decreases the disturbing effect of DCA.

Hemisynthetic trifluralin analogues incorporated in liposomes for the treatment of leishmanial infections.

Leishmaniasis, a vector-borne parasitic disease caused by Leishmania protozoa, is one of the most neglected tropical diseases in terms of drug discovery and development. Current treatment is based on a limited number of chemotherapeutic agents all of which present either/or resistance issues, severe toxicities and adverse reactions associated with extended treatment regimens, and high cost of therapy. Dinitroanilines are a new class of drugs with proven in vitro antileishmanial activity. In previous work a liposomal formulation of one dinitroaniline (TFL) was found to be active against Leishmania parasites in a murine model of visceral leishmaniasis (VL) and in the treatment of experimental canine leishmaniasis. In this study we have investigated the use of dinitroaniline analogues (TFL-A) associated to liposomes, as means to further improve TFL antileishmanial activity. The potential of the liposomal formulations was assessed in vitro against Leishmania infantum promastigotes and intracellular amastigotes and in vivo in a murine model of zoonotic VL. Free and liposomal TFL-A were active in vitro against Leishmania parasites, and they also exhibited reduced cytotoxicity and haemolytic activity. Treatment of infected mice with liposomal TFL-A reduced the amastigote loads in the spleen up to 97%, compared with the loads for untreated controls. These findings illustrate that chemical synthesis of new molecules associated with the use of Nano Drug Delivery Systems that naturally target the diseased organs could be a promising strategy for effective management of VL.

Widespread correction of central nervous system disease after intracranial gene therapy in a feline model of Sandhoff disease.

Sandhoff disease (SD) is caused by deficiency of N-acetyl-ß-hexosaminidase (Hex) resulting in pathological accumulation of GM2 ganglioside in lysosomes of the central nervous system (CNS) and progressive neurodegeneration. Currently, there is no treatment for SD, which often results in death by the age of five years. Adeno-associated virus (AAV) gene therapy achieved global CNS Hex restoration and widespread normalization of storage in the SD mouse model. Using a similar treatment approach, we sought to translate the outcome in mice to the feline SD model as an important step toward human clinical trials. Sixteen weeks after four intracranial injections of AAVrh8 vectors, Hex activity was restored to above normal levels throughout the entire CNS and in cerebrospinal fluid, despite a humoral immune response to the vector. In accordance with significant normalization of a secondary lysosomal biomarker, ganglioside storage was substantially improved, but not completely cleared. At the study endpoint, 5-month-old AAV-treated SD cats had preserved neurological function and gait compared with untreated animals (humane endpoint, 4.4±0.6 months) demonstrating clinical benefit from AAV treatment. Translation of widespread biochemical disease correction from the mouse to the feline SD model provides optimism for treatment of the larger human CNS with minimal modification of approach.

Gene therapy approach to FAP: in vivo influence of T119M in TTR deposition in a transgenic V30M mouse model.

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of amyloid fibrils composed by mutated transthyretin (TTR) mainly in the peripheral nervous system. At present, liver transplantation is still the standard treatment to halt the progression of clinical symptoms in FAP, but new therapeutic strategies are emerging, including the use of TTR stabilizers. Here we propose to establish a new gene therapy approach using adeno-associated virus (AAV) vectors to deliver the trans-suppressor TTR T119M variant to the liver of transgenic TTR V30M mice at different ages. This TTR variant is known for its ability to stabilize the tetrameric protein. Analysis of the gastrointestinal tract of AAV-treated animals revealed a significant reduction in deposition of TTR non-fibrillar aggregates in as much as 34% in stomach and 30% in colon, as well as decreased levels of biomarkers associated with TTR deposition, namely the endoplasmic reticulum stress marker BiP and the extracellular matrix protein MMP-9. Moreover, we showed with different studies that our approach leads to an increase in tetrameric and more stable forms of TTR, in favor of destabilized monomers. Altogether our data suggest the possibility to use this gene therapy approach in a prophylactic manner to prevent FAP pathology.

Targeted expression of human folylpolyglutamate synthase for selective enhancement of methotrexate chemotherapy in osteosarcoma cells.

The antifolate methotrexate (MTX) is an important chemotherapeutic agent for treatment of osteosarcoma. This drug is converted intracellularly into polyglutamate derivates by the enzyme folylpolyglutamate synthase (FPGS). MTX polyglutamates show an enhanced and prolonged cytotoxicity in comparison to the monoglutamate. In the present study, we proved the hypothesis that transfer of the human fpgs gene into osteosarcoma cells may augment their MTX sensitivity. For this purpose, we employed the human osteocalcin (OC) promoter, which had shown marked osteosarcoma specificity in promoter studies using different luciferase assays in osteosarcoma and non-osteosarcoma cell lines. A recombinant lentiviral vector was generated with the OC promoter driving the expression of fpgs and the gene for enhanced green fluorescent protein (egfp), which was linked to fpgs by an internal ribosomal entry site (IRES). As the vector backbone contained only a self-inactivating viral LTR promoter, any interference of the OC promoter by unspecific promoter elements was excluded. We tested the expression of FPGS and enhanced green fluorescent protein (EGFP) after lentiviral transduction in various osteosarcoma cell lines (human MG-63 cells and TM 791 cells; rat osteosarcoma (ROS) 17/2.8 cells) and non-osteogenic tumor cell lines (293T human embryonic kidney cells, HeLa human cervix carcinoma cells). EGFP expression and MTX sensitivity were assessed in comparison with non-transduced controls. Whereas the OC promoter failed to enhance MTX sensitivity via FPGS expression in non-osteogenic tumor cell lines, the OC promoter mediated a markedly increased MTX cytotoxicity in all osteosarcoma cell lines after lentiviral transduction. The present chemotherapy-enhancing gene therapy system may have great potential to overcome in future MTX resistance in human osteosarcomas.

Leptospirosis porcina: prevalencia serológica en establecimientos productores de la República Argentina / Swine leptospirosis: Serological prevalence inproducing establishments in Argentina Republic

Objetivo. Detectar la presencia de anticuerpos contra Leptospira sp en cerdos que no presentaban sintomatología clínica, pertenecientes a establecimientos de producción porcina ubicados en todo el territorio de la República Argentina. Materiales y métodos. La asignación de predios y muestras se realizó en forma proporcional a los registrados en cada provincia a lo largo de todo el país. En total se estudiaron 1.524 predios, de los cuales se tomaron 19.872 muestras de suero y en la primera etapa se procesaron 3.631 de los mismos. Este estudio toma en consideración zonas identificadas por provincia, municipio y predios. Los sueros fueron analizados por la técnica de MAT (prueba de microaglutinación). Resultados. El 30% de las muestras resultaron positivas a la prueba tamiz empleada (primera etapa del MAT). La mayoría presentó coaglutininas a dos o a tres serovariedades. Al realizar la titulación de los sueros (segunda etapa del MAT), el porcentaje de positividad se mantuvo, siendo los serovares de mayor prevalencia Castellonis e Icterohaemorrhagiae. El 90% de las muestras presentó un título final de 1:200. Conclusiones. La existencia de sueros positivos en todas las provincias indica el contacto de los animales con la leptospira a lo largo de todo el país.

Objective. To detect the presence of antibodies to leptospira sp in pigs that didn't show clinical symptoms, of swine production farms located throughout Argentina. Materials and methods. The location of farms and samples were chosen in proportion to those recorded in each province covering the whole country. The number of farms studied was 1,524, with 19,872 serum samples. This study takes into consideration areas identified by provinces, municipalities and properties. In the first phase 3,631 sera were processed and analyzed by MAT (microscopic agglutination test). Results. The 30% of the samples tested were positive for the screening test (MAT). Most of these samples presented coagglutinins for two or three serovars. In the titration of sera, the percentage of positives was the same, the most prevalent serovars were Icterohaemorrhagiae and Castellonis. The 90% of the samples had a final titer of 1:200. Conclusions. The existence of positive sera in all provinces indicates the contact of animals with leptospira throughout the country.

A novel tripodal tris-hydroxypyrimidinone sequestering agent for trivalent hard metal ions: synthesis, complexation and in vivo studies.

A new tripodal hexadentate ligand, NTP(PrHPM)(3), having three hydroxypyrimidinone (HPM) chelating units attached to a nitrilotripropionic acid (NTP) has been prepared and studied in terms of thermodynamic stability of the complexes with iron, aluminium and gallium and it has been subsequently in vivo assayed for its capacity to remove hard metal ions from an animal model overloaded with (67)Ga. The anchoring of the HPM units to the NTP scaffold revealed to be an interesting alternative to the reported hexadentate tris(3-hydroxy-4-pyridinone) analogue, NTP(PrHP)(3), because the new tris-HPM ligand still keeps high chelating capacity for hard metal ions and presents better water-solubility (log P = -1.51). The in vivo studies show that NTP(PrHPM)(3) induces a faster clearance from main organs and an enhancement of overall excretion, as compared with the commercial drug, DFP, or the bidentate HPM compound (HOPY-PrN), albeit slightly lower than the tris-hydroxypyridinone analogue, NTP(PrHP)(3). The solution and in vivo results herein presented encourage further studies envisaging the potential clinical applications of hexadentate HPM derivatives as metal sequestering agents.

Evaluation of the growth-inhibitory effect of trifluralin analogues on in vitro cultured Babesia bovis parasites.

Bovine babesiosis, caused by Babesia bovis, is a global tick borne hemoprotozoan parasite disease characterized by fever, anemia, weight losses and ultimately death. Several babesicidal drugs that have been in use in cattle for years have proven to be only partially effective and the development of alternative chemotherapeutics that are highly specific and have low toxicity against babesiosis is needed. Trifluralin derivatives specifically bind alpha-tubulin in plants and protozoa parasites causing growth inhibition. A set of 12 trifluralin analogues (TFLA) has previously been shown to be inhibitory for the growth of Leishmania species. The conservation of several key amino acids involved in the trifluralin binding site of alpha-tubulin among Leishmania sp. and B. bovis provides rationale for testing these compounds also as babesiacides. The previously tested Leishmania inhibitory, TFLA 1-12 minus TFLA 5, in addition to three novel TFLA (termed TFLA 13-15), were tested against in vitro cultured B. bovis parasites. While all of the TFLA tested in the study showed inhibition of B. bovis growth in vitro TFLA 7, TFLA 10 and TFLA 13, were the most effective inhibitors with estimated IC50 (µM) at 72 h of 8.5 ± 0.3; 9.2 ± 0.2; 8.9 ± 0.7, respectively for the biologically attenuated cloned B. bovis Mo7 strain, and 13.6 ± 1.5; 18.7 ± 1.6; 10.6 ± 1.9, respectively for the virulent B. bovis T3Bo strain. The differences found between the two strains were not statistically significant. Importantly, these drugs displayed low levels of toxicity for the host erythrocytes and bovine renal arterial endothelial cells at the doses tested. The demonstrated ability of trifluralin analogues to inhibit in vitro growth of B. bovis parasites combined with their low toxicity for host cells suggests that these compounds may be further developed as novel alternatives for the treatment of bovine babesiosis.

Finding the striatum in sheep: use of a multi-modal guided approach for convection enhanced delivery.

Our goal is delivery of a long-term treatment for Huntington's disease. We administer intracerebrally in sheep adeno-associated virus (AAV) to establish optimal safety, spread and neuronal uptake of AAV based therapeutics. Sheep have large gyrencephalic brains and offer the opportunity to study a transgenic Huntington's disease model. However, lack of a relevant brain stereotactic atlas and the difficulty of skull fixation make conventional stereotaxy unreliable. We describe a multi-modal image-guidance technique to achieve accurate placement of therapeutics into the sheep striatum.

[Intussusception in the adult: a rare cause of mechanical obstruction]. / Invaginación intestinal en el adulto. Una causa infrecuente de obstrucción mecánica.

Intussusception is an infrequent cause of mechanical intestinal obstruction in the adult. We present herein two clinical cases of intussusception with different etiologies. In the first case, the underlying cause was a lipoma, and in the second, it was metastasis from melanoma. In both cases the intussusception was identified through computed tomography and treatment was intestinal resection. Pathologic anatomy provided the definitive diagnosis. Etiology is diverse and it is more common for obstruction to be due to organic lesions that are malignant at the level of the colon and benign at the level of the small bowel. Currently there are more preoperative diagnoses thanks to the advances made in imaging study techniques. Intestinal resection continues to be the treatment of choice in the majority of cases, because of the high percentage of malignant lesions as the underlying cause.