J A García de Jalón

Universidad de Navarra, Pamplona, Navarre, Spain

Are you J A García de Jalón?

Claim your profile

Publications (22)62.61 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: To prepare and evaluate the in vitro release of memantine-loaded poly(anhydride) (Gantrez®) nanoparticles (NPs). The clinical safety and retinal toxicity caused by unloaded NPs after sub-Tenon and intravitreal ocular injections were also evaluated. Methods: Preparation and characterization of this type of NP as well as the in vitro release study are described. Twenty-three healthy New Zealand rabbits were used for clinical and histological assessment after sub-Tenon and intravitreal ocular injections of unloaded NPs. Results: The amount of drug associated with NPs was 55 µg of memantine/mg of NP. The release profile of memantine from this type of NPs was characterized by an initial burst effect, followed by continuous release of the drug for at least 15 days. No relevant complications were found during the clinical follow-up. The histological evaluation suggested that Gantrez NPs are well tolerated after sub-Tenon ocular injection and that signs of inflammation during the first days after intravitreal ocular injections can be considered a normal reaction of the eye's defence mechanism.
    Ophthalmic Research 04/2012; 48(3):109-17. · 1.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AIMS: To determine the long-term effect of transplantation of adipose-derived stromal cells (ADSCs) in a preclinical model of ischemia/reperfusion (I/R).METHODS AND RESULTS: I/R was induced in 28 Goettingen minipigs by 120 minutes coronary artery occlusion followed by reperfusion. Nine days later, surviving animals were allocated to receive trans-endocardial injection of a mean of 213.6±41.78 million green fluorescent protein (GFP)-expressing ADSCs (n=7) or culture medium as control (n=9). Heart function, cell engraftment and histological analysis were performed 3 months after transplantation. Transplantation of ADSCs induced a statistically significant long-lasting (3 months) improvement in cardiac function and geometry in comparison with control animals.Functional improvement was associated with an increase in angiogenesis and vasculogenesis and a positive effect on heart remodeling with a decrease in fibrosis and cardiac hypertrophy in animals treated with ADSCs. Despite the lack of cell engraftment after 3 months, ADSC transplantation induced changes in the ratio between MMP/TIMP.CONCLUSION: Our results indicate that transplantation of ADSCs, despite the lack of longterm significant cell engraftment, increases vessel density and prevents adverse remodeling in a clinically relevant model of myocardial infarction, strongly suggesting a paracrine mediated effect. ADSCs thus constitute an attractive candidate for the treatment of myocardial infarction.
    Cell Transplantation 04/2012; · 4.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ovine pulmonary adenocarcinoma (OPA) is a contagious tumour caused by infection of sheep with Jaagsiekte sheep retrovirus. Two forms of OPA have been identified, classical and atypical, which can be distinguished clinically and pathologically. Most notably classical OPA is progressive until death, while atypical OPA remains subclinical. In the present study the local immune responses in the lungs of cases of atypical OPA were compared with those from classical cases by immunohistochemistry using a panel of mouse anti-sheep mAbs. Distinct differences in the distribution of immune cell subsets in the two forms of OPA were observed. In particular there was an intratumoural influx of T cell subsets and MHC Class II expression on the tumour cells in atypical OPA, neither of which was seen in classical OPA. It is possible that these differences may contribute, at least in part, to determining the progressive course of classical OPA compared with the subclinical nature of atypical OPA.
    Veterinary Immunology and Immunopathology 03/2012; 146(1):1-7. · 1.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Histone deacetylases (HDACs) have been identified as therapeutic targets due to their regulatory function in chromatin structure and organization. Here, we analyzed the therapeutic effect of LBH589, a class I-II HDAC inhibitor, in acute lymphoblastic leukemia (ALL). In vitro, LBH589 induced dose-dependent antiproliferative and apoptotic effects, which were associated with increased H3 and H4 histone acetylation. Intravenous administration of LBH589 in immunodeficient BALB/c-RAG2(-/-)γc(-/-) mice in which human-derived T and B-ALL cell lines were injected induced a significant reduction in tumor growth. Using primary ALL cells, a xenograft model of human leukemia in BALB/c-RAG2(-/-)γc(-/-) mice was established, allowing continuous passages of transplanted cells to several mouse generations. Treatment of mice engrafted with T or B-ALL cells with LBH589 induced an in vivo increase in the acetylation of H3 and H4, which was accompanied with prolonged survival of LBH589-treated mice in comparison with those receiving vincristine and dexamethasone. Notably, the therapeutic efficacy of LBH589 was significantly enhanced in combination with vincristine and dexamethasone. Our results show the therapeutic activity of LBH589 in combination with standard chemotherapy in pre-clinical models of ALL and suggest that this combination may be of clinical value in the treatment of patients with ALL.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2012; 26(7):1517-26. · 10.16 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Histone deacetylases (HDACs) have been identified as therapeutic targets due to their regulatory function in chromatin structure and organization. Here we analyzed the therapeutic effect of LBH589, a class I-II HDAC inhibitor, in acute lymphoblastic leukemia (ALL). In vitro, LBH589 induced dose-dependent antiproliferative and apoptotic effects, which were associated with increased H3 and H4 histone acetylation. Intravenous (i.v.) administration of LBH589 in immunodeficient BALB/c-RAG2(-/-)γc(-/-) mice in which human-derived T and B-ALL cell lines were injected induced a significant reduction in tumor growth. Using primary ALL cells, a xenograft model of human leukemia in BALB/c-RAG2(-/-)γc(-/-) mice was established, allowing continuous passages of transplanted cells to several mouse generations. Treatment of mice engrafted with T or B-ALL cells with LBH589 induced an in vivo increase in the acetylation of H3 and H4, which was accompanied with prolonged survival of LBH589-treated mice in comparison with those receiving Vincristine and Dexametasone. Notably, the therapeutic efficacy of LBH589 was significantly enhanced in combination with Vincristine and Dexametasone. Our results demonstrate the therapeutic activity of LBH589 in combination with standard chemotherapy in pre-clinical models of ALL and suggest that this combination may be of clinical value in the treatment of patients with ALL.
    Leukemia. 01/2012;
  • The Veterinary record. 06/2010; 166(24):757-8.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The human XY gonadal sex reversal is a rare disease. Primary amenorrhea, lack of secondary sexual characteristics and the possible existence of streak gonads are the most common signs of this syndrome. Five cases of this syndrome have been described in the last 42 years in bovines. However, to the knowledge of the authors, no similar descriptions are available in sheep. In the present report, we are presenting the case of a 4 year old ewe 2n = 54,XY showing primary sterility and total absence of masculinization signs. The promoter and the complete coding segment of the sex determining region Y (SRY) were sequenced and found to be absolutely normal. The presence of the testis-specific protein gene (TSPY) was also verified by means of PCR. Necropsy findings include short vagina, lack of uterus and complete absence of masculine remains. Streak gonads concordant with previous descriptions in humans were also found.
    Cytogenetic and Genome Research 10/2009; 126(4):329-32. · 1.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although transplantation of skeletal myoblast (SkM) in models of chronic myocardial infarction (MI) induces an improvement in cardiac function, the limited engraftment remains a major limitation. We analyse in a pre-clinical model whether the sequential transplantation of autologous SkM by percutaneous delivery was associated with increased cell engraftment and functional benefit. Chronically infarcted Goettingen minipigs (n = 20) were divided in four groups that received either media control or one, two, or three doses of SkM (mean of 329.6 x 10(6) cells per dose) at intervals of 6 weeks and were followed for a total of 7 months. At the time of sacrifice, cardiac function was significantly better in animals treated with SkM in comparison with the control group. A significantly greater increase in the DeltaLVEF was detected in animals that received three doses vs. a single dose of SkM. A correlation between the total number of transplanted cells and the improvement in LVEF and DeltaLVEF was found (P < 0.05). Skeletal myoblast transplant was associated with an increase in tissue vasculogenesis and decreased fibrosis (collagen vascular fraction) and these effects were greater in animals receiving three doses of cells. Repeated injection of SkM in a model of chronic MI is feasible and safe and induces a significant improvement in cardiac function.
    European Heart Journal 08/2009; 31(8):1013-21. · 14.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization was defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from the kidney, liver, lung, and stomach evaluated. Microscopic evaluation revealed clusters of 10-30 microspheres (15-30 microm in diameter) in the small vessels of the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15-30 microm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization.
    CardioVascular and Interventional Radiology 06/2009; 32(4):727-36. · 2.09 Impact Factor
  • D. Marteles, M. Borobia, J A García de Jalón, A Ortín, A Loste, A Fernández
    [Show abstract] [Hide abstract]
    ABSTRACT: ResumenUna oveja de raza Rasa Aragonesa, procedente de una explotación de laprovincia de Zaragoza, fue remitida a la Facultad de Veterinaria,presentando un historial de descarga vaginal sanguinolenta, oscura ymaloliente, por lo que se sospechó de un proceso de metritis y seadministró oxitocina para favorecer la eliminación de la secreción. Otros síntomas encontrados tras la exploración fueron caquexia, palidez de mucosas y debilidad. A la palpación del abdomen se detectaron varios nódulos, destacando por su tamaño uno localizado en la región umbilical, que podían corresponder con abscesos.El estado de la oveja empeoró progresivamente, por lo que se decidió su sacrificio humanitario. En la necropsia de observaron múltiples nódulos distribuidos en la zona abdominal (peritoneo, hígado y bazo), y uno de enorme tamaño localizado en el cuello del útero. No se encontraron lesiones en ninguna otra localización. Se tomaron muestras para el estudio anatomopatológico, que dio como resultado un carcinoma de células escamosas. Los carcinomas de células escamosas se han descrito en ganado ovino localizados en cabeza (fosas nasales y tercer párpado), asociados normalmente a una alta exposición a radiaciones solares en zonas desprotegidas de la piel y mucosas. En la bibliografía no se ha encontrado ninguna descripción de carcinoma de células escamosas de localización abdominal en ganado ovino. Dado que no se encontró en la necropsia ningún foco primario de localización típica en esta especie, se especula con el posible origen de la neoplasia a nivel del cuello del útero.SummaryA Rasa Aragonesa sheep from a flock of Zaragoza (Spain), was sent to the Veterinary Faculty with a history of bleeding, dark and smelly vaginal discharge. Metritis was suspected and treated with oxitocina in order to eliminate the secretion. Clinical exploration reveled caquexia, mucous paleness and weakness, and also several nodules were detected by abdominal palpation. These nodules could fit with abscesses, the biggest one was located near the umbilican region.The sheep was humanely euthanathed due to it´s deteroration. At necropsy, multiple nodules distributed in the abdominal area (peritoneum, liver and spleen) and a larger one located in the umbilical region were found. Samples were taken for histological studies and a scaly cells carcinoma was diagnosed. Scaly cells carcinoma has been described in sheep located at the face (nasalpit and the third eyelid), normally associated with a high exhibition to solar radiations in unprotected zones of skin and mucous. To our knowledge, this is the first description in sheep of a scaly cells carcinoma with abdominal location. As there was not found in this animal any typical primary afected area, the possible origin of the neoplasia could be at the cervix. This location and the invasion of adjacent areas has been described in human medicine.
    REDVET. 01/2009;
  • [Show abstract] [Hide abstract]
    ABSTRACT: To perform a study in a porcine model comparing four different spherical embolic particles in terms of postembolization patency, deformation, and potential for recanalization, with a focus on a relatively new agent--HepaSphere. Partial embolization of both kidneys was performed in 18 pigs. Nine animals were sacrificed at 48 hours and nine at 4 weeks. In the same animal, the right kidney was embolized with HepaSphere particles ("dry" size, 50-100 microm; presumed final size, 200-300 microm), and the left kidney was alternatively embolized with EmboSphere (100-300 microm), Contour (150-350 microm), or Bead Block (150-350 microm) particles. The authors analyzed the size, deformation, and number of particles in each vessel, their morphologic characteristics, and recanalization. Particle sizes and deformation (1,096 particles) were as follows: HepaSphere, 225.3 microm +/- 67 and 26% +/- 19.7, respectively; EmboSphere, 132.9 microm +/- 36 and 18.1% +/- 14.2; Bead Block, 108.1 microm +/- 38 and 16.5% +/- 13.9; and Contour, 240.8 microm +/- 135 and 55.5% +/- 33. HepaSphere and Bead Block particles were distally located, and EmboSphere and Contour particles were located more proximally. EmboSphere and Bead Block particles were round, HepaSphere particles were round and/or ovoid, and Contour particles had an amorphous aspect. EmboSphere particles had a higher tendency to aggregate. No recanalization was seen with HepaSphere particles, and variable recanalization was observed with the others. Despite similar initial morphologic characteristics, the performance of the agents tested in this study differed in terms of final size, shape, deformation, and luminal recanalization. These differences have potential clinical relevance, and the knowledge of the differing embolic performance may be helpful in choosing agents for specific therapeutic purposes.
    Journal of vascular and interventional radiology: JVIR 10/2008; 19(11):1625-38. · 1.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. ANIMALS, METHODS: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p < 0.05) that persisted throughout the study. Semiquantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p < 0.001). The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration.
    Nuklearmedizin 01/2007; 46(4):149-54. · 1.67 Impact Factor
  • Source
    A Ortín, L M Ferrer, A Loste, J A García de Jalón, P Gómez, J J Ramos
    The Veterinary record 12/2006; 159(21):718-9. · 1.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Our aim was to compare the efficacy of surgical versus percutaneous administration of skeletal myoblasts (SkM) in a swine model of chronic myocardial infarction and to determine the mechanism(s) involved in their beneficial effect. Two months after induction of myocardial infarction (MI), Goettingen miniature pigs underwent autologous SkM transplant either by direct surgical injection (n=6) or percutaneous access and intramyocardial delivery under fluoroscopic and echocardiographic guidance (n=6). Control animals received media alone (n=4). Functional analysis was performed by 2D echocardiography. Myoblast engraftment, in vivo cell differentiation, vessel formation, fibrosis, and the ratio between collagen type I/III deposition were analyzed in the infarct (IA) and non-infarct area (NIA) by immunohistochemistry. Animals received a median of 407.55+/-115x10(6) BrdU-labeled autologous SkM. Myoblast transplant was associated with a statistically significant increase in left ventricular ejection fraction (p<0.01), increased vasculogenesis and decreased fibrosis (p<0.05), and reduced collagen type I/III ratio in the IA and NIA areas as compared with control animals. No differences were found between groups receiving SkM by percutaneous or surgical access. Our results indicate that increased vasculogenesis and changes in matrix remodeling with decreased fibrosis are associated with the beneficial effect of SkM transplant in chronic MI. The equivalent benefit observed from surgical and percutaneous delivery has important clinical implications.
    Cardiovascular Research 09/2006; 71(4):744-53. · 5.81 Impact Factor
  • Source
    T Sáez, J J Ramos, J A Garcia De Jalon, A Unzueta, A Loste
    The Veterinary record 08/2003; 153(1):27-8. · 1.80 Impact Factor
  • J J Ramos, C Marca, A Loste, J A García de Jalón, A Fernández, T Cubel
    [Show abstract] [Hide abstract]
    ABSTRACT: Blood samples were obtained for determination of the activities of lactate, pyruvate and erythrocyte transketolase, and faeces as samples for estimation of thiaminase, from 190 apparently healthy sheep from 19 flocks in which at least one animal had been diagnosed with polioencephalomalacia (PEM), from 59 control animals and from 7 affected by PEM. Feed and pasture grass samples were collected for thiaminase analysis and thiaminase was assayed in ryegrass and fescue. Decreased erythrocyte transketolase activity, accompanied by a corresponding rise in the thiamin pyrophosphate effect, and estimation of the thiaminase content in faeces, may be useful diagnostic procedures by which to identify periods of greater risk, during which animals could develop PEM. The changes in the diet probably acted as a primary factor for microbial production of thiaminases in replacement ewes. In these, the prevalence was higher in the spring months.
    Veterinary Research Communications 03/2003; 27(2):111-24. · 1.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The successful experimental transmission of enzootic intranasal tumor (EIT) from goat to goat is described. Ten kids, less than 48 hours old, from a flock free of the disease and seronegative for ruminant lentiviruses were inoculated intranasally or intrasinusally with either nasal fluid from goats with naturally occurring EIT or EIT retrovirus concentrated from such fluids. EIT was induced in three kids after 12-24 months. The EIT retrovirus was demonstrated in tumor material from each of the three kids by western blotting and electron microscopy. All kids were seronegative for ruminant lentiviruses.
    Veterinary Pathology 02/1995; 32(1):19-23. · 1.93 Impact Factor
  • M De las Heras, J M Sharp, L M Ferrer, J A García de Jalón, L M Cebrian
    The Veterinary record 05/1993; 132(17):441. · 1.80 Impact Factor
  • Source
    M De las Heras, J A Garcia de Jalon, J M Sharp
    [Show abstract] [Hide abstract]
    ABSTRACT: Intranasal tumors were studied in 38 goats ranging from 7 months to 8 years of age of both Murciana-Granadina and crossed breeds. Tumors were diagnosed in eight herds. Clinically, the affected goats showed a copious seromucous nasal discharge, ocular protrusion, and skull deformations. The tumors originated from the ethmoid region. They involved one or both nasal cavities, although most were bilateral (26/38). The tumors were generally accompanied by inflammatory polyps. The histologic patterns were very similar in all cases, and the tumors were classified as low grade adenocarcinomas of the nasal glands. Histochemical, immunohistochemical, and ultrastructural studies suggested that the serous glands of nasal mucosa were the probable origin of the neoplastic cells. Budding and extracellular retrovirus-like particles were observed ultrastructurally in 6/8 tumors. The similarities between these caprine tumors and nasal tumors in sheep and the etiologic role of the retrovirus are discussed.
    Veterinary Pathology 12/1991; 28(6):474-81. · 1.93 Impact Factor
  • Source
    M De las Heras, J M Sharp, J A Garcia de Jalon, P Dewar
    [Show abstract] [Hide abstract]
    ABSTRACT: Nasal exudate and tumour tissue from goats with enzootic nasal tumours were shown to contain a reverse transcriptase activity associated with a particle of buoyant density typical of retroviruses. The same particle contained a 25,000 Mr protein that cross-reacted with the p27 of Mason-Pfizer monkey virus (MPMV) and with p25 of sheep pulmonary adenomatosis retrovirus. It also contained a low Mr protein related to p10-12 of MPMV.
    Journal of General Virology 11/1991; 72 ( Pt 10):2533-5. · 3.13 Impact Factor

Publication Stats

185 Citations
62.61 Total Impact Points

Institutions

  • 2009
    • Universidad de Navarra
      • Department of Radiology
      Pamplona, Navarre, Spain
  • 2008
    • University of Zaragoza
      Caesaraugusta, Aragon, Spain
  • 1991
    • Moredun Research Institute
      Penicuik, Scotland, United Kingdom