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1.
J Comp Pathol ; 170: 86-90, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31375164

RESUMEN

Granulomatous lesions were observed in the swim bladder, kidney, spleen and gills of two farmed Japanese pufferfish (Takifugu rubripes) infected with Mycobacterium chelonae. Three types of lesions were noted: unencapsulated clusters of epithelioid cells without central necrosis (type 1), encapsulated granulomas without central necrosis (type 2) and encapsulated granulomas with central necrosis (type 3). Type 3 lesions occurred most frequently in the swim bladder, while type 1 and type 2 lesions occurred frequently in the kidney and spleen, and the gills exhibited mostly type 1 lesions. This suggests that the lesions in the swim bladder were more fully developed than those occurring elsewhere and that the swim bladder may be more susceptible to infection with M. chelonae. This is the first report describing the histopathological features of M. chelonae infection in Tetraodontidae.


Asunto(s)
Enfermedades de los Peces/microbiología , Enfermedades de los Peces/patología , Infecciones por Mycobacterium no Tuberculosas/veterinaria , Tetraodontiformes/microbiología , Animales , Acuicultura , Japón , Mycobacterium chelonae
3.
Opt Express ; 25(16): 18774-18783, 2017 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-29041071

RESUMEN

Hydrogen clusters with diameters of a few micrometer range, composed of 108-10 hydrogen molecules, have been produced for the first time in an expansion of supercooled, high-pressure hydrogen gas into a vacuum through a conical nozzle connected to a cryogenic pulsed solenoid valve. The size distribution of the clusters has been evaluated by measuring the angular distribution of laser light scattered from the clusters. The data were analyzed based on the Mie scattering theory combined with the Tikhonov regularization method including the instrumental functions, the validity of which was assessed by performing a calibration study using a reference target consisting of standard micro-particles with two different sizes. The size distribution of the clusters was found discrete peaked at 0.33 ± 0.03, 0.65 ± 0.05, 0.81 ± 0.06, 1.40 ± 0.06 and 2.00 ± 0.13 µm in diameter. The highly reproducible and impurity-free nature of the micron-size hydrogen clusters can be a promising target for laser-driven multi-MeV proton sources with the currently available high power lasers.

4.
AJNR Am J Neuroradiol ; 38(11): 2100-2104, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28818825

RESUMEN

Neuronal intranuclear inclusion disease is a neurodegenerative disorder pathologically characterized by eosinophilic hyaline intranuclear inclusions. A high-intensity signal along the corticomedullary junction on DWI has been described as a specific MR imaging finding of the cerebrum in neuronal intranuclear inclusion disease. However, MR imaging findings of the cerebellum in neuronal intranuclear inclusion disease have not been fully evaluated. Here, we review MR imaging findings of the cerebellum in a series of 8 patients with pathologically confirmed neuronal intranuclear inclusion disease. The MR imaging results showed cerebellar atrophy (8/8 patients) and high-intensity signal on FLAIR images in the medial part of the cerebellar hemisphere right beside the vermis (the "paravermal area") (6/8) and in the middle cerebellar peduncle (4/8). The paravermal abnormal signals had a characteristic distribution, and they could be an indicator of the diagnosis of neuronal intranuclear inclusion disease even when using the results of past MR imaging examinations in which DWI findings were not examined.


Asunto(s)
Cerebelo/diagnóstico por imagen , Enfermedades Neurodegenerativas/diagnóstico por imagen , Anciano , Atrofia , Cerebelo/patología , Pedúnculo Cerebral/diagnóstico por imagen , Proteínas del Líquido Cefalorraquídeo/análisis , Cerebro/diagnóstico por imagen , Demencia/etiología , Demencia/psicología , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Cuerpos de Inclusión Intranucleares , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/complicaciones , Enfermedades Neurodegenerativas/psicología , Pruebas Neuropsicológicas , Estudios Retrospectivos
5.
Vet Comp Oncol ; 15(3): 731-739, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26766288

RESUMEN

5-Aminolevulinic acid (5-ALA) is widely used in photodynamic detection (PDD) and therapy. We evaluated the pharmacokinetics of 5-ALA-induced porphyrins and its effectiveness in PDD in dogs with mammary gland tumours (MGTs) following oral administration. Healthy dogs and those with MGTs (nine each) were orally administered 4 mg kg-1 5-ALA. Protoporphyrin IX (PpIX) was not detected in the plasma of healthy dogs but it peaked in dogs with MGT at 2 h after 5-ALA administration. In the PDD study, 16 dogs with MGT were orally administered 40 mg kg-1 5-ALA, and MGT but not normal tissue showed red fluorescence after 2-4 h. Photon counts were 6635-63 890 and 59-4011 (median, 19 943 and 919) for MGT and non-tumour tissues, respectively. Cell density strongly correlated with PpIX photon counts of MGT tissue of the dogs (R = 0.743, P = 0.0009). We suggest that 5-ALA-PDD might be an effective diagnostic tool for MGTs.


Asunto(s)
Ácido Aminolevulínico/farmacología , Enfermedades de los Perros/diagnóstico , Neoplasias Mamarias Animales/diagnóstico , Fármacos Fotosensibilizantes/farmacología , Espectrometría de Fluorescencia/veterinaria , Administración Oral , Ácido Aminolevulínico/administración & dosificación , Animales , Perros , Femenino , Fármacos Fotosensibilizantes/administración & dosificación , Porfirinas/metabolismo
6.
Allergol. immunopatol ; 43(3): 249-253, mayo-jun. 2015. tab
Artículo en Inglés | IBECS | ID: ibc-136330

RESUMEN

BACKGROUND: The precise pathogenesis of chronic spontaneous urticaria (CSU) remains unknown. However, an important association between CSU and autoimmune disorders such as Hashimoto's disease (HD) has been reported. We investigated the frequency of HD as a comorbidity of CSU and the prevalence rate of autoreactivity among CSU patients with HD. PATIENTS AND METHODS: The presence of thyroid autoantibodies and the levels of thyroid hormones were examined in 40 CSU patients who showed urticaria symptoms for >4 weeks. Patients who were diagnosed with HD, including subclinical ones, and were in need of treatment received thyroid therapy, and the changes in their urticarial symptoms were observed. An autologous serum skin test (ASST) was also performed to examine the relation of CSU with autoreactivity. RESULTS: Eleven of the 40 CSU patients were diagnosed with HD, and 4 of the 5 patients who received and completed thyroid therapy showed considerable remission of urticarial symptoms during and after treatment. In addition, the rate of positive ASST results tended to be higher in CSU patients with HD (5 of 7) than in those without HD (2 of 6). CONCLUSIONS: The comorbidity rate of HD in CSU patients was high, and such patients tended to have a positive ASST. Thyroid therapy in CSU patients with HD can lead to a considerable remission of urticarial symptoms, which may suggest that HD is possibly involved in the aetiology of CSU, or is at least a potential exacerbating factor for CSU


No disponible


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Enfermedad de Hashimoto/epidemiología , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/prevención & control , Urticaria/complicaciones , Urticaria/diagnóstico , Urticaria/inmunología , Tiroxina , Tiroxina/inmunología , Comorbilidad , Autoinmunidad , Autoinmunidad/inmunología , Pruebas Cutáneas/métodos , Pruebas Cutáneas , Receptores de Tirotropina/inmunología , Tirotropina , Tirotropina/inmunología
7.
Allergol Immunopathol (Madr) ; 43(3): 249-53, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25088672

RESUMEN

BACKGROUND: The precise pathogenesis of chronic spontaneous urticaria (CSU) remains unknown. However, an important association between CSU and autoimmune disorders such as Hashimoto's disease (HD) has been reported. We investigated the frequency of HD as a comorbidity of CSU and the prevalence rate of autoreactivity among CSU patients with HD. PATIENTS AND METHODS: The presence of thyroid autoantibodies and the levels of thyroid hormones were examined in 40 CSU patients who showed urticaria symptoms for >4 weeks. Patients who were diagnosed with HD, including subclinical ones, and were in need of treatment received thyroid therapy, and the changes in their urticarial symptoms were observed. An autologous serum skin test (ASST) was also performed to examine the relation of CSU with autoreactivity. RESULTS: Eleven of the 40 CSU patients were diagnosed with HD, and 4 of the 5 patients who received and completed thyroid therapy showed considerable remission of urticarial symptoms during and after treatment. In addition, the rate of positive ASST results tended to be higher in CSU patients with HD (5 of 7) than in those without HD (2 of 6). CONCLUSIONS: The comorbidity rate of HD in CSU patients was high, and such patients tended to have a positive ASST. Thyroid therapy in CSU patients with HD can lead to a considerable remission of urticarial symptoms, which may suggest that HD is possibly involved in the aetiology of CSU, or is at least a potential exacerbating factor for CSU.


Asunto(s)
Enfermedad de Hashimoto/epidemiología , Glándula Tiroides/inmunología , Urticaria/epidemiología , Adolescente , Adulto , Anciano , Autoanticuerpos/sangre , Enfermedad Crónica , Comorbilidad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Hormonas Tiroideas/metabolismo , Adulto Joven
8.
Respir Med ; 107(6): 875-82, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23582576

RESUMEN

BACKGROUND: Forced oscillometry is a non-invasive method to measure respiratory resistance and reactance. In this study, we investigated the characteristics of measurements obtained with an impulse oscillation system (IOS) for patients with interstitial lung disease (ILD). METHOD: IOS and spirometry were performed in 64 ILD patients, 54 asthma patients, 49 chronic obstructive pulmonary disease (COPD) patients, and 29 controls. Respiratory resistance and reactance were assessed as measurements averaged over several tidal breaths (whole-breath analysis) and as measurements separately averaged during inspiration and expiration (inspiratory-expiratory analysis). RESULTS: Whole-breath IOS analyses for ILD patients showed increased resistance at 5 Hz and decreased reactance at 5 Hz (X5) compared with controls, although these features were also found in asthma and COPD patients. Inspiratory-expiratory analysis demonstrated that the changes in X5 and reactance area (AX) between inspiration and expiration (ΔX5 and ΔAX, respectively) were significantly different from those in asthma patients, COPD patients, and controls. However, multiple linear regression analysis showed that the presence of ILD was independently associated with ΔX5, but not with ΔAX. Furthermore, ΔX5 was inversely correlated with vital capacity and diffusing capacity of carbon monoxide in ILD patients. CONCLUSIONS: Our results suggest that ΔX5 is a characteristic feature of IOS measurements in ILD patients, which is clearly different from those in asthma and COPD patients. This within-breath X5 change in ILD might be associated with its severity and physiological abnormality, although further studies are needed to investigate its cause.


Asunto(s)
Resistencia de las Vías Respiratorias/fisiología , Espiración/fisiología , Inhalación/fisiología , Enfermedades Pulmonares Intersticiales/fisiopatología , Adulto , Anciano , Asma/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oscilometría/métodos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Estudios Retrospectivos , Espirometría/métodos
9.
J Dairy Sci ; 95(1): 127-38, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22192192

RESUMEN

Computed tomography (CT) was performed on 400 claws (200 inner and 200 outer claws) of 100 pairs of bovine hind limbs to investigate the etiological theory that an exacerbating factor for ulceration is exostosis of the tuberculum flexorium within the distal phalanx. A variety of morphological changes of the tuberculum flexorium of bovine hind limb claws was visualized by 3-dimensional CT, and the geometry of these claws suggested a growth pattern of bone development with respect to the assumed daily loading patterns. This growth occurs initially at the abaxial caudal aspect of the distal phalanx and is followed by horizontal progression toward the axial aspect. The length of downward bone development on the solar face of the distal phalanx was 2.73±1.32 mm in the outer claws, significantly greater than in the inner claws (2.38±0.96 mm). Ratios of downward (vertical) bone development to the thickness of the subcutis and the corium (VerBD ratios) did not differ between the outer and inner claws (36.7 vs. 38.3%, respectively). Ratios of horizontal bone development to the axial-to-abaxial line of the tuberculum flexorium (HorBD ratios) were approximately 60% for both outer and inner claws. These quantitative measures regarding horizontal and vertical bone development within the distal phalanx were positively correlated with age and VerBD ratios (r=0.53 and r=0.36 for the inner and outer claws, respectively). Correlations between claw width of the outer claw and length of vertical bone development (r=0.43), the HorBD ratio (r=0.51), and the VerBD ratio (r=0.42) suggested that the relative size difference between the inner and outer claws enhances bone development in the outer claw. Correlation coefficients between VerBD and HorBD ratios (r=0.52 and 0.63 for the inner and outer claws, respectively) suggested that horizontal and vertical bone development occurs as a synchronized process within the tuberculum flexorium. This age-related progress of bone development within the tuberculum flexorium is associated with increased exposure to several exacerbating factors and the laminitic process.


Asunto(s)
Desarrollo Óseo , Bovinos/crecimiento & desarrollo , Miembro Posterior/crecimiento & desarrollo , Pezuñas y Garras/crecimiento & desarrollo , Falanges de los Dedos del Pie/crecimiento & desarrollo , Tomografía Computarizada por Rayos X/veterinaria , Animales , Bovinos/anatomía & histología , Femenino , Miembro Posterior/anatomía & histología , Pezuñas y Garras/anatomía & histología , Falanges de los Dedos del Pie/anatomía & histología , Tomografía Computarizada por Rayos X/métodos
10.
Plant Biol (Stuttg) ; 13(2): 411-5, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21309988

RESUMEN

Flavonoids are natural compounds found in many plants, including the important fruit crop, tomato. Prenylated flavonoids consist of a large group of compounds, which often exhibit antitumour, antibacterial and/or anti-androgen activities. In this study, we engineered the biosynthesis of prenylated flavonoids using a Streptomyces prenyltransferase HypSc (SCO7190) possessing broad-range substrate specificity, in tomato as a host plant. LC/MS/MS analysis demonstrated the generation of 3'-dimethylallyl naringenin in tomato fruits when recombinant HypSc protein was targeted to the plastids, whereas the recombinant protein hardly produced this compound in vitro. This is the first report confirming the accumulation of a prenylated flavonoid using a bacterial prenyltransferase in transgenic plants, and our results suggest that the product specificities of prenyltransferases can be significantly influenced by the host plant.


Asunto(s)
Dimetilaliltranstransferasa/metabolismo , Flavonoides/biosíntesis , Solanum lycopersicum/química , Streptomyces coelicolor/enzimología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Dimetilaliltranstransferasa/genética , Flavanonas/biosíntesis , Frutas/química , Frutas/genética , Solanum lycopersicum/genética , Plantas Modificadas Genéticamente/enzimología , Plantas Modificadas Genéticamente/genética , Prenilación , Regiones Promotoras Genéticas , ARN de Planta/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Streptomyces coelicolor/genética , Espectrometría de Masas en Tándem
11.
J Periodontal Res ; 46(1): 13-20, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20663020

RESUMEN

BACKGROUND AND OBJECTIVE: Nitrogen-containing bisphosphonates (NBPs) are widely used as anti-bone-resorptive drugs. However, use of NBPs results in inflammatory side-effects, including jaw osteomyelitis. In the present study, we examined the effects of alendronate, a typical NBP, on cytokine production by human peripheral blood mononuclear cells (PBMCs) and gingival fibroblasts incubated with lipid A. METHODS: The PBMCs and gingival fibroblasts were pretreated with or without alendronate for 24 h. Cells were then incubated in the presence or absence of lipid A for a further 24 h. Levels of secreted human interleukin (IL)-1ß, IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) in culture supernatants were measured by ELISA. We also examined nuclear factor-κB (NF-κB) activation in both types of cells by ELISA. Activation of Smad3 in the cells was assessed by flow cytometry. In addition, we performed an inhibition assay using SIS3, a specific inhibitor for Smad3. RESULTS: Pretreatment of PBMCs with alendronate promoted lipid A-induced production of IL-1ß and IL-6, but decreased lipid A-induced IL-8 and MCP-1 production. In human gingival fibroblasts, alendronate pretreatment increased lipid A-induced production of IL-6 and IL-8, and increased NF-κB activation in gingival fibroblasts but not PBMCs stimulated with lipid A. In contrast, alendronate activated Smad3 in both types of cells. Finally, SIS3 inhibited alendronate-augmented IL-6 and IL-8 production by human gingival fibroblasts but up-regulated alendronate-decreased IL-8 production by PBMCs. CONCLUSION: These results suggest that alendronate-mediated changes in cytokine production by gingival fibroblasts occur via regulation of NF-κB and Smad3 activity.


Asunto(s)
Alendronato/farmacología , Conservadores de la Densidad Ósea/farmacología , Citocinas/biosíntesis , Encía/efectos de los fármacos , FN-kappa B/metabolismo , Proteína smad3/metabolismo , Activación Transcripcional/efectos de los fármacos , Análisis de Varianza , Células Cultivadas , Quimiocina CCL2/biosíntesis , Quimiocina CCL2/genética , Citocinas/genética , Fibroblastos/efectos de los fármacos , Fibroblastos/inmunología , Fibroblastos/metabolismo , Regulación de la Expresión Génica , Encía/citología , Encía/metabolismo , Humanos , Interleucina-1beta/biosíntesis , Interleucina-1beta/genética , Interleucina-6/biosíntesis , Interleucina-6/genética , Interleucina-8/biosíntesis , Interleucina-8/genética , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Lípido A/inmunología , Proteína smad3/antagonistas & inhibidores
12.
Opt Lett ; 35(10): 1497-9, 2010 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-20479787

RESUMEN

Optical parametric chirped-pulse amplification (OPCPA) operation with low gain by seeding with high-energy, clean pulses is shown to significantly improve the contrast to better than 10(-10) to 10(-11) in a high-intensity Ti:sapphire laser system that is based on chirped-pulse amplification. In addition to the high-contrast broadband, high-energy output from the final amplifier is achieved with a flat-topped spatial profile of filling factor near 77%. This is the result of pump beam spatial profile homogenization with diffractive optical elements. Final pulse energies exceed 30 J, indicating capability for reaching peak powers in excess of 500 TW.


Asunto(s)
Óxido de Aluminio , Rayos Láser , Titanio , Factores de Tiempo
13.
Br J Pharmacol ; 158(5): 1366-74, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19785655

RESUMEN

BACKGROUND AND PURPOSE: The heart of the canine model of chronic atrioventricular block is known to have a ventricular electrical remodelling, which mimics the pathophysiology of long QT syndrome. Using this model, we explored a new pharmacological therapeutic strategy for the prevention of cardiac sudden death. EXPERIMENTAL APPROACH: The L-type Ca(2+) channel blocker amlodipine (2.5 mg.day(-1)), L/N-type Ca(2+) channel blocker cilnidipine (5 mg.day(-1)), or the angiotensin II receptor blocker candesartan (12 mg.day(-1)) was administered orally to the dogs with chronic atrioventricular block for 4 weeks. Electropharmacological assessments with the monophasic action potential (MAP) recordings and blood sample analyses were performed before and 4 weeks after the start of drug administration. KEY RESULTS: Amlodipine and cilnidipine decreased the blood pressure, while candesartan hardly affected it. The QT interval, MAP duration and beat-to-beat variability of the ventricular repolarization period were shortened only in the cilnidipine group, but such effects were not observed in the amlodipine or candesartan group. Plasma concentrations of adrenaline, angiotensin II and aldosterone decreased in the cilnidipine group. In contrast, plasma concentrations of angiotensin II and aldosterone were elevated in the amlodipine group, whereas in the candesartan group an increase in plasma levels of angiotensin II and a decrease in noradrenaline and adrenaline concentrations were observed. CONCLUSIONS AND IMPLICATIONS: Long-term blockade of L/N-type Ca(2+) channels ameliorated the ventricular electrical remodelling in the hypertrophied heart which causes the prolongation of the QT interval. This could provide a novel therapeutic strategy for the treatment of cardiovascular diseases.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L/fisiología , Canales de Calcio Tipo N/fisiología , Cardiomegalia/fisiopatología , Dihidropiridinas/farmacología , Potenciales de Acción/efectos de los fármacos , Amlodipino/sangre , Amlodipino/farmacología , Angiotensina II/sangre , Bloqueadores del Receptor Tipo 1 de Angiotensina II/sangre , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Bloqueo Atrioventricular/tratamiento farmacológico , Bloqueo Atrioventricular/fisiopatología , Bencimidazoles/sangre , Bencimidazoles/farmacología , Compuestos de Bifenilo , Bloqueadores de los Canales de Calcio/sangre , Bloqueadores de los Canales de Calcio/uso terapéutico , Enfermedad Crónica , Dihidropiridinas/sangre , Dihidropiridinas/uso terapéutico , Perros , Electrocardiografía , Epinefrina/sangre , Femenino , Masculino , Neurotransmisores/sangre , Norepinefrina/sangre , Tetrazoles/sangre , Tetrazoles/farmacología , Factores de Tiempo
14.
Phys Rev Lett ; 102(5): 051802, 2009 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-19257503

RESUMEN

We performed a search for a light pseudoscalar particle X in the decay K_{L};{0}-->pi;{0}pi;{0}X, X-->gammagamma with the E391a detector at KEK. Such a particle with a mass of 214.3 MeV/c;{2} was suggested by the HyperCP experiment. We found no evidence for X and set an upper limit on the product branching ratio for K_{L};{0}-->pi;{0}pi;{0}X, X-->gammagamma of 2.4x10;{-7} at the 90% confidence level. Upper limits on the branching ratios in the mass region of X from 194.3 to 219.3 MeV/c;{2} are also presented.

15.
Phys Rev Lett ; 103(19): 194803, 2009 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-20365929

RESUMEN

A high stability electron bunch is generated by laser wakefield acceleration with the help of a colliding laser pulse. The wakefield is generated by a laser pulse; the second laser pulse collides with the first pulse at 180 degrees and at 135 degrees realizing optical injection of an electron bunch. The electron bunch has high stability and high reproducibility compared with single pulse electron generation. In the case of 180 degrees collision, special measures have been taken to prevent damage. In the case of 135 degrees collision, since the second pulse is countercrossing, it cannot damage the laser system.

16.
Phys Rev Lett ; 100(20): 201802, 2008 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-18518524

RESUMEN

We performed a search for the K L0-->pi0nu nu[over] decay at the KEK 12-GeV proton synchrotron. No candidate events were observed. An upper limit on the branching ratio for the decay was set to be 6.7 x 10(-8) at the 90% confidence level.

17.
Br J Pharmacol ; 154(7): 1528-37, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18552873

RESUMEN

As an increasing number of non-cardiac drugs have been reported to cause QT interval prolongation and torsades de pointes (TdP), we extensively studied the utility of atrioventricular (AV) block animals as a model to predict their torsadogenic action in human. The present review highlights such in vivo proarrhythmia models. In the case of the canine model, test substances were administered p.o. at conscious state >4 weeks after the induction of AV block, with subsequent Holter ECG monitoring to evaluate drug effects. Control AV block dogs (no pharmacological treatment) survive for several years without TdP attack. For pharmacologically treated dogs, drugs were identified as high, low or no risk. High-risk drugs induced TdP at 1-3 times the therapeutic dose. Low-risk drugs did not induce TdP at this dose range, but induced it at higher doses. No-risk drugs never induced TdP at any dose tested. Electrophysiological, anatomical histological and biochemical adaptations against persistent bradycardia-induced chronic heart failure were observed in AV block dogs. Recently, we have developed another highly sensitive proarrhythmia model using a chronic AV block cynomolgus monkey, which possesses essentially the same pathophysiological adaptations and drug responses as those demonstrated in the canine model. As a common remodelling process leading to a diminished repolarization reserve may present in patients who experience drug-induced TdP and in the AV block animals, the in vivo proarrhythmia models described in this review may be useful for predicting the risk of pharmacologically induced TdP in humans.


Asunto(s)
Modelos Animales de Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Torsades de Pointes/inducido químicamente , Animales , Bloqueo Atrioventricular/fisiopatología , Perros , Relación Dosis-Respuesta a Droga , Humanos , Macaca fascicularis , Preparaciones Farmacéuticas/administración & dosificación , Medición de Riesgo , Torsades de Pointes/fisiopatología , Pruebas de Toxicidad/métodos , Remodelación Ventricular/fisiología
18.
J Comp Pathol ; 137(2-3): 174-8, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17706243

RESUMEN

This report describes a 5-year-old female cat with lymphangiosarcoma arising within the dermis and subcutis of the caudal mammary region. The mass presented as a large, poorly demarcated and fluctuant swelling with bruising of the overlying skin. Histopathologically, the dermis and subcutis in the affected region were diffusely oedematous, haemorrhagic, and infiltrated by plump spindle cells that formed irregular vascular clefts and cavernous channels. Neoplastic cells were aligned in one or more layers along oedematous collagenous trabeculae. The vascular clefts and channels contained only a few or no erythrocytes. The neoplastic cells had moderate to marked nuclear pleomorphism and prominent nucleoli. Lymphocytes and plasma cells were scattered throughout the neoplasm and the adjacent soft tissues. Immunohistochemical labelling revealed the neoplastic cells to express vimentin, factor VIII-related antigen and the lymphatic endothelial cell marker PROX-1, but the cells did not express cytokeratin. The nuclei of many neoplastic cells expressed the proliferation marker Ki67. These histopathological and immunohistochemical findings confirmed the diagnosis of lymphangiosarcoma. This is the first report describing the usefulness of expression of PROX-1 for differentiating between angiosarcoma of lymphatic and vascular origin in cats.


Asunto(s)
Enfermedades de los Gatos/patología , Linfangiosarcoma/veterinaria , Neoplasias Cutáneas/veterinaria , Animales , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/metabolismo , Gatos , Dermis/metabolismo , Dermis/patología , Diagnóstico Diferencial , Femenino , Proteínas de Homeodominio/metabolismo , Linfangiosarcoma/metabolismo , Linfangiosarcoma/patología , Glándulas Mamarias Animales , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Proteínas Supresoras de Tumor/metabolismo , Vimentina/metabolismo , Factor de von Willebrand/metabolismo
19.
J Comp Pathol ; 137(1): 71-77, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17537453

RESUMEN

Renal lesions of the type usually found in claudin-16 (CL-16) defective Japanese Black cattle (homozygous for CL-16 deficiency) were identified in six animals of this breed, aged 28-59 months, which were either heterozygous for CL-16 deficiency (type 1) or normal, as judged by a DNA-based test associated with the CL-16 gene. Histopathologically, all six cases showed elongated focal lesions which ran through the cortex to terminate in the outer zone of the medulla. The lesions contained components that included: (1) immature tubules, (2) small irregularly shaped tubules with thickening of the basement membrane, (3) mesenchymal cells in an increased interstitium, (4) small atrophic glomeruli, and (5) immature glomeruli. The glomeruli were noticeably reduced in number, and large glomeruli with an increased number of mesangial cells were observed throughout the entire cortical area. Cystic dilation of tubules and flattening of the epithelium were noted in all areas of the kidney. Histopathologically, the renal lesions in the six cases were indistinguishable from those reported previously in cattle homozygous for CL-16 deficiency. These findings demonstrate that such renal lesions in Japanese Black cattle are not necessarily associated with homozygous deletion of the CL-16 gene.


Asunto(s)
Enfermedades de los Bovinos/genética , Proteínas de la Membrana/genética , Riñón Displástico Multiquístico/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/patología , Claudinas , Regulación de la Expresión Génica , Heterocigoto , Homocigoto , Japón , Riñón/metabolismo , Riñón/patología , Proteínas de la Membrana/metabolismo , Riñón Displástico Multiquístico/genética , Riñón Displástico Multiquístico/patología
20.
Clin Exp Immunol ; 148(3): 529-36, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17335558

RESUMEN

Porphyromonas gingivalis is a Gram-negative anaerobic oral black-pigmented bacterium closely associated with chronic periodontitis. Lipopolysaccharide (LPS) derived from P. gingivalis is shown to be unusual because the LPS contains a greater number of lipid A species, such as tri-, tetra-, and/or penta-acylated lipid As. In this study, a lipid A possessing penta-fatty acyl chains derived from P. gingivalis strain 381 (compound PG-381-5FA) was synthesized, and examined for its immunobiological activities, compared with a tri-acylated lipid A (compound PG-381-3FA) synthesized previously. Compound PG-381-5FA, similar to compound PG-381-3FA, demonstrated weaker activity in a Limulus test as compared with Escherichia coli-type synthetic lipid A (compound 506). Compound PG-381-5FA, followed by compound PG-381-3FA, induced KC, interleukin-6, and tumour necrosis factor-alpha production in peritoneal macrophages from LPS-responsive C3H/HeN mice, but not in those from LPS-hyporesponsive C3H/HeJ mice. Furthermore, compound PG-381-5FA, as well as compound PG-381-3FA, activated nuclear factor-kappaB via Toll-like receptor (TLR)4/mD-2, but not TLR2, in a manner similar to compound 506, and worked as an antagonist for compound 506-induced cell activation. In the case of human peripheral blood mononuclear cells, compound PG-381-5FA showed much stronger IL-6-inducing activity than compound PG-381-3FA. The present results demonstrate that the chemical synthesis of a penta-acylated lipid A, mimicking the natural lipid A portion of LPS from P. gingivalis, is attributable to immune cell activation through TLR4, similar to that of compound 506.


Asunto(s)
Lípido A/inmunología , Porphyromonas gingivalis/inmunología , Receptor Toll-Like 4/inmunología , Adulto , Animales , Humanos , Interleucina-6/biosíntesis , Leucocitos Mononucleares/inmunología , Lípido A/síntesis química , Lípido A/química , Lipopolisacáridos/inmunología , Macrófagos Peritoneales/inmunología , Masculino , Ratones , Ratones Endogámicos C3H , FN-kappa B/metabolismo , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/biosíntesis
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