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1.
Psychol Med ; 50(10): 1680-1686, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31327333

RESUMEN

BACKGROUND: The association between schizophrenia and decreased vitamin D levels is well documented. Low maternal and postnatal vitamin D levels suggest a possible etiological mechanism. Alternatively, vitamin D deficiency in patients with schizophrenia is presumably (also) the result of disease-related factors or demographic risk factors such as urbanicity. METHODS: In a study population of 347 patients with psychotic disorder and 282 controls, group differences in vitamin D concentration were examined. Within the patient group, associations between vitamin D, symptom levels and clinical variables were analyzed. Group × urbanicity interactions in the model of vitamin D concentration were examined. Both current urbanicity and urbanicity at birth were assessed. RESULTS: Vitamin D concentrations were significantly lower in patients (B = -8.05; 95% confidence interval (CI) -13.68 to -2.42; p = 0.005). In patients, higher vitamin D concentration was associated with lower positive (B = -0.02; 95% CI -0.04 to 0.00; p = 0.049) and negative symptom levels (B = -0.03; 95% CI -0.05 to -0.01; p = 0.008). Group differences were moderated by urbanicity at birth (χ2 = 6.76 and p = 0.001), but not by current urbanicity (χ2 = 1.50 and p = 0.224). Urbanicity at birth was negatively associated with vitamin D concentration in patients (B = -5.11; 95% CI -9.41 to -0.81; p = 0.020), but not in controls (B = 0.72; 95% CI -4.02 to 5.46; p = 0.765). CONCLUSIONS: Lower vitamin D levels in patients with psychotic disorder may in part reflect the effect of psychosis risk mediated by early environmental adversity. The data also suggest that lower vitamin D and psychopathology may be related through direct or indirect mechanisms.


Asunto(s)
Trastornos Psicóticos/sangre , Población Urbana , Vitamina D/sangre , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Países Bajos/epidemiología , Densidad de Población , Trastornos Psicóticos/epidemiología , Análisis de Regresión , Factores de Riesgo , Adulto Joven
2.
Phys Chem Chem Phys ; 22(36): 20507-20514, 2020 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-32966421

RESUMEN

In the field of additive manufacturing DLP vat technologies are promising 3D printing techniques. The need of highly efficient photoiniating systems drives us to the development of photocyclic 3-component initiators. In order to improve the 3D printing sensitivity, we present in this paper the use of synthesized clay to tune up the photochemistry underlying the initiating radical production. Therefore, a three-component initiating system, based on a cationic dye, two coinitiators and with a clay filler suitable for DLP 3D printing of acrylate resins leading to high quality of parts and low printing time, is developed.

3.
BMC Musculoskelet Disord ; 21(1): 241, 2020 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-32290832

RESUMEN

BACKGROUND: Haemophilic arthropathy is a chronic and debilitating joint disease caused by recurrent spontaneous joint bleeds in patients with haemophilia. Understanding how characteristics of individual joint bleeds relate to the subsequent development of arthropathy could improve management and prevention of this joint disease. Here, we aimed to explore relations between joint bleed characteristics and development of bone pathology in a mouse model of haemophilic arthropathy by using novel in vivo imaging methodology. METHODS: We characterised induced knee bleeds in a murine model of haemophilic arthropathy by quantitative in vivo fluorescence molecular tomography (FMT) and by measurements of changes in the diameter of the injured knee. Wild-type mice and non-injured haemophilic mice acted as controls. Development of arthropathy was characterised by post mortem evaluation of bone pathology by micro-CT 14 days after bleed-induction. In an in vitro study, we assessed the effect of blood on the quantification of fluorescent signal with FMT. RESULTS: In most injured haemophilic mice, we observed significant loss of trabecular bone, and half of the mice developed pathological bone remodelling. Development of pathological bone remodelling was associated with significantly increased fluorescent signal and diameter of the injured knee just 1 day after induction of the bleed. Further, a correlation between the fluorescent signal 1 day after induction of the bleed and loss of trabecular bone reached borderline significance. In the in vitro study, we found that high concentrations of blood significantly decreased the fluorescent signal. CONCLUSION: Our results add novel insights on the pathogenesis of haemophilic arthropathy and underline the importance of the acute phase of joint bleeds for the subsequent development of arthropathy.


Asunto(s)
Huesos/patología , Hemartrosis/diagnóstico , Hemofilia A/patología , Microtomografía por Rayos X , Animales , Remodelación Ósea , Modelos Animales de Enfermedad , Fluorescencia , Hemartrosis/complicaciones , Hemartrosis/patología , Hemofilia A/complicaciones , Miembro Posterior/anatomía & histología , Miembro Posterior/diagnóstico por imagen , Miembro Posterior/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
4.
AIDS Care ; 31(2): 255-259, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-29962226

RESUMEN

Physical activity (PA) is healthy for People Living with HIV and AIDS (PLWHA). This study examined the PA profile of 978 PLWHA based on PA domains and PA intensity. The study also sought to determine whether employment status and level of education can predict PA among PLWHA of low SES. PA and sociodemographic data of 978 PLWHA of mean age 35 (8.77) years were collected using the global physical activity questionnaire and a sociodemographic questionnaire. Results showed that, participants engaged more in work-related PA [160.11 (346.95) min/wk], followed by transport related PA [115.21(SD = 142.04) min/wk], and lastly in leisure related PA [40.84 (SD = 110.37) min/wk]. Participants also engaged more in moderate PA [265.86 (SD = 335.45) min/wk], than in vigorous PA [50.29 (SD = 205.30) min/wk]. Employment was a significant predictor of overall PA controlling for age, CD4 count and education level. The model explained 2.5% of the variance (R2 = 0.025) on overall PA and tested significant at a 0.01 alpha level (p < 0.01). PA interventions for this population should be domain- and intensity-specific. Researchers promoting healthy lifestyle behaviour change can benefit from determining the factors that facilitate domain-specific PA.


Asunto(s)
Empleo/estadística & datos numéricos , Ejercicio Físico , Infecciones por VIH/psicología , Esfuerzo Físico , Adulto , Anciano , Escolaridad , Femenino , Humanos , Actividades Recreativas , Masculino , Persona de Mediana Edad , Conducta Sedentaria , Clase Social , Encuestas y Cuestionarios , Transportes , Lugar de Trabajo , Adulto Joven
5.
BMC Public Health ; 19(1): 774, 2019 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-31208375

RESUMEN

BACKGROUND: Regular physical activity (PA) has been recommended for the management of HIV and AIDS. The purpose of this study was to develop a contextualised intervention for promoting PA among women living with HIV and AIDS (WLWHA) of low socioeconomic status (SES). A secondary aim of the study was to optimise the PA intervention using behavioural theory/ frameworks derived from preliminary studies and the literature. METHODS: The Behaviour Change Wheel (BCW) for designing behaviour change interventions was used. This method was further supplemented by evidence from the literature, systematic literature review (SLR), a concurrent mixed methods study and two cross-sectional studies. The SLR aided in determining the theoretical frameworks to inform the intervention, the specific PA behaviours to be targeted by the intervention, the intervention functions, the intervention policy category and the mode of delivery of the intervention. The concurrent mixed methods study was used to identify key factors that needed to change in order for participants to engage in regular PA. The first cross-sectional study was used to determine the gender to be targeted by the study. The second cross-sectional study was used to determine the domain and intensity of PA to target in the intervention. RESULTS: A face-to-face context-sensitive PA intervention employing 14 behavioural change techniques was designed. The PA intervention (a) utilised the Transtheoretical model of behaviour change and the Social Cognitive theory as the underpinning theoretical frameworks (b) included convenient PAs, such as walking, doing simple home-based exercises, engaging in activities of daily living or doing simple exercises at the community centre (c) used education, reward, training in PA, modelling exercise activities and enablement to increase the opportunity to engage in PA as intervention functions (d) used service provision as policy priorities, and (e) used a direct face-to-face mode of delivery. CONCLUSIONS: The PA intervention emphasises behavioural techniques for increasing PA participation, such as goal-setting, self-monitoring, strategies for overcoming PA barriers, social support and rewards. The intervention employs strategies that highlight low-cost local PA resources and opportunities to help HIV infected women of low SES to participate in PA. The BCW provides a useful and comprehensive framework for the development of evidence and theory-based PA interventions for PLWHA of low SES. The BCW can thus be used in the development of interventions that 'talk' to policy by bridging the health inequality gap.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/terapia , Ejercicio Físico/psicología , Infecciones por VIH/terapia , Promoción de la Salud/organización & administración , Pobreza , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Estudios Transversales , Práctica Clínica Basada en la Evidencia , Femenino , Infecciones por VIH/epidemiología , Promoción de la Salud/métodos , Humanos , Revisiones Sistemáticas como Asunto
6.
AIDS Care ; 30(sup2): 61-65, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29848009

RESUMEN

Research has consistently shown the benefits of regular physical activity (PA) for women living with HIV and AIDS (WLWHA). This study is a pilot, randomised controlled crossover trial, reporting the effects of a contextualised PA intervention amongst a sample of 21 HIV positive Xhosa-speaking women of low socioeconomic status (SES). The study determined total moderate-to-vigorous PA (TMVPA) as measured subjectively by the Global Physical Activity Questionnaire (GPAQ), total weekly steps (TWS) as measured by a pedometer, and self-efficacy for PA as measured by the Physical Exercise Self-efficacy scale (PESES). Multivariate analysis of covariance (MANCOVA) was used to compute the impact of the intervention on TMVPA, TWS, and self-efficacy for PA from baseline to six weeks, and baseline to 12 weeks post-intervention controlling for pre-test differences in TMVPA. Results showed that participants exposed to the intervention had significant increases in PA as measured by TMVPA (p = .027), TWS (p = .032), as well as exercise self-efficacy (p = .000) from pre-test to 6 weeks. Insignificant findings were reported for all three variables when measured from baseline to 12 weeks. In conclusion, the findings of the pilot study suggest that the intervention was effective in producing significant increases in PA in a sample of PLWHA of low SES over six weeks. Careful consideration of behavioural constructs, such as self-efficacy, can help WLWHA of low SES to adopt regular PA as a complementary therapy for managing their health.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/terapia , Ejercicio Físico/psicología , Infecciones por VIH/terapia , Promoción de la Salud/métodos , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Actigrafía , Adulto , Estudios Cruzados , Ejercicio Físico/fisiología , Femenino , Infecciones por VIH/epidemiología , Humanos , Renta , Persona de Mediana Edad , Proyectos Piloto , Pobreza , Autoeficacia , Clase Social , Resultado del Tratamiento
7.
Vet Pathol ; 54(3): 445-456, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28129094

RESUMEN

Articular osteochondrosis (OC) often develops in typical locations within joints, and the characterization of OC distribution in the pig tarsus is incomplete. Prevalence of OC is high in domestic pigs but is presumed to be low in wild boars. Postmortem and computed tomography (CT) examinations of the talus and distal tibia from 40 domestic pigs and 39 wild boars were evaluated for the locations and frequencies of OC, synovial fossae, and other articular indentations, and frequency distribution maps were made. All domestic pigs but only 5 wild boars (13%) had OC on the talus. In domestic pigs, OC consistently affected the axial aspect of the medial trochlea tali in 11 (28%) joints and the distomedial talus in 26 (65%) joints. In wild boars, all OC lesions consistently affected the distomedial talus. On the articular surface of the distal tibia, all domestic pigs and 34 wild boars (87%) had synovial fossae and 7 domestic pigs (18%) had superficial cartilage fibrillation opposite an OC lesion (kissing lesion). Other articular indentations occurred in the intertrochlear groove of the talus in all domestic pigs and 13 wild boars (33%) and were less common on the trochlea tali. The prevalence of tarsal OC in wild boars is low. In domestic pigs and wild boars, OC is typically localized to the distomedial talus and in domestic pigs also to the medial trochlea tali. Further investigations into the reasons for the low OC prevalence in wild boars may help in developing strategies to reduce OC incidence in domestic pigs.


Asunto(s)
Osteocondrosis/veterinaria , Enfermedades de los Porcinos/patología , Astrágalo/patología , Tibia/patología , Animales , Femenino , Masculino , Osteocondrosis/diagnóstico por imagen , Osteocondrosis/patología , Sus scrofa/crecimiento & desarrollo , Porcinos/crecimiento & desarrollo , Enfermedades de los Porcinos/diagnóstico por imagen , Membrana Sinovial/patología , Astrágalo/diagnóstico por imagen , Tibia/diagnóstico por imagen , Tomografía Computarizada por Rayos X/veterinaria
8.
Photochem Photobiol Sci ; 15(8): 1054-60, 2016 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-27443964

RESUMEN

The efficiency of free radical polymerization by photoinitiating systems based on two Astrazon orange cyanine dyes was shown to be directly related to the isomerization process of the dye in the excited states. The impact of resin viscosity on photopolymerization reactions was measured and related to the overall radical quantum yields. The quantum yields were calculated according to the photocyclic behaviour of the initiating systems based on the Astrazon orange dyes. These dyes are characterized by a viscosity dependent photophysics, which leads to an isomerization-diffusion-controlled photopolymerization. Besides this demonstration, Astrazon orange dyes appeared to be very good candidates for free radical photopolymerization in the visible, presenting high absorption coefficient, low cost and good sensitivity.

9.
Phys Chem Chem Phys ; 17(26): 16677-81, 2015 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-26028222

RESUMEN

The combination of an organic dye with clays leads to very interesting hybrid materials with original properties. It is found that LAPONITE® nanoparticles have an impact on the photophysical properties of the crystal violet dye inducing a kinetic stabilization of its excited emissive state, turning this nonemissive dye into a fluorescent compound.

10.
Eur Cell Mater ; 27: 213-36; discussion 234-6, 2014 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-24668595

RESUMEN

Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA) in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining) and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints.


Asunto(s)
Calcinosis/veterinaria , Enfermedades de los Caballos/patología , Cartílago Hialino/patología , Articulaciones/patología , Osteocondrosis/veterinaria , Tarso Animal/patología , Animales , Calcinosis/patología , Caballos , Osteocondrosis/patología
11.
Photochem Photobiol Sci ; 11(11): 1682-90, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22782454

RESUMEN

A set of photoinitiating systems (PIS) for free radical photopolymerization was studied using time-resolved spectroscopic experiments, real-time FTIR and holographic recording. It is shown that the efficiency of the photoinitiating system can be drastically increased when a redox additive is added to the conventional dye/coinitiator system by virtue of photocyclic behaviour. The homogeneous photopolymerization process was found to reach a fast vitrification, limiting the conversion at about 55%. By contrast, holographic recording underlines the differences in photoinitiating system reactivity, allowing diffraction efficiencies close to unity for the most reactive PIS.

12.
J Comp Pathol ; 176: 116-121, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32359623

RESUMEN

Hypophysitis has been reported occasionally in dogs, with most cases resembling primary lymphocytic hypophysitis in man. Although it is generally assumed that lymphocytes are not present normally in the canine pituitary gland, few studies have investigated this hypothesis. However, lymphocytes are recognized in the pituitary gland of people and horses without signs of pituitary disease. It is unknown to what degree lymphocyte infiltration of the pituitary gland might occur as an incidental finding in dogs. The aim of the present study was to investigate the presence and distribution of lymphocytes in the pituitary gland of dogs without clinical suspicion of pituitary disease. Twenty dogs were subjected to routine necropsy examination. Formalin-fixed and paraffin wax-embedded sections of pituitary were stained with haematoxylin and eosin (HE) or subjected to immunohistochemistry (IHC) using primary antibodies specific for the T-cell marker CD3 and the B-cell marker CD79a. The number of CD3+ and CD79a+ cells per area unit (CPA) was determined for different pituitary regions. Two dogs had extensive neoplastic lesions in the pituitary gland and were excluded from analysis. In the remaining 18 dogs, occasional scattered CD3+ cells were found in the pituitary gland. There was a significant difference in CD3+ CPA between pituitary regions (P = 0.001). The highest CD3+ CPA was found in the pars tuberalis (median 41.3 cells/mm2, interquartile range 20.9-50.5 cells/mm2). In six of the 18 dogs (33%), CD79a+ cells were detected in small number (median total cell number 0 cells/section, interquartile range 0-1.0 cells/section). This study shows that T cell, and fewer B cells, may be found in the pituitary gland of dogs without clinical suspicion of pituitary disease. Regional difference in T-cell density, with the highest CD3+ CPA in the pars tuberalis, may imply regional immunoregulatory functions in the canine pituitary gland.


Asunto(s)
Enfermedades de los Perros/epidemiología , Hipofisitis/veterinaria , Linfocitos , Hipófisis/inmunología , Animales , Autopsia , Complejo CD3/inmunología , Antígenos CD79/inmunología , Perros , Femenino , Hipofisitis/epidemiología , Hallazgos Incidentales , Masculino , Hipófisis/patología
13.
Int J Tryptophan Res ; 13: 1178646920972657, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33447045

RESUMEN

Alzheimer's disease (AD) is associated with progressive endogenous neurotoxicity and hampered inflammatory regulation. The kynurenine (Kyn) pathway, which is controlled by tryptophan 2,3-dioxygenase (TDO), produces neuroactive and anti-inflammatory metabolites. Age-related Kyn pathway activation might contribute to AD pathology in humans, and inhibition of TDO was found to reduce AD-related cellular toxicity and behavioral deficits in animal models. To further explore the effect of aging on the Kyn pathway in the context of AD, we analyzed Kyn metabolite profiles in serum and brain tissue of the APP23 amyloidosis mouse model. We found that aging had genotype-independent effects on Kyn metabolite profiles in serum, cortex, hippocampus and cerebellum, whereas serum concentrations of many Kyn metabolites were reduced in APP23 mice. Next, to further establish the role of TDO in AD-related behavioral deficits, we investigated the effect of long-term pharmacological TDO inhibition on cognitive performance in APP23 mice. Our results indicated that TDO inhibition reversed recognition memory deficits without producing measurable changes in cerebral Kyn metabolites. TDO inhibition did not affect spatial learning and memory or anxiety-related behavior. These data indicate that age-related Kyn pathway activation is not specific for humans and could represent a cross-species phenotype of aging. These data warrant further investigation on the role of peripheral Kyn pathway disturbances and cerebral TDO activity in AD pathophysiology.

14.
Res Vet Sci ; 86(3): 490-7, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19041991

RESUMEN

Cytokine production in synovial membranes (SM) and osteochondral fragments (OCF) may influence the development of equine osteoarthritis (OA). In this study, the presence of interleukin (IL)-6 and cytoplasmic and extracellular high mobility group box protein (HMGB)-1 in SM and osteochondral tissue from healthy and diseased equine joints was investigated by immunohistochemistry. Additionally, microscopic synovitis was graded. IL-6 was commonly found in SM cells and in chondrocytes in uncalcified cartilage of OCF, whereas little staining was detected in healthy cartilage. Cytoplasmic and/or extracellular HMGB-1 was widespread only in SM from diseased joints, and also detected in OCF in areas of cartilage damage, fibrous repair tissue, and tidemark reduplication. Joints with OCF and cartilage lesions (without OCF) showed significantly higher median synovitis scores than healthy joints (p=0.013 and p=0.042, respectively). The study identifies OCF as a source of inflammatory mediators in equine OA, as shown by the presence of IL-6 and extracellular HMGB-1 in the fragment. Based upon HMGB-1 release in SM and OCF, further studies to investigate possible involvement of HMGB-1 in the pathogenesis of OA are warranted.


Asunto(s)
Proteína HMGB1/metabolismo , Enfermedades de los Caballos/metabolismo , Interleucina-6/metabolismo , Osteoartritis/veterinaria , Osteocondritis/veterinaria , Envejecimiento/fisiología , Animales , Artroscopía/métodos , Artroscopía/veterinaria , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/cirugía , Caballos , Articulaciones/metabolismo , Articulaciones/patología , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoartritis/cirugía , Osteocondritis/metabolismo , Osteocondritis/patología , Valores de Referencia
15.
Neuron ; 1(5): 395-401, 1988 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-3272173

RESUMEN

A cDNA (199E) specific for the 57 kd neural IF protein has been isolated from a PC12 cell lambda gt11 library. Antibody eluted from the fusion protein produced by 199E recognizes the 57 kd protein on immunoblots and, in PC12 cells, labels a pattern of fibrillar structures identical to that seen with 57 kd antiserum. In situ hybridization using antisense RNA transcripts labels areas of the nervous system known to contain the 57 kd protein. 199E hybridizes with a single mRNA species of approximately 2.0 kb from PC12 cells. A 199E-reactive message can be detected as early as E10 in rat embryos. Southern analyses suggest that there is only one gene for this protein. Amino acid sequence predicted from 199E indicates that the 57 kd protein is a type III IF protein like vimentin and desmin. Thus, expression of IF structural genes in neurons is not limited to the type IV neuronal IF triplet proteins.


Asunto(s)
Genes , Proteínas de Filamentos Intermediarios/genética , Neuronas/metabolismo , Neoplasias de las Glándulas Suprarrenales , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Línea Celular , ADN/genética , Expresión Génica , Biblioteca de Genes , Datos de Secuencia Molecular , Peso Molecular , Feocromocitoma , Biosíntesis de Proteínas , ARN Mensajero/análisis , ARN Mensajero/genética , Ratas , Homología de Secuencia de Ácido Nucleico , Transcripción Genética
16.
J Thromb Haemost ; 16(7): 1369-1382, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29758126

RESUMEN

Essentials The efficacy of systemic antifibrinolytics for hemophilic non-mucosal bleeding is undetermined. The effect of systemically inhibiting fibrinolysis in hemophilic mice and rats was explored. Neither bleeding nor the response to factor treatment was improved after inhibiting fibrinolysis. The non-mucosal bleeding phenotype in hemophilia A appears largely unaffected by fibrinolysis. SUMMARY: Background Fibrinolysis may exacerbate bleeding in patients with hemophilia A (HA). Accordingly, antifibrinolytics have been used to help maintain hemostatic control. Although antifibrinolytic drugs have been proven to be effective in the treatment of mucosal bleeds in the oral cavity, their efficacy in non-mucosal tissues remain an open question of significant clinical interest. Objective To determine whether inhibiting fibrinolysis improves the outcome in non-mucosal hemophilic tail vein transection (TVT) bleeding models, and to determine whether a standard ex vivo clotting/fibrinolysis assay can be used as a predictive surrogate for in vivo efficacy. Methods A highly sensitive TVT model was employed in hemophilic rodents with a suppressed fibrinolytic system to examine the effect of inhibiting fibrinolysis on bleeding in non-mucosal tissue. In mice, induced and congenital hemophilia models were combined with fibrinolytic attenuation achieved either genetically or pharmacologically (tranexamic acid [TXA]). In hemophilic rats, tail bleeding was followed by whole blood rotational thromboelastometry evaluation of the same animals to gauge the predictive value of such assays. Results The beneficial effect of systemic TXA therapy observed ex vivo could not be confirmed in vivo in hemophilic rats. Furthermore, neither intravenously administered TXA nor congenital knockout of the fibrinolytic genes encoding plasminogen or tissue-type plasminogen activator markedly improved the TVT bleeding phenotype or response to factor therapy in hemophilic mice. Conclusions The findings here suggest that inhibition of fibrinolysis is not effective in limiting the TVT bleeding phenotype of HA rodents in non-mucosal tissues.


Asunto(s)
Antifibrinolíticos/farmacología , Coagulantes/farmacología , Factor VIII/farmacología , Factor VIIa/farmacología , Fibrinólisis/efectos de los fármacos , Hemofilia A/tratamiento farmacológico , Cola (estructura animal)/irrigación sanguínea , Ácido Tranexámico/farmacología , Lesiones del Sistema Vascular/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Factor VIII/genética , Factor VIII/metabolismo , Fibrinólisis/genética , Predisposición Genética a la Enfermedad , Hemofilia A/sangre , Hemofilia A/genética , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Plasminógeno/deficiencia , Plasminógeno/genética , Ratas Transgénicas , Proteínas Recombinantes/farmacología , Activador de Tejido Plasminógeno/deficiencia , Activador de Tejido Plasminógeno/genética , Lesiones del Sistema Vascular/sangre , Lesiones del Sistema Vascular/genética
17.
J Clin Invest ; 62(5): 923-30, 1978 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-361756

RESUMEN

Prostacyclin (PGI(2)) is an unstable prostaglandin which inhibits platelet aggregation and serotonin release and causes vasodilation. The PGI(2) activity produced by monolayers of cultured human endothelial cells and fibroblasts was measured by the ability of their supernates to inhibit platelet aggregation in platelet-rich plasma, or to inhibit thrombin-induced [(14)C]serotonin release from aspirin-treated, washed platelet suspensions. Monolayers of cultured human endothelial cells, stimulated with sodium arachidonate, thrombin, the ionophore A 23187, or trypsin, secreted PGI(2) into the supernatant medium. Monolayers of fibroblasts produced PGI(2) activity only when stimulated by arachidonate. "Resting," intact monolayers did not produce detectable PGI(2), nor did monolayers treated with ADP or epinephrine. Production of PGI(2) activity was abolished by treatment of the monolayers with indomethacin, tranylcypromine, or 15-hydroperoxy arachidonic acid. The PGI(2) activity of the supernates was destroyed by boiling or acidification. Inhibition of thrombin with diisopropylfluoro-phosphate, and of trypsin with soybean trypsin inhibitor, abolished the stimulation of PGI(2) production by these enzymes. Production of thrombin at a site of vascular injury could, by stimulating PGI(2) synthesis by endothelial cells adjacent to the injured area, limit the number of platelets involved in the primary hemostatic response and help to localize thrombus formation.


Asunto(s)
Antibacterianos/farmacología , Calcimicina/farmacología , Endotelio/metabolismo , Epoprostenol/biosíntesis , Prostaglandinas/biosíntesis , Trombina/metabolismo , Tripsina/metabolismo , Ácidos Araquidónicos/metabolismo , Plaquetas/metabolismo , Células Cultivadas , Quimotripsina/metabolismo , Humanos , Agregación Plaquetaria/efectos de los fármacos , Serotonina/metabolismo , Venas Umbilicales/metabolismo
18.
Benef Microbes ; 8(4): 507-519, 2017 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-28618862

RESUMEN

Probiotic use by patients and physicians has dramatically increased over the last decade, although definitive evidence is often lacking for their use. We examined probiotic-prescribing practices among health care providers (HCP) at a tertiary medical centre and compared these practices to clinical guidelines. HCP at the Stanford Medical Center received a survey on probiotic prescribing practices including choice of probiotic and primary indications. A broad overview of the literature was performed. Among 2,331 HCP surveyed, 632 responded. Of the 582 of these who routinely prescribed medications, 61% had recommended probiotic foods or supplements to their patients. Women and gastroenterologists were more likely to prescribe probiotics (odds ratio (OR): 1.5, 95% confidence interval (CI): 1.0-2.1; OR: 3.9, 95% CI: 1.5-10.1, respectively). Among probiotic prescribers, 50% prescribed inconsistently or upon patient request, and 40% left probiotic choice to the patient. Common indications for probiotics, particularly Lactobacillus GG, were prevention and treatment of antibiotic-associated diarrhoea (79 and 66%, respectively). Probiotics were often prescribed for 'general bowel health' or at patient request (27 and 39% of responders, respectively). Most respondents (63%) thought an electronic medical record (EMR) pop-up would change probiotic prescribing patterns. However, a review of published guidelines and large trials found inconsistencies in probiotic indications, dosages and strain selection. Probiotic prescribing is common but lacks consistency, with choice of probiotic frequently left to the patient, even for indications with some strain-specific evidence. Implementation of EMR pop-ups/pocket guides may increase consistency in probiotic prescribing, although the lack of clear and consistent guidelines must first be addressed with large, well-designed clinical trials.


Asunto(s)
Pautas de la Práctica en Medicina/normas , Probióticos/uso terapéutico , Estudios Transversales , Guías como Asunto , Humanos , Médicos/psicología , Pautas de la Práctica en Medicina/estadística & datos numéricos , Probióticos/normas
19.
Benef Microbes ; 8(3): 345-351, 2017 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-28403649

RESUMEN

Probiotic use has skyrocketed in recent years. Little is known, however, about patient knowledge and practices regarding probiotic use, especially in the context of antibiotic use. An invitation to complete a short, anonymous, electronic survey was sent by email to 965 patients at a tertiary medical centre in California who had agreed to be contacted for participation in research studies. Questions were asked about both probiotic and antibiotic use in the prior three months. Of 333 survey respondents, 55% had recently used probiotics, including food products and/or supplements (90 and 60% of probiotic users, respectively). Women were more likely than men to have used probiotics (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.2-3.4). Health care providers (HCP) had prescribed antibiotics to 79 (24%) respondents in the preceding three months. Among antibiotic users, 33% had initiated or changed probiotics at the time of antibiotic use, usually without a recommendation from their prescribing HCP (72%). Only 12% of those who took probiotics with antibiotics had received a specific recommendation from their HCP. Most patients chose to take probiotic mixtures (56%), with few selecting evidence-based strains, such as Lactobacillus rhamnosus GG (11%). Regular probiotic use among patients is common. Typically, these probiotics are not recommended by a HCP, even in conjunction with antibiotic prescriptions. While a growing body of evidence supports specific probiotic strains for the prevention of antibiotic-associated diarrhoea, patients are often not receiving a specific recommendation from their HCP and appear to be taking strains without guidance from supporting evidence.


Asunto(s)
Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Probióticos/uso terapéutico , Diarrea/inducido químicamente , Diarrea/prevención & control , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Lacticaseibacillus rhamnosus , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Centros de Atención Terciaria
20.
J Vet Intern Med ; 31(3): 805-813, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28370332

RESUMEN

BACKGROUND: Increased concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in dogs with azotemia have been documented. Knowledge of mechanisms behind increased concentrations of cardiac biomarkers in dogs with azotemia is warranted for correct interpretation of test results. OBJECTIVES: The aim of the article was to investigate possible associations between plasma concentrations of cTnI and NT-proBNP, respectively, and patient characteristics, glomerular filtration rate (GFR), a plasma volume factor (PVF) derived from scintigraphic examination (PVf), systolic blood pressure (SBP), selected hematologic and biochemical variables, and echocardiographic measurements in dogs with stable chronic kidney disease (CKD) and in healthy dogs. ANIMALS: Fifty student-, staff-, and client-owned dogs were included. Twenty-three of the dogs were healthy and 27 were diagnosed with CKD. METHODS: In this cross-sectional observational study, dogs with a previous diagnosis of CKD and healthy control dogs were included. At inclusion, all dogs were characterized by physical examination, repeated blood pressure measurements, complete urinalysis, hematology and biochemistry panel, echocardiography, abdominal ultrasound examination of the entire urinary tract, and scintigraphic examination for measurement of GFR. RESULTS: Plasma volume factor and PCV were independently associated with NT-proBNP (Radj2 = 0.42; P < .0001). Age, body weight (BW), and SBP were independently associated with cTnI (Radj2 = 0.50; P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Neither NT-proBNP nor cTnI concentrations were independently associated with measured GFR. Thus, findings were not suggestive of passive accumulation of either marker, suggesting that increased circulating concentrations of cTnI and NT-proBNP can be interpreted similarly in dogs with stable CKD as in dogs without CKD.


Asunto(s)
Enfermedades de los Perros/sangre , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Insuficiencia Renal Crónica/veterinaria , Troponina I/sangre , Animales , Azotemia/sangre , Azotemia/veterinaria , Presión Sanguínea , Estudios de Casos y Controles , Estudios Transversales , Perros , Femenino , Tasa de Filtración Glomerular/veterinaria , Masculino , Volumen Plasmático/veterinaria , Insuficiencia Renal Crónica/sangre
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