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1.
J Small Anim Pract ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39238283

RESUMEN

OBJECTIVES: To describe the techniques for preparation and placement of peripheral intravenous catheters (PIVCs), to describe the complications associated with PIVCs, and to identify factors associated with PIVC complications in small animal practice in the United Kingdom. MATERIALS AND METHODS: A prospective multicentre observational study was undertaken between January 2022 and January 2023. Data collected included patient information, information regarding the placement and maintenance of PIVCs, and PIVC complications, from privately owned cats and dogs presenting to veterinary institutes in the United Kingdom. Patients required a PIVC to be placed as part of their care and the PIVC was anticipated to be in situ for >24 hours to be eligible for PIVC complication analysis. RESULTS: A total of 19 institutes recorded data regarding 382 PIVCs, with 325 (85.1%) placed in dogs and 57 (14.9%) in cats. The most common reasons for placement were to administer intravenous fluid therapy (74.3%) and intravenous medications (71.7%). There were 102 of 382 (26.7%) PIVCs associated with a complication, with limb swelling/suspected phlebitis in 44 of 382 (11.5%) and PIVC dislodgement/patient interference in 30 of 382 (7.9%) PIVCs. Factors associated with increased risk of complication were more than 1 attempt to place the PIVC, a second or subsequent PIVC being placed during hospitalisation, flush frequency different than every 1 to 24 hours, and flush solution with compound sodium lactate. CLINICAL SIGNIFICANCE: Veterinary professionals must be vigilant when monitoring a patient with a PIVC in situ, particularly if a PIVC is associated with one of the aforementioned factors of increased likelihood of complication.

2.
J Public Health (Oxf) ; 43(2): e213-e223, 2021 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-31832667

RESUMEN

BACKGROUND: Secondary schools are an important setting for preventing obesity in adolescence. Headteachers and chairs of governors are identified in national guidance as crucial stakeholders for school-based preventative action. Despite this, their views remain unexplored and unrepresented. METHODS: A sequential mixed method study was conducted. Semi-structured interviews were undertaken with a purposive sample of 22 secondary school headteachers and chairs of governors in England. Data were thematically analysed and informed the development of a descriptive cross-sectional survey, completed by 127 participants from the same population. RESULTS: Unhealthy dietary and sedentary behaviours were viewed as a more significant problem than adolescent obesity. Obesity was perceived as complex and multi-causal, and a range of stakeholders were deemed to have responsibility for its prevention, most notably parents. Support was identified for the role of secondary schools, although this was not an explicit priority and extensive internal and external barriers exist, which hinder preventative action. CONCLUSIONS: Whilst secondary school settings in England remain an important setting for the prevention of adolescent obesity, it is crucial for policy makers and public health professionals to recognize the factors affecting school leaders' ability and willingness to contribute to this agenda.


Asunto(s)
Obesidad Infantil , Adolescente , Estudios Transversales , Inglaterra , Humanos , Obesidad Infantil/prevención & control , Investigación Cualitativa , Servicios de Salud Escolar , Instituciones Académicas
3.
Phys Rev Lett ; 119(18): 182501, 2017 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-29219591

RESUMEN

We report the measurement of the beam-vector and tensor asymmetries A_{ed}^{V} and A_{d}^{T} in quasielastic (e[over →],e^{'}p) electrodisintegration of the deuteron at the MIT-Bates Linear Accelerator Center up to missing momentum of 500 MeV/c. Data were collected simultaneously over a momentum transfer range 0.1

4.
Methods Cell Biol ; 136: 35-56, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27473902

RESUMEN

Much about septin function has been inferred from in vivo studies using mainly genetic methods, and much of what we know about septin organization has been obtained through examination of static structures in vitro primarily by electron microscopy. Deeper mechanistic insight requires real-time analysis of the dynamics of the assembly of septin-based structures and how other proteins associate with them. We describe here a Förster resonance energy transfer (FRET)-based approach for measuring in vitro the rate and extent of filament formation from septin complexes, binding of other proteins to septin structures, and the apparent affinities of these interactions. FRET is particularly well suited for interrogating protein-protein interactions, especially on a rapid timescale; the spectral change provides an unambiguous indication of whether two elements within the system under study are associating and serves as a molecular-level "ruler" because it is very sensitive to the separation between the donor and acceptor fluorophores over biologically relevant distances (≤10nm). The necessary procedures involve generation of appropriate cysteine-less and single cysteine-containing septin variants, expression and purification of the heterooctameric complexes containing them, efficient labeling of the purified complexes with desired fluorophores, fluorimetric measurement of FRET, and appropriate safeguards and controls in data acquisition and analysis. Our methods can be used to interrogate the effects of buffer conditions, small molecules, and septin-binding proteins on septin filament assembly or stability; determine the effect of alternative septin subunits, mutational alterations, or posttranslational modifications on assembly; and, delineate the location of septin-binding proteins.


Asunto(s)
Citoesqueleto/química , Transferencia Resonante de Energía de Fluorescencia/métodos , Microscopía Electrónica/métodos , Septinas/química , Citoesqueleto/genética , Colorantes Fluorescentes/química , Mutación , Polimerizacion , Unión Proteica , Saccharomyces cerevisiae/química
5.
QJM ; 104(5): 403-10, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21186178

RESUMEN

BACKGROUND: Annual foot checks are recommended in patients with diabetes mellitus (DM) to identify those at risk of foot ulceration. Systematic reviews have found few studies evaluating the predictive value of tests in community-based diabetic populations. AIM: To quantify the predictive value of clinical risk factors in relation to foot ulceration in a community population. METHODS: A cohort of 1192 people with diabetes receiving care in community settings was recruited and a screening procedure, covering symptoms, signs and diagnostic tests was conducted at baseline. At an average 1-year follow-up patients who developed a foot ulcer were identified by an independent blind assessor. Multivariable analysis was performed to identify clinical predictors of foot ulceration. FINDINGS: The incidence of foot ulceration was 1.93% [95% confidence interval (CI) 1.27-2.89). Three time-independent clinical predictors with five factors were selected: previous amputation [odds ratio (OR) 14.7, 95% CI 3.1-69.5), use of insulin before 3 months with inability to distinguish between cool and cold temperatures (OR 2.97, 95% CI 1.9-4.5) and failure to obtain at least one blood pressure reading for the calculation of ankle-brachial index with the failure to feel touch with a 10-g monofilament (OR 1.7, 95% CI 1.3-2.2). INTERPRETATION: Recommendations for annual diabetic foot check in low-risk, community-based patients should be reviewed as absolute events of ulceration are low. The accuracy of foot risk assessment tools to predict ulceration requires evaluation in randomized controlled trials with concurrent economic evaluations.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Pie Diabético/diagnóstico , Tamizaje Masivo/normas , Adulto , Anciano , Anciano de 80 o más Años , Atención a la Salud/normas , Pie Diabético/epidemiología , Pie Diabético/etiología , Neuropatías Diabéticas/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Escocia/epidemiología
6.
Phys Rev Lett ; 107(25): 252501, 2011 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-22243068

RESUMEN

We report a precision measurement of the deuteron tensor analyzing powers T(20) and T(21) at the MIT-Bates Linear Accelerator Center. Data were collected simultaneously over a momentum transfer range Q=2.15-4.50 fm(-1) with the Bates Large Acceptance Spectrometer Toroid using a highly polarized deuterium internal gas target. The data are in excellent agreement with calculations in a framework of effective field theory. The deuteron charge monopole and quadrupole form factors G(C) and G(Q) were separated with improved precision, and the location of the first node of G(C) was confirmed at Q=4.19±0.05 fm(-1). The new data provide a strong constraint on theoretical models in a momentum transfer range covering the minimum of T(20) and the first node of G(C).

7.
Phys Rev Lett ; 101(4): 042501, 2008 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-18764321

RESUMEN

We report new measurements of the neutron charge form factor at low momentum transfer using quasielastic electrodisintegration of the deuteron. Longitudinally polarized electrons at an energy of 850 MeV were scattered from an isotopically pure, highly polarized deuterium gas target. The scattered electrons and coincident neutrons were measured by the Bates Large Acceptance Spectrometer Toroid (BLAST) detector. The neutron form factor ratio GEn/GMn was extracted from the beam-target vector asymmetry AedV at four-momentum transfers Q2=0.14, 0.20, 0.29, and 0.42 (GeV/c)2.

8.
Phys Rev Lett ; 98(5): 052301, 2007 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-17358849

RESUMEN

We report the first precision measurement of the proton electric to magnetic form factor ratio from spin-dependent elastic scattering of longitudinally polarized electrons from a polarized hydrogen internal gas target. The measurement was performed at the MIT-Bates South Hall Ring over a range of four-momentum transfer squared Q2 from 0.15 to 0.65 (GeV/c)(2). Significantly improved results on the proton electric and magnetic form factors are obtained in combination with existing cross-section data on elastic electron-proton scattering in the same Q2 region.

9.
Xenobiotica ; 34(1): 31-48, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14742135

RESUMEN

1. The metabolism of [1,2-(14)C]-ethylene glycol and [1,2-(14)C]-glycolic acid was studied in vitro using precision-cut tissue slices prepared from the livers of female Sprague-Dawley rats, New Zealand white rabbits and humans. The time-course for production of metabolites formed from ethylene glycol at concentrations from 3 to 40 mM was determined to compare quantitatively the differences between species in the rates and amounts of formation of glycolic acid, the presumed developmental toxicant of ethylene glycol. The rates of metabolism of glycolic acid to glyoxylic acid at concentrations from 0.05 to 16 mM by liver tissue from the different species were also determined. The apparent V(max)/K(m) for the metabolic conversions of ethylene glycol to glycolic acid and for glycolic acid to glyoxylic acid in liver tissue from the different species were obtained. 2. There were qualitative differences in the metabolic profiles and quantitative differences in the formation of glycolic acid between the mammalian liver systems. There was an average of 10-fold less glycolic acid produced by liver slices from rabbits compared with rats. With the human liver, the formation of glycolic acid was not detectable using tissue from three of four human donors. A low level of glycolic acid was detected in one liver slice incubation from one of the four subjects, but only at one extended time point; glyoxylate was detected with liver slices from all four humans. 3. Liver slices prepared from female Sprague-Dawley rats, female New Zealand White rabbits and three female human subjects all metabolized glycolic acid to glyoxylic acid. Human liver tissue was the most effective at further metabolizing glycolic acid to glyoxylic acid. The ratios of V(max)/K(m), representing the relative clearance of glycolic acid from liver tissue, were approximately 14:9:1 for human, rat and rabbit liver, respectively. 4. Precision-cut liver slices maintained in dynamic organ culture are good predictors of metabolism by liver tissue in vivo. The results of the present study therefore indicate that levels of glycolic acid, if formed in vivo, following exposures to similar concentrations of ethylene glycol, would be lower in humans than in rabbits and rats.


Asunto(s)
Glicol de Etileno/metabolismo , Glicolatos/metabolismo , Hígado/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Radioisótopos de Carbono , Cromatografía Líquida de Alta Presión , Glicol de Etileno/química , Glicol de Etileno/farmacocinética , Femenino , Glicolatos/química , Glicolatos/farmacocinética , Humanos , Microtomía , Persona de Mediana Edad , Conejos , Ratas , Ratas Sprague-Dawley , Especificidad de la Especie
11.
Arch Toxicol ; 73(6): 316-22, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10447559

RESUMEN

The effect of solvent polarity and lipophilicity on DNA adduct formation by polycyclic aromatic hydrocarbons in skin and lung has been studied in CD1 mice exposed cutaneously in vivo to benzo(a)pyrene ( approximately 0.01-7.0 microg/animal) in either tetrahydrofuran or n-dodecane. The nature and amounts of DNA adducts, measured as 7R,8S, 9R-trihydroxy-10S-(N(2)-deoxyguanosyl-3'-phosphate)-7,8,9, 10-tetrahydrobenzo(a)pyrene, in relation to exposure dose and treatment regime was determined by (32)P-postlabelling. In skin DNA there was a linear relationship between exposure dose and adduct formation with both solvents, though the amount of adduct formed was significantly lower from treatment with benzo(a)pyrene in n-dodecane than in tetrahydrofuran. The amounts of adducts measured in skin DNA ranged from 67 amol adducts/microg DNA at the lowest exposure dose of benzo(a)pyrene in n-dodecane to 3.5 fmol adducts/microg DNA (1 adduct in 5 x 10(7) nucleotides to 1 adduct in 9 x 10(5) nucleotides) at the highest dose. In tetrahydrofuran the corresponding levels were 89 amol adducts/microg DNA (1 adduct in 3 x 10(7) nucleotides) to 16.9 fmol adducts/microg DNA (1 adduct in 2 x 10(5) nucleotides). DNA adducts could not be detected in lung tissue following cutaneous treatment of animals with benzo(a)pyrene in n-dodecane. Cutaneous treatment of animals with benzo(a)pyrene in tetrahydrofuran, however, resulted in adducts in lung DNA at a level of 88 amol/microg DNA from exposures only at the highest dose (6.72 microg/animal). The difference in octanol-water partition coefficient, log P(ow) between n-dodecane compared to tetrahydrofuran is considered to be the most likely reason for the reduction in the bioavailability of benzo(a)pyrene and/or its metabolites and hence the degree of genotoxicity in tissues. The results suggest that other paraffinic hydrocarbon solvents may moderate the genotoxicity of polycyclic aromatic hydrocarbons in vivo. The assessment of the genotoxicity in vivo of mixtures of compounds should be carried out on complete mixtures of substances of interest in order to take account of these possible antagonistic or synergistic effects.


Asunto(s)
Alcanos/farmacología , Benzo(a)pireno/metabolismo , Carcinógenos Ambientales/metabolismo , Aductos de ADN/metabolismo , ADN/metabolismo , Furanos/farmacología , Pulmón/metabolismo , Piel/metabolismo , Administración Tópica , Animales , Benzo(a)pireno/farmacocinética , Disponibilidad Biológica , Carcinógenos Ambientales/farmacocinética , ADN/efectos de los fármacos , Femenino , Pulmón/efectos de los fármacos , Ratones , Vehículos Farmacéuticos/farmacología , Radioisótopos de Fósforo , Piel/efectos de los fármacos , Solventes
12.
Arch Toxicol ; 73(3): 129-40, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10401678

RESUMEN

The assessment of skin penetration by viscous oil products is an important element in the risk assessment of these materials where skin contact is likely. Systemic bioavailability (body uptake) is viewed as a good indicator of skin penetration following cutaneous exposures. The results of this study provide quantitative information on the influence of viscosity on the bioavailability of a specific polycyclic aromatic compound (benzo(a)pyrene) in base oils, residual aromatic extracts and bitumens following skin exposures to mice. The materials studied were a base mineral oil (viscosity 32 cSt at 35 degrees C), a 1:1 blend of the mineral base oil and a residual aromatic extract (198 cSt), several residual aromatic extracts (ca. 5000 cSt, 35 degrees C) and a range of bitumens (0.65-69 x 10(6) cSt, 35 degrees C). These were each spiked with 0.1% radiolabelled benzo(a)pyrene, as a representative carcinogenic polycyclic aromatic compound, then used for cutaneous exposures to mice. The results indicate that as viscosity increased in the range ca. 30 to 5000 cSt (base oil to residual aromatic extract) the uptake of the radiolabelled benzo(a)pyrene into blood was reduced by ca. fivefold. Further increases in viscosity from ca. 5000 to 69 x 10(6) cSt (i.e. residual aromatic extract to bitumen) resulted in a further but smaller (ca. twofold) reduction in uptake. The relationship between the amounts of free benzo(a)pyrene measured in blood and viscosity showed the same trend. This trend was also mirrored by the degree of binding of benzo(a)pyrene metabolites to DNA in skin. The findings in mouse skin in vivo indicate that viscosity can significantly affect skin penetration and systemic bioavailability of polycyclic aromatic compound components of oil products. Results obtained with viable human skin in vitro also showed that the bioavailability of benzo(a)pyrene was reduced by the viscosity of the oil product matrix. It is thus necessary to take account of physical properties such as viscosity in the overall risk assessment of viscous oil products, particularly in the case of very viscous materials such as bitumens. The significantly reduced bioavailability of hazardous compounds from undiluted materials is thus an important factor to consider when assessing the risks from dermal exposures.


Asunto(s)
Benzo(a)pireno/farmacocinética , Aceite Mineral/química , Hidrocarburos Policíclicos Aromáticos/farmacocinética , Absorción Cutánea/fisiología , Animales , Cromatografía Líquida de Alta Presión , ADN/análisis , ADN/aislamiento & purificación , Femenino , Humanos , Técnicas In Vitro , Ratones , Organismos Libres de Patógenos Específicos , Viscosidad
13.
Arch Toxicol ; 73(3): 180-8, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10401685

RESUMEN

Polycyclic aromatic compounds (PACs) present in oil streams and formulated products are important determinants of possible carcinogenicity. Following dermal exposures the transport of the PACs from oil (the carrier) into the skin is a factor that may affect macromolecular (DNA) adduct formation and thus determine carcinogenicity. We have developed a mathematical model, which describes the flux into the skin for a representative carcinogenic PAC, benzo(a)pyrene. The model is based on measurements of the amount of benzo(a)pyrene bound to skin DNA or blood observed in mouse skin painting studies. The degree of adduct formation from a particular oil product, which we term the Bioavailability Index (BI), was shown to be a function of both the viscosity of the oil product, which affected the transport of the PAC through the carrier, and the aromaticity, which affected the partition of PAC between the carrier and the skin. Literature data were analysed from mouse skin painting studies with mineral oils of known carcinogenicity. A linear relationship was shown between the amount of DNA adduct formation, expressed as alkylation frequency, and the arithmetic product of the total (3-6) ring PAC content and the BI, which we have termed the Carcinogenic Potency Index (CPI). Comparison of literature data on DNA alkylation frequencies for oil products and their carcinogenicity indicated that oils giving rise to an alkylation frequency below a certain threshold (ca. 1 adduct in 10(8) nucleotides) are non-carcinogenic to mouse skin. This threshold level can be translated into a value for the CPI, below which the genotoxic carcinogenic risk arising from skin contact with the oil product is considered to be negligible. The CPI for bitumens is well below this value, being both due to the low BI from bitumen, but more so, due to their low PAC content. For some bitumens diluted with solvents, i.e. cutback-bitumens, the CPI may exceed this value, indicating a possible carcinogenic risk for some of the cutback-bitumens. The main determining factor is the PAC content which is principally determined by the nature of the diluent used.


Asunto(s)
Benzo(a)pireno/farmacocinética , Disponibilidad Biológica , Carcinógenos/farmacocinética , Absorción Cutánea/fisiología , Administración Cutánea , Animales , Carcinógenos/toxicidad , ADN/metabolismo , Aductos de ADN , Ratones , Modelos Teóricos , Solubilidad , Viscosidad
14.
Toxicol Sci ; 49(2): 186-201, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10416264

RESUMEN

1,3-Butadiene (butadiene) is a potent carcinogen in mice, but not in rats. Metabolic studies may provide an explanation of these species differences and their relevance to humans. Male Sprague-Dawley rats and B6C3F1 mice were exposed for 6 h to 200 ppm [2,3-14C]-butadiene (specific radioactivity [sa] 20 mCi/mmol) in a Cannon nose-only system. Radioactivity in urine, feces, exhaled volatiles and 14C-CO2 were measured during and up to 42 h after exposure. The total uptake of butadiene by rats and mice under these experimental conditions was 0.19 and 0.38 mmol (equivalent to 3.8 and 7.5 mCi) per kg body weight, respectively. In the rat, 40% of the recovered radioactivity was exhaled as 14C-CO2, 70% of which was trapped during the 6-h exposure period. In contrast, only 6% was exhaled as 14C-CO2 by mice, 3% during the 6-h exposure and 97% in the 42 h following cessation of exposure. The formation of 14C-CO2 from [2,3-14C]-labeled butadiene indicated a ready biodegradability of butadiene. Radioactivity excreted in urine accounted for 42% of the recovered radioactivity from rats and 71% from mice. Small amounts of radioactivity were recovered in feces, exhaled volatiles and carcasses. Although there was a large measure of commonality, the exposure to butadiene also led to the formation of different metabolites in rats and mice. These metabolites were not found after administration of [4-14C]-1,2-epoxy-3-butene to animals by i.p. injection. The results show that the species differences in the metabolism of butadiene are not simply confined to the quantitative formation of epoxides, but also reflect a species-dependent selection of metabolic pathways. No metabolites other than those formed via an epoxide intermediate were identified in the urine of rats or mice after exposure to 14C-butadiene. These findings may have relevance for the prediction of butadiene toxicity and provide a basis for a revision of the existing physiologically based pharmacokinetic models.


Asunto(s)
Butadienos/metabolismo , Carcinógenos/metabolismo , Administración por Inhalación , Animales , Autorradiografía , Butadienos/farmacocinética , Butadienos/orina , Carcinógenos/farmacocinética , Susceptibilidad a Enfermedades , Cromatografía de Gases y Espectrometría de Masas , Masculino , Ratones , Ratas , Ratas Sprague-Dawley , Especificidad de la Especie , Distribución Tisular
15.
J Cardiovasc Pharmacol ; 34(1): 153-61, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10413082

RESUMEN

Activation of the complement system contributes to the tissue destruction associated with myocardial ischemia/reperfusion. Pentosan polysulfate (PPS), a negatively charged sulfated glycosaminoglycan (GAG) and an effective inhibitor of complement activation, was studied for its potential to decrease infarct size in an experimental model of myocardial ischemia/reperfusion injury. Open-chest rabbits were subjected to 30-min occlusion of the left coronary artery followed by 5 h of reperfusion. Vehicle (saline) or PPS (30 mg/kg/h) was administered intravenously immediately before the onset of reperfusion and every hour during the reperfusion period. Treatment with PPS significantly (p < 0.05) reduced infarct size as compared with vehicle-treated animals (27.5+/-2.9% vs. 13.34+/-2.6%). Analysis of tissue demonstrated decreased deposition of membrane-attack complex and neutrophil accumulation in the area at risk. The results indicate that, like heparin and related GAGs, PPS possesses the ability to decrease infarct size after an acute period of myocardial ischemia and reperfusion. The observations are consistent with the suggestion that PPS may mediate its cytoprotective effect through modulation of the complement cascade.


Asunto(s)
Quimiotaxis/efectos de los fármacos , Infarto del Miocardio/patología , Poliéster Pentosan Sulfúrico/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Animales , Anticuerpos/inmunología , Plaquetas/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proteínas Inactivadoras de Complemento/farmacología , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Vasos Coronarios/fisiología , Inhibidores Enzimáticos/farmacología , Eritrocitos/efectos de los fármacos , Glicosaminoglicanos/uso terapéutico , Hemodinámica/efectos de los fármacos , Técnicas In Vitro , Ligadura , Neutrófilos/fisiología , Conejos , Ovinos
16.
Brain Inj ; 13(4): 229-43, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10230524

RESUMEN

Carbon monoxide (CO) poisoning has been shown to result in neuropathologic changes and cognitive impairments due to anoxia and other related biochemical mechanisms. The present study investigated brain-behaviour relationships between neuropsychological outcome and SPECT, MRI, and Quantitative magnetic resonance imaging (QMRI) in 21 patients with CO poisoning. Ninety-three per cent of the patients exhibited a variety of cognitive impairments, including impaired attention, memory, executive function, and mental processing speed. Ninety-five per cent of the patients experienced affective changes including depression and anxiety. The results from the imaging studies revealed that 38% of the patients had abnormal clinical MRI scans, 67% had abnormal SPECT scans, and 67% had QMRI findings including hippocampal atrophy and/or diffuse cortical atrophy evidenced by an enlarged ventricle-to-brain ratio (VBR). Hippocampal atrophy was also found on QMRI. SPECT and QMRI appear to be sensitive tools which can be used to identify the neuropathological changes and cerebral perfusion defects which occur following CO poisoning. Cerebral perfusion defects include frontal and temporal lobe hypoperfusion. Significant relationships existed between the various imaging techniques and neuropsychological impairments. The data from this study indicate that a multi-faceted approach to clinical evaluation of the neuropathological and neurobehavioural changes following CO poisoning may provide comprehensive information regarding the neuroanatomical and neurobehavioural effects of CO poisoning.


Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/patología , Intoxicación por Monóxido de Carbono/complicaciones , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/diagnóstico , Adulto , Atrofia/patología , Encéfalo/irrigación sanguínea , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Índice de Severidad de la Enfermedad , Tomografía Computarizada de Emisión de Fotón Único
17.
Pharmacology ; 58(3): 120-31, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9925968

RESUMEN

The ability of the heparin derivative, N-acetylheparin (NHEP) to protect the heart from regional ischemia/reperfusion injury was examined in vivo. NHEP (2 mg/kg i.v.) or vehicle was administered 2 h before occlusion of the left circumflex coronary (LCX) artery. Open-chest, anesthetized rabbits were subjected to 30 min of regional myocardial ischemia followed by 5 h of reperfusion. Myocardial myeloperoxidase activity, membrane attack complex (MAC) deposition and IL-8 generation were assessed in supernatant samples from the area at risk. Infarct size in rabbits pretreated with NHEP (32.5 +/- 3.8%, n = 10) decreased by 41% compared to infarct size in rabbits that received vehicle (55.3 +/- 4.9%, n = 10; p = 0.002). Accumulation of neutrophils within the ischemic region, as assessed by myeloperoxidase activity, declined by 45% (p < 0.05) in AAR from NHEP-treated animals compared to AAR from vehicle-treated animals. Levels of MAC and IL-8 obtained from AAR were less in NHEP-pretreated animals compared to controls. These results suggest that NHEP may protect the myocardium by inhibiting complement activation and subsequent neutrophil infiltration.


Asunto(s)
Heparina/análogos & derivados , Infarto del Miocardio/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Animales , Calcio/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Hemodinámica/efectos de los fármacos , Heparina/farmacología , Interleucina-8/metabolismo , Recuento de Leucocitos , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocardio/enzimología , Miocardio/patología , Activación Neutrófila/efectos de los fármacos , Peroxidasa/metabolismo , Conejos
18.
Arch Toxicol ; 72(8): 505-13, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9765066

RESUMEN

The in vivo genotoxic activities in mouse skin of the dimethyl sulphoxide (DMSO) extracts of a range of oil products [residual aromatic extract; untreated heavy paraffinic distillate aromatic extract; mildly refined light naphthenic base oil; bitumen (vacuum residue); high viscosity index base oil obtained by catalytic hydrogenation] were evaluated by 32P-postlabelling DNA analysis. The results of quantitative 32P-postlabelling analyses of epidermal DNA from mice treated with the DMSO extracts showed linear relationships with the total polycyclic aromatic compound (PAC) contents, determined by the Institute of Petroleum method IP 346 and also the 3-6 ring PAC contents, measured by on-line liquid-liquid extraction using flow injection analysis. The 32P-postlabelling data also showed a linear relationship with the mutagenicity indices of these oil products determined in S. typhimurium TA98 using the modified Ames Salmonella microsome test. The in vivo genotoxicity of the DMSO extracts from the oil products was low, judged by 32P-postlabelling analysis of DNA adducts measured in epidermal DNA of treated mouse skin, and ranging from 2 to 723 attomole/microg DNA per mg oil product. The in vivo 32P-postlabelling data from this study are consistent with these materials expressing low genotoxicity in mouse skin in vivo. The DMSO extraction procedure coupled with 32P-postlabelling DNA analysis is useful for ranking the relative genotoxic potency in vivo of a wide range of oil products. In general the trend observed is similar to rankings based on physicochemical measurements of total PAC contents or 3 6 ring PAC contents of the oil products.


Asunto(s)
Carcinógenos/química , Aductos de ADN/metabolismo , Mutágenos/toxicidad , Petróleo/toxicidad , Hidrocarburos Policíclicos Aromáticos/química , Salmonella typhimurium/genética , Piel/metabolismo , Animales , Autorradiografía , Aductos de ADN/química , Aductos de ADN/genética , Epidermis/química , Epidermis/metabolismo , Femenino , Ratones , Pruebas de Mutagenicidad , Mutágenos/química , Petróleo/análisis , Salmonella typhimurium/efectos de los fármacos , Piel/química
19.
J Pharmacol Exp Ther ; 285(3): 987-94, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9618399

RESUMEN

Pentosan polysulfate (PPS) is a highly sulfated semisynthetic polysaccharide possessing a higher negative charge density and degree of sulfation than heparin. Like other glycosaminoglycans, the structural and chemical properties of PPS promote binding of the drug to the endothelium. Glycosaminoglycans, including heparin, inhibit complement activation independent of an action on the coagulation system. This ability provides a compelling argument for the implementation of this class of compounds in experimental models of cellular injury mediated by complement. The objective of this study was to examine whether PPS could reduce myocardial injury resulting from activation of the complement system. We used the rabbit isolated heart perfused with 4% normal human plasma as a source of complement. Hemodynamic variables were obtained before addition of PPS (0.03 01 mg/ml) and every 10 min after the addition of human plasma. Compared with vehicle-treated hearts, left ventricular end-diastolic pressure was improved at the conclusion of the 60-min protocol in hearts treated with PPS (58.9 +/- 13.6 vs. 15. 2 +/- 4.8 mm Hg). Further evidence as to the protective effects of PPS was demonstrated by decreased creatine kinase release compared with vehicle (86.5 +/- 28.5 U/l vs. 631.0 +/- 124.8 U/l). An enzyme-linked immunosorbent assay for the presence of the membrane attack complex in lymph and tissue samples demonstrated decreased membrane attack complex formation in PPS-treated hearts, which suggests inhibition of complement activation. This conclusion was supported further by the ability of PPS to inhibit complement-mediated red blood cell lysis in vitro. The results of this study indicate that PPS can reduce tissue injury and preserve organ function that otherwise would be compromised during activation of the human complement cascade.


Asunto(s)
Anticoagulantes/farmacología , Activación de Complemento/efectos de los fármacos , Corazón/efectos de los fármacos , Daño por Reperfusión Miocárdica/prevención & control , Poliéster Pentosan Sulfúrico/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Proteínas del Sistema Complemento/análisis , Proteínas del Sistema Complemento/efectos de los fármacos , Creatina Quinasa/metabolismo , Relación Dosis-Respuesta a Droga , Glicoproteínas/análisis , Glicoproteínas/efectos de los fármacos , Corazón/fisiología , Humanos , Masculino , Daño por Reperfusión Miocárdica/inmunología , Conejos , Función Ventricular Izquierda/efectos de los fármacos
20.
Chem Biol Interact ; 110(1-2): 85-102, 1998 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-9566727

RESUMEN

32P-postlabelling analysis for detecting DNA adducts formed by polycyclic aromatic compounds is one of the most widely used techniques for assessing genotoxicity associated with these compounds. In cases where the formation of adducts is extremely low, a crucial step in the analysis is an enrichment procedure for adducts prior to the radiolabelling step. The nuclease P1 enhancement procedure is the most established and frequently used of these methods. An immunoaffinity procedure developed for class specific recognition for polycyclic aromatic hydrocarbon (PAH)-DNA adducts has therefore been compared with the nuclease P1 method for a range of DNA adducts formed by PAHs. The evaluation was carried out with skin DNA from mice treated topically with benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, 5-methylchrysene or chrysene. The immobilised antibody had the highest affinity for adducts structurally similar to the BPDE-I-deoxyguanosine adduct ([+/-]-N2-(7r,8t,9r-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-1 0t-yl)-2'-deoxyguanosine) against which the antibody had been raised. Of the PAH-modified DNAs evaluated, the maximum adduct recovery was obtained for DNA containing the BPDE I-deoxyguanosine adduct. With DMBA-modified DNA, the profiles of adducts recovered from the column were similar when the column material was treated either with a digest of DMBA-modified DNA or with 32P-labelled DMBA adducts. I-compounds (endogenous adducts in tissue DNA of unexposed animals), which had similar chromatographic properties to PAH-DNA adducts, were not enriched by the immunoaffinity procedure. Compared to the simple nuclease P1 enhancement procedure, the immunoaffinity methods were lengthier and more labour intensive. Advantages of the immunoaffinity procedure include: specificity, allowing the selective detection of a certain class of adducts: efficient adduct enrichment, providing a viable alternative to other enrichment procedures; adequate sensitivity for model studies and the potential to purify adducts for further characterisation. However, as a general screen for detecting the formation of DNA adducts, the nuclease P1 procedure was viewed as the initial method of choice since it was capable of detecting a wider range of PAH-DNA adducts.


Asunto(s)
Carcinógenos/toxicidad , Cromatografía de Afinidad/métodos , Aductos de ADN/análisis , Mutágenos/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Hidrocarburos Policíclicos Aromáticos/toxicidad , Endonucleasas Específicas del ADN y ARN con un Solo Filamento/química , 9,10-Dimetil-1,2-benzantraceno/análogos & derivados , 9,10-Dimetil-1,2-benzantraceno/análisis , Animales , Anticuerpos Monoclonales , Benzo(a)pireno/toxicidad , Crisenos/toxicidad , Aductos de ADN/química , Técnica del Anticuerpo Fluorescente , Marcaje Isotópico , Ratones , Pruebas de Mutagenicidad , Radioisótopos de Fósforo , Hidrocarburos Policíclicos Aromáticos/química , Piel/efectos de los fármacos
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