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Geochemical interfaces can impact the fate and transport of aqueous species in the environment including biomolecules. In this study, we investigate the surface chemistry of adsorbed nucleotides on two different minerals, hematite and goethite, using infrared spectroscopy and density functional theory (DFT) calculations. Attenuated total reflectance-Fourier transform infrared spectroscopy is used to probe the adsorption of deoxyadenosine monophosphate (dAMP), deoxyguanosine monophosphate (dGMP), deoxycytidine monophosphate (dCMP), and deoxythymidine monophosphate (dTMP) onto either hematite or goethite particle surfaces. The results show preferential adsorption of the phosphate group to either surface. Remarkably, surface adsorption of the four nucleotides onto either hematite or goethite have nearly identical experimental spectra in the phosphate region (900 to 1200 cm-1) for each mineral surface yet are distinctly different between the two minerals, suggesting differences in binding of these nucleotides to the two mineral surfaces. The experimental absorption frequencies in the phosphate region were compared to DFT calculations for nucleotides adsorbed through the phosphate group to binuclear clusters in either a monodentate or bidentate bridging coordination. Although the quality of the fits suggests that both binding modes may be present, the relative amounts differ on the two surfaces with preferential bonding suggested to be monodentate coordination on hematite and bidentate bridging on goethite. Possible reasons for these differences are discussed.
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Objective. To determine the validity and reliability of the Pharmacist Interprofessional Competencies Tool (PICT). Methods. Faculty members at Ferris State University, College of Pharmacy developed the PICT, which has five interprofessional criterion (collaboration, ownership, respect, engagement, and application) and four competency levels (unacceptable, novice, competent, and proficient) to assess the interprofessional competencies of pharmacy students. Fourteen pharmacy faculty members were trained in how to use the PICT and then used it to assess students' behaviors in four to six video-recorded interprofessional education (IPE) learning activities. A subset of these faculty members evaluated the video-recorded IPE learning activities using two other previously validated interprofessional assessment tools. Psychometric analysis of the PICT, including internal consistency and inter-rater reliability, was conducted, along with a correlation analysis and factor analysis, and the results were compared to those from the other validated assessment tools. Results. The overall rating of the internal consistency of the PICT was excellent and item-total correlations of the individual criterion were fair to good, with the exception of the respect criterion. The PICT demonstrated excellent overall inter-rater reliability, and individual criterion rated as fair to excellent with the exception of the respect criterion. Specific dimensions of the PICT showed high convergence with previously validated interprofessional assessment tools. Conclusion. The PICT exhibited overall validity and reliability as an assessment tool for measuring the interprofessional competencies of pharmacy students. In establishing the overall validity and reliability of the assessment tool, the respect criterion was not proved to be reliable or valid. Additional training and slight modifications to the PICT and associated IPE learning activities are planned to assist with longitudinal assessment of student performance across the curriculum.
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Educación Basada en Competencias/métodos , Educación en Farmacia/métodos , Curriculum , Docentes de Farmacia , Humanos , Relaciones Interprofesionales , Farmacéuticos , Aprendizaje Basado en Problemas/métodos , Reproducibilidad de los Resultados , Estudiantes de FarmaciaRESUMEN
Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in HDLs. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes. Chimeric mice exhibited a human-like ratio of serum LDL cholesterol (LDL-C) to HDL cholesterol (HDL-C) at baseline. OCA treatment in chimeric mice increased circulating LDL-C and decreased circulating HDL-C levels, demonstrating that these mice closely model the cholesterol effects of FXR activation in humans. Mechanistically, OCA treatment increased hepatic cholesterol in chimeric mice but not in control mice. This increase correlated with decreased SREBP-2 activity and target gene expression, including a significant reduction in LDL receptor protein. Cotreatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-C. Treatment with two clinically relevant nonsteroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting that the increase in circulating LDL-C is a class effect of FXR activation.
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Ácido Quenodesoxicólico/análogos & derivados , Quimera , Colesterol/metabolismo , Lipoproteínas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Animales , Atorvastatina/farmacología , Ácido Quenodesoxicólico/farmacología , Colesterol/sangre , Humanos , Lipoproteínas/sangre , Hígado/citología , Masculino , RatonesRESUMEN
A great deal of attention has been paid to brown carbon aerosol in the troposphere because it can both scatter and absorb solar radiation, thus affecting the Earth's climate. However, knowledge of the optical and chemical properties of brown carbon aerosol is still limited. In this study, we have investigated different aspects of the optical properties of brown carbon aerosol that have not been previously explored. These properties include extinction spectroscopy in the mid-infrared region and light scattering at two different visible wavelengths, 532 and 402 nm. A proxy for atmospheric brown carbon aerosol was formed from the aqueous reaction of ammonium sulfate with methylglyoxal. The different optical properties were measured as a function of reaction time for a period of up to 19 days. UV/vis absorption experiments of bulk solutions showed that the optical absorption of aqueous brown carbon solution significantly increases as a function of reaction time in the spectral range from 200 to 700 nm. The analysis of the light scattering data, however, showed no significant differences between ammonium sulfate and brown carbon aerosol particles in the measured scattering phase functions, linear polarization profiles, or the derived real parts of the refractive indices at either 532 or 402 nm, even for the longest reaction times with greatest visible extinction. The light scattering experiments are relatively insensitive to the imaginary part of the refractive index, and it was only possible to place an upper limit of k ≤ 0.01 on the imaginary index values. These results suggest that after the reaction with methylglyoxal the single scattering albedo of ammonium sulfate aerosol is significantly reduced but that the light scattering properties including the scattering asymmetry parameter, which is a measure of the relative amount of forward-to-backward scattering, remain essentially unchanged from that of unprocessed ammonium sulfate. The optical extinction properties in the mid-IR range (800 to 7000 cm(-1)) also showed no significant changes in either the real or the imaginary parts of the refractive indices for brown carbon aerosol particles when compared to ammonium sulfate. Therefore, changes in the optical properties of ammonium sulfate in the mid-IR spectral range due to reaction with methylglyoxal appear to be insignificant. In addition to these measurements, we have characterized additional physicochemical properties of the brown carbon aerosol particles including hygroscopic growth using a tandem-differential mobility analyzer. Compared to ammonium sulfate, brown carbon aerosol particles are found to have lower deliquescence relative humidity (DRH), efflorescence relative humidity (ERH), and hygroscopic growth at the same relative humidities. Overall, our study provides new details of the optical and physicochemical properties of a class of secondary organic aerosol which may have important implications for atmospheric chemistry and climate.
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Doppler ultrasonography plays a key role in the diagnosis of peripheral arterial disease, but is often limited by pitfalls that may be overcome by B-flow imaging. Thus far, there is little information on B-flow imaging for the assessment of peripheral arterial disease and bypass grafts in lower limbs. This article describes the authors' early experience with B-flow in the lower extremities. Sixty patients were included among a large cohort of patients routinely referred to the vascular laboratory for peripheral arterial disease and bypass graft assessments. Two experienced vascular sonographers performed all scans, comparing color Doppler ultrasonography with B-flow imaging. All scans were performed using a combination of the 9 L linear and C2-9 curvilinear transducers with the LOGIQ E9 system (GE Healthcare, Waukesha, WI, USA). Our experience indicates that this relatively unexplored technology has the potential to significantly improve peripheral blood flow evaluation. Nevertheless, B-flow imaging is not exempt from limitations and should be considered complementary to color Doppler ultrasonography.
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Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/cirugía , Ultrasonografía/métodos , Anciano , Anastomosis Quirúrgica , Femenino , Humanos , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/diagnóstico por imagen , Extremidad Inferior/cirugía , Masculino , Reproducibilidad de los Resultados , Ultrasonografía Doppler en ColorRESUMEN
Malemide polyethylene glycol-conjugated Hb (MP4OX, Sangart Inc.), a high-affinity low-concentration acellular hemoglobin (P50 = 5 mmHg, 4.3 g/dl) solution, has been shown to optimize microvascular perfusion and target oxygen delivery to anoxic tissue. Microvascular perfusion during an acute hypoxic challenge in a transgenic anemic sickle cell disease mouse model was studied with MP4OX and saline. Arterioles were dilated in both groups. Functional capillary density (FCD) was maintained at a higher level with MP4OX. In conclusion, MP4OX treatment reduced the hypoxia-mediated decline in FCD, an effect in part due to higher arterial pressure resulting in increased microvascular perfusion pressures.
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Anemia de Células Falciformes/terapia , Sustitutos Sanguíneos/farmacología , Hemoglobinas/farmacología , Hipoxia/terapia , Polietilenglicoles/farmacología , Enfermedad Aguda , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/patología , Animales , Sustitutos Sanguíneos/química , Capilares/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Modelos Animales de Enfermedad , Femenino , Hemoglobinas/química , Heterocigoto , Hipoxia/sangre , Hipoxia/patología , Masculino , Maleimidas/química , Ratones , Ratones Transgénicos , Microcirculación/efectos de los fármacos , Oxígeno/metabolismo , Polietilenglicoles/químicaRESUMEN
BACKGROUND: Extracellular hemoglobin (Hb)-based oxygen carriers (HBOCs) are under extensive consideration as oxygen therapeutics. Their effects on cellular mechanisms related to apoptosis are of particular interest, because the onset of proapoptotic pathways may give rise to tissue damage. STUDY DESIGN AND METHODS: The objective was to assess whether the properties of the Hb that replaces blood during an isovolemic hemodilution would modulate apoptotic-response mechanisms in rat brain and whether such signaling favors cytoprotection or damage. We exposed rats to exchange transfusion (ET; 50% blood volume and isovolemic replacement with Hextend [negative colloid control], MP4OX [PEGylated HBOC with high oxygen affinity], and ααHb [αα-cross-linked HBOC with low oxygen affinity; n=4-6/group]). Sham rats acted as control. Animals were euthanized at 2, 6, and 12 hours after ET; brain tissue was harvested and processed for analysis. RESULTS: In MP4OX animals, the number of neurons that overexpressed the hypoxia-inducible factor (HIF)-1α was higher than in ααHb, particularly at the early time points. In addition, MP4OX was associated with greater phosphorylation of protein kinase B (Akt), a well-known cytoprotective factor. Indeed, the degree of apoptosis, measured as terminal deoxynucleotidyl transferase-positive neurons and caspase-3 cleavage, ranked in order of MP4OX < Hextend < ααHb. CONCLUSION: Even though both HBOCs showed increased levels of HIF-1α compared to shams or Hextend-treated animals, differences in signaling events resulted in very different outcomes for the two HBOCs. ααHb-treated brain tissue showed significant neuronal damage, measured as apoptosis. This was in stark contrast to the protection seen with MP4OX, apparently due to recruitment of Akt and neuronal specific HIF-1α pathways.
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Apoptosis/efectos de los fármacos , Aspirina/análogos & derivados , Sustitutos Sanguíneos/farmacología , Encéfalo/efectos de los fármacos , Hemoglobinas/farmacología , Hemorragia/terapia , Derivados de Hidroxietil Almidón/farmacología , Hipoxia Encefálica/prevención & control , Maleimidas/farmacología , Neuronas/efectos de los fármacos , Oxígeno/sangre , Polietilenglicoles/farmacología , Animales , Aspirina/farmacología , Aspirina/uso terapéutico , Sustitutos Sanguíneos/uso terapéutico , Encéfalo/patología , Hipoxia de la Célula/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Recambio Total de Sangre , Hemodilución , Hemoglobinas/uso terapéutico , Hemorragia/complicaciones , Derivados de Hidroxietil Almidón/uso terapéutico , Hipoxia Encefálica/etiología , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Maleimidas/uso terapéutico , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Neuronas/patología , Polietilenglicoles/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Ratas Sprague-DawleyRESUMEN
The heterogeneous chemistry and photochemistry of ozone on oxide components of mineral dust aerosol, including α-Fe(2)O(3), TiO(2), and α-Al(2)O(3), at different relative humidities have been investigated using an environmental aerosol chamber. The rate and extent of ozone decomposition on these oxide surfaces are found to be a function of the nature of the surface as well as the presence of light and relative humidity. Under dark and dry conditions, only α-Fe(2)O(3) exhibits catalytic decomposition toward ozone, whereas the reactivity of TiO(2) and α-Al(2)O(3) is rapidly quenched upon ozone exposure. However, upon irradiation, TiO(2) is active toward O(3) decomposition and α-Al(2)O(3) remains inactive. In the presence of relative humidity, ozone decay on α-Fe(2)O(3) subject to irradiation or under dark conditions is found to decrease. In contrast, ozone decomposition is enhanced for irradiated TiO(2) as relative humidity initially increases but then begins to decrease at higher relative humidity levels. A kinetic model was used to obtain heterogeneous reaction rates for different homogeneous and heterogeneous reaction pathways taking place in the environmental aerosol chamber. The atmospheric implications of these results are discussed.
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Óxidos/química , Ozono/química , Cinética , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Mineral dust aerosol is known to provide a reactive surface in the troposphere for heterogeneous chemistry to occur. Certain components of mineral dust aerosol, such as semiconductor metal oxides, can act as chromophores that initiate chemical reactions, while adsorbed organic and inorganic species may also be photoactive. However, relatively little is known about the impact of heterogeneous photochemistry of mineral dust aerosol in the atmosphere. In this study, we investigate the heterogeneous photochemistry of trace atmospheric gases including HNO(3) and O(3) with components of mineral dust aerosol using an environmental aerosol chamber that incorporates a solar simulator. For reaction of HNO(3) with aluminum oxide, broadband irradiation initiates photoreactions to form gaseous NO and NO(2). A complex dynamic balance between surface adsorbed nitrate and gaseous nitrogen oxide products including NO and NO(2) is observed. For heterogeneous photoreactions of O(3), iron oxide shows catalytic decompositions toward O(3) while aluminum oxide is deactivated by ozone exposure. Furthermore, the role of relative humidity, and, thus, adsorbed water, on heterogeneous photochemistry has been explored. The atmospheric implications of these results are discussed.
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We have carried out kinetic and reaction yield studies to determine the effect of O(3) on the heterogeneous reaction of two cyclic volatile methylsiloxanes (cVMS), octamethylcyclotetrasiloxane (D(4)) and decamethylcyclopentasiloxane (D(5)), with model mineral dust aerosol in order to obtain a better understanding of the atmospheric fate of cVMS. The heterogeneous chemistry was studied in an environmental reaction chamber using FT-IR spectroscopy to monitor the reaction progress. The uptake kinetics and the reaction extent for D(4) and D(5) in the presence of O(3) were quantified for two components of mineral dust aerosol, hematite and kaolinite. Some experiments with a carbonaceous particulate, carbon black, were also performed for D(5). The relative humidity (RH) inside the chamber was varied to investigate the influence of surface adsorbed water on the heterogeneous chemistry of the dust samples. With the dust samples, but not carbon black, the coadsorption of O(3) introduced a new reaction pathway, characterized by a linear, zero-order, decay of both gas phase cVMS and ozone. The new pathway does not saturate on the time scale of our experiments. Elevated RH was observed to decrease the total uptake of cVMS and ozone by the end of the experiment, but the characteristic linear decay was still present. The atmospheric loss of cVMS due to heterogeneous uptake is enhanced due to O(3), even at higher RH values, but the overall loss rate is reduced at RH values typical of the troposphere.
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Aerosoles/química , Polvo , Ozono/química , Siloxanos/química , Humedad , Cinética , Modelos Químicos , Factores de TiempoRESUMEN
OBJECTIVES: Hemospan (Sangart Inc, San Diego, CA) (MP4) is a hemoglobin-based oxygen carrier consisting of human hemoglobin modified with polyethylene glycol. This study evaluated the effects of MP4 on blood volume, hemodynamics, and metabolic stability in a rat model of hemodilution and hemorrhage. MP4 was compared with hydroxyethyl starch solutions of differing concentrations (ie, HES 260/0.45 and HES 130/0.4). DESIGN: An open-label, randomized comparison of treatments. SETTING: Pharmaceutical industry. PARTICIPANTS: Sprague Dawley rats. INTERVENTIONS: Rats underwent 50% hemodilution with one of the solutions. Control rats were not hemodiluted. Blood volume was determined at baseline and 0, 60, and 120 minutes after exchange. In separate groups, hemodilution and subsequent 60% hemorrhage were examined to determine effectiveness of hemodilution. MEASUREMENTS AND MAIN RESULTS: Endpoints were blood volume after hemodilution and survival, hemodynamics, and acid-base status during hemorrhage. Volume expansion was similar with MP4 (159% of infused volume) and HES 260/0.45 (145%) and less with HES 130/0.4 (104%). The duration of expansion was longest with MP4 (1-2 hours). In the hemorrhage studies, 2-hour survival was 90% with MP4, 50% with controls, and 10% and 0% with HES 260/0.45 and HES 130/0.4, respectively. The severity of hemodynamic and acid-base changes paralleled the survival, with the least disturbance observed in MP4-treated animals. CONCLUSIONS: Hemodilution with MP4 was more effective in maintaining hemodynamic and metabolic stability than starch solutions or no hemodilution before simulated intraoperative hemorrhage. The benefit of MP4 is not ascribed solely to volume expansion. The results suggest that perioperative administration of MP4 may improve outcomes in surgical settings.
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Sustitutos Sanguíneos/uso terapéutico , Modelos Animales de Enfermedad , Hemodilución/métodos , Hemoglobinas/uso terapéutico , Derivados de Hidroxietil Almidón/uso terapéutico , Maleimidas/uso terapéutico , Polietilenglicoles/uso terapéutico , Hemorragia Posoperatoria/tratamiento farmacológico , Animales , Humanos , Masculino , Hemorragia Posoperatoria/etiología , Ratas , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate interference by the hemoglobin-based oxygen carrier Hemospan on clinical laboratory assays. DESIGN AND METHODS: Interfering Hemospan concentrations were determined for general chemistry and cardiac marker analytes in pooled serum and the corresponding hemolysis index was calculated. RESULTS: Hemospan did not interfere with 20 of 35 analytes. Hemospan produced a negative interference in serum creatinine, amylase, alkaline phosphatase, uric acid, and GGT assays and a positive interference in serum phosphate, LDH, iron, triglycerides, total protein, AST, cholesterol, magnesium, and albumin assays, and appeared to positively bias the serum cardiac troponin I (cTnI) assay only when cTnI is present in the sample. CONCLUSIONS: We present a report of assays affected by Hemospan and the threshold concentrations for interference. This study highlights the importance of interference studies in understanding the effects of hemoglobin-based oxygen carriers on results reported by the clinical laboratory.
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Análisis Químico de la Sangre/normas , Sustitutos Sanguíneos , Química Clínica/normas , Química Clínica/métodos , Errores Diagnósticos , Hemoglobinas , Humanos , Maleimidas , Polietilenglicoles , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Chronic plantar heel pain (CPHP) is common and is thought to have a detrimental impact on health-related quality of life. However, no study has used normative data or a control data set for comparison of scores. Therefore, we describe the impact of CPHP on foot-specific and general health-related quality of life by comparing CPHP subjects with controls. METHODS: Foot Health Status Questionnaire scores were compared in 80 subjects with CPHP and 80 sex- and age-matched controls without CPHP. RESULTS: The CPHP group demonstrated significantly poorer foot-specific quality of life, as evidenced by lower scores on the foot pain, foot function, footwear, and general foot health domains of the Foot Health Status Questionnaire. The group also demonstrated significantly poorer general health-related quality of life, with lower scores on the physical activity, social capacity, and vigor domains. In multivariate analysis, CPHP remained significantly and independently associated with Foot Health Status Questionnaire scores after adjustment for differences in body mass index. Age, sex, body mass index, and whether symptoms were unilateral or bilateral had no association with the degree of impairment in people with CPHP. CONCLUSION: Chronic plantar heel pain has a significant negative impact on foot-specific and general health-related quality of life. The degree of negative impact does not seem to be associated with age, sex, or body mass index.
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Fascitis Plantar , Calidad de Vida , Adulto , Comorbilidad , Fascitis Plantar/epidemiología , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
It has become increasingly clear that heterogeneous and multiphase chemistry of tropospheric aerosols can change the chemical balance of the atmosphere. In this review, we focus on recent laboratory studies of the heterogeneous and multiphase chemistry and photochemistry of mineral dust aerosol, a large mass fraction of the tropospheric aerosol. Mineral dust aerosol contains a mixture of oxides, clays, and carbonates. Molecular-based studies of reactions of these dust components provide insights into the chemistry of Earth's atmosphere. We discuss several different types of heterogeneous and multiphase reactions, including (a) ozone decomposition, (b) nitrogen dioxide and nitrate photochemistry, and (c) the dissolution and redox chemistry of Fe-containing dust. We also review some of the important chemical concepts that have recently emerged.
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The heterogeneous chemistry of gas-phase acetic acid with CaCO(3)(calcite) aerosol was studied under varying conditions of relative humidity (RH) in an environmental reaction chamber. Infrared spectroscopy showed the loss of gas-phase reactant and the appearance of a gaseous product species, CO(2). The acetic acid is observed to adsorb onto the calcite aerosol through both a fast and a slow uptake channel. While the fast channel is relatively independent of RH, the slow channel exhibits enhanced uptake and reaction as the RH is increased. In additional experiments, the calcite aerosol was exposed to both nitric and acetic acids in the presence of water vapor. The rapid conversion of the particulate carbonate to nitrate and subsequent deliquescence significantly enhances the uptake and reaction of acetic acid. These results suggest a possible mechanism for observed correlations between particulate nitrate and organic acids in the atmosphere. Calcium rich mineral dust may be an important sink for simple organic acids.
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Acetatos/química , Aerosoles/química , Carbonato de Calcio/química , Ácido Nítrico/química , Cámaras de Exposición Atmosférica , Dióxido de Carbono/química , Polvo , Humedad , Presión , Espectrofotometría Infrarroja/métodos , Factores de Tiempo , Agua/químicaRESUMEN
Maleimide-polyethylene glycol-modified (MalPEG) hemoglobin, 4.3 g/dL (MP4; Hemospan), is a hemoglobin-based oxygen carrier consisting of human hemoglobin (Hb) modified with maleimide polyethylene glycol. This study evaluates the potential toxicity and hemodynamic actions of a single dose of MP4 administered by exchange transfusion to rhesus monkeys. Monkeys were administered MP4 (21 mL/kg, or approximately 30% of estimated blood volume) or an equivalent volume of lactated Ringer's solution (LR). In the toxicity study, blood samples were obtained predose and 3, 7, and 13 days after dosing for clinical chemistry and hematology. Animals were euthanized for complete necropsy and histopathology on day 3 or day 13. A separate group of animals was used for evaluation of arterial pressure, core temperature, and electrocardiogram, by telemetry, for 7 days after dosing with MP4. The results demonstrate no significant toxicity, with only modest, transient elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) on day 3. Mild anemia caused by hemodilution was observed at each time point in both groups, but to a slightly greater degree in the MP4-treated animals. Histologic observations included foamy or vacuolated macrophages in the spleen and marrow of the sternum, rib, and femur, representing the accumulation of test article or a metabolite. In the telemetry study, no changes occurred in arterial pressure, heart rate, or electrocardiogram attributable to administration of MP4 at any time for 7 days after administration. These results demonstrate that MP4 is safe and is without hemodynamic effects when administered as an exchange transfusion of 30% of estimated blood volume.
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Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hemoglobinas/toxicidad , Maleimidas/toxicidad , Polietilenglicoles/toxicidad , Alanina Transaminasa/sangre , Anemia/inducido químicamente , Anemia/patología , Animales , Aspartato Aminotransferasas/sangre , Temperatura Corporal/efectos de los fármacos , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/patología , Pruebas de Química Clínica , Electrocardiografía , Femenino , Células Espumosas/efectos de los fármacos , Células Espumosas/patología , Pruebas Hematológicas , Humanos , Infusiones Intravenosas , L-Lactato Deshidrogenasa/sangre , Macaca mulatta , Masculino , Bazo/efectos de los fármacos , Bazo/patología , Pruebas de ToxicidadRESUMEN
BACKGROUND: Chronic plantar heel pain (CPHP) is one of the most common musculoskeletal disorders of the foot, yet its aetiology is poorly understood. The purpose of this study was to examine the association between CPHP and a number of commonly hypothesised causative factors. METHODS: Eighty participants with CPHP (33 males, 47 females, mean age 52.3 years, S.D. 11.7) were matched by age (+/- 2 years) and sex to 80 control participants (33 males, 47 females, mean age 51.9 years, S.D. 11.8). The two groups were then compared on body mass index (BMI), foot posture as measured by the Foot Posture Index (FPI), ankle dorsiflexion range of motion (ROM) as measured by the Dorsiflexion Lunge Test, occupational lower limb stress using the Occupational Rating Scale and calf endurance using the Standing Heel Rise Test. RESULTS: Univariate analysis demonstrated that the CPHP group had significantly greater BMI (29.8 +/- 5.4 kg/m2 vs. 27.5 +/- 4.9 kg/m2; P < 0.01), a more pronated foot posture (FPI score 2.4 +/- 3.3 vs. 1.1 +/- 2.3; P < 0.01) and greater ankle dorsiflexion ROM (45.1 +/- 7.1 degrees vs. 40.5 +/- 6.6 degrees; P < 0.01) than the control group. No difference was identified between the groups for calf endurance or time spent sitting, standing, walking on uneven ground, squatting, climbing or lifting. Multivariate logistic regression revealed that those with CPHP were more likely to be obese (BMI > or = 30 kg/m2) (OR 2.9, 95% CI 1.4 - 6.1, P < 0.01) and to have a pronated foot posture (FPI > or = 4) (OR 3.7, 95% CI 1.6 - 8.7, P < 0.01). CONCLUSION: Obesity and pronated foot posture are associated with CPHP and may be risk factors for the development of the condition. Decreased ankle dorsiflexion, calf endurance and occupational lower limb stress may not play a role in CPHP.