RESUMO
OBJECTIVES: Our objective was to identify patient factors associated with being untreated for hepatitis C virus (HCV) infection in HIV-coinfected patients. METHODS: A prospective longitudinal study was carried out. HIV-infected patients with active chronic HCV infection included in the HERACLES cohort (NCT02511496) constituted the study population. The main study outcome was receipt of HCV direct-acting antiviral (DAA) treatment from 1 May 2015 to 1 May 2017. The population was divided into patients who were receiving HCV treatment during follow-up and those who were not. RESULTS: Of the 15 556 HIV-infected patients in care, 3075 (19.7%) presented with chronic HCV infection and constituted the study population. At the end of the follow-up, 1957 patients initiated HCV therapy (63.6%). Age < 50 years, absence of or minimal liver fibrosis, being treatment-naïve, HCV genotype 3 infection, being in the category of people who inject drugs using opioid substitutive therapy (OST-PWID), and being in the category of recent PWID were identified as significant independent risk factors associated with low odds of DAA implementation. When a multivariate analysis was performed including only the PWID population, both OST-PWID [odds ratio (OR) 0.552; 95% confidence interval (CI) 0.409-0.746) and recent PWID (OR 0.019; 95% CI 0.004-0.087) were identified as independent factors associated with low odds of treatment implementation. CONCLUSIONS: We identified factors, which did not include prioritization of a DAA uptake strategy, that limited access to HCV therapy. The low treatment uptake in several populations seriously jeopardizes the elimination of HCV infection in the coming years.
Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Uso de Medicamentos/estatística & dados numéricos , Infecções por HIV/complicações , Hepatite C Crônica/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Conventional approaches to bone regeneration rarely use multiwall carbon nanotubes (MWCNTs) but instead use polymeric matrices filled with hydroxyapatite, calcium phosphates and bioactive glasses. In this study, we prepared composites of MWCNTs/polycaprolactone (PCL) for bone regeneration as follows: (a) MWCNTs randomly dispersed on PCL, (b) MWCNTs aligned with an electrical field to determine if the orientation favors the growing of human dental pulp stem cells (HDPSCs), and (c) MWCNTs modified with ß-glycerol phosphate (BGP) to analyze its osteogenic potential. Raman spectroscopy confirmed the presence of MWCNTs and BGP on PCL, whereas the increase in crystallinity by the addition of MWCNTs to PCL was confirmed by X-ray diffraction and differential scanning calorimetry. A higher elastic modulus (608 ± 4.3 MPa), maximum stress (42 ± 6.1 MPa) and electrical conductivity (1.67 × 10(-7) S/m) were observed in non-aligned MWCNTs compared with the pristine PCL. Cell viability at 14 days was similar in all samples according to the live/dead assay, but the 21 day cell proliferation, measured by MTT was higher in MWCNTs aligned with BGP. Von Kossa and Alizarin red showed larger amounts of mineral deposits on MWCNTs aligned with BGP, indicating that at 21 days, this scaffold promotes osteogenic differentiation of HDPSCs.
Assuntos
Regeneração Óssea , Polpa Dentária/citologia , Nanotubos de Carbono/química , Poliésteres/química , Células-Tronco/citologia , Alicerces Teciduais/química , Adolescente , Adulto , Osso e Ossos/citologia , Osso e Ossos/fisiologia , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Células Cultivadas , Polpa Dentária/fisiologia , Humanos , Teste de Materiais , Osteogênese/fisiologia , Células-Tronco/fisiologia , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos , Adulto JovemRESUMO
BACKGROUND: Keratinocyte life span is modulated by receptors that control proliferation and differentiation, key processes during cutaneous tissue repair. The kinin B(1) receptor (B(1)R) has been reported in normal and pathological human skin, but so far there is no information about its role in keratinocyte biology. OBJECTIVES: To determine the consequence of kinin B(1)R stimulation on tyrosine phosphorylation, a key signalling mechanism involved in keratinocyte proliferation and differentiation. METHODS: Subconfluent primary cultures of human keratinocytes were used to investigate tyrosine phosphorylation, epidermal growth factor receptor (EGFR) transactivation, cell proliferation and keratinocyte differentiation. Cell proliferation was assessed by measuring bromodeoxyuridine incorporation whereas assessment of cell differentiation was based on the expression of filaggrin, cytokeratin 10 (CK10) and involucrin. RESULTS: The major proteins phosphorylated, after B(1)R stimulation, were of molecular mass 170, 125, 89 and 70 kDa. The 170- and 125-kDa proteins were identified as EGFR and p125(FAK), respectively. Phosphorylation was greatly reduced by GF109203X and by overexposure of keratinocytes to phorbol 12-myristate 13-acetate, indicating the participation of protein kinase C. B(1)R stimulation did not increase [Ca(2+)]i, but triggered EGFR transactivation, an event that involved phosphorylation of Tyr(845), Tyr(992) and Tyr(1068) of EGFR. B(1)R stimulation did not elicit keratinocyte proliferation, but triggered cell differentiation, visualized as an increase of filaggrin, CK10 and involucrin. Blockade of EGFR tyrosine kinase by AG1478, before B(1)R stimulation, produced an additional increase in filaggrin expression. CONCLUSIONS: The kinin B(1)R may contribute to keratinocyte differentiation and migration by triggering specific tyrosine signalling pathways or by interacting with the ErbB receptor family.
Assuntos
Diferenciação Celular , Receptores ErbB/metabolismo , Queratinócitos/citologia , Cininas/metabolismo , Receptor B1 da Bradicinina/metabolismo , Receptor B2 da Bradicinina/metabolismo , Células Cultivadas/metabolismo , Proteínas Filagrinas , Humanos , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Pele/metabolismoRESUMO
OBJECTIVES: The Postoperative Analgesic Therapy Observational Survey (PATHOS) was designed to identify the current state of postoperative pain in specific areas and the needs and opportunities for improving treatment. We compared the results obtained in Spain with those obtained in the rest of Europe between August 2004 and June 2005. MATERIAL AND METHODS: A prospective observational multicenter, multinational study in 7 European countries. The data on postoperative pain management were obtained anonymously by means of a standardized multiple-choice questionnaire. RESULTS: Participation was higher among surgeons (68%) in Spain and among anesthesiologists (69%) in other European countries. Systematic presurgical information on the treatment of postoperative pain was provided to 22.2% of patients undergoing surgery in Spain. Organized structures for the treatment of postoperative pain are less common in Spanish hospitals (47%) than in other European hospitals (69%). Anesthesiologists are less often those who inform patients about postoperative pain in Spain than in other European countries. Only 25.9% of Spanish hospitals have written protocols for treating postoperative pain. Pain was not evaluated in 39% of patients who underwent surgery in Spain. CONCLUSIONS: There is inadequate treatment of postoperative pain, and the problem is greater in Spain than in the other European countries participating in PATHOS. The results should help to identify opportunities for improvement.
Assuntos
Analgesia , Dor Pós-Operatória/terapia , Europa (Continente) , Humanos , Estudos Prospectivos , Índice de Gravidade de Doença , Espanha , Inquéritos e QuestionáriosRESUMO
REASON FOR PERFORMING STUDY: The frequent use of intra-articular triamcinolone acetonide (TA) in performance horses warrants further study of the duration of as well as the beneficial and detrimental effects on gene expression associated with administration. OBJECTIVES: To assess the effects of intra-articular administration of TA on the expression of selected anti- and proinflammatory and structural matrix genes following its administration into joints of exercised Thoroughbred horses and to correlate these effects with plasma and synovial fluid drug concentrations. STUDY DESIGN: Block design experiment. METHODS: Eight exercised horses received a single intra-articular administration of 9 mg of TA. Synovial fluid samples were collected from the treated and contralateral joints prior to and up to 49 days following drug administration. Microarray and quantitative reverse transcription polymerase chain reaction analysis were used to assess changes in expression levels of various inflammatory and structural genes post drug administration. RESULTS: Drug concentrations in plasma and synovial fluid, were no longer quantifiable by 6 and 28 days following drug administration respectively. In total, the expression level of 5490 genes were significantly altered on micro array analysis, following intra-articular TA administration. Of the genes selected for further study by quantitative reverse transcription polymerase chain reaction analysis, significant changes in inflammatory genes (annexin type 1, cyclooxygenase-1 and tumour necrosis factor stimulated gene 6) and structural genes (collagen and aggrecan) were noted. CONCLUSIONS: This study supports the use of synovial fluid as a biological matrix for studying the effects of corticosteroids on gene expression. For the majority of genes studied the effects on expression relative to baseline for both inflammatory and matrix genes were prolonged relative to plasma and synovial fluid TA concentrations. Downregulation of collagen gene expression warrants the careful use of TA in horses.
Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Cavalos/fisiologia , Líquido Sinovial/química , Triancinolona Acetonida/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Biomarcadores , Citocinas/química , Citocinas/genética , Injeções Intra-Articulares/veterinária , Condicionamento Físico Animal , Análise Serial de Proteínas/veterinária , Triancinolona Acetonida/administração & dosagemRESUMO
OBJECTIVE: Our objective was to evaluate efficacy, side effects, and hemodynamic alterations during anesthetic induction with sevoflurane in patients undergoing coronary artery bypass surgery, comparing the techniques of administration with tidal volume breathing and with vital capacity breaths. MATERIAL AND METHODS: This was a randomized controlled trial enrolling 30 patients scheduled for myocardial revascularization. Anesthetic induction with inhaled sevoflurane was performed with 2 techniques: sevoflurane administered with tidal volume breathing (n=15) and with vital capacity breaths (n=15). We assessed time until a bispectral index (BIS) of 50 or less was reached. We also recorded adverse effects and alterations in hemodynamic variables during induction. RESULTS: The time to induction was significantly shorter in the tidal volume group. The time until reaching a BIS of 50 or less was significantly shorter in the vital capacity group. Hemodynamics were similar in both groups (no significant differences). In both groups mean arterial pressure decreased significantly from baseline (P<0.05) and systolic and diastolic blood pressures both decreased slightly, with no significant heart rate or ST segment changes. Adverse effects were few and not serious. CONCLUSIONS: Mean arterial pressure decreased in both groups, with no significant differences. The results indicate that hemodynamic stability seems to be similar with both techniques for providing inhaled anesthetic induction with sevoflurane.
Assuntos
Anestesia por Inalação/métodos , Anestésicos Inalatórios/administração & dosagem , Ponte de Artéria Coronária , Éteres Metílicos/administração & dosagem , Volume de Ventilação Pulmonar , Capacidade Vital , Adulto , Idoso , Anestésicos Inalatórios/efeitos adversos , Anestésicos Inalatórios/farmacocinética , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipotensão/induzido quimicamente , Complicações Intraoperatórias/induzido quimicamente , Masculino , Éteres Metílicos/efeitos adversos , Éteres Metílicos/farmacocinética , Pessoa de Meia-Idade , Estudos Prospectivos , SevofluranoRESUMO
Prophylactic treatment with low molecular weight heparins (LMWH) is currently widely used to prevent thromboembolic events. However, such treatment is not free of risk. Among the possible complications described is rectus sheath hematoma. We report the case of a patient undergoing surgery for a hypophysial adenoma approached by the transsphenoidal route. He received LMWH prophylaxis for thromboembolism and showed a tendency to hypotension during surgery. The patient's condition deteriorated to hypovolemic shock accompanied by episodes of atrial fibrillation with rapid ventricular response. With the transfusion of medications, blood products and plasma volume expanders, the patient was stabilized and surgery was completed. A computed tomography scan then revealed a hematoma occupying the greater part of the left anterior rectus muscle. With conservative wait-and-see treatment the abdominal symptoms disappeared and the hematoma gradually receded until fully resolved. Spontaneous rectus sheath hematoma is a rare condition. Presentation is quite nonspecific and computed tomography is needed for reaching a firm diagnosis. When a hematoma is large, the initial clinical picture may include hypovolemic shock, which may develop during surgery if the hematoma is not diagnosed early. Intraoperative management will be much more difficult than it would have been if diagnosis and treatment had taken place before the operation.
Assuntos
Anticoagulantes/efeitos adversos , Hematoma/complicações , Complicações Intraoperatórias/etiologia , Nadroparina/efeitos adversos , Pré-Medicação , Reto do Abdome/irrigação sanguínea , Choque/etiologia , Adenoma/cirurgia , Anticoagulantes/administração & dosagem , Fibrilação Atrial/etiologia , Hematoma/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Nadroparina/administração & dosagem , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Reto do Abdome/diagnóstico por imagem , Ruptura Espontânea , Tromboembolia/prevenção & controle , Tomografia Computadorizada por Raios XRESUMO
The IgG fraction obtained from pooled human plasma by eluting a protein A column with a buffer at pH 2.5 was contaminated with approximately 30% of the IgM originally present in the sample. Both the IgM and the IgA contamination can be reduced and the IgG recovery maintained at 90% of the bound IgG when elution of the column is performed at pH 4.0
Assuntos
Imunoglobulina G/isolamento & purificação , Proteína Estafilocócica A/imunologia , Cromatografia de Afinidade , Humanos , Imunoeletroforese , Imunoglobulina A/isolamento & purificação , Imunoglobulina M/isolamento & purificaçãoRESUMO
Human immunoglobulin M binds to protein A-bearing Staphylococcus aureus. This binding is specific for protein A since it is inhibited by rabbit Fab against Staphylococcal protein A. Analysis of the IgM binding data gives an apparent KD of 0.94 nM and a maximum capacity of approximately 2 X 10(3) binding sites of IgM per bacteria.
Assuntos
Sítios de Ligação de Anticorpos , Imunoglobulina M/metabolismo , Proteína Estafilocócica A/metabolismo , Animais , Especificidade de Anticorpos , Ligação Competitiva , Humanos , Concentração de Íons de Hidrogênio , Fragmentos Fab das Imunoglobulinas , Coelhos , Proteína Estafilocócica A/imunologia , Staphylococcus aureus/metabolismo , Fatores de TempoRESUMO
The cellular and subcellular distribution of 2,4-dinitrophenyl (DNP) groups in the epidermis and regional lymph nodes of the mouse was investigated after epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to sensitized and non-sensitized mice. The peroxidase-antiperoxidase method and the immunogold technique were used to visualize the DNP groups at both light and electron microscopic levels. The highest intensity of immunolabelling was found on tonofilaments of keratinocytes present in the upper layers of the epidermis. On the other hand, in vitro experiments showed that DNFB has the capacity to bind keratin which, together with immunocytochemistry, suggests that this molecule may be one of the skin protein carriers for DNFB. In addition, intense immunostaining for DNP was observed in the Golgi area of some epidermal Langerhans cells. Cells immunoreactive to DNP were also observed in the marginal sinus of cervical lymph nodes 6, 12 and 24 h after challenge. Immunoelectron microscopy revealed immunoreactive DNP groups in phagosomes of Langerhans cells at this site. The present findings support the hypothesis that the hapten DNFB penetrates passively into the cytoplasm of Langerhans cells, concentrates in the Golgi area and, during the migration of Langerhans cells to the lymph nodes, it is probably processed in the lysosomes before its presentation to T lymphocytes.
Assuntos
Dinitrobenzenos/metabolismo , Dinitrofluorbenzeno/farmacologia , Epiderme/metabolismo , Linfonodos/metabolismo , Animais , Dinitrobenzenos/análise , Dinitrofluorbenzeno/metabolismo , Epiderme/química , Epiderme/ultraestrutura , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Queratinócitos/química , Queratinócitos/metabolismo , Queratinócitos/ultraestrutura , Queratinas/metabolismo , Células de Langerhans/química , Células de Langerhans/metabolismo , Células de Langerhans/ultraestrutura , Linfonodos/química , Linfonodos/ultraestrutura , Camundongos , Microscopia Eletrônica , Microscopia ImunoeletrônicaRESUMO
OBJECTIVE: The aim of the present study was to analyse the relation between age and both dietary habits and leisure-time physical activity, and to determine nutrient inadequacy of aged groups in our population. DESIGN: Cross-sectional study. SETTING: A random sample of the 25-74-y-old population of Gerona, Spain. SUBJECTS: A total of 838 men and 910 women were selected from among the general population according to the 1991 census. OUTCOME MEASURES: Analysis of dietary habits, including amount and type of alcohol consumption, and detailed evaluation of leisure-time physical activity. RESULTS: Nutrient densities of carbohydrates, vitamin B(1), vitamin B(12), vitamin C, vitamin E, folate, potassium, iron, magnesium, copper, and dietary fiber increased significantly (P<0.05) with age in both genders, whereas an inverse trend was observed for total fat, saturated fatty acids, cholesterol, and sodium. Multiple linear regression analysis revealed a direct association of healthy dietary habits, characterized through a composite dietary score, with age after adjusting for several confounders both in men and women (P<0.001). This score was composed of folate, vitamin C, vitamin E, beta-carotene, dietary fibre, cholesterol, saturated fatty acids, and sodium. In all, 29 and 10% of male and female subjects aged 65-74 y, respectively, reported inadequate intakes of six or more of 16 nutrients. Total leisure-time physical activity increased with age in men (P<0.002), and was not different among female age groups. CONCLUSION: Dietary behaviours and levels of physical activity spent during leisure time indicate a healthy lifestyle of the aged men and women in the present population. Nutrient inadequacy observed in some aged men and women, however, deserves particular intervention of health-care programmes for this growing part of our society.
Assuntos
Ingestão de Energia , Exercício Físico , Comportamento Alimentar , Atividades de Lazer , Adulto , Fatores Etários , Idoso/fisiologia , Consumo de Bebidas Alcoólicas/epidemiologia , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/análise , Estudos Transversais , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/análise , Fibras na Dieta/administração & dosagem , Fibras na Dieta/análise , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/análise , Humanos , Masculino , Micronutrientes/administração & dosagem , Micronutrientes/análise , Pessoa de Meia-Idade/fisiologia , Avaliação Nutricional , Valor Nutritivo , Fatores Sexuais , Espanha/epidemiologiaRESUMO
A method is described for preparing IgM from normal serum in two chromatographic steps. A gel filtration column gives a macroglobulin peak containing the IgM, purified by affinity chromatography on protein A--Sepharose. Immunoglobulin recovery is around 50%.
Assuntos
Imunoglobulina M/isolamento & purificação , Proteína Estafilocócica A , Cromatografia de Afinidade/métodos , Eletroforese em Gel de Poliacrilamida , Humanos , Radioimunoensaio , SefaroseRESUMO
Remifentanil is an ultra-short-acting opioid that is frequently used in adults for surgical anesthesia or conscious sedation, but its use in children is much less common. We report the case of a 7-year-old boy with lateral cervical tumors displacing all cervical and facial structures. An emergency tracheostomy was performed when he developed respiratory difficulty due to partial airway obstruction. Because of the size and location of the intraoral tumors and a history of bleeding, orotracheal intubation and other airway management techniques were ruled out. The tracheostomy was performed under local anesthesia and sedation with a perfusion of 0.05 x microgKg(-1) x min(-1) provided the necessary relaxation and immobility for surgery. Sedation under observation with monitoring is among the indications of remifentanil. Spontaneous breathing is maintained with infusions less than 0.05 to 0.1 microg x Kg(-1) x min(-1). In the case we report, the patient's risk of complete airway obstruction due to bleeding upon manipulation had to be assessed and compared with the respiratory depression that might possibly have been caused by remifentanil perfusion. We judged that the option of sedation would cause less morbidity and offered greater safety for the patient. The outcome of this case is consistent with reports that remifentanil is a good option for adequately sedating children who are breathing spontaneously.
Assuntos
Obstrução das Vias Respiratórias/cirurgia , Sedação Consciente , Hipnóticos e Sedativos/administração & dosagem , Piperidinas/administração & dosagem , Traqueostomia , Obstrução das Vias Respiratórias/etiologia , Criança , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Masculino , Remifentanil , Fatores de RiscoRESUMO
REASONS FOR PERFORMING STUDY: Intra-arterial (i.a.) and intravenous (i.v.) regional limb perfusions (RLP) through the median artery and cephalic vein, respectively, have been previously investigated for administration of mesenchymal stem cells (MSCs) to the equine distal limb. Limitations due to thrombosis of the arteries after i.a. RLP and poor distribution of MSCs to the foot with i.v. RLP were observed. These techniques need to be modified for clinical use. OBJECTIVES: Evaluate the distribution, uptake and persistence of radiolabelled MSCs after i.a. injection through the median artery without a tourniquet and after i.v. RLP through the lateral palmar digital vein. STUDY DESIGN: In vivo experimental study. METHODS: (99m) Tc-HMPAO-labelled MSCs were injected through the median artery of one limb and the lateral palmar digital vein of the other limb of 6 horses under general anaesthesia. No tourniquet was used for the i.a. injection. A pneumatic tourniquet was placed on the metacarpus for i.v. injection. Scintigraphic images were obtained up to 24 h after injection. RESULTS: Intra-arterial injection resulted in MSCs retention within the limb despite the absence of a tourniquet and no thrombosis was observed. Both i.a. injection and i.v. RLP led to distribution of MSCs to the foot. The i.a. injection resulted in a more homogeneous distribution. The MSC uptake was higher with i.v. RLP at the initial timepoints, but no significant difference was present at 24 h. CONCLUSIONS: Both i.a. injection through the median artery without a tourniquet and i.v. RLP performed through the lateral palmar digital vein under general anaesthesia are safe and reliable methods for administration of MSCs to the equine foot. The i.a. technique is preferred owing to the better distribution, but is technically more challenging. The feasibility of performing these techniques on standing horses remains to be investigated.
Assuntos
Pé/irrigação sanguínea , Cavalos , Infusões Intra-Arteriais/veterinária , Infusões Intravenosas/veterinária , Transplante de Células-Tronco Mesenquimais/veterinária , Cintilografia/veterinária , Animais , Infusões Intra-Arteriais/métodos , Infusões Intravenosas/métodos , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Compostos Radiofarmacêuticos/farmacologia , Tecnécio Tc 99m Exametazima/farmacologiaRESUMO
REASON FOR PERFORMING STUDY: The use of triamcinolone acetonide (TA) in performance horses necessitates establishing appropriate withdrawal times prior to performance. OBJECTIVES: To describe the plasma pharmacokinetics of TA and time-related urine and synovial fluid concentrations following i.m. and intra-articular administration to exercised Thoroughbred horses. STUDY DESIGN: Block design. METHODS: Twelve racing fit adult Thoroughbred horses received a single i.m. administration of TA (0.1 mg/kg bwt). After an appropriate washout period, the same horses then received a single intra-articular TA administration (9 mg) into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to, and at various times, up to 60 days post drug administration and analysed using liquid chromatography-mass spectrometry. Plasma data were analysed using noncompartmental analysis. RESULTS: Maximum measured plasma TA concentrations were 0.996 ± 0.391 at 13.2 h and 1.27 ± 0.278 ng/ml at 6.5 h for i.m. and intra-articular administration, respectively. The plasma terminal elimination half-life was 11.4 ± 6.53 and 0.78 ± 1.00 days for i.m. and intra-articular administration, respectively. Following i.m. administration, TA was below the limit of detection (LOD) by Days 52 and 60 in plasma and urine, respectively. Following intra-articular administration TA was undetectable by Day 7 in plasma and Day 8 in urine. Triamcinolone acetonide was also undetectable in any of the joints sampled following i.m. administration and remained above the limit of quantitation (LOQ) for 21 days following intra-articular administration. CONCLUSIONS AND POTENTIAL RELEVANCE: This study extends previous studies describing the pharmacokinetics of TA following i.m. and intra-articular administration to the horse and suggests that plasma and urine concentrations are not a good indicator of synovial fluid concentrations. Furthermore, results of this study supports an extended withdrawal time for TA given i.m.
Assuntos
Anti-Inflamatórios/farmacocinética , Cavalos/metabolismo , Condicionamento Físico Animal/fisiologia , Triancinolona Acetonida/farmacocinética , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/sangue , Área Sob a Curva , Feminino , Meia-Vida , Injeções Intra-Articulares , Injeções Intramusculares , Masculino , Triancinolona Acetonida/administração & dosagem , Triancinolona Acetonida/sangueRESUMO
REASONS FOR PERFORMING STUDY: Intralesional (i.l.) injection is currently the most commonly used technique for stem cell therapy in equine tendon injury. A comparison of different techniques of injection of mesenchymal stem cells for the treatment of tendon lesions is required. OBJECTIVES: We hypothesised that vascular perfusion of the equine distal limb with mesenchymal stem cells (MSCs) would result in preferential distribution of MSCs to acute tendon injuries. STUDY DESIGN: In vivo experimental study. METHODS: Lesions were surgically induced in forelimb superficial digital flexor tendons of 8 horses. Three or 10 days after lesion induction, technetium-99 hexamethyl propylene amine oxime-labelled MSCs were injected via i.v. or intra-arterial (i.a.) regional limb perfusion (RLP) at the level of the distal antebrachium and compared to i.l. injection. Mesenchymal stem cell persistence and distribution within the forelimb and tendon lesions was assessed with scintigraphy for 24 h. RESULTS: Lesion uptake was higher with i.l. injection than with RLP, but MSC persistence decreased similarly over time in all 3 techniques. Intra-arterial RLP resulted in a better distribution of MSCs and a higher uptake at the lesion site than i.v. RLP. Limbs perfused i.a. on Day 10 showed greater accumulation of MSCs in the lesion than limbs perfused on Day 3. Arterial thrombosis occurred in 50% of the i.v. RLP limbs and in 100% of the i.a. RLP limbs, which led to clinical complications in one horse. CONCLUSIONS AND POTENTIAL RELEVANCE: Compared with i.l. injection, RLP results in lower uptake but similar persistence of MSCs at the site of tendon lesions. A time dependent accumulation of MSCs was identified with i.a. RLP. The i.a. RLP appears more advantageous than the i.v. RLP in terms of distribution and uptake. However, the described i.a. technique produced arterial thrombosis and thus cannot currently be recommended for clinical use.
Assuntos
Doenças dos Cavalos/terapia , Macrófagos/metabolismo , Transplante de Células-Tronco Mesenquimais/veterinária , Tecnécio Tc 99m Exametazima/farmacologia , Traumatismos dos Tendões/terapia , Animais , Feminino , Membro Anterior , Doenças dos Cavalos/diagnóstico por imagem , Cavalos , Masculino , Cintilografia/veterinária , Traumatismos dos Tendões/diagnóstico por imagem , UltrassonografiaRESUMO
REASONS FOR PERFORMING STUDY: Mesenchymal stem cells (MSCs) are commonly injected intralesionally for treatment of soft tissue injuries in the horse. Alternative routes of administration would be beneficial for treatment of lesions that cannot be accessed directly or to limit needle-induced iatrogenic damage to the surrounding tissue. OBJECTIVES: The purpose of our study was to evaluate MSC distribution after intra-arterial (IA) and intravenous (IV) regional limb perfusions (RLP) using scintigraphy. We hypothesised that MSCs would persist in the distal limb after tourniquet removal and that both techniques would lead to diffuse MSC distribution. METHODS: Six horses were used in the study. MSCs were labelled with hexamethyl propylene amine oxime (HMPAO) and technetium-99m. RLP was performed through the median artery of one forelimb and the cephalic vein of the opposite limb under general anaesthesia. The tourniquet was left in place for 45 min. Scintigraphic images were obtained at 0, 45, 75 min, 6 h and 24 h post injection. RESULTS: Distribution of labelled MSCs through the entire distal limb was achieved with all 6 IA RLP, but 3 out of 6 IV RLP showed poor or absent uptake distal to the metacarpus. Mesenchymal stem cell persistence was 39% (30-60%) and 28% (14-50%) (median [minimum-maximum]) at 6 h for IA and IV RLP, respectively. Severe arterial thrombosis occurred in one horse after IA RLP. CONCLUSIONS: Both IA and IV RLP of the distal limb result in MSC persistence in perfused tissues. The IA perfusion resulted in more reliable cell distribution to the pastern and foot area. POTENTIAL RELEVANCE: Regional limb perfusion of MSCs might be used in cases where intralesional injection is not possible or in order to avoid iatrogenic needle damage. Further work is needed to assess the safety of IA RLP before its clinical use.
Assuntos
Células da Medula Óssea/fisiologia , Membro Anterior/irrigação sanguínea , Transplante de Células-Tronco Mesenquimais/veterinária , Cintilografia/veterinária , Tecnécio Tc 99m Exametazima/farmacologia , Animais , Feminino , Infusões Intra-Arteriais , Injeções Intravenosas , Masculino , Cintilografia/métodos , Compostos Radiofarmacêuticos/farmacologia , Transplante HomólogoAssuntos
Analgésicos Opioides/efeitos adversos , Artralgia/tratamento farmacológico , Buprenorfina/efeitos adversos , Dor no Peito , Infarto do Miocárdio/diagnóstico , Administração Cutânea , Idoso , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Angioplastia Coronária com Balão , Artralgia/etiologia , Buprenorfina/administração & dosagem , Buprenorfina/uso terapêutico , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Isquemia Miocárdica/complicações , Osteoartrite do Quadril/complicações , StentsRESUMO
In this work, films of horizontally aligned single-walled carbon nanotubes were thermally and electrically characterized in order to determine the bolometric performance. An average thermal time constant of τ = 420 µs along with a temperature coefficient of resistance of TCR = -2.94% K(-1) were obtained. The maximum voltage responsivity and detectivity obtained were R(V) =230 V/W and D* = 1.22 × 10(8) cm Hz(1/2)/W, respectively. These values are higher than the maximum voltage responsivity (150 V/W) and maximum temperature coefficient of resistance (1.0% K(-1)) previously reported for carbon nanotube films at room temperature. The maximum detectivity was obtained at a frequency of operation of 1.25 kHz.