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OBJECTIVE: We conducted a systematic review in order to understand the relationship between imaging-visualised meniscus pathologies, hyaline cartilage, joint replacement and pain in knee osteoarthritis (OA). DESIGN: A search of the Medline, Excerpta Medica database (EMBASE) and Cochrane library databases was performed for original publications reporting association between imaging-detected meniscal pathology (extrusion or tear/damage) and longitudinal and cross-sectional assessments of hyaline articular cartilage loss [assessed on magnetic resonance imaging (MRI)], incident joint replacement and pain (longitudinal and cross-sectional) in knee OA. Each association was qualitatively characterised by a synthesis of data from each analysis, based upon study design and quality scoring (including risk of bias assessment and adequacy of covariate adjustment using Cochrane recommended methodology). RESULTS: In total 4,878 abstracts were screened and 82 publications were included (comprising 72 longitudinal analyses and 49 cross-sectional). Using high quality, well-adjusted data, meniscal extrusion and meniscal tear/damage were associated with longitudinal progression of cartilage loss, cross-sectional cartilage loss severity and joint replacement, independently of age, sex and body mass index (BMI). Medial and lateral meniscal tears were associated with cartilage loss when they occurred in the body and posterior horns, but not the anterior horns. There was a lack of high quality, well-adjusted meniscal pathology and pain publications and no clear independent association between meniscal extrusion or tear/damage with pain severity, progression in pain or incident frequent knee symptoms. CONCLUSION: Meniscal features have strong associations with cartilage loss and joint replacement in knee OA, but weak associations with knee pain. Systematic review PROSPERO registration number: CRD 42020210910.
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Artroplastia de Substituição , Cartilagem Articular , Osteoartrite do Joelho , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Estudos Transversais , Humanos , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/patologia , Meniscos Tibiais/cirurgia , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Dor/patologiaRESUMO
OBJECTIVE: Bone shape and bone marrow lesions (BMLs) represent different features of Magnetic resonance imaging (MRI)-detected subchondral pathology in osteoarthritis (OA). The aim of this study was to determine how these features are related and how they change in OA progression. METHODS: 600 participants from the Osteoarthritis Initiative (OAI) FNIH Biomarkers Initiative were included, having Kellgren-Lawrence grade 1-3, at baseline and MRI data at baseline and 24 months. The associations between 3D quantitative bone shape vectors and presence of (MRI Osteoarthritis Knee Score) MOAKS semi-quantitative BMLs (total BML size ≥1) were analysed for femurs and tibias using linear regression. Responsiveness over 24 months was calculated for both features in four pre-defined progression groups and reported as standardised response means (SRMs). Multilevel models investigated the longitudinal relationship between change in BML size and change in bone shape. RESULTS: Mean age was 61.5, 59% female and mean body mass index (BMI) 30.7. Correlation between baseline femur vector and BML was r = 0.28, P < 0.001. The presence of BMLs was associated with higher bone shape vector; coefficient (95% CI) 0.75 (0.54, 0.96) and 0.57 (0.38, 0.77) for femur and tibia respectively, both P < 0.001. After covariate adjustment, only the femur remained significant [coefficient 0.49, (95% CI 0.30, 0.68)]. Longitudinally bone vector demonstrated more responsiveness to change than BMLs (SRM 0.89 vs 0.13) while multilevel models revealed that increase in BML size was related to a more positive bone shape vector (representing worsening OA). CONCLUSION: There is a relationship between bone shape and BMLs, with prevalence of BMLs associated with increasing OA bone shape. Bone shape demonstrated greater responsiveness than semi-quantitative BMLs.
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Medula Óssea/patologia , Fêmur/patologia , Imageamento Tridimensional , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/diagnóstico , Tíbia/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
Split Hopkinson pressure bar experiments on soils are often carried out using a rigid steel confining ring to provide plane strain conditions, and measurements of the circumferential strain in the ring can be used to infer the radial stress on the surface of the specimen. Previous experiments have shown evidence of irregular electromagnetic interference in measurements of radial stress, which obscures the signals and impedes analysis. The development of robust constitutive models for soils in blast and impact events relies on the accurate characterisation of this behaviour, and so it is necessary to isolate and remove the source of interference. This paper uses an induction coil to identify the source of the anomalous signals, which are found to be due to induced currents in the gauge lead wires from the movement of magnetised pressure bars (martensitic stainless steel, 440C). Comparative experiments on sand and rubber specimens are used to show that the deforming soil specimen does not make a significant contribution to this activity, and recommendations are made on reducing electromagnetic interference to provide reliable radial stress measurements.
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Pairs of asteroids sharing similar heliocentric orbits, but not bound together, were found recently. Backward integrations of their orbits indicated that they separated gently with low relative velocities, but did not provide additional insight into their formation mechanism. A previously hypothesized rotational fission process may explain their formation-critical predictions are that the mass ratios are less than about 0.2 and, as the mass ratio approaches this upper limit, the spin period of the larger body becomes long. Here we report photometric observations of a sample of asteroid pairs, revealing that the primaries of pairs with mass ratios much less than 0.2 rotate rapidly, near their critical fission frequency. As the mass ratio approaches 0.2, the primary period grows long. This occurs as the total energy of the system approaches zero, requiring the asteroid pair to extract an increasing fraction of energy from the primary's spin in order to escape. We do not find asteroid pairs with mass ratios larger than 0.2. Rotationally fissioned systems beyond this limit have insufficient energy to disrupt. We conclude that asteroid pairs are formed by the rotational fission of a parent asteroid into a proto-binary system, which subsequently disrupts under its own internal system dynamics soon after formation.
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PURPOSE: Clozapine is an antipsychotic drug with superior efficacy in treatment-resistant schizophrenia. Clozapine is associated with a low likelihood of extrapyramidal symptoms and other neurological side-effects but a high propensity to induce weight gain and general metabolic dysregulation. Various pharmacological and behavioral treatment approaches for reducing clozapine-associated weight gain exist in the literature; however, there are currently no clear clinical guidelines as to which method is preferred. The aim of the current review is to systematically summarize studies that have studied both pharmacological and non-pharmacological interventions to attenuate or reverse clozapine-associated weight gain. METHODS: A systematic review of EMBASE and MEDLINE databases of all articles published prior to January 2014 was conducted. Seventeen studies were identified as meeting inclusion criteria and included in the review. RESULTS: Aripiprazole, fluvoxamine, metformin, and topiramate appear to be beneficial; however, available data are limited to between one and three randomized controlled trials per intervention. Orlistat shows beneficial effects, but in males only. Behavioral and nutritional interventions also show modest effects on decreasing clozapine-associated weight gain, although only a small number of such studies exist. CONCLUSIONS: While a number of pharmacological interventions can produce modest weight loss, each may be associated with negative side effects, which should be considered before beginning treatment. Given the pressing need to improve cardiometabolic health in most clozapine-treated patients, substantially more research is needed to develop sound clinical practice guidelines for the treatment of clozapine-associated weight gain.
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Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Aumento de Peso/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológicoRESUMO
BACKGROUND: Radiographic measures of osteoarthritis (OA) are based upon two dimensional projection images. Active appearance modelling (AAM) of knee magnetic resonance imaging (MRI) enables accurate, 3D quantification of joint structures in large cohorts. This cross-sectional study explored the relationship between clinical characteristics, radiographic measures of OA and 3D bone area (tAB). METHODS: Clinical data and baseline paired radiographic and MRI data, from the medial compartment of one knee of 2588 participants were obtained from the NIH Osteoarthritis Initiative (OAI). The medial femur (MF) and tibia (MT) tAB were calculated using AAM. 'OA-attributable' tAB (OA-tAB) was calculated using data from regression models of tAB of knees without OA. Associations between OA-tAB and radiographic measures of OA were investigated using linear regression. RESULTS: In univariable analyses, height, weight, and age in female knees without OA explained 43.1%, 32.1% and 0.1% of the MF tAB variance individually and 54.4% when included simultaneously in a multivariable model. Joint space width (JSW), osteophytes and sclerosis explained just 5.3%, 14.9% and 10.1% of the variance of MF OA-tAB individually and 17.4% when combined. Kellgren Lawrence (KL) grade explained approximately 20% of MF OA-tAB individually. Similar results were seen for MT OA-tAB. CONCLUSION: Height explained the majority of variance in tAB, confirming an allometric relationship between body and joint size. Radiographic measures of OA, derived from a single radiographic projection, accounted for only a small amount of variation in 3D knee OA-tAB. The additional structural information provided by 3D bone area may explain the lack of a substantive relationship with these radiographic OA measures.
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Fêmur/patologia , Osteoartrite do Joelho/patologia , Tíbia/patologia , Fatores Etários , Idoso , Estatura , Peso Corporal , Feminino , Fêmur/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Obesidade/complicações , Tamanho do Órgão , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteófito/diagnóstico por imagem , Osteófito/etiologia , Osteófito/patologia , Radiografia , Tíbia/diagnóstico por imagemRESUMO
Second generation antipsychotic (SGA) drugs are effective treatments for psychosis. Common side-effects of SGAs include metabolic dysregulation and risk of cardiometabolic disorders. Metabolic side-effects, including glucose intolerance, can be accurately modelled in rodents. The benefits of interventions used for treating metabolic side-effects of SGAs are mostly unknown. In a 9 wk longitudinal study, female rats were given daily olanzapine (10 mg/kg s.c.) or vehicle. Animals were either sedentary or allowed 1 or 3 h daily access to a running wheel, with total wheel revolutions electronically quantified to reflect exercise intensity. Glucose tolerance tests were performed once weekly to measure glycemic control. Drug levels were measured at week 4. At week 9, abdominal fat and skeletal muscle levels of Glucose Transporter 4 (GLUT4) were measured. Exercise intensity progressively increased over time in all groups given access to running wheels; however, rats treated with olanzapine consistently exercised less than those given the vehicle. Olanzapine caused acute and persistent glucose intolerance throughout the study, which was markedly, though incompletely, ameliorated by exercise. Exercise did not affect glycemic regulation in vehicle-treated rats. Olanzapine-treated rats showed greater central adiposity. Levels of GLUT4 in skeletal muscle were higher in both groups of exercising than in sedentary rats, and GLUT4 values were negatively correlated with glucose intolerance. Routine exercise reduced olanzapine-induced glucose intolerance and increased skeletal muscle levels of GLUT 4, the insulin-responsive transporter that mediates glucose uptake into cells. The current animal model is suitable for evaluating physiological pathways involved with glucose intolerance.
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Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Atividade Motora/fisiologia , Gordura Abdominal/efeitos dos fármacos , Animais , Antipsicóticos/sangue , Benzodiazepinas/sangue , Feminino , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4/metabolismo , Atividade Motora/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Olanzapina , RatosRESUMO
Ultracold atoms confined to optical lattices provide a platform for simulation of phenomena not readily accessible in condensed matter and chemical systems. One area of growing interest is the mechanism by which isolated condensed matter systems can thermalize. The mechanism for thermalization of quantum systems has been directly linked to a transition to chaos in their classical counterpart. Here we show that the broken spatial symmetries of the honeycomb optical lattice leads to a transition to chaos in the single-particle dynamics which, in turn, causes mixing of the energy bands of the quantum honeycomb lattice. For systems with single-particle chaos, "soft" interactions between atoms can cause the system to thermalize (achieve a Fermi-Dirac distribution for fermions or a Bose-Einstein distribution for bosons).
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BACKGROUND: Institutions undertaking transfusion have a responsibility to ensure safe and appropriate practice. The hospital transfusion committee (HTC) plays a major role in monitoring all aspects of transfusion. Dedicated staff with the responsibility of undertaking transfusion education and audit have been employed at many hospitals. The question is 'Do these positions improve practice?'. STUDY DESIGN AND METHODS: In 2005, a transfusion coordinator was employed by the King Edward Memorial Hospital (KEMH) and Princess Margaret Hospital (PMH) in Perth, Western Australia. After an initial audit to collect baseline data on transfusion documentation and compliance with national guidelines, a series of interventions was undertaken. In addition, the transfusion protocols were rewritten and published electronically. Further audits were undertaken in 2006, 2007 and 2009. RESULTS: Sequential audits show measured improvements in transfusion documentation. Baseline, hourly and completion observations are now correctly recorded in >94% of records at KEMH and >96% of records at PMH. Compliance with recording of 15 min observations has shown a 23% magnitude increase at KEMH and 36% at PMH. Compliance with recording of consent has increased by 20% at KEMH and 31% at PMH. Promotion of positive patient identification, when collecting specimens and administering blood, has been undertaken. CONCLUSION: The initiatives implemented by the transfusion coordinator and endorsed by the HTCs have improved the standard of transfusion documentation and practice at both institutions.
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Transfusão de Sangue/normas , Hospitais/normas , Auditoria Médica/normas , Corpo Clínico/educação , Coleta de Amostras Sanguíneas , Documentação/normas , Humanos , Austrália OcidentalRESUMO
Integrated analysis of land use change and its effect on catchment water balance allows the selection of appropriate water and land management options for new urban developments to minimise the environmental impacts of urbanisation. A process-based coupled surface water-groundwater model was developed for Southern River catchment (Perth, Western Australia) to investigate the effect of urban development on catchment water balance. It was shown that urbanisation of highly permeable flat catchments with shallow groundwater resulted in significant increase in net groundwater recharge. The increased recharge creates the opportunity to use local groundwater resources for non-potable water supply with the added advantage of reducing the total discharge from new urban developments. This minimises the environmental impacts of increased urbanisation, as higher discharge is often associated with greater nutrient loads to receiving environments. Through the used of water balance modelling it was demonstrated that there are both water and nutrient benefits from local groundwater use in terms of reduced nutrient exports to receiving waters and additional water resources for non-potable water supply.
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Cidades , Purificação da Água/métodos , Abastecimento de Água , Monitoramento Ambiental , Movimentos da ÁguaRESUMO
Regional populations of rhesus and long-tailed macaques exhibit fundamental differences in mitochondrial DNA, short tandem repeat and single nucleotide polymorphism variation between mainland and insular Southeast Asian populations. Some studies have revealed genetic admixture between these species due to natural hybridization and human-assisted intercrosses. A quantitative real-time PCR (qPCR) assay was developed to efficiently determine the species of origin of a macaque biological sample, and to quantify the species-specific template DNA. Prior knowledge of species identity and DNA concentrations are crucial for maintaining cost-effective methods and accurate DNA analysis. DNA from 109 regionally representative rhesus and long-tailed macaques was qPCR amplified to determine the species and template quantities. Of the 19 Vietnamese long-tailed macaques, 3 samples were discovered to be hybrids.
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Macaca fascicularis/genética , Macaca mulatta/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Fator de Transcrição STAT6/genética , Animais , Sudeste Asiático , China , Hibridização Genética , Índia , Macaca fascicularis/sangue , Macaca mulatta/sangue , Repetições de Microssatélites , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real/economia , Reação em Cadeia da Polimerase em Tempo Real/instrumentação , Fator de Transcrição STAT6/sangue , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Especificidade da EspécieRESUMO
REASONS FOR PERFORMING STUDY: Evidence-based information is limited on distribution of local anaesthetic solution following perineural analgesia of the palmar (Pa) and palmar metacarpal (PaM) nerves in the distal aspect of the metacarpal (Mc) region ('low 4-point nerve block'). OBJECTIVES: To demonstrate the potential distribution of local anaesthetic solution after a low 4-point nerve block using a radiographic contrast model. METHODS: A radiodense contrast medium was injected subcutaneously over the medial or the lateral Pa nerve at the junction of the proximal three-quarters and distal quarter of the Mc region (Pa injection) and over the ipsilateral PaM nerve immediately distal to the distal aspect of the second or fourth Mc bones (PaM injection) in both forelimbs of 10 mature horses free from lameness. Radiographs were obtained 0, 10 and 20 min after injection and analysed subjectively and objectively. Methylene blue and a radiodense contrast medium were injected in 20 cadaver limbs using the same techniques. Radiographs were obtained and the limbs dissected. RESULTS: After 31/40 (77.5%) Pa injections, the pattern of the contrast medium suggested distribution in the neurovascular bundle. There was significant proximal diffusion with time, but the main contrast medium patch never progressed proximal to the mid-Mc region. The radiological appearance of 2 limbs suggested that contrast medium was present in the digital flexor tendon sheath (DFTS). After PaM injections, the contrast medium was distributed diffusely around the injection site in the majority of the limbs. In cadaver limbs, after Pa injections, the contrast medium and the dye were distributed in the neurovascular bundle in 8/20 (40%) limbs and in the DFTS in 6/20 (30%) of limbs. After PaM injections, the contrast and dye were distributed diffusely around the injection site in 9/20 (45%) limbs and showed diffuse and tubular distribution in 11/20 (55%) limbs. CONCLUSIONS AND POTENTIAL RELEVANCE: Proximal diffusion of local anaesthetic solution after a low 4-point nerve block is unlikely to be responsible for decreasing lameness caused by pain in the proximal Mc region. The DFTS may be penetrated inadvertently when performing a low 4-point nerve block.
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Meios de Contraste/farmacocinética , Membro Anterior/inervação , Bloqueio Nervoso/veterinária , Animais , Cadáver , Pé/diagnóstico por imagem , Pé/inervação , Membro Anterior/diagnóstico por imagem , Doenças dos Cavalos , Cavalos , Injeções Intra-Articulares/métodos , Injeções Intra-Articulares/veterinária , Articulação Metacarpofalângica , Bloqueio Nervoso/métodos , Radiografia , Distribuição TecidualRESUMO
RATIONALE: The second generation antipsychotic drug clozapine is a psychotherapeutic agent with superior efficacy for treatment-resistant schizophrenia. Clozapine is associated with a low likelihood of neurological side-effects, but a high propensity to induce weight gain and metabolic dysregulation. The primary metabolite of clozapine is norclozapine (N-Desmethylclozapine), which has psychoactive properties itself, but its effects on metabolic function remains unknown. The goal of the present study was to determine whether directly administered norclozapine could cause metabolic dysregulation, similar to clozapine. METHODS: Adult female rats were treated with a range of doses of clozapine and norclozapine (0.5, 2, 8 & 20â¯mg/kg, i.p.) and then subjected to the intraperitoneal glucose tolerance test (IGTT), where glucose levels were recorded for 2â¯h following a glucose challenge. In parallel, rats were tested with two doses of clozapine and norclozapine (2 & 20â¯mg/kg, i.p.) in the hyperinsulinemic-euglycemic clamp (HIEC), to measure whole body insulin resistance. RESULTS: In the IGTT, clozapine demonstrated dose-dependent effects on fasting glucose levels and total glucose area-under-the-curve following the glucose challenge, with the two highest doses strongly increasing glucose levels. Only the highest dose of norclozapine increased fasting glucose levels, and caused a non-significant increase in glucose levels following the challenge. By contrast, both doses of clozapine and norclozapine caused a potent and long-lasting decrease in the glucose infusion rate in the HIEC, indicating that both compounds cause whole body insulin resistance. ABSTRACT: While not as potent as its parent compound, norclozapine clearly exerts acute metabolic effects, particularly on insulin resistance. This article is part of the issue entitled 'Special Issue on Antipsychotics'.
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Antipsicóticos/administração & dosagem , Clozapina/análogos & derivados , Clozapina/administração & dosagem , Glucose/metabolismo , Insulina/metabolismo , Animais , Feminino , Teste de Tolerância a Glucose , Resistência à Insulina , Ratos Sprague-DawleyRESUMO
Aerobic exercise has been associated with hippocampal plasticity, both in healthy adults and in psychosis patients, but its impact on cortical regions remains unclear. The entorhinal cortex serves as a critical gateway for the hippocampus, and recent studies suggest that this region may also be impacted following an exercise regime. In order to investigate the effects of antipsychotic medications and exercise on the entorhinal cortex, female rats were chronically administered either olanzapine or vehicle and were either sedentary or had access to a running wheel for 9 weeks. Olanzapine-treated rats had decreased medial entorhinal cortical thickness compared to vehicle-treated rats. A statistically significant interaction was observed for layer II of the entorhinal cortex, with exercising rats having significantly greater thickness compared to sedentary rats in the vehicle group, but not the olanzapine group. Greater total entorhinal and lateral entorhinal cortical thickness was associated with greater average activity. In exercising rats, decreasing glucose intolerance was associated with larger total entorhinal and layer II cortical thickness. Lower fasting insulin levels were associated with greater total entorhinal, lateral entorhinal, and layer II cortical thickness. The relationship between increased activity and greater entorhinal cortical thickness was mediated by reduced fasting insulin, indicating that regulation of metabolic risk factors may contribute to impact of aerobic exercise on the entorhinal cortex. Aerobic exercise may be helpful in counteracting metabolic side effects of antipsychotic medications and managing these side effects may be key to promoting entorhinal cortical plasticity in patients treated with second-generation antipsychotic drugs.
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Antipsicóticos/toxicidade , Espessura Cortical do Cérebro , Córtex Entorrinal/efeitos dos fármacos , Córtex Entorrinal/metabolismo , Olanzapina/toxicidade , Condicionamento Físico Animal/fisiologia , Animais , Córtex Entorrinal/patologia , Feminino , Condicionamento Físico Animal/psicologia , Ratos , Ratos Sprague-Dawley , Comportamento SedentárioRESUMO
Repetitive strain injuries (RSI), which include several musculoskeletal disorders and nerve compression injuries, are associated with performance of repetitive and forceful tasks. In this study, we examined in young, adult Sprague-Dawley rats, the effects of performing a voluntary, moderate repetition, high force (MRHF; nine reaches/min; 60% maximum pulling force) task for 12 weeks on motor behavior and nerve function, inflammatory responses in forearm musculoskeletal and nerve tissues and serum, and neurochemical immunoexpression in cervical spinal cord dorsal horns. We observed no change in reach rate, but reduced voluntary participation and grip strength in week 12, and increased cutaneous sensitivity in weeks 6 and 12, the latter indicative of mechanical allodynia. Nerve conduction velocity (NCV) decreased 15% in the median nerve in week 12, indicative of low-grade nerve compression. ED-1 cells increased in distal radius and ulna in week 12, and in the median nerve and forearm muscles and tendons in weeks 6 and 12. Cytokines IL-1alpha, IL-1beta, TNF-alpha, and IL-10 increased in distal forearm bones in week 12, while IL-6 increased in tendon in week 12. However, serum analysis revealed only increased TNF-alpha in week 6 and macrophage inflammatory protein 3a (MIP3a) in weeks 6 and 12. Lastly, Substance P and neurokinin-1 were both increased in weeks 6 and 12 in the dorsal horns of cervical spinal cord segments. These results show that a high force, but moderate repetition task, induced declines in motor and nerve function as well as peripheral and systemic inflammatory responses (albeit the latter was mild). The peripheral inflammatory responses were associated with signs of central sensitization (mechanical allodynia and increased neurochemicals in spinal cord dorsal horns).
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Citocinas/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Movimento/fisiologia , Neuralgia/patologia , Neuralgia/fisiopatologia , Medula Espinal/metabolismo , Análise de Variância , Animais , Osso e Ossos/metabolismo , Modelos Animais de Doenças , Ectodisplasinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Macrófagos/metabolismo , Sistema Musculoesquelético/metabolismo , Condução Nervosa/fisiologia , Neurocinina A/metabolismo , Ratos , Ratos Sprague-Dawley , Limiar Sensorial/fisiologia , Pele/inervação , Substância P/metabolismo , Fatores de Tempo , Extremidade Superior/inervaçãoRESUMO
Rickets, hypocalcemia, decreased duodenal calcium transport, and reduction of calcium binding protein have been produced in chicks treated with diphenylhydantoin. These effects are directly related to diphenylhydantoin dose and inversely related to the intake of vitamin D(3) (cholecalciferol).
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Cálcio/metabolismo , Fenitoína/farmacologia , Animais , Peso Corporal , Osso e Ossos/metabolismo , Cálcio/sangue , Radioisótopos de Cálcio , Galinhas , Colecalciferol/farmacologia , Relação Dose-Resposta a Droga , Duodeno/metabolismo , Hipocalcemia/induzido quimicamente , Mucosa Intestinal/metabolismo , Masculino , Fenitoína/efeitos adversos , Ligação Proteica , Raquitismo/induzido quimicamente , Deficiência de Vitamina D/metabolismoRESUMO
BACKGROUND: A number of case reports link the use of 5-aminosalicylic acid (5-ASA) to interstitial nephritis in patients with inflammatory bowel disease (IBD). OBJECTIVE: To investigate whether the long-term use of 5-ASA has harmful effects on renal function in patients with IBD. METHODS: A retrospective analysis of 171 consecutive outpatients with Crohn's disease or ulcerative colitis was conducted. Serum creatinine levels and body weight were measured before and after treatment to calculate the creatinine clearance (CrCl) rate. RESULTS: In 171 patients (93 women, 78 men), the mean (+/- SD) dose of 5-ASA was 3.65+/-0.85 g/day with a cumulative dose of 11+/-7.7 kg over an interval of 8.4+/-5.9 years. Serum creatinine concentrations increased from 76.8 micromol/L to 88.7 micromol/L (n=171; P<0.0001) and the CrCl rate fell significantly from 104.6 mL/min to 93.1 mL/min (n=81; P<0.0001). There was one case of interstitial nephritis reported. Treatment groups included mesalamine (74.3%), sulfasalazine (15.2%) and combination (sulfalsalazine/mesalamine [10.5%]) with treatment durations of 7.2+/-4.5, 12.3+/-8.7 and 11.2+/-6.7 years, respectively. The duration of treatment was the most important covariate for change in CrCl and when analyzed by treatment group, those treated with sulfasazine had a strong correlation (r=-0.54, P=0.0145), while nonsignificant in the mesalamine group (r=0.06, P=0.7017). The decline in CrCl was negatively correlated with the pretreatment CrCl rate (r=-0.34; P=0.0024) and positively correlated with the mean daily dose of 5-ASA (r=0.32; P=0.0034). CONCLUSION: The present study is the first to demonstrate a significant dose- and treatment duration-dependant decline in CrCl. The risks need to be further evaluated because 5-ASA is widely used for long-term maintenance therapy in patients with IBD.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Mesalamina/efeitos adversos , Nefrite Intersticial/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Creatinina/sangue , Creatinina/urina , Doença de Crohn/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Mesalamina/administração & dosagem , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Sulfassalazina/administração & dosagem , Sulfassalazina/efeitos adversos , Sulfassalazina/uso terapêutico , Fatores de Tempo , Adulto JovemRESUMO
Net ecosystem productivity (NEP) of boreal coniferous forests is believed to rise with climate warming, thereby offsetting some of the rise in atmospheric CO(2) concentration (C(a)) by which warming is caused. However, the response of conifer NEP to warming may vary seasonally, with rises in spring and declines in summer. To gain more insight into this response, we compared changes in CO(2) exchange measured by eddy covariance and simulated by the ecosystem process model ecosys under rising mean annual air temperatures (T(a)) during 2004-2006 at black spruce stands in Saskatchewan, Manitoba and Quebec. Hourly net CO(2) uptake was found to rise with warming at T(a) < 15 degrees C and to decline with warming at T(a) > 20 degrees C. As mean annual T(a) rose from 2004 to 2006, increases in net CO(2) uptake with warming at lower T(a) were greater than declines with warming at higher T(a) so that annual gross primary productivity and hence NEP increased. Increases in net CO(2) uptake measured at lower T(a) were explained in the model by earlier recovery of photosynthetic capacity in spring, and by increases in carboxylation activity, using parameters for the Arrhenius temperature functions of key carboxylation processes derived from independent experiments. Declines in net CO(2) uptake measured at higher T(a) were explained in the model by sharp declines in mid-afternoon canopy stomatal conductance (g(c)) under higher vapor pressure deficits (D). These declines were modeled from a hydraulic constraint to water uptake imposed by low axial conductivity of conifer roots and boles that forced declines in canopy water potential (psi(c)), and hence in g(c) under higher D when equilibrating water uptake with transpiration. In a model sensitivity study, the contrasting responses of net CO(2) uptake to specified rises in T(a) caused annual NEP of black spruce in the model to rise with increases in T(a) of up to 6 degrees C, but to decline with further increases at mid-continental sites with lower precipitation. However, these contrasting responses to warming also indicate that rises in NEP with climate warming would depend on the seasonality (spring versus summer) as well as the magnitude of rises in T(a).
Assuntos
Dióxido de Carbono/metabolismo , Efeito Estufa , Fotossíntese/fisiologia , Picea/metabolismo , Biomassa , Canadá , Ecossistema , Temperatura Alta , Modelos Biológicos , Picea/crescimento & desenvolvimento , Chuva , Solo , Energia Solar , Árvores/metabolismo , Água/fisiologiaRESUMO
REASONS FOR PERFORMING STUDY: Lameness is highly prevalent in working horses, but published reports on the associated pathological abnormalities are lacking. With over 42 million horses in developing countries and the majority used for work, lameness has major welfare implications. OBJECTIVES: To describe the range and prevalence of pathological abnormalities associated with lameness in working horses. METHODS: A standard lameness assessment was adapted for field use in working equids. Data on pathological abnormalities and pain responses in the feet, limbs and spine were collected through observation, palpation, manipulations and gait assessment in working horses from India (n = 110) and Pakistan (n = 117). Lameness at the walk was scored on a scale of 0-4 (sound-nonweightbearing). RESULTS: All horses examined were lame. Overall, 98% showed a gait abnormality in all 4 limbs and 87% had at least one limb scoring 3 or 4 on the lameness scale. Multiple pathological abnormalities within each limb were associated with lameness, with similar results in both countries. Chronic foot pathology was seen in every horse; 94% horses showed signs of chronic joint disease; 83% had digital flexor tendonitis in at least one limb. Lameness and pathological abnormalities were associated with specific pain responses in the feet, limbs and spine. CONCLUSIONS: The extremely high prevalence of multilimb lameness and its association with pain is of great concern. The multiple pathological abnormalities present in working horses makes lameness complex to address. POTENTIAL RELEVANCE: The results of this detailed study of lameness should facilitate the identification of risk factors and the implementation of interventions to reduce the prevalence of lameness in working equids.