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1.
Acta Orthop ; 95: 157-165, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38597226

RESUMO

BACKGROUND AND PURPOSE: Different marker-selection methods are applied to represent implant and tibial segments in radiostereometric analysis (RSA) studies of total knee arthroplasty (TKA). Either a consistent set of markers throughout subsequent RSA examinations ("consistent-marker method") is used or all available markers at each follow-up ("all-marker method"). The aim of this secondary analysis was to compare marker-selection methods on individual and group level TKA migration results. METHODS: Data from a randomized RSA study with 72 patients was included. Tibial baseplate migration was evaluated at 3 months, 1, 2, and 5 years postoperatively with both marker-selection methods. Additionally, migration was calculated using 5 fictive points, either plotted based on the consistent set of markers or all available markers. RESULTS: Migration could be calculated with both marker-selection methods for 248 examinations. The same prosthesis and bone markers (n = 136), different prosthesis markers (n = 71), different bone markers (n = 21), or different prosthesis and bone markers (n = 20) were used. The mean difference in maximum total point motion (MTPM) between all examinations was 0.02 mm, 95% confidence interval -0.26 to 0.31 mm. 5 implants were classified as continuously migrating with the consistent-marker method versus 6 implants (same 5 plus one additional implant) with the all-marker method. Using fictive points, fewer implants were classified as continuously migrating in both marker-selection methods. Differences between TKA groups in mean MTPM were comparable with both marker-selection methods, also when fictive points were used. CONCLUSION: Estimated group differences in mean MTPM were similar between marker-selection methods, but individual migration results differed. The latter has implications when classifying implants for estimated risk of future loosening.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Seguimentos , Análise Radioestereométrica , Falha de Prótese , Desenho de Prótese , Osteoartrite do Joelho/cirurgia
2.
Osteoarthritis Cartilage ; 31(3): 351-362, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36473675

RESUMO

OBJECTIVE: Drug delivery platforms that allow for gradual drug release after intra-articular administration have become of much interest as a treatment strategy for osteoarthritis (OA). The aim of this study was to investigate the safety and efficacy of an intra-articular sustained release formulation containing celecoxib (CXB), a cyclooxygenase-2 (COX-2) selective inhibitor. METHODS: Amino acid-based polyesteramide microspheres (PEAMs), a biodegradable and non-toxic platform, were loaded with CXB and employed in two in vivo models of arthritis: an acute inflammatory arthritis model in rats (n = 12), and a randomized controlled study in chronic OA dog patients (n = 30). In parallel, the bioactivity of sustained release of CXB was evaluated in monolayer cultures of primary dog chondrocytes under inflammatory conditions. RESULTS: Sustained release of CXB did not alleviate acute arthritis signs in the rat arthritis model, based on pain measurements and synovitis severity. However, in OA dog patients, sustained release of CXB improved limb function as objective parameter of pain and quality of life based on gait analysis and owner questionnaires. It also decreased pain medication dependency over a 2-month period and caused no adverse effects. Prostaglandin E2 levels, a marker for inflammation, were lower in the synovial fluid of CXB-treated dog OA patients and in CXB-treated cultured dog chondrocytes. CONCLUSION: These results show that local sustained release of CXB is less suitable to treat acute inflammation in arthritic joints, while safe and effective in treating pain in chronic OA in dogs.


Assuntos
Osteoartrite , Qualidade de Vida , Animais , Cães , Ratos , Anti-Inflamatórios não Esteroides/uso terapêutico , Celecoxib/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/uso terapêutico , Inflamação/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico
3.
Knee Surg Sports Traumatol Arthrosc ; 30(5): 1629-1638, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34347140

RESUMO

PURPOSE: The purpose of this study was to assess whether the vascularisation of the meniscus could be visualised intra-operatively using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) in patients undergoing total knee arthroplasty (TKA). METHODS: The anterior horn (i.e., Cooper classification: zones C and D) of the meniscus that was least affected (i.e., least degenerative) was removed during TKA surgery in ten patients to obtain a cross section of the inside of the meniscus. Thereafter, 10 mg of ICG was injected intravenously, and vascularisation of the cross section of the meniscus was assessed using the Quest spectrum NIRF camera system. We calculated the percentage of patients in whom vascularisation was observed intra-operatively using NIRF imaging compared to immunohistochemistry. RESULTS: Meniscal vascularisation using NIRF imaging was observed in six out of eight (75%) patients in whom vascularisation was demonstrated with immunohistochemistry. The median extent of vascularisation was 13% (interquartile range (IQR) 3-28%) using NIRF imaging and 15% (IQR 11-23%) using immunohistochemistry. CONCLUSION: This study shows the potential of NIRF imaging to visualise vascularisation of the meniscus, as vascularisation was observed in six out of eight patients with histologically proven meniscal vascularisation. LEVEL OF EVIDENCE: IV.


Assuntos
Menisco , Imagem Óptica , Humanos , Verde de Indocianina , Imagem Óptica/métodos
4.
Phys Rev Lett ; 112(11): 112502, 2014 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-24702355

RESUMO

Gamow-Teller (GT) transitions in atomic nuclei are sensitive to both nuclear shell structure and effective residual interactions. The nuclear GT excitations were studied for the mass number A = 42, 46, 50, and 54 "f-shell" nuclei in ((3)He, t) charge-exchange reactions. In the (42)Ca → (42)Sc reaction, most of the GT strength is concentrated in the lowest excited state at 0.6 MeV, suggesting the existence of a low-energy GT phonon excitation. As A increases, a high-energy GT phonon excitation develops in the 6-11 MeV region. In the (54)Fe → (54)Co reaction, the high-energy GT phonon excitation mainly carries the GT strength. The existence of these two GT phonon excitations are attributed to the 2 fermionic degrees of freedom in nuclei.

5.
Sci Rep ; 14(1): 22264, 2024 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333374

RESUMO

This study assesses the use of fructosamine as a diagnostic tool for hyperglycemia in alpacas in view of their sensitivity to stress and susceptibility to conditions like lipid mobilization syndrome. Plasma fructosamine, like in diagnosing diabetes in cats and dogs, can reveal long-term blood glucose trends, differentiating stress-induced spikes from persistent diabetic hyperglycemia. In 125 alpacas presented as patients of a veterinary clinic, plasma glucose and fructosamine concentrations were compared for correlations with findings of the general clinical examination, laboratory parameters, demographic data, and a behavioral stress assessment processed by using principal component analysis. Hyperglycemia was observed on admission of 71% (89/125) of the animals. This was significantly associated with a higher concentration of serum cortisol and a higher behavioral stress scoring. Fructosamine above the reference limit was detected in only 15% (13/89) of the hyperglycemic individuals. In addition to a positive correlation of fructosamine to glucose concentration, positive relationships with different plasma proteins were detected. A relationship to stress parameters was not observed. These findings underscore stress as a significant trigger for hyperglycemia in alpacas and suggest fructosamine as a valuable parameter for distinguishing between stress-induced and diabetic hyperglycemia. However, the dependence of fructosamine formation on total plasma protein concentration should be considered to avoid misinterpretation.


Assuntos
Glicemia , Camelídeos Americanos , Frutosamina , Hiperglicemia , Frutosamina/sangue , Animais , Camelídeos Americanos/sangue , Glicemia/análise , Glicemia/metabolismo , Masculino , Feminino , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/metabolismo
6.
J Bone Joint Surg Am ; 106(16): 1479-1485, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-38941476

RESUMO

BACKGROUND: Radiostereometric analysis (RSA) provides highly accurate data about the migration of a total knee arthroplasty (TKA) component. However, patient-reported outcome measures (PROMs) reflect the patients' perspective of their functional status, pain, and overall health after TKA. The aim of this study was to evaluate the association between tibial implant migration and change in postoperative PROMs and clinical scores, using data pooled from long-term follow-up RSA studies. METHODS: Individual implant migration data were collected from 5 randomized RSA studies, including a total of 300 patients with 6 distinct TKA implant designs (all Stryker). Tibial implant migration (maximum total point motion [MTPM]) was evaluated with RSA at 3 months, 1 year, and 2, 5, 7, and 10 years postoperatively. The Knee Society Score (KSS)-Knee and KSS-Function and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales were collected in all studies at the same follow-up times. Linear mixed-effects models, with adjustment for TKA implant design and patient characteristics, were used to analyze the data. The 3-month follow-up visit was used as the baseline to assess the association between implant migration and PROMs across the 10-year follow-up. RESULTS: No association between tibial implant migration and change in KSS-Knee (p = 0.384), KSS-Function (p = 0.737), KOOS-Symptoms (p = 0.398), KOOS-Pain (p = 0.699), KOOS-Activities of Daily Living (p = 0.205), KOOS-Sport and Recreation (p = 0.702), or KOOS-Quality of Life (p = 0.368) was found across the entire follow-up. Similar results were found when using the 2-year follow-up as the baseline, after which both cemented and uncemented implants are expected to have stabilized. CONCLUSIONS: Tibial baseplate migration was not associated with postoperative worsening in PROMs or clinical scores in patients who underwent TKA. These findings suggest that implant migration, as measured with RSA, measures a different parameter (i.e., implant-bone fixation) than PROMs (i.e., patient perception) and clinical scores. Therefore, to assess the performance and safety of TKA implant designs, RSA and PROMs cannot be used interchangeably during the postoperative follow-up of patients and evaluation of the fixation of knee implants. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Medidas de Resultados Relatados pelo Paciente , Falha de Prótese , Análise Radioestereométrica , Tíbia , Humanos , Artroplastia do Joelho/métodos , Feminino , Masculino , Idoso , Seguimentos , Pessoa de Meia-Idade , Tíbia/cirurgia , Osteoartrite do Joelho/cirurgia , Desenho de Prótese
7.
Sci Rep ; 14(1): 20152, 2024 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-39215118

RESUMO

Anemia is a common problem in South American camelids (SACs). Infections with Candidatus Mycoplasma haemolamae (CMh), a cell-wall free, hemotropic bacterium, are often suspected to be an important cause of anemia, as the pathogen infects the erythrocytes and is found in the blood of up to 30% of SACs. The information on the clinical signs of animals infected with this pathogen vary widely. Most infections are clinically inapparent. Treatment is usually carried out with oxytetracycline. A detailed overview of the clinical and hematological findings in 13 alpacas infected with Candidatus M. haemolamae (CMh+), based on patients from our university clinic and comparing those findings with the results of 22 negative alpacas (CMh-) is provided. Assignment to both groups was based on the PCR result. No relevant clinical or hematological differences between CMh+ and CMh- were found, the clinical signs in CMh+ were usually due to comorbidities. The examination of a blood smear alone proved to be insufficient; a PCR test should be carried out to confirm or rule out an infection. A critical review of the need for antibiotic treatment on the basis of a positive test result alone is recommended.


Assuntos
Camelídeos Americanos , Infecções por Mycoplasma , Mycoplasma , Camelídeos Americanos/microbiologia , Infecções por Mycoplasma/veterinária , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/sangue , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/diagnóstico , Animais , Mycoplasma/isolamento & purificação , Mycoplasma/genética , Masculino , Feminino , Anemia/microbiologia , Anemia/sangue , Anemia/veterinária , Antibacterianos/uso terapêutico , Oxitetraciclina/uso terapêutico
8.
Bone Joint J ; 106-B(2): 136-143, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38295835

RESUMO

Aims: The objective of this study was to compare the two-year migration and clinical outcomes of a new cementless hydroxyapatite (HA)-coated titanium acetabular shell with its previous version, which shared the same geometrical design but a different manufacturing process for applying the titanium surface. Methods: Overall, 87 patients undergoing total hip arthroplasty (THA) were randomized to either a Trident II HA or Trident HA shell, each cementless with clusterholes and HA-coating. All components were used in combination with a cemented Exeter V40 femoral stem. Implant migration was measured using radiostereometric analysis (RSA), with radiographs taken within two days of surgery (baseline), and at three, 12, and 24 months postoperatively. Proximal acetabular component migration was the primary outcome measure. Clinical scores and patient-reported outcome measures (PROMs) were collected at each follow-up. Results: Mean proximal migrations at three, 12, and 24 months were 0.08 mm (95% confidence interval (CI) 0.03 to 0.14), 0.11 mm (95% CI 0.06 to 0.16), and 0.14 mm (95% CI 0.09 to 0.20), respectively, in the Trident II HA group, versus 0.11 mm (95% CI 0.06 to 0.16), 0.12 mm (95% CI 0.07 to 0.17), and 0.14 mm (95% CI 0.09 to 0.19) in the Trident HA group (p = 0.875). No significant differences in translations or rotations between the two designs were found in any other direction. Clinical scores and PROMs were comparable between groups, except for an initially greater postoperative improvement in Hip disability and Osteoarthritis Outcome Symptoms score in the Trident HA group (p = 0.033). Conclusion: The Trident II clusterhole HA shell has comparable migration with its predecessor, the Trident hemispherical HA cluster shell, suggesting a similar risk of long-term aseptic loosening.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Durapatita , Análise Radioestereométrica , Titânio , Seguimentos , Desenho de Prótese , Falha de Prótese , Resultado do Tratamento
9.
Pathologe ; 34(5): 463-5, 2013 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-23949605

RESUMO

A cystic entity from the porta hepatis of a 64-year-old female patient was sent in for rapid section diagnostics with a clinical suspicion of pancreatic cancer. The rapid section diagnostics revealed aspects of glandular proliferation with mucous-like material in the lumina which led to the suspicion of infiltration of a highly differentiated mucinous adenocarcinoma. However, conventional paraffin-section histology and the immunohistochemical marker profile could not confirm this suspicion but an adenomatoid tumor was diagnosed. In typical locations in the genital area of both genders, this entity is a current differential diagnosis to infiltrations of an adenocarcinoma.


Assuntos
Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Tumor Adenomatoide/patologia , Tumor Adenomatoide/cirurgia , Cistadenoma/patologia , Cistadenoma/cirurgia , Cistos/patologia , Hepatopatias/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Biomarcadores Tumorais/análise , Colangiopancreatografia por Ressonância Magnética , Cistos/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Fígado/patologia , Fígado/cirurgia , Hepatopatias/cirurgia , Pessoa de Meia-Idade
10.
J Bone Joint Surg Am ; 105(21): 1686-1694, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37651549

RESUMO

BACKGROUND: Three-dimensional (3D) printing of highly porous orthopaedic implants aims to promote better osseointegration, thus preventing aseptic loosening. However, short-term radiostereometric analysis (RSA) after total knee arthroplasty (TKA) has shown higher initial migration of cementless 3D-printed tibial components compared with their cemented counterparts. Therefore, critical evaluation of longer-term tibial component migration is needed. We investigated migration of a cementless 3D-printed and a cemented tibial component with otherwise similar TKA design during 5 years of follow-up, particularly the progression in migration beyond 2 years postoperatively. METHODS: Seventy-two patients were randomized to a cementless 3D-printed Triathlon Tritanium (Stryker) cruciate-retaining (CR) TKA or a cemented Triathlon CR (Stryker) TKA implant. Implant migration was evaluated with RSA at baseline and postoperatively at 3 months and at 1, 2, and 5 years. The maximum total point motion (MTPM) of the tibial component was compared between the groups at 5 years, and progression in migration was assessed between 2 and 5 years. Individual implants were classified as continuously migrating if the MTPM was ≥0.1 mm/year beyond 2 years postoperatively. Clinical scores were evaluated, and a linear mixed-effects model was used to analyze repeated measurements. RESULTS: At 5 years, the mean MTPM was 0.66 mm (95% confidence interval [CI], 0.56 to 0.78 mm) for the cementless group and 0.53 mm (95% CI, 0.43 to 0.64 mm) for the cemented group (p = 0.09). Between 2 and 5 years, there was no progression in mean MTPM for the cementless group (0.02 mm; 95% CI, -0.06 to 0.10 mm) versus 0.07 mm (95% CI, 0.00 to 0.14) for the cemented group. One implant was continuously migrating in the cementless group, and 4 were continuously migrating in the cemented group. The clinical scores were comparable between the groups across the entire time of follow-up. CONCLUSIONS: No significant difference in mean migration was found at 5 years between the cementless and cemented TKA implants. Progression of tibial component migration was present beyond 2 years for the cemented implant, whereas the cementless implant remained stable after initial early migration. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/métodos , Análise Radioestereométrica/métodos , Osteoartrite do Joelho/cirurgia , Cimentos Ósseos/uso terapêutico , Impressão Tridimensional , Falha de Prótese , Desenho de Prótese , Resultado do Tratamento
11.
Knee ; 38: 91-106, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35964436

RESUMO

BACKGROUND: Considerable interindividual variation in meniscal microvascularization has been reported. The purpose of this review was to identify which patient characteristics affect meniscal microvascularization and provide a structured overview of angiogenic therapies that influence meniscal neovascularization. METHODS: A systematic literature search was undertaken using PubMed, Embase, Web of Science, Cochrane library and Emcare from inception to November 2021. Studies reporting on (1) Patient characteristics that affect meniscal microvascularization, or (2) Therapies that induce neovascularization in meniscal tissue were included. Studies were graded in quality using the Anatomical Quality Assessment (AQUA) tool. The study was registered with PROSPERO(ID:CRD42021242479). RESULTS: Thirteen studies reported on patient characteristics and eleven on angiogenic therapies. The influence of Age, Degenerative knee, Gender, and Race was reported. Age is the most studied factor. The entire meniscus is vascularized around birth. With increasing age, vascularization decreases from the inner to the peripheral margin. Around 11 years, blood vessels are primarily located in the peripheral third of the menisci. There seems to be a further decrease in vascularization with increasing age in adults, yet conflicting literature exists. Degenerative changes of the knee also seem to influence meniscal vascularization, but evidence is limited. Angiogenic therapies to improve meniscal vascularization have only been studied in preclinical setting. The use of synovial flap transplantation, stem cell therapy, vascular endothelial growth factor, and angiogenin has shown promising results. CONCLUSION: To decrease failure rates of meniscal repair, a better understanding of patient-specific vascular anatomy is essential. Translational clinical research is needed to investigate the clinical value of angiogenic therapies.


Assuntos
Menisco , Lesões do Menisco Tibial , Adulto , Humanos , Meniscectomia/métodos , Meniscos Tibiais/cirurgia , Microvasos , Lesões do Menisco Tibial/cirurgia , Fator A de Crescimento do Endotélio Vascular
12.
Microb Ecol ; 58(1): 23-35, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19381712

RESUMO

Microbial community composition was examined in two soil types, Anthrosols and adjacent soils, sampled from three locations in the Brazilian Amazon. The Anthrosols, also known as Amazonian dark earths, are highly fertile soils that are a legacy of pre-Columbian settlement. Both Anthrosols and adjacent soils are derived from the same parent material and subject to the same environmental conditions, including rainfall and temperature; however, the Anthrosols contain high levels of charcoal-like black carbon from which they derive their dark color. The Anthrosols typically have higher cation exchange capacity, higher pH, and higher phosphorus and calcium contents. We used culture media prepared from soil extracts to isolate bacteria unique to the two soil types and then sequenced their 16S rRNA genes to determine their phylogenetic placement. Higher numbers of culturable bacteria, by over two orders of magnitude at the deepest sampling depths, were counted in the Anthrosols. Sequences of bacteria isolated on soil extract media yielded five possible new bacterial families. Also, a higher number of families in the bacteria were represented by isolates from the deeper soil depths in the Anthrosols. Higher bacterial populations and a greater diversity of isolates were found in all of the Anthrosols, to a depth of up to 1 m, compared to adjacent soils located within 50-500 m of their associated Anthrosols. Compared to standard culture media, soil extract media revealed diverse soil microbial populations adapted to the unique biochemistry and physiological ecology of these Anthrosols.


Assuntos
Bactérias/genética , Bactérias/isolamento & purificação , Microbiologia do Solo , Bactérias/classificação , Brasil , Meios de Cultura , DNA Bacteriano/genética , Filogenia , Polimorfismo de Fragmento de Restrição , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Solo/análise , Clima Tropical
14.
J Microbiol Methods ; 75(1): 55-63, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18584903

RESUMO

The analysis of T-RFLP data has developed considerably over the last decade, but there remains a lack of consensus about which statistical analyses offer the best means for finding trends in these data. In this study, we empirically tested and theoretically compared ten diverse T-RFLP datasets derived from soil microbial communities using the more common ordination methods in the literature: principal component analysis (PCA), nonmetric multidimensional scaling (NMS) with Sørensen, Jaccard and Euclidean distance measures, correspondence analysis (CA), detrended correspondence analysis (DCA) and a technique new to T-RFLP data analysis, the Additive Main Effects and Multiplicative Interaction (AMMI) model. Our objectives were i) to determine the distribution of variation in T-RFLP datasets using analysis of variance (ANOVA), ii) to determine the more robust and informative multivariate ordination methods for analyzing T-RFLP data, and iii) to compare the methods based on theoretical considerations. For the 10 datasets examined in this study, ANOVA revealed that the variation from Environment main effects was always small, variation from T-RFs main effects was large, and variation from T-RFxEnvironment (TxE) interactions was intermediate. Larger variation due to TxE indicated larger differences in microbial communities between environments/treatments and thus demonstrated the utility of ANOVA to provide an objective assessment of community dissimilarity. The comparison of statistical methods typically yielded similar empirical results. AMMI, T-RF-centered PCA, and DCA were the most robust methods in terms of producing ordinations that consistently reached a consensus with other methods. In datasets with high sample heterogeneity, NMS analyses with Sørensen and Jaccard distance were the most sensitive for recovery of complex gradients. The theoretical comparison showed that some methods hold distinct advantages for T-RFLP analysis, such as estimations of variation captured, realistic or minimal assumptions about the data, reduced weight placed on rare T-RFs, and uniqueness of solutions. Our results lead us to recommend that method selection be guided by T-RFLP dataset complexity and the outlined theoretical criteria. Finally, we recommend using binary or relativized peak height data with soil-based T-RFLP data for ordination-based exploratory microbial analyses.


Assuntos
Impressões Digitais de DNA/métodos , Polimorfismo de Fragmento de Restrição , Microbiologia do Solo , Estatística como Assunto/normas , Impressões Digitais de DNA/estatística & dados numéricos , Análise Multivariada , Projetos de Pesquisa
15.
J Control Release ; 286: 439-450, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30110616

RESUMO

Low back pain, related to degeneration of the intervertebral disc (IVD), affects millions of people worldwide. Clinical studies using oral cyclooxygenase-2 (COX-2) inhibitors have shown beneficial effects, although side-effects were reported. Therefore, intradiscal delivery of nonsteroidal anti-inflammatory drugs can be an alternative treatment strategy to halt degeneration and address IVD-related pain. In the present study, the controlled release and biologic potency of celecoxib, a selective COX-2 inhibitor, from polyesteramide microspheres was investigated in vitro. In addition, safety and efficacy of injection of celecoxib-loaded microspheres were evaluated in vivo in a canine IVD degeneration model. In vitro, a sustained release of celecoxib was noted for over 28 days resulting in sustained inhibition of inflammation, as indicated by decreased prostaglandin E2 (PGE2) production, and anti-catabolic effects in nucleus pulposus (NP) cells from degenerated IVDs on qPCR. In vivo, there was no evidence of adverse effects on computed tomography and magnetic resonance imaging or macroscopic evaluation of IVDs. Local and sustained delivery of celecoxib prevented progression of IVD degeneration corroborated by MRI, histology, and measurement of NP proteoglycan content. Furthermore, it seemed to harness inflammation as indicated by decreased PGE2 tissue levels and decreased neuronal growth factor immunopositivity, providing indirect evidence that local delivery of a COX-2 inhibitor could also address pain related to IVD degeneration. In conclusion, intradiscal controlled release of celecoxib from polyesteramide microspheres prevented progression of IVD degeneration both in vitro and in vivo. Follow-up studies are warranted to determine the clinical efficacy of celecoxib-loaded PEAMs in chronic back pain.


Assuntos
Celecoxib/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Preparações de Ação Retardada/química , Degeneração do Disco Intervertebral/tratamento farmacológico , Poliésteres/química , Animais , Celecoxib/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Modelos Animais de Doenças , Progressão da Doença , Cães , Sistemas de Liberação de Medicamentos , Injeções Espinhais , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Masculino , Microesferas
16.
Drug Deliv ; 25(1): 1438-1447, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29890922

RESUMO

Major hallmarks of osteoarthritis (OA) are cartilage degeneration, inflammation and osteophyte formation. COX-2 inhibitors counteract inflammation-related pain, but their prolonged oral use entails the risk for side effects. Local and prolonged administration in biocompatible and degradable drug delivery biomaterials could offer an efficient and safe treatment for the long-term management of OA symptoms. Therefore, we evaluated the disease-modifying effects and the optimal dose of polyesteramide microspheres delivering the COX-2 inhibitor celecoxib in a rat OA model. Four weeks after OA induction by anterior cruciate ligament transection and partial medial meniscectomy, 8-week-old female rats (n = 6/group) were injected intra-articular with celecoxib-loaded microspheres at three dosages (0.03, 0.23 or 0.39 mg). Unloaded microspheres served as control. During the 16-week follow-up, static weight bearing and plasma celecoxib concentrations were monitored. Post-mortem, micro-computed tomography and knee joint histology determined progression of synovitis, osteophyte formation, subchondral bone changes, and cartilage integrity. Systemic celecoxib levels were below the detection limit 6 days upon delivery. Systemic and local adverse effects were absent. Local delivery of celecoxib reduced the formation of osteophytes, subchondral sclerosis, bone cysts and calcified loose bodies, and reduced synovial inflammation, while cartilage histology was unaffected. Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA.


Assuntos
Osso e Ossos/diagnóstico por imagem , Celecoxib/farmacologia , Cistos/tratamento farmacológico , Preparações de Ação Retardada/farmacologia , Inflamação/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Animais , Ligamento Cruzado Anterior/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Modelos Animais de Doenças , Feminino , Osteófito/tratamento farmacológico , Ratos
17.
J Microbiol Methods ; 69(2): 256-67, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17343936

RESUMO

Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of digested genomic DNA has been previously used in comparative genomics studies of closely related bacteria species. However, a two-dimensional gel electrophoresis approach for examining microbial community structures in environmental samples has not yet been developed. We determined that it is theoretically possible to separate internal transcribed spacer regions (ITS) of bacterial communities into hundreds of operational taxonomic units (OTUs) using 2D-PAGE. Application of 2D-PAGE for separating Bacterial ITS sequences that have been PCR-amplified from replicate soil samples taken from along a Zn gradient resulted in reproducible gels containing hundreds of spots. Clear differences in spot patterns were observed between soil samples that differed in both sampling location and Zn content. The number of OTUs detected using 2D-PAGE of ITS regions was much greater than that observed using Automated Ribosomal Internal Transcribed Spacer Analysis (ARISA), Terminal Restriction Fragment Length Polymorphism (T-RFLP), or Denaturing Gradient Gel Electrophoresis (DGGE). Principal Component Analysis (PCA) of community spot patterns resulted in similar groupings of samples as those obtained using other molecular methods, however, excised spots were found to contain a far lower diversity of different sequences than excised ITS bands of the same length, as determined by RFLP analysis of excision clone libraries and subsequent sequencing of DNA eluted from excised spots. This increase in resolution makes 2D-PAGE of Bacteria ITS fragments from complex microbial communities a viable method for detecting differences between highly similar communities, as well as in streamlining follow-on sequencing efforts by reducing the level of homoplasy (co-migration of heterogeneous sequences) often seen in band-based community fingerprinting methods.


Assuntos
Bactérias/isolamento & purificação , DNA Espaçador Ribossômico/análise , Eletroforese em Gel Bidimensional/métodos , Microbiologia do Solo , Bactérias/genética , Sequência de Bases , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Ecossistema , Dados de Sequência Molecular , Filogenia , Polimorfismo de Fragmento de Restrição , Análise de Componente Principal , Alinhamento de Sequência , Análise de Sequência de DNA , Solo/análise , Zinco/análise
18.
J Nematol ; 39(4): 327-32, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19259507

RESUMO

Meloidogyne mayaguensis is a damaging root-knot nematode able to reproduce on root-knot nematode-resistant tomato and other economically important crops. In a growth chamber experiment conducted at 22 and 33 degrees C, isolate 1 of M. mayaguensis reproduced at both temperatures on the Mi-1-carrying tomato lines BHN 543 and BHN 585, whereas M. incognita race 4 failed to reproduce at 22 degrees C, but reproduced well at 33 degrees C. These results were confirmed in another experiment at 26 +/- 1.8 degrees C, where minimal or no reproduction of M. incognita race 4 was observed on the Mi-1-carrying tomato genotypes BHN 543, BHN 585, BHN 586 and 'Sanibel', whereas heavy infection and reproduction of M. mayaguensis isolate 1 occurred on these four genotypes. Seven additional Florida M. mayaguensis isolates also reproduced on resistant 'Sanibel' tomato at 26 +/- 1.8 degrees C. Isolate 3 was the most virulent, with reproduction factor (Rf) equal to 8.4, and isolate 8 was the least virulent (Rf = 2.1). At 24 degrees C, isolate 1 of M. mayaguensis also reproduced well (Rf >/= 1) and induced numerous small galls and large egg masses on the roots of root-knot nematode-resistant bell pepper 'Charleston Belle' carrying the N gene and on three root-knot nematode-resistant sweet pepper lines (9913/2, SAIS 97.9001 and SAIS 97.9008) carrying the Tabasco gene. In contrast, M. incognita race 4 failed to reproduce or reproduced poorly on these resistant pepper genotypes. The ability of M. mayaguensis isolates to overcome the resistance of tomato and pepper genotypes carrying the Mi-1, N and Tabasco genes limits the use of resistant cultivars to manage this nematode species in infested tomato and pepper fields in Florida.

19.
Med Phys ; 43(3): 1235-48, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26936708

RESUMO

PURPOSE: To allow for a purely image-based motion estimation and compensation in weight-bearing cone-beam computed tomography of the knee joint. METHODS: Weight-bearing imaging of the knee joint in a standing position poses additional requirements for the image reconstruction algorithm. In contrast to supine scans, patient motion needs to be estimated and compensated. The authors propose a method that is based on 2D/3D registration of left and right femur and tibia segmented from a prior, motion-free reconstruction acquired in supine position. Each segmented bone is first roughly aligned to the motion-corrupted reconstruction of a scan in standing or squatting position. Subsequently, a rigid 2D/3D registration is performed for each bone to each of K projection images, estimating 6 × 4 × K motion parameters. The motion of individual bones is combined into global motion fields using thin-plate-spline extrapolation. These can be incorporated into a motion-compensated reconstruction in the backprojection step. The authors performed visual and quantitative comparisons between a state-of-the-art marker-based (MB) method and two variants of the proposed method using gradient correlation (GC) and normalized gradient information (NGI) as similarity measure for the 2D/3D registration. RESULTS: The authors evaluated their method on four acquisitions under different squatting positions of the same patient. All methods showed substantial improvement in image quality compared to the uncorrected reconstructions. Compared to NGI and MB, the GC method showed increased streaking artifacts due to misregistrations in lateral projection images. NGI and MB showed comparable image quality at the bone regions. Because the markers are attached to the skin, the MB method performed better at the surface of the legs where the authors observed slight streaking of the NGI and GC methods. For a quantitative evaluation, the authors computed the universal quality index (UQI) for all bone regions with respect to the motion-free reconstruction. The authors quantitative evaluation over regions around the bones yielded a mean UQI of 18.4 for no correction, 53.3 and 56.1 for the proposed method using GC and NGI, respectively, and 53.7 for the MB reference approach. In contrast to the authors registration-based corrections, the MB reference method caused slight nonrigid deformations at bone outlines when compared to a motion-free reference scan. CONCLUSIONS: The authors showed that their method based on the NGI similarity measure yields reconstruction quality close to the MB reference method. In contrast to the MB method, the proposed method does not require any preparation prior to the examination which will improve the clinical workflow and patient comfort. Further, the authors found that the MB method causes small, nonrigid deformations at the bone outline which indicates that markers may not accurately reflect the internal motion close to the knee joint. Therefore, the authors believe that the proposed method is a promising alternative to MB motion management.


Assuntos
Artefatos , Tomografia Computadorizada de Feixe Cônico , Imageamento Tridimensional/métodos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiologia , Movimento , Humanos , Suporte de Carga
20.
J Med Chem ; 33(2): 789-808, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1688947

RESUMO

A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.


Assuntos
Anticonvulsivantes/síntese química , Ácido Aspártico/análogos & derivados , Iminas/síntese química , Compostos Policíclicos/síntese química , Receptores de Neurotransmissores/efeitos dos fármacos , Animais , Ácido Aspártico/antagonistas & inibidores , Ligação Competitiva , Córtex Cerebral/metabolismo , Fenômenos Químicos , Química , Desenho de Fármacos , Iminas/farmacologia , Técnicas In Vitro , Canais Iônicos/efeitos dos fármacos , Modelos Moleculares , N-Metilaspartato , Compostos Policíclicos/farmacologia , Ratos , Ratos Endogâmicos , Receptores de N-Metil-D-Aspartato , Termodinâmica
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