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1.
Stem Cells Int ; 2022: 5394441, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440184

RESUMO

Background: Intra-articular bone marrow concentrate (BMC) and aspirate (BMA) injections have been used with mixed results to treat osteoarthritis (OA). Given the various aspiration and concentration methods available for preparing bone marrow, more data are needed to identify the optimal bone marrow harvesting techniques to treat OA. Methods: This retrospective cohort study examined the effect of using low-volume BMAs harvested using the Marrow Cellution™ (MC) device on 160 patients (262 knees) suffering from pain due to knee OA, KL grades 2-4, that did not respond to conservative treatment. Changes in visual analog scores (VAS) for overall daily activity were examined over a six-month time frame in these patients (63.5 ± 0.97 years of age; 48.1% male). In addition, changes in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Patient Global Impression of Change (PGIC scores) were examined over the same time frame in a smaller subset of patients (95 patients including 172 knees). Results: There was a statistically significant improvement in VAS scores for overall daily activity 6 months postprocedure in the study population, 7.29 ± 0.27 vs. 3.76 ± 0.34 (p < 0.0001), as well as statistically significant improvements in WOMAC scores, 49.3 ± 4.27 vs. 66.3 ± 4.08 (p < 0.0001). On the individual level, 71% of the cases displayed VAS improvements and 61% of the cases displayed WOMAC improvements that exceeded levels previous studies determined to be the minimal clinically important difference (MCID) for knee OA treatments. The improvements in WOMAC scores were also seen in both the WOMAC pain subscore, 52.2 ± 4.39 vs. 72.2 ± 4.36 (p < 0.0001) and the WOMAC function subscore, 51.6 ± 4.67 vs. 69.0 ± 4.36 (p < 0.0001). In addition, the PGIC scores measuring patient satisfaction improved from 4.03 ± 0.26 at 6 weeks postprocedure to 4.65 ± 0.28 at 6 months postprocedure (p < 0.0001). Conclusions: Knee OA patients treated with MC BMA intra-articular injections exhibited significant reductions in VAS pain scores and significant improvements in WOMAC scores that exceeded the minimal clinically important difference thresholds. In addition, reductions in VAS pain scores and improvements in WOMAC scores correlated with higher PGIC scores.

2.
Vaccines (Basel) ; 10(10)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36298625

RESUMO

The COVID-19 pandemic has revealed a crucial need for rapid, straightforward collection and testing of biological samples. Serological antibody assays can analyze patient blood samples to confirm immune response following mRNA vaccine administration or to verify past exposure to the SARS-CoV-2 virus. While blood tests provide vital information for clinical analysis and epidemiology, sample collection is not trivial; this process requires a visit to the doctor's office, a professionally trained phlebotomist to draw several milliliters of blood, processing to yield plasma or serum, and necessitates appropriate cold chain storage to preserve the specimen. A novel whole blood collection kit (truCOLLECT) allows for a lancet-based, decentralized capillary blood collection of metered low volumes and eliminates the need for refrigerated transport and storage through the process of active desiccation. Anti-SARS-CoV-2 spike (total and neutralizing) and nucleocapsid protein antibody titers in plasma samples obtained via venipuncture were compared to antibodies extracted from desiccated whole blood using Adaptive Focused Acoustics (AFA). Paired plasma versus desiccated blood extracts yields Pearson correlation coefficients of 0.98; 95% CI [0.96, 0.99] for anti-SARS-CoV-2 spike protein antibodies, 0.97; 95% CI [0.95, 0.99] for neutralizing antibodies, and 0.97; 95% CI [0.94, 0.99] for anti-SARS-CoV-2 nucleocapsid protein antibodies. These data suggest that serology testing using desiccated and stabilized whole blood samples can be a convenient and cost-effective alternative to phlebotomy.

3.
Emerg Microbes Infect ; 11(1): 250-259, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34951566

RESUMO

Testing and vaccination have been major components of the strategy for combating the ongoing COVID-19 pandemic. In this study, we have developed a quantitative anti-SARS-CoV-2 spike (S1) IgG antibody assay using a fingerstick dried blood sample. We evaluated the feasibility of using this high-throughput and quantitative anti-SARS-CoV-2 spike (S1) IgG antibody testing assay in vaccinated individuals. Fingerstick blood samples were collected and analyzed from 137 volunteers before and after receiving the Moderna or Pfizer mRNA vaccine. Anti-SARS-CoV-2 S1 IgG antibody could not be detected within the first 7 days after receiving the first vaccine dose, however, the assay reliably detected antibodies from day 14 onwards. In addition, no anti-SARS-CoV-2 nucleocapsid (N) protein IgG antibody was detected in any of the vaccinated or healthy participants, indicating that the anti-SARS-CoV-2 S1 IgG assay is specific for the mRNA vaccine-induced antibodies. The S1 IgG levels detected in fingerstick samples correlated with the levels found in venous blood plasma samples and with the efficacy of venous blood plasma samples in the plaque reduction neutralization test (PRNT). The assay displayed a limit of quantification (LOQ) of 0.59 µg/mL and was found to be linear in the range of 0.51-1000 µg/mL. Finally, its clinical performance displayed a Positive Percent Agreement (PPA) of 100% (95% CI: 0.89-1.00) and a Negative Percent Agreement (NPA) of 100% (95% CI: 0.93-1.00). In summary, the assay described here represents a sensitive, precise, accurate, and simple method for the quantitative detection and monitoring of post-vaccination anti-SARS-CoV-2 spike IgG responses.


Assuntos
Teste Sorológico para COVID-19/métodos , Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Ensaios de Triagem em Larga Escala/métodos , Imunoensaio/métodos , SARS-CoV-2/imunologia , Manejo de Espécimes/métodos , Anticorpos Antivirais/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Glicoproteína da Espícula de Coronavírus , Vacinação
4.
Epilepsy Res ; 155: 106153, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31260938

RESUMO

OBJECTIVE: To investigate the effect that a diet supplemented with KetoCal 4:1, a commercially available dietary formula consisting of a 4:1 ratio of fats to carbohydrates plus proteins, had on the seizure-like activity (SLA) and paralysis normally exhibited by the Drosophila Bang-sensitive (BS) paralytic mutants following mechanical shock. METHODS: Given that dietary changes are known to reduce seizures in humans and animal models, three BS mutants, easily-shocked (eas), bang-senseless (parabss), and technical knockout (tko), were fed a standard cornmeal/yeast/sugar diet supplemented with 10% KetoCal 4:1 (KetoCal-sup diet). Newly eclosed BS flies were fed this diet for 3-7 days and the effect this had on SLA, paralysis, locomotor activity, triglyceride levels, and glucose levels was examined. RESULTS: All three genotypes displayed significant reductions in SLA and BS sensitivity following mechanical shock. After only 3 days on the diet, 95% of tko flies no longer exhibited SLA or paralysis, and near complete suppression of the BS phenotype was seen by day 7. In the case of eas, there was a 78% reduction of SLA after 3 days on the diet and SLA was completely suppressed by day 7. The parabss flies showed a similar but less robust reduction of SLA on the diet as there was only a 68% reduction of SLA and paralysis following 7 days on the diet. The diet did not suppress activity globally as tko flies had increased basal locomotor activity on the diet while the parabss and eas flies showed no significant change in basal activity. The KetoCal-sup diet did not significantly alter the triglyceride levels or the total glucose levels in the BS mutants. In addition, the SLA and BS suppression was maintained even when the BS mutants were transitioned back to a standard fly diet. CONCLUSIONS: The SLA and paralysis associated with the Drosophila BS phenotype can be effectively suppressed by transient exposure to a KetoCal-sup diet. This suppression was not dependent upon long term maintenance of the diet and it was not associated with alterations in total glucose or triglyceride levels in these flies.


Assuntos
Dieta Cetogênica/métodos , Locomoção , Paralisia/dietoterapia , Convulsões/dietoterapia , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Drosophila melanogaster , Genótipo , Masculino , Fenótipo , Resultado do Tratamento
5.
J Transl Med ; 17(1): 10, 2019 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-30611285

RESUMO

BACKGROUND: This study examined the quality of bone marrow aspirates extracted using a novel, FDA cleared method to optimally target cells from the inner cortical iliac bone surface without the need for centrifugation. This method employs small draws from a single puncture that promote only lateral flow from multiple sites (SSLM method). The study utilized the Marrow Cellutions bone marrow aspiration system (MC system) which is based on the SSLM method and compared the MC system directly to bone marrow concentrates (BMAC) generated by centrifugation of aspirates harvested with a standard aspiration needle. METHODS: Three direct comparisons were conducted evaluating the SSLM draws and BMACs derived from the same patient from contralateral iliac crests. The levels of TNCs/mL, CD34+ cells/mL, CD117+ cells/mL, and CFU-f/mL were compared between the various bone marrow preparations. The cellular content of a series of SSLM draws was also analyzed to determine the total nucleated cell (TNC) count and the concentration of mesenchymal stem/progenitor cells as measured by colony forming unit fibroblasts (CFU-f). RESULTS: In direct comparisons with BMAC systems, SSLM draws yielded significantly higher CFU-f concentrations and comparable concentrations of CD34+ and CD117+ cells. In addition, the average quantity of TNCs/mL in a series of 30 patients utilizing the SSLM draw was 35.2 × 106 ± 17.1 × 106 and the average number of CFU-f/mL was 2885 ± 1716. There were small but significant correlations between the TNCs/mL and the CFU-fs/mL using the SSLM method as well as between the age of the patient and the CFU-fs/mL. CONCLUSIONS: The MC Device, using the SSLM draw technique, produced concentrations of CFU-fs, CD34+ cells and CD117+ cells that were comparable or greater to BMACs derived from the same patient. Given the rapid speed and simplicity of the MC Device, we believe this novel system possesses significant practical advantages to other currently available centrifugation based systems.


Assuntos
Células da Medula Óssea/citologia , Separação Celular/métodos , Células-Tronco Mesenquimais/citologia , Contagem de Células , Núcleo Celular/metabolismo , Centrifugação , Ensaio de Unidades Formadoras de Colônias , Humanos , Sucção
6.
J Biomed Mater Res B Appl Biomater ; 106(8): 2731-2740, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29437272

RESUMO

There are a wide variety of extracellular matrices that can be used for regenerative purposes. Placental tissue-based matrices are quickly becoming an attractive option given the availability of the tissue source and the wide variety of bioactive molecules knows to exist in unprocessed placental tissues. As fresh placental tissues are seldom an option at the point of care, we examined both the composition and bioactivity of a commercially packaged flowable placental connective tissue matrix (FPTM) (BioECM® , Skye Biologics, Inc.) that was preserved by the proprietary HydraTek® process. The FPTM contained significant amounts of collagen and various growth factors such as bFGF, EGF, PDGF, KGF, and PIGF. In addition, it contained high levels of tissue inhibitors of metalloproteinases (TIMP-1 and 2) and molecules known to modulate the immune response including TGF-ß and IL-4. In terms of its bioactivity, the FPTM displayed the ability (1) to suppress INF-γ secretion in activated T-cells nearly fourfold over control media, (2) to inhibit methicillin resistant Staphylococcus aureus (MRSA) and Staphylococcus saprophyticus proliferation, (3) to increase the migration of adipose-derived stem cells (ASCs) nearly threefold over control media and (4) to adhere to ASCs in culture. When ASCs were exposed to FPTM in culture, the cells maintained healthy morphology and showed no significant changes in the expression of five genes involved in tissue growth and repair as compared to culture in standard growth media. © 2018 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2731-2740, 2018.


Assuntos
Tecido Adiposo/imunologia , Proliferação de Células , Matriz Extracelular/química , Placenta/química , Preservação Biológica , Células-Tronco/imunologia , Tecido Adiposo/citologia , Técnicas de Cultura de Células , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Gravidez , Staphylococcus aureus/imunologia , Staphylococcus saprophyticus/imunologia , Células-Tronco/citologia
7.
Stem Cells Int ; 2016: 7183734, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26823671

RESUMO

The administration of human adipose-derived stem cells (ASCs) represents a promising regenerative therapy for the treatment of orthopedic injuries. While ASCs can be easily isolated from liposuction-derived adipose tissue, most clinical applications will likely require in vitro culture expansion of these cells using nonxenogeneic components. In this study, platelet releasate was generated using a novel rapid thrombin activation method (tPR). ASCs grown in media supplemented with tPR proliferated much faster than ASCs grown in media supplemented with 10% fetal bovine serum. The cells also retained the ability to differentiate along chondrogenic, adipogenic, and osteogenic lineages. The tPR cultured ASCs displayed elevated expression of BMP-4 (5.7 ± 0.97-fold increase) and BMP-2 (4.7 ± 1.3-fold increase) and decreased expression of PDGF-B (4.0 ± 1.4-fold decrease) and FGF-2 (33 ± 9.0-fold decrease). No significant changes in expression were seen with TGF-ß and VEGF. This pattern of gene expression was consistent across different allogeneic tPR samples and different ASC lines. The use of allogeneic rapidly activated tPR to culture ASCs is associated with both an increased cell yield and a defined gene expression profile making it an attractive option for cell expansion prior to cell-based therapy for orthopedic applications.

8.
J Vis Exp ; (84): e51460, 2014 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-24637378

RESUMO

Video tracking systems have been used widely to analyze Drosophila melanogaster movement and detect various abnormalities in locomotive behavior. While these systems can provide a wealth of behavioral information, the cost and complexity of these systems can be prohibitive for many labs. We have developed a low-cost assay for measuring locomotive behavior and seizure movement in D. melanogaster. The system uses a web-cam to capture images that can be processed using a combination of inexpensive and free software to track the distance moved, the average velocity of movement and the duration of movement during a specified time-span. To demonstrate the utility of this system, we examined a group of D. melanogaster mutants, the Bang-sensitive (BS) paralytics, which are 3-10 times more susceptible to seizure-like activity (SLA) than wild type flies. Using this novel system, we were able to detect that the BS mutant bang senseless (bss) exhibits lower levels of exploratory locomotion in a novel environment than wild type flies. In addition, the system was used to identify that the drug metformin, which is commonly used to treat type II diabetes, reduces the intensity of SLA in the BS mutants.


Assuntos
Comportamento Animal/fisiologia , Drosophila melanogaster/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Gravação em Vídeo/métodos , Animais , Locomoção/fisiologia , Atividade Motora/fisiologia , Convulsões/fisiopatologia , Software
9.
Brain Res ; 1496: 94-103, 2013 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-23247062

RESUMO

There is increasing evidence that alterations in metabolism can affect seizure susceptibility in a wide range of organisms. In order to investigate the link between metabolism and seizures, we took advantage of a group of Drosophila mutants, the Bang-sensitive (BS) paralytics, which are 3-10 times more susceptible to seizure-like activity (SLA) than wild type flies following a variety of stimuli including mechanical shock. To alter metabolism, we introduced the atsugari (atu) mutation into three of the BS mutants, easily shocked (eas), bang senseless (bss), and technical knockout (tko). The atu mutants, which exhibit reduced expression of the Drosophila ortholog of dystroglycan gene, have previously been shown to have a higher metabolic rate than wild type flies. Following mechanical shock, all three BS;atu double mutants displayed a reduction in SLA and the eas;atu and tko;atu double mutants recovered from the shock quicker than the respective single mutant BS flies. In addition, the eas;atu and tko;atu flies displayed higher levels of metabolism as compared to the single mutant BS flies. To further study the correlation between metabolism and seizure susceptibility, the three BS strains were fed a sulfonylurea drug (tolbutamide) known to both increase heamolymph glucose concentrations and stimulate lipid metabolism in flies. Following mechanical shock, the eas and tko mutants fed tolbutamide displayed less SLA and recovered quicker than unfed flies. While the bss mutants fed tolbutamide did not display a reduction in SLA, they did recover quicker than unfed controls. These data indicate that the upregulation of metabolism can have a protective effect against seizure susceptibility, a result that suggests new avenues for possible drug development.


Assuntos
Proteínas de Drosophila/genética , Hipoglicemiantes/uso terapêutico , Mutação/genética , Convulsões , Estresse Mecânico , Tolbutamida/uso terapêutico , Animais , Animais Geneticamente Modificados , Dióxido de Carbono/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Drosophila , Locomoção/efeitos dos fármacos , Locomoção/genética , Masculino , Estimulação Física/efeitos adversos , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/genética , Convulsões/etiologia , Convulsões/genética , Convulsões/terapia , Estatísticas não Paramétricas , Fatores de Tempo
10.
Brain Res ; 1316: 120-8, 2010 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-20034480

RESUMO

Human seizure disorders represent a heterogeneous collection of neuropathies, many of which are poorly understood. To investigate the etiology of seizure disorders, we have used a group of Drosophila mutants known as the bang-sensitive (BS) paralytics. The BS mutants exhibit seizure-like activity (SLA) following a wide variety of insults including mechanical shock, electrical shock, high frequency light and cold temperatures. In this study, we show that two novel insults, hypoxia and hypercapnia (elevated CO(2) levels) are potent triggers of SLA in a number of the BS mutants. We also show that both of these insults, hypoxia and hypercapnia, can trigger SLA in wild-type flies as well. However, we find that the BS mutants are more susceptible than wild-type flies to these insults as they exhibit more SLA following these insults and, in the case of hypercapnia, they exhibit SLA at a lower threshold. In addition, we demonstrate that the BS mutants are more susceptible to the anesthetizing effects of CO(2) as compared to wild-type flies. The increased sensitivity to both hypoxia and hypercapnia in these BS mutants suggests possible physiological defects that may underlie seizure susceptibility.


Assuntos
Hipercapnia/fisiopatologia , Hipóxia/fisiopatologia , Convulsões/fisiopatologia , Doença Aguda , Anestésicos/farmacologia , Animais , Animais Geneticamente Modificados , Dióxido de Carbono/metabolismo , Dióxido de Carbono/farmacologia , Drosophila , Mutação , Dor/tratamento farmacológico , Dor/fisiopatologia , Especificidade da Espécie , Fatores de Tempo
11.
Brain Res ; 958(1): 36-42, 2002 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-12468028

RESUMO

Despite the frequency of seizure disorders in the human population, the genetic basis for these defects remains largely unclear. Currently, only a fraction of the epilepsies can be linked conclusively to a genetic determinant. In addition, a significant number of epileptics do not respond to the current anticonvulsant therapies. We have turned to Drosophila as a model to address these problems and have identified genetic mutants that are more sensitive to seizures, bang-sensitive (BS) mutants, such as slamdance (sda), bangsenseless (bss) and easily shocked (eas), as well as mutants that are resistant to seizures, such as paralytic, maleless(napts), shaking-B(2) and Shaker. Here, we have developed a new method for evaluating compounds with anticonvulsant activity. The methodology uses Drosophila BS mutants to assay the ability of compounds to suppress the seizure susceptible phenotype normally seen in the BS mutants. To test the effectiveness of this method, two BS mutant strains were administered the anticonvulsant valproate and in both cases the drug was able to suppress seizures. The Drosophila system provides a potentially powerful way of developing and testing new drugs with anticonvulsant properties.


Assuntos
Anticonvulsivantes/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Predisposição Genética para Doença/genética , Mutação/efeitos dos fármacos , Convulsões/tratamento farmacológico , Ácido Valproico/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Estimulação Elétrica , Epilepsia/genética , Epilepsia/fisiopatologia , Genótipo , Humanos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Mutação/genética , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/metabolismo , Sistema Nervoso/fisiopatologia , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Convulsões/genética , Convulsões/fisiopatologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia
12.
Genetics ; 162(3): 1283-99, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12454073

RESUMO

We report here the characterization of slamdance (sda), a Drosophila melanogaster "bang-sensitive" (BS) paralytic mutant. This mutant exhibits hyperactive behavior and paralysis following a mechanical "bang" or electrical shock. Electrophysiological analyses have shown that this mutant is much more prone to seizure episodes than normal flies because it has a drastically lowered seizure threshold. Through genetic mapping, molecular cloning, and RNA interference, we have demonstrated that the sda phenotype can be attributed to a mutation in the Drosophila homolog of the human aminopeptidase N (APN) gene. Furthermore, using mRNA in situ hybridization and LacZ staining, we have found that the sda gene is expressed specifically in the central nervous system at particular developmental stages. Together, these results suggest that the bang sensitivity in sda mutants is caused by a defective APN gene that somehow increases seizure susceptibility. Finally, by using the sda mutation as a sensitized background, we have been able to identify a rich variety of sda enhancers and other independent BS mutations.


Assuntos
Aminopeptidases/genética , Drosophila/genética , Proteínas de Insetos/genética , Sequência de Aminoácidos , Aminopeptidases/metabolismo , Animais , Sequência de Bases , Northern Blotting , Drosophila/metabolismo , Elementos Facilitadores Genéticos , Genes Reporter , Hibridização In Situ , Proteínas de Insetos/metabolismo , Dados de Sequência Molecular , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/metabolismo , Interferência de RNA , RNA Mensageiro
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