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Flor Bertolini, Gladson Ricardo. "Crioterapia como fator interveniente na dor muscular de início tardio." Revista Brasileira de Fisiologia do Exercício 13, no. 4 (2014): 197. http://dx.doi.org/10.33233/rbfe.v13i4.136.
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Este trabalho teve como objetivo investigar, em indivíduos sedentários, a interferência do uso da crioterapia na dor muscular de início tardio. Para tanto, a amostra foi composta por 20 indivíduos, sedentários, divididos em dois grupos: controle (GCO), apenas exercícios; e crioterapia (GCR) exercícios e posterior crioterapia, por 20 minutos, na região de gastrocnêmios mediais. O exercício foi constituído por cinco séries, de vinte repetições cada, de planti/dorsiflexão exercitando o grupo tríceps sural. Ambos os grupos foram avaliados antes do exercício (AV1) e reavaliados após 24 (AV2), 48 (AV3) e 72 (AV4) horas após o exercício, quanto ao seu grau de dor utilizando-se a escala analógica de dor (EVA) e um dolorímetro de pressão. Observou-se pela EVA redução do quadro álgico em AV4, ao comparar com AV2 e AV3, apenas para o grupo tratado. Na avaliação do limiar de pressão, observaram-se diferenças entre os grupos, em AV3 e AV4, tendo o grupo tratado maior limiar. Conclui-se que a crioterapia se mostrou eficaz na melhora da sensação de dor de início tardio em indivíduos sedentários.Palavras-chave: medição da dor, crioterapia, modalidades de fisioterapia.
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Karvat, Jhenifer, Camila M. M. Kakihata, Jéssica A. Malanotte, Daniele Pelissar, Assis R. Escher, and Gladson R. F. Bertolini. "Reduction of joint nociception induced by formalin in rats treated ith low level laser therapy 670 or 830 nm." Medicina (Ribeirao Preto. Online) 48, no. 6 (2015): 533. http://dx.doi.org/10.11606/issn.2176-7262.v48i6p533-538.
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Modelo do estudo: estudo experimental, de caráter transversal. Objetivo: avaliar os efeitos do laser de baixa potência (LBP), com comprimento de onda de 670nm e 820nm, na nocicepção de ratos Wistar submetidos à hipernocicepção articular no joelho direito. Metodologia: foram utilizados 18 ratos Wistar, separados em 3 grupos: G1 – não tratados; G2 – tratados com LBP 670 nm; G3 – tratados com LBP 830 nm. Para a indução da hipernocicepção foi injetado no espaço articular tíbio-femoral 100 µL de formalina 5%. Para avaliar a nocicepção foi utilizado o filamento de von Frey digital, tanto com pressão sobre o joelho, quanto na região plantar; esta avaliação aconteceu: pré-lesão (AV1), após 15 (AV2), 30 (AV3) e 60 (AV4) minutos da indução da hipernocicepção. Para o tratamento com LBP foi usada fluência de 8 J/cm, logo após AV2. Resultados: o limiar de retirada, quando a pressão foi realizada no joelho, mostrou que 670 nm produziu elevação do limiar em AV3 e AV4, retornando para valores semelhantes aos de AV1. Para a região plantar, apenas 830 nm mostrou restauração dos valores em AV4, e foi maior em AV3 ao comparar com o grupo controle. Conclusão: ambos os comprimentos de onda produziram elevação do limiar de retirada da pata, em ratos com hipernocicepção em joelho
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Narayanan Nair, Dhanya, and S. Padmavathy. "Molecular Docking Studies of Phytocompounds from Aloe vera (L.) Burm.f. having Anticancer Property, against an Antiapoptotic Bcl-2 Protein." Biosciences, Biotechnology Research Asia 14, no. 4 (2017): 1449–56. http://dx.doi.org/10.13005/bbra/2590.
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ABSTRACT: B-cell lymphocyte-2 (Bcl-2) is an antiapoptotic protein, which is an important member of Bcl-2 family. The current study involves molecular docking of six antineoplastic phytocompounds from Aloe vera (L.) Burm.f. against the protein Bcl-2. Docetaxel, a known inhibitor of Bcl-2 was used as a control in this study. All the studied phytocompounds bound within the same binding pocket as that of Docetaxel and thus can be considered as potential inhibitors of Bcl-2 protein. Among the six phytocompounds studied, AVG4 showed the best docking result, with a minimum pharmacological energy, -198.9 kcal/mol, followed by AVG6 and AVG3 as the second and third best phytocompound while AVL3 has the maximum pharmacological energy -103.8 kcal/mol. AVL3 is involved in cation-pi interactions with the Tyr9 residue of the Bcl-2 protein which is not considered while calculating pharmacological energy scoring function. Calculation of energy due to cation-pi interactions may result in the increase in total binding energy of AVL3, which may significantly increase the pharmacological energy, EPharma by approximately -8 kcal/mol, resulting in another potential anticancer phytocompound.
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Busatta, Bethina Bernardon, Karoline Calichio Medeiro, Lorrainy Rufino Velozo, et al. "Uso do laser de baixa potência em estrias de distensão: ensaio clínico randomizado controlado." Scientia Medica 28, no. 2 (2018): 28710. http://dx.doi.org/10.15448/1980-6108.2018.2.28710.
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AIMS: To analyze the effects of low-level laser therapy (660nm) in the treatment of striae alba.METHODS: A randomized clinical trial was conducted with 20 women equally divided into a control group and a treatment group. For inclusion, they should have striae alba in the gluteal region and accept to participate in the study. Exclusion criteria were other treatment for striae, pregnancy, steroid use, smoking, cancer diagnosis, hemorrhagic areas on the skin, diagnosis of epilepsy, diagnosis of thrombosis, or any cognitive impairment. Twelve applications of 660 nm laser were performed for four weeks. After another four weeks of follow-up, a reevaluation was performed. After each application, photos were taken from the region to evaluate the size of the striae by means of scanned planimetry, which calculates the percentage of area occupied by the striae. For this evaluation, the photos taken at the first application (AV1), the sixth (AV2), the 12th (AV3) and the last evaluation, after four weeks of treatment completion (AV4), were used. Qualitative evaluations were also performed by touch (depth) and visual inspection (hue and size).RESULTS: The analysis by planimetry showed that there was no difference between the area occupied by the striae when comparing the various evaluations of the same group, until the AV3. However in AV4 (four weeks after the last laser application) of the treatment group, there was a statistically significant decrease of the stria area in relation to AV1. In the control group, there was no difference between AV4 and the other evaluations. In the comparison between the two groups, there was no difference in the first three evaluations. However in AV4 the treatment group showed a smaller area of the striae in relation to the control group. In the qualitative analysis the treated group had lower visibility and less depth of the striae to the touch.CONCLUSIONS: Therapy with 12 sessions of low-level laser for four weeks had a positive effect on the treatment of striae alba, with results becoming evident only four weeks after the last application. The 660 nm laser showed to be a non-invasive, painless and fast-applied method.
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Bertolini, Gladson Ricardo Flor, Taciane Stein da Silva, Adriano Polican Ciena, and Elisângela Lourdes Artifon. "Comparação do ultrassom pulsado e contínuo no reparo tendíneo de ratos." Fisioterapia e Pesquisa 19, no. 3 (2012): 242–47. http://dx.doi.org/10.1590/s1809-29502012000300009.
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No tratamento de lesões tendíneas, o uso do ultrassom surge como possibilidade terapêutica, apesar de lacunas sobre seus efeitos clínicos. O objetivo foi avaliar dois protocolos de ultrassom terapêutico sobre dor e edema após trauma tendíneo. Vinte e um ratos Wistar foram submetidos a trauma no tendão calcâneo e divididos em três grupos: sham (GS); ultrassom contínuo (GUC); e ultrassom pulsado (GUP). O trauma ocorreu sobre a face lateral do tendão calcâneo direito, com energia de 0,40 J. A dor foi avaliada pelo teste de incapacidade funcional e o edema, pelo diâmetro laterolateral. Foram realizadas avaliações previamente à lesão; após 1 hora da indução da lesão; após o 1º tratamento; 2, 8 e 24 horas após lesão; e após o 5º dia. O tratamento ocorreu em 5 dias, com transdutor de 1 MHz, durante 3 minutos, sobre o local do trauma, com dose de 0,4 W/cm² SATA. Os resultados da incapacidade funcional para GS mostraram aumento da nocicepção. Para GUC houve aumento ao comparar a avaliação 1 (AV1) com as avaliações 2 (AV2), 3 (AV3) e 4 (AV4); ao comparar AV2 com as avaliações 5 (AV5) e 6 (AV6) houve diminuição de valores. Para GUP houve aumento ao comparar AV1 com AV2 e AV3, mas ao comparar AV2 com as seguintes, houve diminuição significativa a partir de AV4. Para o edema, os grupos tratados produziram aumento inicial, com redução nas últimas avaliações. O ultrassom terapêutico produziu diminuição de dor e edema, mais precocemente para a forma pulsada.
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Treshchalina, Yelena, Natalya Andronova, Galina Smirnova, et al. "ANTITUMOR ACTIVITY OF ANTI-INTEGRIN PROTEIN SAV-RGD ON XENOGRAFTED HUMAN SKIN MELANOMA WITH INTEGRIN AVG3 EXPRESSION." Problems in oncology 65, no. 3 (2019): 458–62. http://dx.doi.org/10.37469/0507-3758-2019-65-3-458-462.
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Anti-integrins are considered as potential anticancer agents capable of inhibiting differentiation and proliferation of various malignant cells, including disseminated melanoma. The possibility of including anti-integrins with different RGD-motives in combined therapy schedules is discussed. We have studied the oridinal recombinant lyophilized protein SAV-RGD (lyo-SAV-RGD), specifically binding to melanoma cells by means of the Tripeptide Arg-Gly-Asp. As models of melanoma of the skin selected amalonaticus MeWo/mel- and pigmented melCher/mel+ with prospectively certain expression of the marker, giving subcutaneous xenograft in mice Balb/c nude. Objective: to evaluate the antitumor activity of lyo-SAV-RGD in vivo on human skin melanoma models melCher and MeWo with different melanogenesis ability and integrin avB3 expression. Both melanomas in vitro were shown to express integrin avB3 detected in melCher/mel+ cells with fluorescent-labeled rat antibodies Luc.H11 according to the expression component integrins avp3, p3-chain (CD61), and MeWo cells/mel- antibodies 23С6. In a high therapeutic total dose of 900 mg/kg, lyo-SAV-RGD inhibited growth of both melanomas in vivo with satisfactory tolerability. Compared to melCher/mel+, MeWo/mel-: T/Cmin=30% (p<0.05) versus T/ Cmin=50% (p=0.001) was more sensitive to treatment. The effect on melCher/mel+ was obtained only in the exponential phase of tumor growth. The results obtained allow us to consider it expedient to conduct an in-depth preclinical study of anti-integrin SAV-RGD, focused on the most aggressive disseminated amelanotic melanoma of the skin, regardless of the nature of blocking receptor expression.
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Battisti, Aline, Danilo De Oliveira Silva, Emanuele Catarine Hirt Kessler, et al. "Comparação do alongamento estático, de 15 ou 30 segundos, na extensibilidade de isquiotibiais." ConScientiae Saúde 11, no. 4 (2013): 566–72. http://dx.doi.org/10.5585/conssaude.v11n4.3559.
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Introdução: Não há um consenso sobre frequência, intensidade, número de repetições e tempo de duração do alongamento muscular. Objetivo: Verificar em que tempo, 15 ou 30 s, é produzido maior ganho de extensibilidade após a intervenção e no decorrer do tempo. Métodos: A amostra foi composta por 16 mulheres com retração de isquiotibiais, divididas em dois grupos, com protocolos em três séries de alongamento estático. O G1 realizou alongamento durante 15s; e o G2, em 30s. Utilizou-se um período controle entre avaliações (AV1-AV2) de sete dias, em seguida, ocorreram os alongamentos por cinco dias consecutivos, com nova avaliação ao final destes (AV3); após dois dias sem intervenção (AV4), e finalmente após cinco dias (AV5). Resultados e Conclusão: Para o G1 e o G2, houve aumento da extensibilidade, mas, na comparação entre os grupos, o G2 mostrou maior aumento e manutenção dos valores.
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Bertolini, Gladson Ricardo Flor, Camila Thieime Rosa, Lígia Inez Silva, Anamaria Meireles, and Bruno Pogorzelski Rocha. "Uso do exercício resistido antagonizado por naloxone como fator de analgesia em sinovite aguda de joelho de ratos Wistar." Revista Brasileira de Medicina do Esporte 18, no. 2 (2012): 126–29. http://dx.doi.org/10.1590/s1517-86922012000200013.
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A analgesia advinda do exercício físico pode ocorrer via liberação de opioides endógenos, no sistema nervoso central e na periferia. Contudo, a literatura ainda é controversa sobre vias e ações do exercício na dor. Assim, o objetivo da pesquisa foi avaliar se o exercício resistido produz alterações sobre o quadro nociceptivo e se sofre interferências pela aplicação de um inibidor de opioides. Foram utilizados 18 ratos, divididos em três grupos: G1 - hiperalgesia no joelho direito e não tratados; G2 - hiperalgesia e tratados com saltos em meio aquático; G3 - hiperalgesia, com prévia injeção de naloxone e posterior saltos. Para produzir a hiperalgesia, foi injetado no espaço articular tibiofemoral 100µl de formalina 5%. Para avaliação da dor foi utilizado o filamento de Von Frey digital na face medial da articulação tibiofemoral direita. Os momentos de avaliação foram: pré-lesão (AV1), após 15 (AV2) e 30 (AV3) minutos e uma hora (AV4). O exercício foi saltos em meio aquático e ocorreu após AV2. Com sobrecarga de 50% do peso, o animal realizou quatro séries de cinco saltos, com intervalo de três minutos. Para G1, houve aumento nociceptivo, com redução significativa e volta dos valores iniciais em AV4; G2 mostrou, após o exercício físico, restauração do limiar, com retorno aos valores basais; para G3, houve diminuição do limiar, sem restauração ou aumento significativo do mesmo. Conclui-se que houve analgesia com uso do exercício físico e que a mesma foi alterada por bloqueador de betaendorfina.
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Wu, Hong-Bing, Zhi-Wei Wang, Feng Shi та ін. "Avβ3 Single-Stranded DNA Aptamer Attenuates Vascular Smooth Muscle Cell Proliferation and Migration via Ras-PI3K/MAPK Pathway". Cardiovascular Therapeutics 2020 (21 січня 2020): 1–12. http://dx.doi.org/10.1155/2020/6869856.
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Objectives. To observe the effect of avβ3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. Background. Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avβ3, which is widely expressed on various cell surfaces, plays an important role in the proliferation and migration of VSMCs. Methods. In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avβ3 ssDNA, which has high affinity and specificity to the avβ3 protein. MTT, Transwell, and cell scratch assays were carried out to examine the effect of avβ3 ssDNA on the proliferation and migration of VSMCs. Flow cytometry was performed to detect apoptosis and cell cycle progression. The effect of avβ3 ssDNA on the Ras-phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) signaling pathway was evaluated by quantitative reverse transcription polymerase chain reaction and western blot. Results. In the present study, we found that avβ3 ssDNA significantly decreased the expression of osteopontin, focal adhesion kinase, Ras, p-PI3K, and p-MAPK at both mRNA and protein levels (P<0.05). Avβ3 ssDNA also inhibited VSMC proliferation and migration while promoting apoptosis (P<0.05), as demonstrated by the upregulation of the proapoptotic proteins Bax and active caspase 3 (P<0.05). Conclusions. The findings suggest that avβ3 ssDNA inhibited the proliferation and migration of VSMCs by suppressing the activation of Ras-PI3K/MAPK signaling.
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Tucci, Marco, Lucia Lombardi, Steve Reshkin, Rosa A. Cardone та Silvestris Franco. "AlphaVBeta3 (αvβ3) Integrin Drives the Osteoclastogenesis through a Osteoclast-Like Functional Differentiation of Myeloma Cells." Blood 110, № 11 (2007): 814. http://dx.doi.org/10.1182/blood.v110.11.814.814.
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Abstract Accelerated osteoclastogenesis is the major event promoting the skeletal impairment in multiple myeloma (MM). Osteoclasts (OC) are directly activated by myeloma cells (MC), although these cells themselves may apparently undergo to OC-like morphologic transformation and produce bone erosion in vitro. Since OCs exert their function and promote osteoclastogenesis through activation of several adhesion molecules, including avb3, we investigated the role of this integrin expressed by MCs in their OC-like activity in vitro. Bone marrow MCs were purified from eight patients with severe skeletal disease (group A) and from two patients without bone lesions (group B). U266 and RPMI-8226 MC lines were the controls. Semi-nested PCR assessed the CDR3 immunoglobulin (Ig) gene rearrangement, whereas OC markers including TRAcP, cathepsin-k, calcitonin-receptor, carbonic anhydrase and vATPase were evaluated by RT-PCR. The cytoskeletal rearrangement of F-actin was analyzed by immunofluorescence. av and b3 expression on MCs was evaluated by flow-cytometry, whereas bone erosion on calcium phosphate discs and number of pits was measured by dedicated software. The effect of avb3 stimulation on the activation of osteoclastogenic function was investigated by exploring the phosphorilation of transcriptional kinases and downstream molecules, as ERK1/2 and cFos, respectively. The primary role of avb3 in OC-like functional transdifferentiation was explored in MCs by siRNA silencing for both chains. Ontogenetic derivation from the B-cell lineage was confirmed by the monoclonal CDR3 rearrangement, CD138/CD38 and Pax-5 expression. Cells from patients of group A expressed OC markers, in contrast with those of group B or U266 and RPMI-8226. Formation of the F-actin ring confirmed the differentiation of MCs toward the OC-like phenotype. Cells from group A expressed av and b3 (80±7% and 75±9%) similarly to U266 and RPMI-8226 (>90% in both instances), whereas a minimal expression was demonstrated in group B (av:6±2%; b3:8±3%). avb3+ cells produced a high number of erosive pits, at variance from avb3− cells (35±8 vs. 4±1 pits/cm2 ). The highest phosphorilation of ERK1/2 and expression of cFos was revealed in patients of group A as compared to B (840±110 OD and 905±210 OD vs. 270±35 OD and 315±80 OD, p<0.0001 in both instances). Finally, the silencing of av and/or b3 chain inhibited the erosion by avb3+ cells, resulting in a reduced number of pits (7±2 pits/cm2) similar to the pattern obtained with avb3− cells. Similarly, an inhibition of both ERK1/2 and cFos was demonstrated in silenced cells from group A with values similar to those of group B. Since avb3 drives both adhesion of Ocs to extracellular matrix and activation of osteoclastogenesis, it is conceivable that avb3+ MCs may functionally transdifferentiate to OCs in response to integrin activation induced by the contact with stromal cells within the marrow environment, thus resulting in a typical OC-like behaviour. In addition, our data suggest that MCs induce this effect by avb3, since its silencing reduces the OC-like activity in vitro.
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Souza, E., and M. E. Sorrells. "Inheritance and distribution of variation at four avenin loci in North American oat germ plasm." Genome 33, no. 3 (1990): 416–24. http://dx.doi.org/10.1139/g90-063.
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Avenins (prolamines of the Avena genus) have been shown to be useful in taxonomic studies and cultivar identification; specific allelic identification could assist in these types of studies as well as providing a basis for future linkage and gene mapping studies. The avenin patterns produced by nondenaturing polyacrylamide gel electrophoresis were compared in 70 North American oat cultivars and germ plasms. Populations of F2 progeny were subsequently evaluated to test for allelism of proteins found to be noncoincident in the survey of homozygous cultivars. A minimum of four loci (Av1, Av2, Av3, and Av4) were found to possess alternate alleles with distinctive electrophoretic mobilities. Segregation of 10 alternate alleles were observed in studies of F2 progeny: four for Av1, and two each for the other three loci. Additional variation found among the surveyed cultivars suggested at least two additional electrophoretically variant polypeptides. Several of the alleles were found to be associated with cultivars from specific geographic regions. Two examples were (i) the near exclusive association of the Av10.76 allele with Canadian cultivars and (ii) the high association of the Av10.58 allele with fall-planted cultivars. Fifty percent (SE ± 10.7%) of the fall-planted cultivars have the Av40.58 allele compared with 27.1% (SE ± 8.8%) of spring-planted cultivars.Key words: avenins, prolamines, polyacrylamide gel electrophoresis, linkage.
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Ho, Hsiang-Ling, Hsin-Yi Lee, Hsien-Ching Liao, and Mei-Yu Chen. "Involvement of Saccharomyces cerevisiae Avo3p/Tsc11p in Maintaining TOR Complex 2 Integrity and Coupling to Downstream Signaling." Eukaryotic Cell 7, no. 8 (2008): 1328–43. http://dx.doi.org/10.1128/ec.00065-08.
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ABSTRACT Target-of-rapamycin proteins (TORs) are Ser/Thr kinases serving a central role in cell growth control. TORs function in two conserved multiprotein complexes, TOR complex 1 (TORC1) and TORC2; the mechanisms underlying their actions and regulation are not fully elucidated. Saccharomyces TORC2, containing Tor2p, Avo1p, Avo2p, Avo3p/Tsc11p, Bit61p, and Lst8p, regulates cell integrity and actin organization. Two classes of avo3 temperature-sensitive (avo3 ts) mutants that we previously identified display cell integrity and actin defects, yet one is suppressed by AVO1 while the other is suppressed by AVO2 or SLM1, defining two TORC2 downstream signaling mechanisms, one mediated by Avo1p and the other by Avo2p/Slm1p. Employing these mutants, we explored Avo3p functions in TORC2 structure and signaling. By observing binary protein interactions using coimmunoprecipitation, we discovered that the composition of TORC2 and its recruitment of the downstream effectors Slm1p and Slm2p were differentially affected in different avo3 ts mutants. These molecular defects can be corrected only by expressing AVO3, not by expressing suppressors, highlighting the role of Avo3p as a structural and signaling scaffold for TORC2. Phenotypic modifications of avo3 ts mutants by deletion of individual Rho1p-GTPase-activating proteins indicate that two TORC2 downstream signaling branches converge on Rho1p activation. Our results also suggest that Avo2p/Slm1p-mediated signaling, but not Avo1p-mediated signaling, links to Rho1p activation specifically through the Rho1p-guanine nucleotide exchange factor Tus1p.
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Tshireletso, Thalosang, Pilate Moyo, and Matongo Kabani. "Predicting the Effects of Climate Change on Water Temperatures of Roode Elsberg Dam Using Nonparametric Machine Learning Models." Infrastructures 6, no. 2 (2021): 14. http://dx.doi.org/10.3390/infrastructures6020014.
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A nonparametric machine learning model was used to study the behaviour of the variables of a concrete arch dam: Roode Elsberg dam. The variables used were ambient temperature, water temperatures, and water level. Water temperature was measured using twelve thermometers; six thermometers were on each flank of the dam. The thermometers were placed in pairs on different levels: avg6 (avg6-R and avg6-L) and avg5 (avg5-R and avg5-L) were on level 47.43 m, avg4 (avg4-R and avg4-L) and avg3 (avg3-R and avg3-L) were on level 43.62 m, and avg2 (avg2-R and avg2-L) and avg1 (avg1-R and avg1-L) were on level 26.23 m. Four neural networks and four random forests were cross-validated to determine their best-performing hyperparameters with the water temperature data. Quantile random forest was the best performer at mtry 7 (Number of variables randomly sampled as candidates at each split) and RMSE (Root mean square error) of 0.0015, therefore it was used for making predictions. The predictions were made using two cases of water level: recorded water level and full dam steady-state at Representative Concentration Pathway (RCP) 4.5 (hot and cold model) and RCP 8.5 (hot and cold model). Ambient temperature increased on average by 1.6 °C for the period 2012–2053 when using recorded water level; this led to increases in water temperature of 0.9 °C, 0.8 °C, and 0.4 °C for avg6-R, avg3-R, and avg1-R, respectively, for the period 2012–2053. The same average temperature increase led to average increases of 0.7 °C for avg6-R, 0.6 °C for avg3-R, and 0.3 °C for avg1-R for a full dam steady-state for the period 2012–2053.
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Moreira, Natália Boneti, Elisângela Lourdes Artifon, Anamaria Meireles, Lígia Inez Silva, Camila Thieime Rosa, and Gladson Ricardo Flor Bertolini. "A influência da crioterapia na dor e edema induzidos por sinovite experimental." Fisioterapia e Pesquisa 18, no. 1 (2011): 79–83. http://dx.doi.org/10.1590/s1809-29502011000100014.
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O objetivo deste estudo foi analisar a influência da crioterapia na dor e edema advindos de sinovite induzida em ratos. Foram utilizados 12 ratos, distribuídos em dois grupos: Controle (GC) - submetido à indução de sinovite no joelho direito, e não tratado; e Tratamento (GT) - submetido à sinovite no joelho direito, e tratado com crioterapia. Para induzir a lesão, foi injetado no espaço tíbio-femoral formalina 5%. Para avaliação da dor foi utilizado o teste de incapacidade funcional, que avaliou a dor durante a marcha do animal (tempo de elevação da pata - TEP); e para quantificar o edema foi utilizado um paquímetro metálico, na região da interlinha do joelho. As avaliações ocorreram antes da injeção de formalina (AV1), 1 (AV2) e 2 horas (AV3) após. Após 10 minutos da lesão, o membro posterior direito foi submerso em água com gelo, à 5ºC por 20 minutos. A avaliação do TEP mostrou aumento de 194,03% (AV2) e 169,26% (AV3) para GC; e 134,25% (AV2) e 103,13% (AV3) para GT, com relação à AV1. Na comparação entre os grupos, em AV3, houve diminuição significativa para GT. A avaliação do edema mostrou aumento do diâmetro, para GC de 39,15% (AV2) e 42,39% (AV3); e 27,91% (AV2) e 14,50% (AV3) para GT, tendo como referência AV1; sendo que apenas GT apresentou diminuição significativa entre AV2 e AV3. Conclui-se que os efeitos em curto prazo, da crioterapia, foram significativos para reduzir a dor e edema, em ratos submetidos à indução de sinovite.
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Stucci, Stefania, Marco Tucci, Anna Passarelli та Franco Silvestris. "Avβ3 integrin: Pathogenetic role in osteotropic tumors". Critical Reviews in Oncology/Hematology 96, № 1 (2015): 183–93. http://dx.doi.org/10.1016/j.critrevonc.2015.05.018.
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Lanferdini, Fábio Juner, Clarice Sperotto dos Santos Rocha, Viviane Bortoluzzi Frasson, and Marco Aurélio Vaz. "Influência do treinamento excêntrico nas razões de torque de flexores/extensores do joelho." Fisioterapia e Pesquisa 17, no. 1 (2010): 40–45. http://dx.doi.org/10.1590/s1809-29502010000100008.
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O treinamento excêntrico (Texc) produz adaptações musculares que minimizam a ocorrência de lesões e é usado em reabilitação e treinamento de força, mas pouco se sabe sobre seus efeitos no equilíbrio entre músculos antagonistas do joelho. As razões de torque permitem determinar esses desequilíbrios musculares. O objetivo do estudo foi avaliar os efeitos de 12 semanas de Texc nas razões de torque excêntrico (Iexc:Qexc) entre os músculos isquiotibiais (I) e quadríceps (Q). Vinte e quatro sujeitos saudáveis do sexo masculino foram distribuídos nos grupos controle (GC, n=13, idade 27,7±4,6 anos) e experimental (GE, n=11, idade 28,5±9,5 anos), submetido ao treinamento. Um dinamômetro isocinético foi utilizado para o Texc (velocidade de -60 º/s) e para as avaliações (uma a cada quatro semanas). As razões de torque medidas foram comparadas estatisticamente entre os grupos e intragrupos entre as avaliações, com nível de significância de 5%. No GE, foi observada redução das razões de torque da avaliação (AV) inicial para as demais: AV1x AV2, p=0,005; AV1x AV3, p=0,001; e AV1x AV4, p<0,001. Na avaliação final, as razões do GE foram menores quando comparadas às do GC (p=0,041). O Texc altera pois o equilíbrio dos músculos flexores e extensores do joelho: doze semanas de Texc levam à redução da razão Iexc:Qexc e ao aumento do torque extensor, sem alteração significativa do torque flexor, podendo ser usado na reabilitação para fortalecimento dos músculos extensores do joelho.
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Moran, Yehu, Roy Kahn, Lior Cohen, et al. "Molecular analysis of the sea anemone toxin Av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated Na+ channels." Biochemical Journal 406, no. 1 (2007): 41–48. http://dx.doi.org/10.1042/bj20070233.
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Av3 is a short peptide toxin from the sea anemone Anemonia viridis shown to be active on crustaceans and inactive on mammals. It inhibits inactivation of Navs (voltage-gated Na+ channels) like the structurally dissimilar scorpion α-toxins and type I sea anemone toxins that bind to receptor site-3. To examine the potency and mode of interaction of Av3 with insect Navs, we established a system for its expression, mutagenized it throughout, and analysed it in toxicity, binding and electrophysiological assays. The recombinant Av3 was found to be highly toxic to blowfly larvae (ED50=2.65±0.46 pmol/100 mg), to compete well with the site-3 toxin LqhαIT (from the scorpion Leiurus quinquestriatus) on binding to cockroach neuronal membranes (Ki=21.4±7.1 nM), and to inhibit the inactivation of Drosophila melanogaster channel, DmNav1, but not that of mammalian Navs expressed in Xenopus oocytes. Moreover, like other site-3 toxins, the activity of Av3 was synergically enhanced by ligands of receptor site-4 (e.g. scorpion β-toxins). The bioactive surface of Av3 was found to consist mainly of aromatic residues and did not resemble any of the bioactive surfaces of other site-3 toxins. These analyses have portrayed a toxin that might interact with receptor site-3 in a different fashion compared with other ligands of this site. This assumption was corroborated by a D1701R mutation in DmNav1, which has been shown to abolish the activity of all other site-3 ligands, except Av3. All in all, the present study provides further evidence for the heterogeneity of receptor site-3, and raises Av3 as a unique model for design of selective anti-insect compounds.
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Colman, Robert W., Noah G. Schmuckler, and Yi Wu. "Cleaved Kininogen Inhibits Endothelial Progenitor Cell Differentiation by Interfering with the avb3 Integrin-MMP-2 Pathway." Blood 110, no. 11 (2007): 3719. http://dx.doi.org/10.1182/blood.v110.11.3719.3719.
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Abstract Circulating endothelial progenitor cells (EPCs) are involved in repairing damaged vasculature and in tumor angiogenesis, thus promoting wide interest in their therapeutic potential in ischemic diseases and cancer. Cleaved high molecular weight kininogen (HKa) potently inhibits endothelial cell (EC) functions including in vivo angiogenesis. We have shown that HKa inhibits differentiation of ECs. We now test a new hypothesis that HKa can inhibit EPC differentiation by blocking matrix metalloprotease-2 (MMP-2) activation. EPCs were isolated from human blood and cultured on collagen type I-coated surface. As detected by flow cytometry and Western-blot, they expressed MMP-2 and membrane-type 1-MMP (MT1-MMP), avb3 integrin, uPAR and caveolin-1, but did not express monocyte markers such as HLA-DR and CD14. A clone-forming assay using retroviral infection indicated that an early single EPC exhibited colony forming property, but mature ECs such as human umbilical vein endothelial cells (HUVECs) did not. Upon stimulation by VEGF, EPCs, but not HUVECs, formed vacuoles and differentiated into capillary networks. Gene silencing of either MT1-MMP or MMP-2 by siRNA completely blocked the vacuole and tube formation by EPCs, suggesting that MT1-MMP and MMP-2 are both essential for differentiation of EPCs. HKa inhibited tube formation by EPCs, as well as the conversion of pro-MMP-2 to MMP-2 as a functioning concentration in the conditioned medium. CS-1 cells expressing endogenous av subunit were transfected with human b3 cDNA. We found that HKa inhibition of MMP-2 activation in these cells is dependent on avb3 heterodimer. The binding of avb3 integrin to MMP-2 was via RGD-dependent and RGD-independent mechanisms, both of which, however, were completely blocked by HKa. Further, we found that HKa inhibited the association of MMP-2 with immunoprecipitated avb3 integrin, and prevented MMP-2 localization in caveolae in EPCs. Since HKa inhibited VEGF-stimulated proliferation of EPCs but not HUVECs on collagen-coated surface, we postulate that EPCs are more sensitive than mature ECs to HKa inhibition. Thus, HKa targets EPCs and inhibits their differentiation via blocking avb3 integrin and MMP-2 interaction. These observations provide novel insight into understanding the interactions between the kallikrein-kinin system and biologic functions of EPCs.
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Gur Barzilai, Maya, Roy Kahn, Noa Regev, Dalia Gordon, Yehu Moran, and Michael Gurevitz. "The specificity of Av3 sea anemone toxin for arthropods is determined at linker DI/SS2–S6 in the pore module of target sodium channels." Biochemical Journal 463, no. 2 (2014): 271–77. http://dx.doi.org/10.1042/bj20140576.
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A sodium channel determinant that dictates the specificity of Av3 sea anemone toxin for arthropods was identified using channel-swapping experiments and mutagenesis. This finding provides a clue as to the receptor site of Av3 on the sodium channel.
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Scatena, Marta, Laura Pritzker, and Cecilia M. Giachelli. "OSTEOPROTEGERIN AN AVB3-INDUCED ENDOTHELIAL CELL SURVIVAL MOLECULE." Cardiovascular Pathology 13, no. 3 (2004): 3–4. http://dx.doi.org/10.1016/j.carpath.2004.03.004.
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Tariq, Huma, Muhammad Zia, Ihsan-ul-Haq, et al. "Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L." BioMed Research International 2019 (July 28, 2019): 1–14. http://dx.doi.org/10.1155/2019/6478187.
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Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world. The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf. Methanolic extract of A. vera leaves was fractionated using column chromatography and ten fractions (AV1-AV10) were obtained. Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols. Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results. Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities. AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay. Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay. The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7). Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant. Therefore, with more studies, A. vera could probably have the potential to be used for drug development against leishmaniasis.
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Marič, Leon, Ilse Cleenwerck, Tomaž Accetto, Peter Vandamme, and Janja Trček. "Description of Komagataeibacter melaceti sp. nov. and Komagataeibacter melomenusus sp. nov. Isolated from Apple Cider Vinegar." Microorganisms 8, no. 8 (2020): 1178. http://dx.doi.org/10.3390/microorganisms8081178.
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Two novel strains AV382 and AV436 were isolated from a submerged industrial bioreactor for production of apple cider vinegar in Kopivnik (Slovenia). Both strains showed very high (≥98.2%) 16S rRNA gene sequence similarities with Komagataeibacter species, but lower 16S–23S rRNA gene internal transcribed spacer (ITS). The highest similarity of the 16S–23S rRNA gene ITS of AV382 was to Komagataeibacter kakiaceti LMG 26206T (91.6%), of AV436 to Komagataeibacter xylinus LMG 1515T (93.9%). The analysis of genome sequences confirmed that AV382 is the most closely related to K. kakiaceti (ANIb 88.2%) and AV436 to K. xylinus (ANIb 91.6%). Genome to genome distance calculations exhibit for both strains ≤47.3% similarity to all type strains of the genus Komagataeibacter. The strain AV382 can be differentiated from its closest relatives K. kakiaceti and Komagataeibacter saccharivorans by its ability to form 2-keto and 5-keto-D-gluconic acids from glucose, incapability to grow in the presence of 30% glucose, formation of C19:0 cyclo ω8c fatty acid and tolerance of up to 5% acetic acid in the presence of ethanol. The strain AV436 can be differentiated from its closest relatives K. xylinus, Komagataeibacter sucrofermentans, and Komagataeibacter nataicola by its ability to form 5-keto-D-gluconic acid, growth on 1-propanol, efficient synthesis of cellulose, and tolerance to up to 5% acetic acid in the presence ethanol. The major fatty acid of both strains is C18:1ω7c. Based on a combination of phenotypic, chemotaxonomic and phylogenetic features, the strains AV382T and AV436T represent novel species of the genus Komagataeibacter, for which the names Komagataeibactermelaceti sp. nov. and Komagataeibacter melomenusus are proposed, respectively. The type strain of Komagataeibacter melaceti is AV382T (= ZIM B1054T = LMG 31303T = CCM 8958T) and of Komagataeibacter melomenusus AV436T (= ZIM B1056T = LMG 31304T = CCM 8959T).
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Martinez Marshall, Maria Nieves, Anita Emmerstorfer-Augustin, Kristin L. Leskoske, Lydia H. Zhang, Biyun Li, and Jeremy Thorner. "Analysis of the roles of phosphatidylinositol-4,5-bisphosphate and individual subunits in assembly, localization, and function of Saccharomyces cerevisiae target of rapamycin complex 2." Molecular Biology of the Cell 30, no. 12 (2019): 1555–74. http://dx.doi.org/10.1091/mbc.e18-10-0682.
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Eukaryotic cell survival requires maintenance of plasma membrane (PM) homeostasis in response to environmental insults and changes in lipid metabolism. In yeast, a key regulator of PM homeostasis is target of rapamycin (TOR) complex 2 (TORC2), a multiprotein complex containing the evolutionarily conserved TOR protein kinase isoform Tor2. PM localization is essential for TORC2 function. One core TORC2 subunit (Avo1) and two TORC2-associated regulators (Slm1 and Slm2) contain pleckstrin homology (PH) domains that exhibit specificity for binding phosphatidylinositol-4,5- bisphosphate (PtdIns4,5P2). To investigate the roles of PtdIns4,5P2 and constituent subunits of TORC2, we used auxin-inducible degradation to systematically eliminate these factors and then examined localization, association, and function of the remaining TORC2 components. We found that PtdIns4,5P2 depletion significantly reduced TORC2 activity, yet did not prevent PM localization or cause disassembly of TORC2. Moreover, truncated Avo1 (lacking its C-terminal PH domain) was still recruited to the PM and supported growth. Even when all three PH-containing proteins were absent, the remaining TORC2 subunits were PM-bound. Revealingly, Avo3 localized to the PM independent of both Avo1 and Tor2, whereas both Tor2 and Avo1 required Avo3 for their PM anchoring. Our findings provide new mechanistic information about TORC2 and pinpoint Avo3 as pivotal for TORC2 PM localization and assembly in vivo.
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Braitseva, Olga A., Vera V. Ponomareva, Leopold D. Sulerzhitsky, Ivan V. Melekestsev, and John Bailey. "Holocene Key-Marker Tephra Layers in Kamchatka, Russia." Quaternary Research 47, no. 2 (1997): 125–39. http://dx.doi.org/10.1006/qres.1996.1876.
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Detailed tephrochronological studies in Kamchatka Peninsula, Russia, permitted documentation of 24 Holocene key-marker tephra layers related to the largest explosive eruptions from 11 volcanic centers. Each layer was traced for tens to hundreds of kilometers away from the source volcano; its stratigraphic position, area of dispersal, age, characteristic features of grain-size distribution, and chemical and mineral composition confirmed its identification. The most important marker tephra horizons covering a large part of the peninsula are (from north to south; ages given in14C yr B.P.) SH2(≈1000 yr B.P.) and SH3(≈1400 yr B.P.) from Shiveluch volcano; KZ (≈7500 yr B.P.) from Kizimen volcano; KRM (≈7900 yr B.P.) from Karymsky caldera; KHG (≈7000 yr B.P.) from Khangar volcano; AV1(≈3500 yr B.P.), AV2(≈4000 yr B.P.), AV4(≈5500 yr B.P.), and AV5(≈5600 yr B.P.) from Avachinsky volcano; OP (≈1500 yr B.P.) from the Baraniy Amfiteatr crater at Opala volcano; KHD (≈2800 yr B.P.) from the “maar” at Khodutka volcano; KS1(≈1800 yr B.P.) and KS2(≈6000 yr B.P.) from the Ksudach calderas; KSht3(A.D. 1907) from Shtyubel cone in Ksudach volcanic massif; and KO (≈7700 yr B.P.) from the Kuril Lake-Iliinsky caldera. Tephra layers SH5(≈2600 yr B.P.) from Shiveluch volcano, AV3(≈4500 yr B.P.) from Avachinsky volcano, OPtr(≈4600 yr B.P.) from Opala volcano, KS3(≈6100 yr B.P.) and KS4(≈8800 yr B.P.) from Ksudach calderas, KSht1(≈1100 yr B.P.) from Shtyubel cone, and ZLT (≈4600 yr B.P.) from Iliinsky volcano cover smaller areas and have local stratigraphic value, as do the ash layers from the historically recorded eruptions of Shiveluch (SH1964) and Bezymianny (B1956) volcanoes. The dated tephra layers provide a record of the most voluminous explosive events in Kamchatka during the Holocene and form a tephrochronological timescale for dating and correlating various deposits.
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Ferreira, Leonardo F., Allison J. Harper, and Thomas J. Barstow. "Frequency-domain characteristics and filtering of blood flow following the onset of exercise: implications for kinetics analysis." Journal of Applied Physiology 100, no. 3 (2006): 817–25. http://dx.doi.org/10.1152/japplphysiol.01036.2005.
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We examined the validity and usefulness of a low-pass filter (LPFILTER) to reduce point-to-point variability and enhance parameter estimation of the kinetics of blood flow (BF). Computer simulations were used to determine the power spectrum of simulated responses. Moreover, we studied the leg BF response to a single transition in four subjects during supine knee-extension exercise using three methods of data processing [beat-by-beat, average of 3 cardiac cycles (AVG3 BEATS), and LPFILTER]. The power spectrum of BF containing the kinetics information (≤0.2 Hz) did not overlap with the oscillations due to muscle contraction and cardiac cycle (simulations and Doppler measurements). There were no significant differences between the parameter estimates for a two-exponential model using Beat-by-Beat, AVG3 BEATS, and LPFILTER ( P > 0.05; n = 4). However, LPFILTER (cutoff = 0.2 Hz) resulted in a significantly lower standard error of the estimate for all parameters ( P < 0.05). The means ± SD for the standard error of the estimate for Beat-by-Beat, AVG3 BEATS, and LPFILTER were, respectively, time constant- phase 1 = 5.0 ± 1.1 s, 4.5 ± 2.1 s, and 0.3 ± 0.2 s; time delay- phase 2 = 17.8 ± 7.9 s, 12.8 ± 7.5 s, and 1.4 ± 1.4 s; time constant- phase 2 = 15.8 ± 4.6 s, 9.9 ± 2.9 s, and 1.1 ± 0.5 s. In conclusion, LPFILTER appeared to be a valid procedure providing a high signal-to-noise ratio and data density and thus LPFILTER resulted in the smallest confidence interval for parameter estimates of BF kinetics.
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Weber, Martin R., Deidre O’Sullivan, Mario P. Tschan, et al. "Understanding Hematogenous Breast Cancer Metastasis: Tumor Cell Integrin Activation Matters." Blood 104, no. 11 (2004): 2613. http://dx.doi.org/10.1182/blood.v104.11.2613.2613.
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Abstract Metastatic disease is the leading cause of morbidity and mortality in patients with breast cancer. Elucidating the mechanisms that govern the hematogenous spread of cancer cells would provide novel targets for the development of new therapeutic strategies. Our group has previously demonstrated that the activated form of integrin specifically promotes breast cancer metastasis. Here, we have investigated the mechanisms by which activated av33 directly impacts defined steps in hematogenous dissemination of cancer cells in vivo. The lung colonization assay was used as a model to analyze tumor cell arrest in the vasculature, extravasation and secondary tumor cell growth at the target site. To address a role of the activation state of adhesion receptor integrin av33 in these steps of the metastatic cascade, we genetically tagged variants of the MDA-MB 435 human breast cancer cell model with dsRed2 or luciferase, and followed cells that express either non-activated 33wild type (WT) or constitutively activated mutant 33D723R, upon injection into the circulation of SCID mice. The presence of the cells and metastatic burden was analyzed by fluorescence imaging of lung whole mounts, supported by real time PCR quantification of human Alu sequences, and by non-invasive whole body imaging based on bioluminescence detection. Within 24 hours after injecting 1 million tumor cells into the tail vein, 90% of 33D723R expressing cells and 99.5% of 33WT expressing cells were cleared from the lungs. In both cell variants, the cleared cells undergo apoptosis as shown by immunohistochemical analysis. However, significantly more 33D723R than 33WT expressing cells consistently arrested and survived in the pulmonary vascular bed. A hallmark of constitutively activated integrin av33 is the ability of the receptor to bind soluble plasma protein ligands and thereby promote tumor cell interaction with platelets, a mechanism that supports tumor cell arrest during blood flow in-vitro. The contribution of platelets to the initial steps of tumor cell target organ colonization was evaluated in mice with experimental thrombocytopenia compared to mice with normal platelet counts. Following initial tumor cell arrest, 33D723R expressing cells showed a significantly shorter lag phase and enhanced proliferation than 33WT expressing cells, and this further determined the development of metastatic foci in the lungs. Slower growth of 33D723R expressing cells in-vitro indicates a specific advantage that these cells have in the microenvironment of the lung tissue. For both cell variants, target organ colonization was restricted to the lungs, as demonstrated using imaging of bioluminescence signal. Thus, we demonstrated that the activated form of integrin av33 confers an advantage on breast cancer cells at two distinct steps within the metastatic cascade. The first step is specific arrest within the pulmonary vascular bed, followed by a critical second step where expression of activated av33 is associated with increased tumor cell survival and a faster transition from a lag phase to rapid proliferation leading to the successful generation of multicellular lesions in the lungs and the establishment of clinically relevant metastatic disease.
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Cheng, Wei Hua, Mian Chang Li, and Chuan Peng Li. "Flow Analysis of Axial Compressor AV63-15 Variable Stator Simulation." Advanced Materials Research 532-533 (June 2012): 474–78. http://dx.doi.org/10.4028/www.scientific.net/amr.532-533.474.
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This paper conducts numerical simulation to a 15-stage civil axial flow compressor and obtains its main parameters distribution and performance curve by a full three-dimensional viscid flow computation software. The computation result indicates that, the developed axial flow compressor meets the anticipated design requirements, and satisfies the customers’ indicators. Under the designed compression ratio, the difference between the maximum air supply quantity in summer and the minimum air supply quantity in winter is 22%. By comparing the operating conditions and data analysis, obtained the change trend of axial velocity, static pressure and temperature, and Ma, and discovered that, under opening of 48° and outlet back pressure of 550KPa, flow separation occurred on the section of machine set close to hud, which indicated that operating condition was close to surging condition.
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Parveen, Atahar, and N. K. Gaur. "Elastic and thermodynamic properties of AVO3 (A=Sr, Pb) perovskites." Physica B: Condensed Matter 407, no. 3 (2012): 500–504. http://dx.doi.org/10.1016/j.physb.2011.11.023.
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Kim, K. B., A. H. Diwan, N. E. Papadopoulos, et al. "A randomized phase II study of EMD 121974 in patients (pts) with metastatic melanoma (MM)." Journal of Clinical Oncology 25, no. 18_suppl (2007): 8548. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.8548.
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8548 Background: EMD 121974 is a selective antagonist of avβ3 integrin, which promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells expressing avβ3 integrin. We conducted a randomized phase II trial of cilengitide in pts with MM to evaluate the clinical efficacy at 2 different doses. Methods: Pts with stage IV or unresectable stage III non-choroidal melanoma who had no more than 1 prior systemic therapy were enrolled. Pts at least 18 years of age and with ECOG performance status of 0 to 2 were eligible. All pts underwent baseline tumor biopsy and were randomly assigned to either 500 mg or 2,000 mg intravenous (IV) EMD 121974 twice weekly, using the following stratification factors: 1) prior systemic treatment; 2) visceral metastases; 3) serum lactate dehydrogenase level; 4) tumor avβ3 overexpression, where overexpression is defined as > 25% of melanoma cells staining positive. The primary objective of this study was to determine the progression-free survival rate at 8 weeks. Results: Twenty-nine pts were enrolled, and 26 pts (14 at 500 mg; 12 at 2,000 mg dose) were treated. Patient characteristics for 500 mg and 2,000 mg arm, respectively, are as follows: median age, 57 and 61; percentage (% age) of male, 50% and 50%; % age of ECOG performance status of 0, 79% and 58%; % age of stage IV, 79% and 75%; % age of tumor avβ3 overexpression, 21% and 25%. Three of 26 pts were progression-free at 8 weeks (2 at 500 mg; 1 at 2,000 mg dose). One pt at 2,000 mg had a prolonged partial response after initial 28% enlargement of target lesions. There were no grade 3 or 4 adverse events (AEs) except one pt with grade 3 lymphopenia at 2,000 mg. Although both doses of EMD 121974 were well tolerated, the 2,000 mg was associated with higher incidences of grade 2 fatigue, arthralgia, lymphopenia, peripheral neuropathy, and GI AEs. Optional tumor biopsies were performed on day 8, and the correlative studies to examine the molecular changes in the tumor are currently in progress. Conclusions: IV EMD 121974, 500 or 2,000 mg twice weekly, was well tolerated but had minimal clinical efficacy as a single-agent for MM. Supported by NCI grant N01 CM-17003 and CA16672 No significant financial relationships to disclose.
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Graef, Thorsten T., Ulrich U. Steidl, Roland R. Fenk, et al. "Use of RNA Interference to Inhibit Integrin Subunit alphaV-Mediated Angiogenesis." Blood 104, no. 11 (2004): 5258. http://dx.doi.org/10.1182/blood.v104.11.5258.5258.
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Abstract Inhibition of angiogenesis is a promising approach for the treatment of solid tumors, inflammatory diseases and different hematological malignancies such as multiple myeloma. One of the central molecules in capillary formation during angiogenesis is the integrin alphaVbeta3 (aVb3), therefore aVb3 is a potential target molecule to inhibit angiogenesis. The aim of this study was to inhibit alphaV-mediated angiogenesis in vitro using RNA interference (RNAi) technology as well as antisense oligodeoxyribonucleotides (asON). We used synthetic small interfering RNAs (siRNA) and asON directed against the alphaV chain of aVb3 to inhibit integrin expression. Five siRNAs were selected on the basis of a systematic alignment of computer-predicted secondary structures of target mRNA and on the basis of current recommendations for siRNA oligonucleotide design. In parallel, 3 asON were examined. They had the sequence of the antisense sequence of 3 of the siRNAs molecules, respectively. SiRNAs, asON and respective control sequences were transfected into human umbilical vein endothelials cells (HUVEC) using lipofection. Following stimulation by phorbol 12-myristate 13-acetate (PMA), two siRNAs showed a dose- and time dependent inhibition of PMA-induced aV-mRNA and -protein upregulation as assessed by real-time RT-PCR and flow cytometry. At a concentration of 25 nM a 100% (SD: 4.9%) inhibition of aV upregulation was observed, whereas transfection of the respective asON sequences resulted in a 63% (SD: 6.1%) inhibition of aV upregulation at 25nM. To evaluate the anti-angiogenic potential of siRNAs in comparison to asON a cell culture model of human angiogenesis based on the co-cultivation of endothelial cells and dermal fibroblasts was used. Transfection of the most efficient siRNA sequence at a concentration of 50nM resulted in an inhibition of total length of capillary-like tubules by 48.7% (SD: 3.6%) in comparison to 21.8% (SD: 9.8%) by the respective asON sequence treated cultures. In conclusion, siRNAs can successfully be selected on the basis of computer-predicted secondary structures. In comparison with asON having the same sequence as the antisense strand of the respective siRNA the siRNA-mediated inhibition of aV expression showed a stronger inhibition of capillary tube formation in an angiogenesis in vitro assay. Therefore, siRNAs are useful tools for functional aV knock-down experiments and might be a therapeutic alternative for antagonists which bind directly to the integrins aVb3 or aVb5.
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Kenny, L. M., E. Aboagye, P. S. Cohen та ін. "Imaging of angiogenesis in metastatic breast cancer by positron emission tomography (PET) using [18F]AH11585, an [18F]- labeled alphaVbeta3 (αvβ3) peptide". Journal of Clinical Oncology 25, № 18_suppl (2007): 14067. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.14067.
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14067 Background: In vivo imaging of avβ3 expression in tumors and tumor endothelial cells may be a useful biomarker of angiogenesis. [18F]AH11585 is a novel peptide containing an Arginine-Glycine-Aspartic Acid (RGD) motif that binds to avβ3 with high affinity designed for use in PET studies. Methods: 7 patients with metastatic breast cancer (aged 37–68 years) received intravenous injections of [18F]AH11585 and were scanned dynamically by PET over 61.5 mins. Radioactivity concentrations, derived from regions of interest placed on tumour and normal tissues, were analysed mathematically to determine the net irreversible uptake (Ki), fractional retention (FRT) and standardized uptake at 56.5min (SUV) of the radiotracer. Computed tomography (CT) was performed within 4 weeks of the scan. Results: Tumor lesions were clearly visible on PET images in 6/7 patients. In one patient with a palpable supraclavicular lymph node not visible on CT, we were unsure if a hyperintense region visible by PET was tumor. In total 18/19 tumor lesions were identified on both PET and corresponding CT images. Tumors in areas of low background were hyperintense (lung, bone, breast) whereas those in areas of high background were hypointense regions (liver). Tumors with central necrosis showed high uptake of [18F]AH11585 around the periphery only. Mathematical analysis demonstrated irreversible retention of [18F]AH11585 in tumors. [18F]AH11585-PET discriminated between non-liver lesions (n=10) and normal tissues: Ki (p=0.002), FRT (p=0.0039), SUV (p=0.002). Corresponding comparisons for liver lesions (n=8) were significant for FRT (p=0.0078) and SUV (p=0.0078) only. Conclusions: [18F]AH11585 PET is a promisng method for in vivo imaging of avβ3 integrin expression in metastatic breast cancer. No significant financial relationships to disclose.
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Kudo, Masako, Hisashi Yonezawa, Toshihide Shibata, et al. "Imaging brain amyloid using the radioligand 18F-AV45 (Florbetapir F 18)." Cerebral Blood Flow and Metabolism (Japanese journal of cerebral blood flow and metabolism) 25, no. 2 (2014): 91–96. http://dx.doi.org/10.16977/cbfm.25.2_91.
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Kessler, Torsten, Ralf Bieker, Teresa Padro, et al. "Inhibition of Tumor Growth by RGD Peptide Directed Delivery of Truncated Tissue Factor to the Tumor Vasculature." Blood 104, no. 11 (2004): 1934. http://dx.doi.org/10.1182/blood.v104.11.1934.1934.
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Abstract Selective activation of blood coagulation in tumor vessels with subsequent tumor infarction is a promising anticancer strategy. To this end, a fusion protein consisting of the extracellular domain of tissue factor (truncated tissue factor, tTF) was fused to the peptide GRGDSP selectively targeting avb3 and avb5 integrins on tumor endothelial cells. The fusion protein tTF-RGD retained its thrombogenic and integrin binding activity as demonstrated by coagulation assays and binding assays with purified avb3 and endothelial cells. In vivo studies in mice bearing established human adenocarcinomas (CCL185), human melanoma (M21) and human fibrosarcoma (HT1080) revealed that i.v. administration of tTF-RGD induced partial or complete thrombotic occlusion of tumor vessels as indicated by histological analysis. Furthermore, treatment studies showed that tTF-RGD but not untargeted tTF induced significant tumor growth retardation or regression in all three types of solid tumors in mice without apparent side effects such as thrombosis in liver, kidney, heart or lung. Thus, selective thrombosis in the tumor vasculature induced by tTF-RGD may be a promising strategy for the treatment of cancer.
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Li, Qianhong, Yiru Guo, Wei Tan, et al. "Gene therapy with iNOS provides long-term protection against myocardial infarction without adverse functional consequences." American Journal of Physiology-Heart and Circulatory Physiology 290, no. 2 (2006): H584—H589. http://dx.doi.org/10.1152/ajpheart.00855.2005.
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Previous studies have shown that gene therapy with inducible nitric oxide synthase (iNOS) protects against myocardial infarction at 3 days after gene transfer. However, the long-term effects of iNOS gene therapy on myocardial ischemic injury and cardiac function are unknown. To address this issue, we used a recombinant adenovirus 5 (Ad5) vector (Av3) with deletions of the E1, E2a, and E3 regions, which enables long-lasting recombinant gene expression for at least 2 mo due to lack of inflammation. Mice received intramyocardial injections in the left ventricular (LV) anterior wall of Av3/LacZ (LacZ group) or Av3/iNOS (iNOS group); 1 or 2 mo later, they were subjected to myocardial infarction (30-min coronary occlusion followed by 4 h of reperfusion). Cardiac iNOS gene expression was confirmed by immunoblotting and activity assays at 1 and 2 mo after gene transfer. In the iNOS group, infarct size (percentage of risk region) was significantly reduced ( P < 0.05) both at 1 mo (24.2 ± 3.4%, n = 6, vs. 48.0 ± 3.6%, n = 8, in the LacZ group) and at 2 mo (23.4 ± 3.1%, n = 8, vs. 36.6 ± 2.4%, n = 7). The infarct-sparing effects of iNOS gene therapy were as powerful as those observed 24 h after ischemic preconditioning (23.1 ± 3.4%, n = 10). iNOS gene transfer had no effect on LV function or dimensions up to 8 wk later (echocardiography). These data demonstrate that iNOS gene therapy mediated by the Av3 vector affords long-term (2 mo) cardioprotection without inflammation or adverse functional consequences, a finding that provides a rationale for further preclinical testing of this therapy.
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Vardy, Emma R. L. C., Rainer Hinz, Tobias Langheinrich, et al. "IC-P-085: Amyloid PET using 18F-AV45 in Frontotemporal Dementia." Alzheimer's & Dementia 6 (July 2010): S35. http://dx.doi.org/10.1016/j.jalz.2010.05.099.
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Rice, Julie, Marta Scatena, and Cecilia Giachelli. "MOLECULAR MEDIATORS OF AVB3 INDUCED NF-KB SURVIVAL SIGNALS IN RAECS." Cardiovascular Pathology 13, no. 3 (2004): 56–57. http://dx.doi.org/10.1016/j.carpath.2004.03.165.
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Wang, K., B. D. E. Chatterton, M. Attrep Jr., and C. J. Orth. "Late Ordovician mass extinction in the Selwyn Basin, northwestern Canada: geochemical, sedimentological, and paleontological evidence." Canadian Journal of Earth Sciences 30, no. 9 (1993): 1870–80. http://dx.doi.org/10.1139/e93-165.
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We present a detailed study of the trace element and stable isotope geochemistry, sedimentology, and fossil distributions in two Avalanche Lake (AV4B, AV1) Ordovician–Silurian boundary sections in the Selwyn Basin. Trilobites and conodonts indicate a profound extinction at the end of the Ordovician, which is constrained stratigraphically within a <60 cm interval at AV4B. Facies analysis suggests that the extinction interval coincides with the maximum shallowing (low stand of sea level), which was probably caused by a galcioeustatic regression induced by the Late Ordovician Gondwanan glaciation. The extinction crisis is also signalled by the change in carbonate δ13C: a sudden "Strangelove ocean" δ13C excursion (>3‰ in magnitude) is recorded in the extinction interval. Iridium abundances (<0.051 ppb) in the extinction interval are low and fail to provide evidence for an impact. The highest Ir abundance is found to be associated with reduced sedimentation in a condensed horizon. Cerium anomalies indicate a short period of basin ventilation in the otherwise anoxic Selwyn Basin. The extinction occurred during the time of this basin ventilation, which was probably caused by the cold climate during the glaciation. The ventilation may have triggered upwelling of the deep water through vertical advection, bringing up toxic material, poisoning the upper-water photic zone, and causing the extinction.
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A. Kinney, William, Diane K. Luci, Rosemary J. Santulli, et al. "A Concise Synthesis of an Indenopyrrolidine-based Dual avb3/avb5 Integrin Antagonist." HETEROCYCLES 62, no. 1 (2004): 543. http://dx.doi.org/10.3987/com-03-s(p)49.
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ZHANG Li, ZHANG Chun Li, YAN Ping, et al. "Design, Preparation and Characterization of Cyclic RGD Dimer for Targeting Integrin aVb3." Journal of Convergence Information Technology 6, no. 12 (2011): 442–50. http://dx.doi.org/10.4156/jcit.vol6.issue12.56.
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Sun, Guangyao, Wenjing Li, Shidong Ji, Xun Cao, and Ping Jin. "Heterogeneity in optimized solid-state synthesis of metavanadate AVO3 (A = Rb, Cs)." Research on Chemical Intermediates 43, no. 1 (2016): 341–52. http://dx.doi.org/10.1007/s11164-016-2625-5.
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Bertolini, Gladson Ricardo Flor, Cecília Matilde Padilha Matos, Elisângela Lourdes Artifon, Deisi Ferrari, and Rogério Fonseca Vituri. "Avaliação funcional da nocicepção do joelho de ratos tratada com laser de baixa potência e natação." Revista Brasileira de Medicina do Esporte 17, no. 1 (2011): 45–48. http://dx.doi.org/10.1590/s1517-86922011000100009.
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O objetivo deste estudo foi avaliar e comparar os efeitos do laser de baixa potência e da natação forçada em modelo de nocicepção articular, de ratos Wistar, avaliando a dor de forma funcional, pelo tempo de elevação da pata (TEP) durante marcha em cilindro metálico. Foram utilizados 32 ratos Wistar, divididos em quatro grupos: GC - animais submetidos à indução de nocicepção no joelho direito e não tratados; GL - nocicepção e tratados com laser de baixa potência 670nm, 8J/cm²; GN - nocicepção e natação por 10 minutos em água a 30-32ºC; GNL - nocicepção e tratados com natação e laser. Para realizar a nocicepção foi injetado, no espaço tibiofemoral medial direito, 50µL de formalina 5%. A avaliação funcional da dor foi realizada com o teste de incapacidade funcional, que avalia o tempo de pata no ar (TEP) da marcha durante um minuto sobre um cilindro metálico, as avaliações ocorreram antes da indução da nocicepção (AV1), após 15 (AV2) e 30 minutos (AV3) da mesma, sendo que após a AV2, ocorreram os protocolos de tratamento. Os resultados mostraram que o grupo laser foi o único a apresentar restauração dos valores na AV3, comparando com AV1. GN foi o único a não apresentar redução ao comparar AV3 com AV2. Conclui-se que, pela avaliação funcional, o laser de baixa potência apresentou efeitos analgésicos, enquanto a natação produziu aumento do quadro de dor, o qual foi parcialmente revertido com o uso do laser associado
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Shergur, J., R. S. Popelka, J. D. Robertson, and D. Pollack. "Distinct Chemical Patterns in Late Mississippian Caborn-Welborn Ceramics of the Lower Ohio River Valley." North American Archaeologist 24, no. 3 (2003): 221–43. http://dx.doi.org/10.2190/pt2q-av4x-uawx-ej1a.
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Kroft, Steven H., Rana Domiati-Saad, William G. Finn, et al. "Precursor B-Lymphoblastic Transformation of Grade I Follicle Center Lymphoma." American Journal of Clinical Pathology 113, no. 3 (2000): 411–18. http://dx.doi.org/10.1309/y2yd-una2-c95r-avm3.
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Sonnenberg, Stephen M., and William Myerson. "The prevention and treatment of organizationally induced trauma." International Journal of Psychoanalysis 87, no. 1 (2006): 243–46. http://dx.doi.org/10.1516/fel2-ava3-t04r-fp33.
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Ortiz, Enrique, and S. Kim MacGregor. "Effects of Logo Programming on Understanding Variables." Journal of Educational Computing Research 7, no. 1 (1991): 37–50. http://dx.doi.org/10.2190/av4a-4hrh-euq4-8kpj.
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Stanley, Ian M., Sarah Peters, and Peter Salmon. "A Primary Care Perspective on Prevailing Assumptions about Persistent Medically Unexplained Physical Symptoms." International Journal of Psychiatry in Medicine 32, no. 2 (2002): 125–40. http://dx.doi.org/10.2190/avm3-8gu8-jw70-5rx5.
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Objective: To re-examine the widespread assumption that medically unexplained physical symptoms represent discrete syndromes resulting from somatization of mental illness. Method: Primary care patients ( N = 223) with medically unexplained symptoms of at least one year's duration were recruited to a study of exercise therapy. Data gathered from patients, from their general practitioners, and from medical records were used to examine relationships between self-defined disability, symptoms, mental state, and use of health care. Results: Levels of disability and health care use were both raised, but were only weakly correlated. While most patients were depressed and/or anxious, a minority (14 percent) were neither. Although mental state correlated with disability, health care use was unrelated to either. Among a wide range of recorded symptoms, few correlations were found to support the existence of discrete syndromes. Analysis of agreement between patients and their doctors in assigning symptoms to broadly defined “syndromes” appears to reflect collaboration that is largely expedient. Conclusions: In this sample of primary care patients with persistent unexplained physical symptoms, we found little evidence of discrete somatic syndromes. The level of health care use is no indication of mental state or level of disability, and the findings are equally consistent with depression or anxiety being secondary to disability and its consequences as with them being primary. The observed collaboration between patients and their doctors carries the risk of shaping, reinforcing, and legitimizing dubious syndromes.
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Smallwood, Jonathan, Marc Obsonsawin, Simona F. Baracaia, Helga Reid, Rory O'Connor, and Derek Heim. "The Relationship between Rumination, Dysphoria, and Self-Referent Thinking: Some Preliminary Findings." Imagination, Cognition and Personality 22, no. 4 (2003): 317–42. http://dx.doi.org/10.2190/2n80-avm3-4a23-leaj.
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Charlton, Steve, and Paul Bakan. "Cognitive Complexity and Creativity." Imagination, Cognition and Personality 8, no. 4 (1989): 315–22. http://dx.doi.org/10.2190/c21k-gm0l-av83-3p4h.
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A number of similar characteristics between creative and cognitively complex people suggests a positive relationship between these variables. However, past empirical research, using purported measures of creativity and cognitive complexity, has reported equivocal findings. The present study hypothesized a positive relationship between high creativity (How Do You Think Test) and cognitive complexity. The subjects were fifty-six female and fifty-six male university students. As predicted, cognitive complexity was significantly related to creativity. In addition, females were significantly more cognitively complex.
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Dallacorte, Dauana Arielli, Giovana Silva Sprizon, Kimberly Suellin Bueno, Pâmela Giovana Hotz, Fernando Amâncio Aragão, and Gladson Ricardo Flor Bertolini. "Comparison of the effects of interferential current between male and female healthy adults." Scientia Medica 27, no. 3 (2017): 27660. http://dx.doi.org/10.15448/1980-6108.2017.3.27660.
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***Comparison of the effects of interferential current between male and female healthy adults***AIMS: To assess accommodation phenomena characteristics (threshold, time and amplitude/intensity) during stimulation with interferential current, comparing male and female healthy adults.METHODS: A non randomized clinical trial with intentional sampling by gender included 30 healthy adult volunteers aged between 18 and 25 years, who were divided in two groups (15 in the Female Group and 15 in the Male Group) and received a tetrapolar interferential current for 20 minutes, close to L1 and L5 vertebrae. The subjects were instructed to refer an intense but comfortable paresthesia sensation and to report the moment it diminished (accommodation), requiring increasing of the current intensity. The first three events of accommodation (AV1, AV2 and AV3), including time and amplitude threshold, were analyzed. The differences from AV1 to AV2 (D1) and AV2 to AV3 (D2) were also considered. The number of accommodations for each subject during the 20 minutes experiment was identified. ANOVA and Student's t-test were used for analysis and the significance level was set at 5%. RESULTS: In the Male Group the mean time for accommodation was higher in AV3 compared to AV1 and AV2. In the Female Group the accommodation mean time was higher in AV3 in relation to AV2, and in AV2 in relation to AV1. No differences were found in the Male Group for D1 and D2, but in the Female Group, D2 was superior to D1. Women were accommodated more quickly than men in all three assessments, but the differences between one evaluation and another were constant considering both groups. Both groups showed similar current intensity behavior comparing the three evaluations within the same group. In the comparison between groups, women had lower mean values of intensity in the three evaluations. The Female Group had 7.5±1.5 accommodations, and the Male Group had 5.9±2.0 accommodations (p=0.0367) during the 20 minutes of the experiment.CONCLUSIONS: In this sample of healthy young adults, men required higher interferential current amplitude to obtain a comfortable paresthesia and took more time to have accommodations, while women had more accommodation episodes.
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Treshchalina, Yelena, Saida Karshieva, Natalya Anisimova, Suriya Sitdikova, and Mikhail Kiselevskiy. "ANTIINTEGRIN AVG3 SAV-RGD AS COMBINANT FOR DTIC WITH HUMAN AMELANOTIC SKIN MELANOMA." Problems in oncology 65, no. 2 (2019): 298–302. http://dx.doi.org/10.37469/0507-3758-2019-65-2-298-302.
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Introduction. The avB3 integrin (cell adhesion molecule) plays the role of the receptor, including, metalloproteinase matrix 2, involved in melanoma metastasis. We have been characterized as an antimelanoma original anti-integrin agent SAV-RGD (lyo-SAV-RGD), specifically binding to melanoma cells by means of the Arg-Gly-Asp tripeptide. More significant inhibited effect was obtained on amelanotic human skin melanoma MeWo. Accordingly, the experimental evaluation of the effectiveness of lyo-SAV-RGD in combination with the «gold» standard of antimelanoma chemotherapy dacarbazine (DTIC) is relevant. Objective: a comparative study of the combination of DTIC+lyo-SAV-RGD on the model of pigmented melanoma of human skin MeWo. Material and methods. The model of human skin melanoma MeWo in vivo/in vitro: s.c. xenografts in Balb/c nude mice, sensitive to DTIC cell line MeWo and obtained prospectively stable subline MeWo/DTIC was used. In vitro experiments the time of cell doubling in both models was determined and the individual range of agent concentrations was studied. Therapy with DTIC+lyo-SAV-RGD were administered in simultaneously sequentially, first the single 150 mg/kg DTIC, then lyo-SAV-RGD 9-fold course in the total dose of 900 mg/kg (the first dose is doubled). To control of the group with single dose 250 mg/kg of DTIC close to the maximum tolerated dose (MTD). All experiments were performed by standard methods using significant evaluation criteria and adequate statistical processing of the results (p<0.05). Results. For MeWo and MeWo/DTIC cells with a certain prospectively identical doubling time of the doubling time of tumor cells (Tpot) at the level of 23.0±2.3 h and 23.1±1.8 h, DTIC was practically non-cytotoxic, IC50=410±4 g/ml and IC50=860±27 g/ml (IC50<1o0 g/ml). However, the absolute value of the active concentrations of DTIC was significantly less known for murine pigmented melanoma, 1200-1400 g/ ml. Lyo-SAV-RGD, on the contrary, was cytotoxic for both melanoma variants at the same level, IC50=100±3.1 g/ml, and in the range from 1,0 to 100 g/kg caused cell death in direct dependence on the concentration. On s.c. MeWo xenografts DTIC at the dose of 250 mg/kg was effective at T/ C<30% (criterion T/C<42%) with partial death of mice from toxicity. The combination of DTIC+lyo-SAV-RGD showed an identical effect regardless of dose reduction by 40%, T/C=38% (p=0.001). Conclusion. A comparative study on the model of human skin melanoma MeWo revealed in vitro the absence of significant cytotoxicity of DTIC and at the same time cytotoxicity of anti-integrin avB3 lyo-SAV-RGD for MeWo and MeWo/DTIC cells. On xenografts MeWo combined therapy DTIC+lyo-SAV-RGD with dose reduction cytostatic 40% made it possible to obtain the maximum antitumor effect (T/C=38% vs 30%) with improved tolerability. The obtained data suggest that the introduction of anti-integrin avB3 into the scheme with DTIC is advisable to increase the selectivity of cytotoxic action of cytostatics.