Ocorrência e fatores de risco da infecção pelo vírus da língua azul em bovinos no Estado de Pernambuco / Occurrence and risk factors of the Bluetongue Virus infeccion in cattle in Pernambuco state, Brazil

Objetivou-se com este estudo determinar os aspectos epidemiológicos da infecção pelo Vírus da Língua Azul (VLA) em bovinos leiteiros na microrregião de Garanhuns, Estado de Pernambuco, Brasil. Foram coletadas 384 amostras de soro de bovinos fêmeas em idade reprodutiva, procedentes de 20 propriedades dos 19 municípios que compõem a região. As amostras foram testadas com a prova de imunodifusão em gel de agarose (IDGA) para pesquisa de anticorpos anti-VLA. Observou-se ocorrência de 71,3% (274/384; IC 95% - 66,5% - 75,7%) de animais positivos. Em 100% das propriedades houve ao menos um animal soropositivo. Os fatores de risco identificados foram: presença de áreas alagadas (OR=11,8; p=0,001), não realizar controle de insetos (OR=2,1; p=0,033), rebanho aberto (OR=2,1; p=0,001) e utilização de inseminação artificial (OR=8,8; p=0,003). Este é o primeiro registro de detecção de anticorpos anti-VLA em bovinos no Estado de Pernambuco. Conclui-se que a infecção pelo VLA ocorre em bovinos na área estudada e sugere-se que medidas de controle baseadas no manejo higiênico-sanitário e biosseguridade sejam implantadas para evitar a propagação do vírus, tais como: eliminação de áreas alagadiças; controle de insetos; utilizar sêmen na inseminação artificial com atestado sanitário; realizar exames sorológicos ao adquirir animais.(AU)

The objective of this study was to determine epidemiological aspects of Bluetongue Virus (BTV) infection on dairy cattle in the Garanhuns microregion, Pernambuco state, Brazil. Three hundred eighty-four (384) serum samples of female bovines of reproductive age were collected from 20 farms of the 19 municipalities that make up the region. Samples were tested with the agarose gel immunodiffusion test (AGID) for anti-VLA antibody screening. There were 71.3% (274/384, 95% CI - 66.5% - 75.7%) positive animals. In 100% of the farms there was at least one seropositive animal. The risk factors identified were: presence of flooded areas (OR=11.8, p=0.001), absence of insect control (OR=2.1, p=0.033), open herd (OR=2.1; p=0.001) and use of artificial insemination (OR=8.8, p=0.003). This is the first record of detection of anti-BTV antibodies in cattle in Pernambuco state. It is concluded that BTV infection occurs in cattle in the studied area, and it is suggested that control measures based on hygienic-sanitary management and biosecurity are in place to prevent the spread of the virus, such as elimination of wetlands; Insect control; semen used in artificial insemination with health certificate; Serological tests when acquiring animals.(AU)

Plasma concentration of 125 I labeled and polyethylene glycol conjugation to EILDVP peptide in mice / 中国药理学通报

Aim To study the pharmacokinetics of po-lyethylene glycol conjugation on EILDVP peptide in mice by injection through tail vein.Methods KM mice,saturated thyroid gland with compound of NaI, were injected for 1 25 I labeled EILDVP-Tyr-NH2 ,EILD-VP-Cys (mPEG2000-MAL)-Tyr-NH2 and EILDVP-Cys (mPEG20000-MAL)-Tyr-NH2 peptides (1 25 I:5 mL · kg -1 volume 3.441 GBq·L -1 concentration)by tail intravenous,respectively.Blood samples at different time intervals were obtained,blood plasma was separa-ted,and the radioactivity of precipitation after trichloro-acetic acid (TCA)treatment was tested.According to standard curve equation, the plasma concentration curve and pharmocokinetic parameters were depicted by means of 3P97 pharmocokinetics software.Results Concentration range of 3.75 ~480 μg·L -1 of three 1 25 I labled peptides in plasma from mice had good line-ar relationship.Recovery of method was 88.92% ~ 1 06.66%,and RSD <1 0%.The half-life time (T1 /2 ) of EILDVP-Tyr-NH2 peptide modified by mPEG2000 and mPEG20000 ,labled by 1 25 I was 0.43h and 1 .94h,re-spectively,which was 1 .54 times and 6.93 times that of prototype peptide (T1 /2 =0.28h),and the clear-ances (Cl)were 1 .23 times and 24.71 times,respec-tively.The apparent distribution volume (V)values of the three species were small,which might mainly dis-tributed in the plasma.Conclusions Suitable for mo-lecular mass mPEG modified the EILDVP peptides could extend to maintain time in vivo,which could play a positive role in improving efficacy.In the experimen-tal range,EILDVP peptide modified by larger molecu-lar mass of mPEG20000 has better effect.

Simultaneous Inhibition of CXCR4 and VLA-4 Exhibits Combinatorial Effect in Overcoming Stroma-Mediated Chemotherapy Resistance in Mantle Cell Lymphoma Cells

There is growing evidence that crosstalk between mantle cell lymphoma (MCL) cells and stromal microenvironments, such as bone marrow and secondary lymphoid tissues, promotes tumor progression by enhancing survival and growth as well as drug resistance of MCL cells. Recent advances in the understanding of lymphoma microenvironment have led to the identification of crucial factors involved in the crosstalk and subsequent generation of their targeted agents. In the present study, we evaluated the combinatory effect of blocking antibodies (Ab) targeting CXCR4 and VLA-4, both of which were known to play significant roles in the induction of environment-mediated drug resistance (EMDR) in MCL cell line, Jeko-1. Simultaneous treatment with anti-CXCR4 and anti-VLA-4 Ab not only reduced the migration of Jeko-1 cells into the protective stromal cells, but also enhanced sensitivity of Jeko-1 to a chemotherapeutic agent to a greater degree than with either Ab alone. These combinatorial effects were associated with decreased phosphorylation of ERK1/2, AKT and NF-kappaB. Importantly, drug resistance could not be overcome once the adhesion of Jeko-1 to the stromal occurred despite the combined use of Abs, suggesting that the efforts to mitigate migration of MCLs should be attempted as much as possible. Our results provide a basis for a future development of therapeutic strategies targeting both CXCR4 and VLA-4, such as Ab combinations or bispecific antibodies, to improve treatment outcomes of MCL with grave prognosis.

Involvement of VLA-5 and VLA-6 in facilitating endothelium-oriented transmigration of hematopoietic stem/progenitor cells / 吉林大学学报(医学版)

Objective:To investigate whether VLA-5 and VLA-6 are involved in facilitating en-dothelium-oriented transmigration of hematopoietic stem/progenitor cells. Methods:Purified hu-man CD34+ cells were subject to ex vivo transmigration assay and blocking experiments throughtranswell filter inserts coated with human umbilical vein endothelial cells (HUVECs). Four-colorfluorescence-activated cell sorting (FACS) analysis was applied to detect the expression profilesof adhesion molecules and chemokine receptor CXCR-4 on CD34bright cells. Results:Stromal cell-derived factor (SDF)-1-induced transmigrations of both mobilized peripheral blood (mPB)-(56.6±20. 1)% and bone marrow (BM)- (15. 6±1. 8)% derived CD34+ cells were significantlyfacilitated through HUVECs-coated transwell filter insters compared with noncoated ones, whichwere efficiently blocked by preincubation of CD34+ cells with neutralizing antibodies to VLA-5,or VLA-6, or both of them; meanwhile the proportions of migrating CD34+ cells through bothHUVECs-coated and noncoated transwell filter inserts in BM were significantly lower than thosein mPB; the different percentages of migrating CD34+ cells between in mPB and BM were corre-lated with their variable expressions of VLA-5 and VLA-6, but not for VLA-4 or chemokine re-ceptor CXCR-4. Conclusion:Facilitating HS/PCs transmigrations through HUVECs are involvedin both VLA-5 and VLA-6.

Cell cycling status of human cord blood CD34+ cells during ex vivo expansion is related to the level of very late antigen expression

Very late antigen-4 (VLA-4), which binds to the extracellular matrix protein fibronectin, is an integrin molecule known to be modulated during mobilization of CD34+ cells, and to be involved in signaling the mobilization stimuli. On the hypothesis that cell cycling status might be different depending on the level of VLA-4 expression, we investigated the DNA contents of human cord blood CD34+ cells during ex vivo expansion by recombinant human thrombopoietin and flt3-ligand with simultaneous measurement of surface VLA-4 at the 1st and 4th week. During this ex vivo expansion, expression of VLA-4 increased and almost all cells became VLA-4+ until the 4th day of culture. Expression of VLA-4 was maintained in the major population of the cultured cells until the 4th week. The cells in S/G2/M phase were greater in number in VLA-4 high fraction than in VLA-4 low fraction (n=4, p<.001). Furthermore, the fraction of cells in S/G2/M phase increased as the expression of VLA-4 became higher. These results suggest that cord blood CD34+ cells expressing high levels of VLA-4 have more proliferative activities.

Vla-Integrin Exprfs Ion In Articular Cartilage / 대한류마티스학회지

OBJECTIVE: The adhesion molecule that mediate cell-cell and cell-extracellular matrix adhes.ion provides very important role in growth and differentiation of cells and tissue. VLA integrin is a prototype of adhesion molecule which participate in cell-cell and cell-extracellular matrix interacton, especially for collagen, laminin and fibronectin. The biologic functions of VLA-integrin are very diverse. Cartilage is the target tissue of various arthritides including rheumatoid arthritis and osteoarthritis and the process of homeostasis in cartilage matrix may be very important in preservation of cartilage. Although VLA integrin may participate in the process of cartilage degeneration and repair mechanism, tissue.distribution and exact role of VLA integtin in cartilage was not yet clearly defined. METHODS:Immunohistochemical analysis of VLA-integrin in cryostat section of articular cartilage was conducted using monoclonal antibody and avidin-biotin complex method. Analysis was performed in 10 rheumatoid arthritis specimens, 7 osteoarthritis specimens and 1 normal control. RESULTS: 1) Normal cartilage showed strong and diffuse stain with CD29, CD51 and moderate stain of VLA-5. Staining pattern of VLA-1 and 3 was inconstant and weak in intensity. 2) The intensity of VLA expression in articular cartilage of osteoarthritis was upregulated chiefly in CD29, CD51 and slightly in VLA-5. The positive rate of VLA-1 and 3 was similar to that of normal cartilage though the intensity was increased especially at cluster of chondrocytes. 3) VLA-integrin expression of rheumatoid arthritis cartilage was similar to that of osteoarthritis cartilage. CONCLUSION: VLA integrins functioning as fibronectin receptor such as VLA-5 and alpha, beta1 were upregulated in osteoarthritis and rheumatoid arthritis. Intensity was increased at clusters of chondrocytes. It was able to presume from above findings that VLA molecule has some role in the maintenance and repair of articular cartilage. The regulation of expression by cytokines and growth factors and exact function of VLA molecule in cartilage have to be elucidated.

The Role of VCAM-1/VLA-4 in the Activation of Allogenic T Cells by Murine Macrophages / 中国肿瘤生物治疗杂志

Vascular cell adhesion molecule 1 (VCAM - 1) is a member of immunoglobulin superfamily. The principal ligand for VCAM - 1 is integrin ?4|?1/VLA - 4(very late antigen 4). In recent years, VCAM - 1 was found to be expressed on macrophages and dendritic cells, but little is known about its identity on these professional antigen presenting cells (APC). In the present study we analyzed VCAM - 1 expression on macrophages by fluorescence - activated cell sorting (FACS) and found that VCAM- 1 was constitutively expressed on macrophages and its expression level was up-regulated by soluble tumor associated antigen (TAA: freeze - thaw lysates of FBL - 3 tumor cells) and TNF - a. In macrophages and allogenic T cells mixed lymphocyte reaction (MLR) assays, we observed that blocking VCAM - 1/VLA - 4 interaction with anti - VCAM - 1 or anti - VLA - 4 mAbs caused significant inhibition of the proliferative response and inhibition of IL - 2 production. These findings suggest that VCAM - 1 on macrophages not only allows for increased cell-to-cell contact through adhesive interaction but also plays a role in the costimulation of T cells via its interaction with VLA-4.

Effect of angelica polysaccharides on adhesion molecules expressions in murine hematopoietic cells / 重庆医科大学学报

Objective:To explore the effect of angelica polysaccharide(APS)on adhesion molecules expressions in murine hematopoietic cells,in order to provide experimental evidence of APS on hematopoietic regulation and the mechanism of mobilizing.Methods:Techniques of peripheral blood white blood cell(WBC)and bone marrow mononuclear cells(MNC)count were made.Flow cytometry detected the rate of Sca-1~+ cells in peripheral blood and bone marrow and the expression of CD49d (VLA-4 of a chain),CD44 on bone marrow MNC and Sca-1~+ cells.Results:1.In APS group(4mg/kg):the number of peripheral blood WBC and Sca-1~+ cells were markedly higher than that of NS group(P