Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Filtros adicionais











Intervalo de ano
1.
Cell Host Microbe ; 25(1): 39-48.e5, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30629917

RESUMO

Passive administration of monoclonal antibodies (mAbs) is a promising therapeutic approach for Ebola virus disease (EVD). However, all mAbs and mAb cocktails that have entered clinical development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against outbreak-causing Bundibugyo virus (BDBV) and Sudan virus (SUDV). Here, we advance MBP134, a cocktail of two broadly neutralizing human mAbs, ADI-15878 from an EVD survivor and ADI-23774 from the same survivor but specificity-matured for SUDV GP binding affinity, as a candidate pan-ebolavirus therapeutic. MBP134 potently neutralized all ebolaviruses and demonstrated greater protective efficacy than ADI-15878 alone in EBOV-challenged guinea pigs. A second-generation cocktail, MBP134AF, engineered to effectively harness natural killer (NK) cells afforded additional improvement relative to its precursor in protective efficacy against EBOV and SUDV in guinea pigs. MBP134AF is an optimized mAb cocktail suitable for evaluation as a pan-ebolavirus therapeutic in nonhuman primates.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Bem-Estar do Animal , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/uso terapêutico , Antivirais , Modelos Animais de Doenças , Ebolavirus/patogenicidade , Epitopos/imunologia , Feminino , Filoviridae/imunologia , Cobaias , Doença pelo Vírus Ebola/virologia , Humanos , Imunoterapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteínas Recombinantes/imunologia , Resultado do Tratamento
2.
Cell Host Microbe ; 25(1): 49-58.e5, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30629918

RESUMO

Recent and ongoing outbreaks of Ebola virus disease (EVD) underscore the unpredictable nature of ebolavirus reemergence and the urgent need for antiviral treatments. Unfortunately, available experimental vaccines and immunotherapeutics are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against other ebolaviruses associated with EVD, including Sudan virus (SUDV) and Bundibugyo virus (BDBV). Here we show that MBP134AF, a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs), affords unprecedented effectiveness and potency as a therapeutic countermeasure to antigenically diverse ebolaviruses. MBP134AF could fully protect ferrets against lethal EBOV, SUDV, and BDBV infection, and a single 25-mg/kg dose was sufficient to protect NHPs against all three viruses. The development of MBP134AF provides a successful model for the rapid discovery and translational advancement of immunotherapeutics targeting emerging infectious diseases.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Ebolavirus/patogenicidade , Furões/virologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Bem-Estar do Animal , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/administração & dosagem , Linhagem Celular , Cercopithecus aethiops , Modelos Animais de Doenças , Feminino , Filoviridae/imunologia , Infecções por Filoviridae/imunologia , Infecções por Filoviridae/prevenção & controle , Infecções por Filoviridae/virologia , Glicoproteínas/imunologia , Cobaias , Células HEK293 , Doença pelo Vírus Ebola/virologia , Humanos , Células Matadoras Naturais , Macaca , Macaca fascicularis , Masculino , Primatas , Análise de Sobrevida , Resultado do Tratamento , Proteínas Virais/imunologia
3.
Sci Rep ; 8(1): 14782, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30283152

RESUMO

Land subsidence associated with overexploitation of aquifers is a hazard that commonly affects large areas worldwide. The Lorca area, located in southeast Spain, has undergone one of the highest subsidence rates in Europe as a direct consequence of long-term aquifer exploitation. Previous studies carried out on the region assumed that the ground deformation retrieved from satellite radar interferometry corresponds only to vertical displacement. Here we report, for the first time, the two- and three-dimensional displacement field over the study area using synthetic aperture radar (SAR) data from Sentinel-1A images and Global Navigation Satellite System (GNSS) observations. By modeling this displacement, we provide new insights on the spatial and temporal evolution of the subsidence processes and on the main governing mechanisms. Additionally, we also demonstrate the importance of knowing both the vertical and horizontal components of the displacement to properly characterize similar hazards. Based on these results, we propose some general guidelines for the sustainable management and monitoring of land subsidence related to anthropogenic activities.

4.
J Infect Dis ; 218(suppl_5): S565-S573, 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29982718

RESUMO

Background: The 2013-2016 Ebola virus disease (EVD) epidemics in West Africa highlighted a need for effective therapeutics for treatment of the disease caused by filoviruses. Monoclonal antibodies (mAbs) are promising therapeutic candidates for prophylaxis or treatment of virus infections. Data about efficacy of human mAb monotherapy against filovirus infections in preclinical nonhuman primate models are limited. Methods: Previously, we described a large panel of human mAbs derived from the circulating memory B cells from Bundibugyo virus (BDBV) infection survivors that bind to the surface glycoprotein (GP) of the virus. We tested one of these neutralizing mAbs that recognized the glycan cap of the GP, designated mAb BDBV289, as monotherapy in rhesus macaques. Results: We found that recombinant mAb BDBV289-N could confer up to 100% protection to BDBV-infected rhesus macaques when treatment was initiated as late as 8 days after virus challenge. Protection was associated with survival and decreased viremia levels in the blood of treated animals. Conclusions: These findings define the efficacy of monotherapy of lethal BDBV infection with a glycan cap-specific mAb and identify a candidate mAb therapeutic molecule that could be included in antibody cocktails for prevention or treatment of ebolavirus infections.

5.
Sci Transl Med ; 9(384)2017 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-28381540

RESUMO

As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (mAbs) are a platform technology in wide use for autoimmune and oncology indications. Previously, we described human mAbs that can protect mice from lethal challenge with Marburg virus. We demonstrate that one of these mAbs, MR191-N, can confer a survival benefit of up to 100% to Marburg or Ravn virus-infected rhesus macaques when treatment is initiated up to 5 days post-inoculation. These findings extend the small but growing body of evidence that mAbs can impart therapeutic benefit during advanced stages of disease with highly virulent viruses and could be useful in epidemic settings.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Infecções por Filoviridae/tratamento farmacológico , Filoviridae/fisiologia , Doença do Vírus de Marburg/tratamento farmacológico , Marburgvirus/fisiologia , Animais , Proteção Cruzada , Infecções por Filoviridae/virologia , Cobaias , Humanos , Macaca fascicularis , Macaca mulatta , Doença do Vírus de Marburg/virologia , Projetos Piloto
6.
Sensors (Basel) ; 16(10)2016 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-27706048

RESUMO

In this work a parametric multi-sensor Bayesian data fusion approach and a Support Vector Machine (SVM) are used for a Change Detection problem. For this purpose two sets of SPOT5-PAN images have been used, which are in turn used for Change Detection Indices (CDIs) calculation. For minimizing radiometric differences, a methodology based on zonal "invariant features" is suggested. The choice of one or the other CDI for a change detection process is a subjective task as each CDI is probably more or less sensitive to certain types of changes. Likewise, this idea might be employed to create and improve a "change map", which can be accomplished by means of the CDI's informational content. For this purpose, information metrics such as the Shannon Entropy and "Specific Information" have been used to weight the changes and no-changes categories contained in a certain CDI and thus introduced in the Bayesian information fusion algorithm. Furthermore, the parameters of the probability density functions (pdf's) that best fit the involved categories have also been estimated. Conversely, these considerations are not necessary for mapping procedures based on the discriminant functions of a SVM. This work has confirmed the capabilities of probabilistic information fusion procedure under these circumstances.

7.
Proc Natl Acad Sci U S A ; 113(16): 4458-63, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27044104

RESUMO

Countermeasures against potential biothreat agents remain important to US Homeland Security, and many of these pharmaceuticals could have dual use in the improvement of global public health. Junin virus, the causative agent of Argentine hemorrhagic fever (AHF), is an arenavirus identified as a category A high-priority agent. There are no Food and Drug Administration (FDA) approved drugs available for preventing or treating AHF, and the current treatment option is limited to administration of immune plasma. Whereas immune plasma demonstrates the feasibility of passive immunotherapy, it is limited in quantity, variable in quality, and poses safety risks such as transmission of transfusion-borne diseases. In an effort to develop a monoclonal antibody (mAb)-based alternative to plasma, three previously described neutralizing murine mAbs were expressed as mouse-human chimeric antibodies and evaluated in the guinea pig model of AHF. These mAbs provided 100% protection against lethal challenge when administered 2 d after infection (dpi), and one of them (J199) was capable of providing 100% protection when treatment was initiated 6 dpi and 92% protection when initiated 7 dpi. The efficacy of J199 is superior to that previously described for all other evaluated drugs, and its high potency suggests that mAbs like J199 offer an economical alternative to immune plasma and an effective dual use (bioterrorism/public health) therapeutic.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Antivirais/farmacologia , Febre Hemorrágica Americana/tratamento farmacológico , Febre Hemorrágica Americana/imunologia , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Cobaias , Humanos , Vírus Junin , Camundongos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/farmacologia
8.
Virology ; 490: 49-58, 2016 03.
Artigo em Inglês | MEDLINE | ID: mdl-26828465

RESUMO

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×10(6) PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Pulmão/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Animais , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Humanos , Pulmão/virologia , Macaca mulatta , Masculino
9.
Biomark Med ; 8(9): 1065-72, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25402577

RESUMO

AIM: To measure midregional pro-adrenomedullin (MR-pro-ADM) in critically ill septic patients to determine its prognostic usefulness as compared with other used biomarkers in pediatric intensive care units, C-reactive protein (CRP) and procalcitonin (PCT). MATERIALS & METHODS: Prospective observational study conducted on 95 patients. RESULTS: Mean levels of MR-pro-ADM were significantly higher when patients needed mechanical ventilation (3.2 ± 4.3 vs 1.6 ± 2.4) and inotropes (4.4 ± 5.2 vs 1.3 ± 1.2). Receiver operating characteristic curves of mortality were higher for MR-pro-ADM (cut-off value of 2.2). This marker showed higher positive predictive prognostic value than PCT and CRP (31 vs 21.6% and 15.8%, respectively). CONCLUSION: MR-pro-ADM levels are good indicators of disease severity and show better reliability than PCT and CRP for predicting in-hospital mortality.


Assuntos
Adrenomedulina/sangue , Sepse/sangue , Sepse/mortalidade , Adolescente , Criança , Pré-Escolar , Estado Terminal , Intervalo Livre de Doença , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Sepse/terapia , Taxa de Sobrevida
10.
Toxicon ; 92: 36-41, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25260254

RESUMO

Due to the fast-acting nature of ricin, staphylococcal enterotoxin B (SEB), and Clostridium perfringens epsilon toxin (ETX), it is necessary that therapeutic interventions following a bioterrorism incident by one of these toxins occur as soon as possible after intoxication. Moreover, because the clinical manifestations of intoxication by these agents are likely to be indistinguishable from each other, especially following aerosol exposure, we have developed a cocktail of chimeric monoclonal antibodies that is capable of neutralizing all three toxins. The efficacy of this cocktail was demonstrated in mouse models of lethal dose toxin challenge.


Assuntos
Anticorpos Monoclonais/farmacologia , Toxinas Bacterianas/toxicidade , Bioterrorismo/prevenção & controle , Enterotoxinas/toxicidade , Envenenamento/prevenção & controle , Proteínas Recombinantes de Fusão/farmacologia , Ricina/toxicidade , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização
11.
Nature ; 514(7520): 47-53, 2014 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-25171469

RESUMO

Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Doença pelo Vírus Ebola/tratamento farmacológico , Imunização Passiva , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/imunologia , Reações Cruzadas/imunologia , Ebolavirus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Guiné , Cobaias , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Macaca mulatta/imunologia , Macaca mulatta/virologia , Masculino , Dados de Sequência Molecular , Alinhamento de Sequência , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/imunologia , Viremia/tratamento farmacológico , Viremia/imunologia , Viremia/virologia
12.
Proc Natl Acad Sci U S A ; 111(16): 5992-7, 2014 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-24711420

RESUMO

Respiratory syncytial virus (RSV) can cause devastating lower respiratory tract infections in preterm infants or when other serious health problems are present. Immunoprophylaxis with palivizumab (Synagis), a humanized IgG1 mAb, is the current standard of care for preventing RSV infection in at-risk neonates. We have explored the contribution of effector function to palivizumab efficacy using a plant-based expression system to produce palivizumab N-glycan structure variants with high homogeneity on different antibody isotypes. We compared these isotype and N-glycoform variants with commercially available palivizumab with respect to both in vitro receptor and C1q binding and in vivo efficacy. Whereas the affinity for antigen and neutralization activity of each variant were indistinguishable from those of palivizumab, their Fcγ receptor binding profiles were very different, which was reflected in either a reduced or enhanced ability to influence the RSV lung titer in challenged cotton rats. Enhanced Fcγ receptor binding was associated with reduced viral lung titers compared with palivizumab, whereas abrogation of receptor binding led to a drastic reduction in efficacy. The results support the hypotheses that classic antibody neutralization is a minor component of efficacy by palivizumab in the cotton rat and that antibody-dependent cell-mediated cytotoxicity activity can significantly enhance the efficacy of this antiviral mAb.


Assuntos
Anticorpos Antivirais/química , Anticorpos Antivirais/uso terapêutico , Polissacarídeos/metabolismo , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/imunologia , Sigmodontinae/virologia , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/farmacologia , Complemento C1q/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Masculino , Testes de Neutralização , Ligação Proteica/efeitos dos fármacos , Receptores Fc/metabolismo , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Sigmodontinae/imunologia , Resultado do Tratamento
13.
Clin Vaccine Immunol ; 21(5): 777-82, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24574537

RESUMO

Recent incidents in the United States and abroad have heightened concerns about the use of ricin toxin as a bioterrorism agent. In this study, we produced, using a robust plant-based platform, four chimeric toxin-neutralizing monoclonal antibodies that were then evaluated for the ability to passively protect mice from a lethal-dose ricin challenge. The most effective antibody, c-PB10, was further evaluated in mice as a therapeutic following ricin exposure by injection and inhalation.


Assuntos
Antitoxinas/administração & dosagem , Imunização Passiva/métodos , Planticorpos/administração & dosagem , Envenenamento/prevenção & controle , Ricina/antagonistas & inibidores , Ricina/toxicidade , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Neutralizantes/administração & dosagem , Feminino , Camundongos Endogâmicos BALB C , Análise de Sobrevida , Resultado do Tratamento
14.
MAbs ; 5(2): 263-9, 2013 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23396091

RESUMO

Severe lower respiratory tract infection in infants and small children is commonly caused by respiratory syncytial virus (RSV). Palivizumab (Synagis(®)), a humanized IgG1 monoclonal antibody (mAb) approved for RSV immunoprophylaxis in at-risk neonates, is highly effective, but pharmacoeconomic analyses suggest its use may not be cost-effective. Previously described potent RSV neutralizers (human Fab R19 and F2-5; human IgG RF-1 and RF-2) were produced in IgG format in a rapid and inexpensive Nicotiana-based manufacturing system for comparison with palivizumab. Both plant-derived (palivizumab-N) and commercial palivizumab, which is produced in a mouse myeloma cell line, showed protection in prophylactic (p < 0.001 for both mAbs) and therapeutic protocols (p < 0.001 and p < 0.05 respectively). The additional plant-derived human mAbs directed against alternative epitopes displayed neutralizing activity, but conferred less protection in vivo than palivizumab-N or palivizumab. Palivizumab remains one of the most efficacious RSV mAbs described to date. Production in plants may reduce manufacturing costs and improve the pharmacoeconomics of RSV immunoprophylaxis and therapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Vírus Sincicial Respiratório Humano/imunologia , Tabaco/imunologia , Animais , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Neutralizantes/economia , Anticorpos Neutralizantes/imunologia , Modelos Animais de Doenças , Humanos , Palivizumab , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/virologia , Sigmodontinae , Resultado do Tratamento
15.
Plant Biotechnol J ; 8(5): 638-54, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20514694

RESUMO

Plants have been proposed as an attractive alternative for pharmaceutical protein production to current mammalian or microbial cell-based systems. Eukaryotic protein processing coupled with reduced production costs and low risk for mammalian pathogen contamination and other impurities have led many to predict that agricultural systems may offer the next wave for pharmaceutical product production. However, for this to become a reality, the quality of products produced at a relevant scale must equal or exceed the predetermined release criteria of identity, purity, potency and safety as required by pharmaceutical regulatory agencies. In this article, the ability of transient plant virus expression systems to produce a wide range of products at high purity and activity is reviewed. The production of different recombinant proteins is described along with comparisons with established standards, including high purity, specific activity and promising preclinical outcomes. Adaptation of transient plant virus systems to large-scale manufacturing formats required development of virus particle and Agrobacterium inoculation methods. One transient plant system case study illustrates the properties of greenhouse and field-produced recombinant aprotinin compared with an US Food and Drug Administration-approved pharmaceutical product and found them to be highly comparable in all properties evaluated. A second transient plant system case study demonstrates a fully functional monoclonal antibody conforming to release specifications. In conclusion, the production capacity of large quantities of recombinant protein offered by transient plant expression systems, coupled with robust downstream purification approaches, offers a promising solution to recombinant protein production that compares favourably to cell-based systems in scale, cost and quality.


Assuntos
Anticorpos Monoclonais/biossíntese , Aprotinina/biossíntese , Engenharia Genética/métodos , Plantas Geneticamente Modificadas/metabolismo , Proteínas Recombinantes/biossíntese , Anticorpos Monoclonais/imunologia , Aprotinina/imunologia , Vírus de Plantas , Plantas Geneticamente Modificadas/imunologia , Proteínas Recombinantes/imunologia , Rhizobium
16.
J Comp Physiol B ; 178(7): 867-75, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18491114

RESUMO

One physiological mechanism used by reptiles to remain within thermal optima is their ability to reversibly alter skin colour, imparting changes in overall reflectance, and influencing the rate of heat gain from incident radiation. The ability to lighten or darken their skin is caused by the movement of pigment within the dermal chromatophore cells. Additionally, lizards, as ectotherms, significantly lower their preferred body temperatures when experiencing stressors such as hypoxia. This decrease in preferred temperature has been proposed to be the result of a downward adjustment of the thermal set-point, the temperature around which the body temperature is typically defended. We tested the hypothesis that lightening of the skin in lizards would be modified by hypoxia in a manner consistent with the known reduction in preferred temperatures. Skin colouration values of the dorsal skin of bearded dragons were analysed at three different levels of oxygen (20.8, 9.9 and 4.9 kPa) and at temperatures spanning the preferred temperature range (30, 32, 34, 36, 38 and 40 C). Hypoxic lizards lightened their skin at lower ambient temperatures more than normoxic ones, and in an oxygen-dependent fashion. The orchestrated adjustment of skin reflectance suggests that this physiological trait is being regulated at a new and lower set-point. Evidence from this study demonstrates that skin colouration plays a role in body temperature regulation and that the reduction in temperature set-point so prevalent in hypoxia is also manifested in this physiological trait.


Assuntos
Temperatura Corporal/fisiologia , Hipóxia/fisiopatologia , Iguanas/fisiologia , Pigmentação da Pele/fisiologia , Animais , Regulação da Temperatura Corporal/fisiologia , Feminino , Masculino , Oxigênio/metabolismo , Temperatura Ambiente
17.
Dis Colon Rectum ; 45(10): 1349-58, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12394434

RESUMO

PURPOSE: The aim of this study was to evaluate the efficacy of preoperative radiation therapy for resectable rectal adenocarcinoma (T3-T4) when delivered in combination with chemotherapy (oral tegafur-uracil modulated with leucovorin). METHODS: Thirty-eight patients (23 males; mean age, 62 years.) with histologically proven rectal adenocarcinoma with primary tumor clinical classification T3-T4 (resectable) and N0 or N1-N2, according to TNM staging system, took part in the present clinical trial. After tumor and metastasis resectability confirmation, radiation therapy was administered by delivering a dose of 45 Gy in 25 fractions for 5 weeks. Chemotherapy treatment was initiated on the same day as radiotherapy and consisted of intravenous infusion of 6S-steroisomer of leucovorin 250 mg/m /day in 2 hours on Day 1, followed by oral 350 or 300 mg/m /day of tegafur (a 5-fluorouracil prodrug) plus uracil on Days 1 to 14 divided into 2 daily doses, and oral 6S-steroisomer of leucovorin 7.5 mg/12 hours on Days 2 to 14, with a total of 102 courses of neoadjuvant chemotherapy (, mean of 2.7 courses per patient). Six additional courses of tegafur-uracil were given postoperatively to all 38 patients but 1 who refused. RESULTS: As a result of preoperative chemoradiation treatment, 4 (10.5 percent) complete responses, 20 (52.6 percent) partial responses, and 14 (36.8 percent) patients with disease stabilization were observed. No patients had preoperative disease progression. Histologically proven downstaging was observed in 23 (60 percent) patients. On initial evaluation, only 39 percent of patients were considered as being good candidates for sphincter-preserving surgery; however, on preoperative chemoradiation completion this figure increased up to 60 percent. For the 23 patients eventually undergoing sphincter-preserving surgery, postoperative sphincter function assessment showed excellent function in 15 (65 percent) patients, good in 5 (22 percent), fair in 2 (9 percent), and poor in 1(4 percent). With a median follow-up of 37 (range, 10-62) months, local failure was found in 3 (8 percent) patients and distant failure in 2 (5 percent). Three-year actuarial disease-free survival and 3-year overall survival rates were 83 and 90 percent, respectively. Local control rate was 92 percent. Toxicity and postoperative complication rates were reasonable. CONCLUSIONS: Our neoadjuvant radiation therapy protocol is efficient for the preoperative treatment of resectable rectal adenocarcinoma when combined with chemotherapy (oral tegafur-uracil modulated with leucovorin). this protocol needs to be tested in a phase-III clinical trial with a larger sample size.


Assuntos
Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Feminino , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Dosagem Radioterapêutica , Radioterapia Adjuvante , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Tegafur/administração & dosagem , Resultado do Tratamento , Uracila/administração & dosagem
18.
Arq. ciênc. vet. zool. UNIPAR ; 4(2): 175-180, jul.-dez. 2001. tab
Artigo em Espanhol | LILACS | ID: lil-306401

RESUMO

En una explotación industrial de ganado ovino de leche se estudia la evolución de Calcio, Fósforo y Magnesio tanto en sangre como en orina, durante gestación y lactación, para ver el efecto de cada momento reproductivo sobre estos parámetros. De forma paralela, se selecciona un lote control, observando si las variaciones apreciadas son achacables o no a la gestación, pues ambos lotes reciben la misma alimentación durante todo el experimento. El resultado muestra como en animales que reciben dietas superiores a las recomendadas por la NRC, el momento fisiológico no supone un riesgo de padecer procesos carenciales, pues el organismo es capaz de adaptarse a cualquier situación


Assuntos
Animais , Sangue , Minerais , Ovinos , Urina
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA