RESUMO
We develop a tensorial constitutive model for dense, shear-thickening particle suspensions subjected to time-dependent flow. Our model combines a recently proposed evolution equation for the suspension microstructure in rate-independent materials with ideas developed previously to explain the steady flow of shear-thickening ones, whereby friction proliferates among compressive contacts at large particle stresses. We apply our model to shear reversal, and find good qualitative agreement with particle-level, discrete-element simulations whose results we also present.
RESUMO
Interleukin (IL)-4, a crucial modulator of the immune system and an active antitumor agent, is also a potent inhibitor of angiogenesis. When incorporated at concentrations of 10 ng/ml or more into pellets implanted into the rat cornea or when delivered systemically to the mouse by intraperitoneal injection, IL-4 blocked the induction of corneal neovascularization by basic fibroblast growth factor. IL-4 as well as IL-13 inhibited the migration of cultured bovine or human microvascular cells, showing unusual dose-response curves that were sharply stimulatory at a concentration of 0.01 ng/ml but inhibitory over a wide range of higher concentrations. Recombinant cytokine from mouse and from human worked equally well in vitro on bovine and human endothelial cells and in vivo in the rat, showing no species specificity. IL-4 was secreted at inhibitory levels by activated murine T helper (TH0) cells and by a line of carcinoma cells whose tumorigenicity is known to be inhibited by IL-4. Its ability to cause media conditioned by these cells to be antiangiogenic suggested that the antiangiogenic activity of IL-4 may play a role in normal physiology and contribute significantly to its demonstrated antitumor activity.
Assuntos
Imunossupressores/farmacologia , Interleucina-4/fisiologia , Neovascularização Fisiológica/imunologia , Adenocarcinoma , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Células Cultivadas , Córnea/irrigação sanguínea , Córnea/efeitos dos fármacos , Córnea/imunologia , Meios de Cultivo Condicionados/química , Meios de Cultura Livres de Soro/química , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/imunologia , Humanos , Injeções Intraperitoneais , Interleucina-4/administração & dosagem , Neoplasias Mamárias Experimentais , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Fisiológica/efeitos dos fármacos , Ratos , Células Tumorais CultivadasRESUMO
The 2,160,837-base pair genome sequence of an isolate of Streptococcus pneumoniae, a Gram-positive pathogen that causes pneumonia, bacteremia, meningitis, and otitis media, contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA. Extracellular enzyme systems for the metabolism of polysaccharides and hexosamines provide a substantial source of carbon and nitrogen for S. pneumoniae and also damage host tissues and facilitate colonization. A motif identified within the signal peptide of proteins is potentially involved in targeting these proteins to the cell surface of low-guanine/cytosine (GC) Gram-positive species. Several surface-exposed proteins that may serve as potential vaccine candidates were identified. Comparative genome hybridization with DNA arrays revealed strain differences in S. pneumoniae that could contribute to differences in virulence and antigenicity.
Assuntos
Genoma Bacteriano , Análise de Sequência de DNA , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Antígenos de Bactérias , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Vacinas Bacterianas , Composição de Bases , Metabolismo dos Carboidratos , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Cromossomos Bacterianos/genética , Biologia Computacional , Elementos de DNA Transponíveis , DNA Bacteriano/química , DNA Bacteriano/genética , Duplicação Gênica , Genes Bacterianos , Hexosaminas/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Recombinação Genética , Sequências Repetitivas de Ácido Nucleico , Especificidade da Espécie , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/metabolismo , Virulência , Óperon de RNArRESUMO
The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.
Assuntos
Genoma Bacteriano , Neisseria meningitidis/genética , Neisseria meningitidis/patogenicidade , Análise de Sequência de DNA , Variação Antigênica , Antígenos de Bactérias/imunologia , Bacteriemia/microbiologia , Cápsulas Bacterianas/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/fisiologia , Elementos de DNA Transponíveis , Evolução Molecular , Fímbrias Bacterianas/genética , Humanos , Meningite Meningocócica/microbiologia , Infecções Meningocócicas/microbiologia , Dados de Sequência Molecular , Mutação , Neisseria meningitidis/classificação , Neisseria meningitidis/fisiologia , Fases de Leitura Aberta , Óperon , Filogenia , Recombinação Genética , Sorotipagem , Transformação Bacteriana , Virulência/genéticaRESUMO
The complete genome sequence of the radiation-resistant bacterium Deinococcus radiodurans R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (177,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284, 156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of D. radiodurans to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified. Deinococcus radiodurans represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell.
Assuntos
Genoma Bacteriano , Cocos Gram-Positivos/genética , Mapeamento Físico do Cromossomo , Análise de Sequência de DNA , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Catalase/genética , Cromossomos Bacterianos/genética , Dano ao DNA , Reparo do DNA/genética , DNA Bacteriano/genética , Metabolismo Energético , Genes Bacterianos , Cocos Gram-Positivos/química , Cocos Gram-Positivos/classificação , Cocos Gram-Positivos/efeitos da radiação , Dados de Sequência Molecular , Fases de Leitura Aberta , Estresse Oxidativo , Plasmídeos , Tolerância a Radiação , Sequências Repetitivas de Ácido Nucleico , Superóxido Dismutase/genética , Thermus/química , Thermus/genética , Raios UltravioletaRESUMO
A study was conducted to evaluate the effect of tail docking on the welfare and performance of victimized pigs by tail biting and tail biters. Pigs ( = 240; 25.7 ± 2.9 kg average weight), including 120 pigs that were tail docked at birth and 120 pigs that remained with intact tails, were used. Pigs were housed in 8 pens of 30 pigs in a confinement barn for 16 wk, with 4 pens each housing pigs of both sexes with docked or intact tails. Tail biters and victimized pigs with damaged tails were identified during outbreaks of tail biting. Growth performance was monitored, and skin lesions on the tail, ears, and body were assessed. Blood samples were collected from focal tail biters, victimized pigs, and nonvictimized pigs for analysis of total serum protein, IgG, and substance P concentrations. When pigs were marketed, carcass weights and the number of pigs with carcass trim loss were recorded. During the growing-finishing period, 48% of pigs with docked tails and 89% of pigs with intact tails experienced lesions on their tails, including 5% of docked pigs and 30% of intact pigs identified as victimized pigs that experienced puncture wounds with signs of infection on their tails or loss of tails ( < 0.001). Victimized pigs tended to gain less weight ( = 0.07) between 17 and 21 wk of age than other pigs when tail biting prevailed in this study. Victimized pigs were more frequently ( = 0.04) sold for less than full value and had a lower dressing percentage ( < 0.001) compared with nonvictimized pigs. For victimized pigs, total serum protein and IgG concentrations were elevated 5 d after tails were injured, suggesting that tail damage can cause inflammation, which may lead to carcass abscesses and trim loss. Compared with victimized pigs and nonvictimized pigs, tail biters had lower total serum protein ( = 0.01) and IgG ( = 0.01) concentrations, indicating that tail biters may experience poor immune functions. Results of this study demonstrated that tail docking reduced tail damage in pigs kept in a confinement system. Tail damage can cause inflammation and reduce the value of market pigs. More research is needed to test whether compromised immune functions predispose pigs to tail biting.
Assuntos
Bem-Estar do Animal , Comportamento Animal , Mordeduras e Picadas/veterinária , Abrigo para Animais , Suínos/fisiologia , Animais , Feminino , Masculino , Suínos/crescimento & desenvolvimento , Cauda/lesõesRESUMO
One challenge presented by large-scale genome sequencing efforts is effective display of uniform information to the scientific community. The Comprehensive Microbial Resource (CMR) contains robust annotation of all complete microbial genomes and allows for a wide variety of data retrievals. The bacterial information has been placed on the Web at http://www.tigr.org/CMR for retrieval using standard web browsing technology. Retrievals can be based on protein properties such as molecular weight or hydrophobicity, GC-content, functional role assignments and taxonomy. The CMR also has special web-based tools to allow data mining using pre-run homology searches, whole genome dot-plots, batch downloading and traversal across genomes using a variety of datatypes.
Assuntos
Bactérias/genética , Bases de Dados Factuais , Genes Bacterianos/genética , Genoma Bacteriano , Serviços de Informação , InternetRESUMO
Transfer of an interleukin 2/interferon-gamma-secreting islet-specific CD4+ T-cell clone, BDC-6.9, in the immunodeficient NOD-scid mouse induces destruction of pancreatic beta-cells without help from host B-cells, CD4+ T-cells, or CD8+ T-cells. However, a second islet-specific T-cell clone, BDC-2.5, showing the same cytokine profile and T-cell receptor Vbeta expression as BDC-6.9 was not capable of inducing diabetes or insulitis in NOD-scid mice. Even though BDC-2.5 by itself readily induces diabetes in young unmanipulated NOD mice, cotransfer of CD8-enriched T-cells was required to induce disease in NOD-scid mice. Immunohistochemical staining of pancreatic lesions in young NOD mice receiving either BDC-2.5 or BDC-6.9 showed the presence of CD4+, CD8+, Vbeta4+, and MAC-1+ cells within the infiltrate, similar to infiltrates in lesions of spontaneously diabetic female NOD mice. In contrast, NOD- scid mice that received BDC-6.9 showed only the presence of CD4+Vb4+ T-cells and a large population of MAC-1+ cells in islet lesions. NOD-scid recipients of cotransferred BDC- 2.5/CD8+ splenic T-cells showed a small population of CD4+ T-cells and a larger population of CD8+ T-cells within the infiltrated islets, whereas no infiltrate was detectable in recipients of CD8+ splenocytes or BDC-2.5 alone. Our results suggest that at least two types of islet-specific CD4+ T-cell clones play a role in diabetes pathogenesis.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/transplante , Linfócitos T CD8-Positivos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Animais , Linfócitos T CD8-Positivos/transplante , Grânulos Citoplasmáticos/patologia , Citometria de Fluxo , Imuno-Histoquímica , Interferon gama/metabolismo , Interleucina-2/metabolismo , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCIDRESUMO
This paper examines the parameters necessary for the efficient measurement of anti-Theiler's murine encephalomyelitis virus (TMEV) antibodies in an affinity-dependent manner using a variation of a solid-phase particle concentration fluorescence immunoassay (PCFIA). By allowing antibody to react with fluorochrome-labelled virus in fluid phase and subsequently capturing the resulting virus-antibody complexes with anti-immunoglobulin coated polystyrene particles (fluid-phase PCFIA), the present assay allows for both greater sensitivity, specificity and preservation of conformational viral epitopes than do solid-phase immunoassays. Fluid-phase PCFIA proved to be a more rapid quantitative assay than ELISA and significantly diminished non-specific binding by both untreated and heat-inactivated normal mouse sera. This methodology also allowed us to perform competition assays and to determine the dissociation kinetics of anti-viral antibody preparations, investigations which cannot generally be performed as solid-phase immunoassays. Thus fluid-phase PCFIA is a rapid and efficient immunoassay with excellent reproducibility and great versatility.
Assuntos
Anticorpos Antivirais/análise , Enterovirus/imunologia , Fluorimunoensaio/métodos , Vírus Elberfeld do Camundongo/imunologia , Animais , Sítios de Ligação de Anticorpos , Ligação Competitiva , Linhagem Celular , Cricetinae , Ensaio de Imunoadsorção Enzimática , Feminino , Fluoresceína-5-Isotiocianato , Fluoresceínas , Fluorimunoensaio/normas , Cinética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , TiocianatosRESUMO
We report differences among BALB/c substrains in susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease, an immune-mediated inflammatory demyelinating disease and experimental model for human multiple sclerosis. BALB/cJ and BALB/cAnNCr mice are susceptible, while BALB/cByJ and BALB/cCum are resistant. Hybrids between BALB/cBy and BALB/cAnNCr were intermediate, although closer to the resistant parent. Backcrosses gave results compatible with differential susceptibility being related to a single segregating locus. Exposure of resistant BALB/cByJ mice to low dose irradiation, 2 days prior to infection, rendered them susceptible to TMEV-induced demyelination. The susceptibility pattern of TMEV-induced demyelinating disease among BALB/c substrains is distinct from those of several autoimmune disorders.
Assuntos
Doenças Desmielinizantes/genética , Theilovirus , Animais , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/imunologia , Suscetibilidade a Doenças , Teste de Histocompatibilidade , Camundongos , Camundongos Endogâmicos BALB C , Especificidade da EspécieRESUMO
Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) into susceptible mouse strains produces a chronic demyelinating disease in which mononuclear cell-rich infiltrates in the central nervous system (CNS) are prominent. Current evidence strongly supports an immune-mediated basis for myelin breakdown, with an effector role proposed for TMEV-specific, major histocompatibility complex (MHC) class II-restricted delayed-type hypersensitivity (DTH) responses in which lymphokine-activated macrophages mediate bystander demyelination. The present study examined the possibility that concomitant or later-appearing neuroantigen-specific autoimmune T cell responses, such as those demonstrated in chronic-relapsing experimental allergic encephalomyelitis (R-EAE), may contribute to the demyelinating process following TMEV infection. T cell responses against intact, purified major myelin proteins (myelin basic protein (MBP) and proteolipid protein (PLP], and against altered myelin constituents were readily demonstrable in SJL/J mice with R-EAE, but were not detectable in SJL/J mice with TMEV-induced demyelinating disease. TMEV-infected mice also did not display T cell responses against the peptide fragments of MBP(91-104) and PLP(139-151) recently shown to be encephalitogenic in SJL/J mice. In addition, induction of neuroantigen-specific tolerance to a heterogeneous mixture of CNS antigens, via the i.v. injection of syngeneic SJL/J splenocytes covalently coupled with mouse spinal cord homogenate, resulted in significant suppression of clinical and histologic signs of R-EAE and the accompanying MBP- and PLP-specific DTH responses. In contrast, neuroantigen-specific tolerance failed to alter the development of clinical and histologic signs of TMEV-induced demyelinating disease or the accompanying virus-specific DTH and humoral immune responses. These findings demonstrate that TMEV-induced demyelinating disease can occur in the apparent absence of neuroantigen-specific autoimmune responses. The relationship of the present results to the immunopathology of multiple sclerosis is discussed.
Assuntos
Doenças Desmielinizantes/imunologia , Infecções por Enterovirus/imunologia , Tolerância Imunológica/fisiologia , Bainha de Mielina/fisiologia , Sistema Nervoso/imunologia , Linfócitos T/fisiologia , Animais , Formação de Anticorpos , Especificidade de Anticorpos , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/patologia , Encefalomielite Autoimune Experimental/fisiopatologia , Infecções por Enterovirus/complicações , Epitopos , Feminino , Vírus Elberfeld do Camundongo , Camundongos , Camundongos Endogâmicos , Proteína Básica da Mielina/imunologia , Proteolipídeos/imunologia , Medula Espinal/fisiologiaRESUMO
Heat-shock proteins of the 70-kD (hsp70) family are targets of humoral and cellular immune responses following bacterial or parasitic infections, including Chagas' disease. In the present study, we measured antibodies in human sera reactive with hsp70s from the cytoplasm (cy-hsp70), mitochondrion (mt-hsp70), and endoplasmic reticulum (grp78) of Trypanosoma cruzi. Of the three hsp70s tested, only grp78 detected T. cruzi infection in more than 90% of nontreated (NT) patients, with cy-hsp70 and mt-hsp70 detecting only 78% and 25% of NT patients, respectively. Reactivity of leishmanial sera was 77% with cy-hsp70, 13% with grp78, and 5% with mt-hsp70. Therefore, considering sensitivity and specificity, the best candidate for T. cruzi serodiagnosis is grp78. Combination of grp78 with a T. cruzi 24-kD flagellar calcium binding protein (FCaBP) increased the diagnostic sensitivity from 90% to 97% but increased leishmanial reactivity from 3% to 8%. To determine whether hsp70s are useful for discriminating between cured and noncured patients treated with trypanocidal drugs, we tested sera from treated noncured (TNC) patients and cured patients who have positive conventional serology, termed treated dissociated (TD). The cy-hsp70 and grp78 reacted with 74% and 68% of TNC patient sera, respectively, but these antigens did not discriminate TNC from TD patients (52% and 45% positive, respectively). The mt-hsp70 was detected by sera from few TNC patients (18%) and no TD patients. Although individual hsp70s were not useful for determining the effect of trypanocidal drugs on T. cruzi infection in individual patients, the majority of TNC patient sera (70-80%) reacted with two or three of the hsp70s. In contrast, no TD sera reacted with all three hsp70s, and 40% did not react with any of the hsp70s, indicating that the number of hsp70s detected decreases following successful treatment. Considered together, these results show that grp78 has potential as a diagnostic antigen and that absence of reactivity to all three hsp70s may be indicative of effective treatment.
Assuntos
Anticorpos Antiprotozoários/biossíntese , Doença de Chagas/imunologia , Proteínas de Choque Térmico HSP70/imunologia , Trypanosoma cruzi/imunologia , Animais , Anticorpos Antiprotozoários/sangue , Doença de Chagas/diagnóstico , Doença de Chagas/tratamento farmacológico , Reações Cruzadas , Citoplasma/imunologia , Retículo Endoplasmático/imunologia , Chaperona BiP do Retículo Endoplasmático , Ensaio de Imunoadsorção Enzimática , Humanos , Leishmania/imunologia , Mitocôndrias/imunologia , Proteínas Recombinantes/imunologia , Resultado do Tratamento , Tripanossomicidas/uso terapêuticoRESUMO
A rapid and efficient method is described for isotype quantitation of antiviral antibodies in mice infected with Theiler's murine encephalomyelitis virus (TMEV). Serum antibodies were reacted with fluorochrome-labeled TMEV in a modified fluid-phase particle concentration fluorescence immunoassay (PCFIA). Biotin and avidin were used to attach anti-immunoglobulin isotype antibodies to polystyrene particles by the separate incubation of biotinylated goat anti-mouse isotypes (IgG1-, IgG2a-, IgG2b-, IgG3-, or IgM-specific) with avidin coupled polystyrene particles. These anti-isotype particles captured the virus-antibody complexes. Mouse myeloma proteins were used to quantitate and standardize isotype profiles of normal mouse serum using fluorescein isothiocyanate (FITC)-labeled, goat anti-mouse isotypes and polystyrene particles coated with goat anti-mouse. These assays quantitated the affinity-purified mouse serum antiviral antibodies for the standardization of antiviral isotype assays. Immunoglobulin of all serum isotypes as well as the amount of virus-specific isotypes can be quantitated rapidly and accurately.
Assuntos
Anticorpos Antivirais/análise , Enterovirus/imunologia , Isotipos de Imunoglobulinas/análise , Vírus Elberfeld do Camundongo/imunologia , Animais , Anticorpos Antivirais/normas , Avidina , Biotina , Infecções por Enterovirus/imunologia , Feminino , Isotipos de Imunoglobulinas/normas , Camundongos , Virologia/métodosRESUMO
Excessive alcohol consumption impairs T-cell-dependent immune function. Whether this impairment results from the direct inhibition of helper T (Th) cells or from inhibition of the cells that process and present antigen to Th cells is unclear. The present study examines the temporal effect of dietary alcohol on the development of delayed hypersensitivity (DTH) in C57BL/6 mice. We find that ethanol consumption just prior to and during the cognitive phase of the immune response impairs the development of a DTH response. Ethanol consumption initiated after the cognitive phase and during the effector phase of the immune response has no significant effect upon the elicitation of a DTH response. The results suggest that significant ethanol-induced impairment of DTH responses occurs during the cognitive phase of the immune response, when antigen presentation and recognition occur.
Assuntos
Etanol/farmacologia , Hipersensibilidade Tardia/imunologia , Animais , Ingestão de Energia , Etanol/administração & dosagem , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/imunologia , Fatores de TempoRESUMO
Disulfide-containing proteins offer unique advantages for mechanistic studies of the formation of native three-dimensional structure from unordered, reduced precursors. The main advantage is that covalent intermediates are formed; by characterizing these intermediates, one obtains substantial information about the reaction pathway. Thiol-disulfide interchange is a major component of most oxidative mechanisms carrying thiol to disulfide; thus, it required some attention in its own right. Afinsen's descriptions of a "shuffle-ase" enzyme led us to examine the rates of the uncatalyzed exchange under physiologically plausible conditions. Somewhat surprisingly, we found that the rates for formation of several native proteins in uncatalyzed systems containing GSSG and GSH are as great as with the "shuffle-ase" enzyme, suggesting that a substantial portion of biological thiol oxidations proceed by uncatalyzed exchange. While thiol-disulfide exchange of course results in no net change in the oxidation level of a system, catalytic linkage of thiol or disulfide to other redox systems provides a mechanism for achieving net changes.
Assuntos
Dissulfetos , Proteínas , Fenômenos Químicos , Química , Glutationa , OxirreduçãoRESUMO
OBJECTIVES: In sclerotherapy, carbon dioxide (CO(2)) or room air can be employed by phlebologists for foam creation. We compared room air (RA) and carbon dioxide in treating reticular leg veins with foam sclerotherapy. METHODS: Twenty patients were randomly treated with RA- or CO(2)-created sodium tetradecyl sulphate (STS) foam. Concentration and volume of STS, side-effects and efficacy were determined. RESULTS: There was no difference in the efficacy, local side-effects or distant side-effects between RA and CO(2) foam in the treatment of reticular leg veins. The total volume of foam sclerosant required for treatment was greater with CO(2) compared with RA (P value = 0.01). CONCLUSION: No differences were found in efficacy or side-effects between RA- and CO(2)-foam sclerotherapy for reticular leg veins. CO(2) foam's shorter half-life was hypothesized to be responsible for larger total volumes of CO(2) foam sclerosant.
Assuntos
Dióxido de Carbono , Soluções Esclerosantes , Escleroterapia , Tetradecilsulfato de Sódio/uso terapêutico , Varizes/terapia , Adulto , Idoso , Ar , Dióxido de Carbono/efeitos adversos , Dióxido de Carbono/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Soluções Esclerosantes/efeitos adversos , Soluções Esclerosantes/uso terapêutico , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Tetradecilsulfato de Sódio/efeitos adversosRESUMO
BACKGROUND: Foam sclerotherapy is an increasingly popular modality in the treatment of varicose veins. Foam stability varies according to foam composition, volume and injection technique. MATERIALS AND METHODS: A disposable plastic connector was used to create foam from 0.50% sodium tetradecyl sulphate (STS) mixed with varying volumes of glycerin. As a measure of foam stability, the half liquid time was defined as the time required for half of the original volume of sclerosing solution to settle. Three recordings were determined for each of the three mixtures of sclerosant foam. RESULTS: The time for sclerosing solution to settle to half of its initial volume was found to be 89 seconds for 0.50% STS alone, 117.7 seconds with the addition of 0.1 mL of 72% glycerin, and 114.7 seconds with the addition of 0.2 mL of 72% glycerin. CONCLUSION: The small volumes of glycerin added to STS prolonged the half liquid time of STS foam up to 35%. As glycerin alone is unable to be foamed with the double-syringe system technique there may be a point at which further addition of glycerin has a negative effect on the half-life of foam.
Assuntos
Glicerol/química , Soluções Esclerosantes/química , Tetradecilsulfato de Sódio/química , Substâncias Viscoelásticas/química , Estabilidade de Medicamentos , Glicerol/uso terapêutico , Humanos , Soluções Esclerosantes/uso terapêutico , Tetradecilsulfato de Sódio/uso terapêutico , Fatores de Tempo , Varizes/terapia , Substâncias Viscoelásticas/uso terapêuticoAssuntos
Insulina/biossíntese , Proinsulina/metabolismo , Sequência de Aminoácidos , Animais , Carboxipeptidases/análise , Bovinos , Endopeptidases/metabolismo , Complexo de Golgi/metabolismo , Haplorrinos , Humanos , Ilhotas Pancreáticas/análise , Ilhotas Pancreáticas/metabolismo , Camundongos , Peptídeos/metabolismo , Proinsulina/análise , Proinsulina/biossíntese , Conformação Proteica , Ratos , Ovinos , Frações Subcelulares/enzimologia , Suínos , Tripsina/análiseRESUMO
Epidermolysis bullosa acquisita is an autoimmune blistering disease characterized by circulating and skin basement membrane-bound IgG autoantibodies to type VII collagen, a major structural protein of the dermal-epidermal junction. Regulatory T cells (T(reg)) suppress self antigen-mediated autoimmune responses. To investigate the role of T(reg) in the the autoimmune response to type VII collagen in a mouse model, a monoclonal antibody against mouse CD25 was used to deplete T(reg). A recombinant mouse type VII collagen NC1 domain protein and mouse albumin were used as antigens. SKH1 mice were used as a testing host. Group 1 mice received NC1 immunization and were functionally depleted of T(reg); group 2 mice received NC1 immunization and rat isotype control; and group 3 mice received albumin immunization and were functionally depleted of T(reg). Results demonstrated that anti-NC1 IgG autoantibodies with high titres, as determined by enzyme-linked immunosorbent assay and Western blotting, developed in all mice immunized with NC1 (groups 1 and 2), but were undetected in group 3 mice. The predominant subclasses of anti-NC1 autoantibodies were IgG1, IgG2a and IgG2b; furthermore, these antibodies carried only the kappa light chain. IgG autoantibodies in the sera of NC1-immunized mice reacted with mouse skin basement membrane in vitro and deposited in skin basement membrane in vivo as detected by indirect and direct immunofluorescence microscopy, respectively. Our data suggest that the development of autoimmunity against type VII collagen in mice is independent of T(reg) function and the autoimmune response is mediated by both Th1 and Th2 cells. We speculate that the basement membrane deposition of IgG may eventually lead to blister development.