The pathogenesis of oral lichen planus

Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8(+) cytotoxic T-cells. Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions. These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T-cell migration, and keratinocyte apoptosis in OLP. OLP chronicity may be due, in part, to deficient antigen-specific TGF-beta1-mediated immunosuppression. The normal oral mucosa may be an immune privileged site (similar to the eye, testis, and placenta), and breakdown of immune privilege could result in OLP and possibly other autoimmune oral mucosal diseases. Recent findings in mucocutaneous graft-versus-host disease, a clinical and histological correlate of lichen planus, suggest the involvement of TNF-alpha, CD40, Fas, MMPs, and mast cell degranulation in disease pathogenesis. Potential roles for oral Langerhans cells and the regional lymphatics in OLP lesion formation and chronicity are discussed. Carcinogenesis in OLP may be regulated by the integrated signal from various tumor inhibitors (TGF-beta1, TNF-alpha, IFN-gamma, IL-12) and promoters (MIF, MMP-9). We present our recent data implicating antigen-specific and non-specific mechanisms in the pathogenesis of OLP and propose a unifying hypothesis suggesting that both may be involved in lesion development. The initial event in OLP lesion formation and the factors that determine OLP susceptibility are unknown.

The role of CD4(+) cells in vivo on the induction of the immune response to Porphyromonas gingivalis in mice

Background: It has previously been suggested that CD4(+) T cells play a pivotal role in regulating the immune response to periodontal pathogens. The aim of the present study therefore was to determine delayed type hypersensitivity (DTH), spleen cell proliferation, serum and splenic anti-Porphyromonas gingivalis antibody levels, and lesion sizes following challenge with viable P. gingiualis in CD4-depleted BALB/c mice immunized with P. gingiualis outer membrane proteins (OMP). Methods: Four groups of BALB/c mice were used. Groups 1 and 2 were injected intraperitoneally (ip) with saline for 3 consecutive days and then weekly throughout the experiment. Groups 3 and 4 were injected ip with rat immunoglobulin and a monoclonal rat anti-mouse CD4 antibody, respectively. Two days later, group 1 mice were injected ip with saline only, while all the other groups were immunized ip with P. gingiualis OMP weekly for 3 weeks. One week later following the last immunization of OMP, 3 separate experiments were conducted to determine: 1) the DTH response to P. gingiualis OMP by measuring footpad swelling; 2) the levels of antibodies to P. gingiualis in serum samples and spleen cell cultures using an enzyme-linked immunosorbent assay, as well as spleen cell proliferation after stimulation with OMP; and 3) the lesion sizes after a subcutaneous challenge with viable P. gingiualis cells. Results: In CD4(+) T-cell-depleted mice (group 4), the DTH response and antigen-stimulated cell proliferation were significantly suppressed when compared to groups 2 and 3. Similarly, the levels of serum and splenic IgM, IgG, and all IgG subclass antibodies to P. gingiualis OMP were depressed. Delayed healing of P. gingivalis-induced lesions was also observed in the CD4(+) T-cell-depleted group. Conclusions: This study has shown that depletion of CD4(+) T cells prior to immunization with P. gingiualis OMP led to the suppression of both the humoral and cell-mediated immune response to this microorganism and that this was associated with delayed healing. These results suggest that the induction of the immune response to P. gingiualis is a CD4(+) T-cell-dependent mechanism and that CD4(+) T cells are important in the healing process.

Transducer for direct measurement of skin friction in hypervelocity impulse facilities

An acceleration compensated transducer was developed to enable the direct measurement of skin friction in hypervelocity impulse facilities. The gauge incorporated a measurement and acceleration element that employed direct shear of a piezoelectric ceramic. The design integrated techniques to maximize rise time and shear response while minimizing the affects of acceleration, pressure, heat transfer, and electrical interference. The arrangement resulted in a transducer natural frequency near 40 kHz. The transducer was calibrated for shear and acceleration in separate bench tests and was calibrated for pressure within an impulse facility. Uncertainty analyses identified only small experimental errors in the shear and acceleration calibration techniques. Although significant errors were revealed in the method of pressure calibration, total skin-friction measurement errors as low as +/-7-12% were established. The transducer was successfully utilized in a shock tunnel, and sample measurements are presented for flow conditions that simulate a flight Mach number near 8.

Iatrogenic bile duct injury: The scourge of laparoscopic cholecystectomy

Background: Laparoscopic cholecystectomy (LC) has become the first-line surgical treatment of calculous gall-bladder disease and the benefits over open cholecystectomy are well known. In the early years of LC, the higher rate of bile duct injuries compared with open cholecystectomy was believed to be due to the 'learning curve' and would dissipate with increased experience. The purpose of the present paper was to review a tertiary referral unit's experience of bile duct injuries induced by LC. Methods: A retrospective analysis was performed on all patients referred for management of an iatrogenic bile duct injury from 1981 to 2000. For injuries sustained at LC, details of time between LC and recognition of the injury, time from injury to definitive repair, type of injury, use of intraoperative cholangiography (IOC), definitive repair and postoperative outcome were recorded. The type of injury sustained at open cholecystectomy was similarly classified to allow the severity of injury to be compared. Results: There were 131 patients referred for management of an iatrogenic bile duct injury that occurred at open cholecystectomy (n = 62), liver resection (n = 5) and at LC (n = 64). Only 39% of bile duct injuries were recognized at the time of LC. Following conversion to open operation, half the subsequent procedures were considered inappropriate. When the injury was not recognized during LC, 70% of patients developed bile leak/peritonitis, almost half of whom were referred, whereas the rest underwent a variety of operative procedures by the referring surgeon. The remainder developed jaundice or abnormal liver function tests and cholangitis. An IOC was performed in 43% of cases, but failed to identify an injury in two-thirds of patients. The bile duct injuries that occurred at LC were of greater severity than with open cholecystectomy. Following definitive repair, there was one death (1.6%). Ninety-two per cent of patients had an uncomplicated recovery and there was one late stricture requiring surgical revision. Conclusions: The early prediction that the rate of injury during LC would decline substantially with increased experience has not been fulfilled. Bile duct injury that occurs at LC is of greater severity than with open cholecystectomy. Bile duct injury is recognized during LC in less than half the cases. Evidence is accruing that the use of cholangiography reduces the risk and severity of injury and, when correctly interpreted, increases the chance of recognition of bile duct injury during the procedure. Prevention is the key but, should an injury occur, referral to a specialist in biliary reconstructive surgery is indicated.

Dietary supplementation with vitamin E modulates avian intestinal immunity

The effect of dietary vitamin E on immunoglobulin A (IgA) antibody production, which acts as the first line of defence at the intestinal mucosa, has not been evaluated in chickens. In the present study the impact of the inclusion of supplementary levels of vitamin E to the diet, on total and antigen-specific IgA antibody titres, T-cell subsets and Ia+ cells, was assessed. From hatching, chickens received a maize-based diet which was supplemented with either 25, 250, 2500 or 5000 mg dl-alpha-tocopherol acetate/kg. Primary immunisation with tetanus toxoid (T. toxoid) emulsified in a vegetable oil-in-water adjuvant was administered by the intraperitoneal route at 21 d of age. At 35 d of age all birds received an oral booster vaccination of T. toxoid. Significantly higher total IgA antibody titres were present in the day 42 intestinal scrapings of birds receiving the 5000 mg/kg vitamin E-supplemented diet (VESD) (P=0.05) and a notable increase was observed in birds receiving the 250 mg/kg VESD (P=0.06). At days 21 and 42 total serum IgA antibody titres of birds receiving the 250 mg/kg VESD was significantly higher (P

The mononuclear phagocyte system revisited

The mononuclear phagocyte system (MPS) was defined as a family of cells comprising bone marrow progenitors, blood monocytes, and tissue macrophages. In this review, we briefly consider markers for cells of this lineage in the mouse, especially the F4/80 surface antigen and the receptor for macrophage colony-stimulating factor. The concept of the MPS is challenged by evidence that there is a separate embryonic phagocyte lineage, the blurring of the boundaries between macrophages and other cells types arising from phenotypic plasticity and transdifferentiation, and evidence of local renewal of tissue macrophage populations as opposed to monocyte recruitment. Nevertheless, there is a unity to cells of the MPS suggested by their location, morphology, and shared markers. We discuss the origins of macrophage heterogeneity and argue that macrophages and antigen-representing dendritic cells are closely related and part of the MPS.

Controle estatístico de processo aplicado no monitoramento da absorção de água por carcaças de frango durante a etapa de pré-resfriamento

A absorção de água por carcaças de frango na etapa de pré-resfriamento da linha abate representa uma característica de qualidade importante relacionada ao rendimento do produto final. Uma forma de manter o padrão de qualidade de um produto é garantir que as etapas do processo sejam estáveis e replicáveis. Ao empregar o Controle Estatístico de Processo (CEP) é possível obter estabilidade e melhorias nos processos, por meio da redução da variabilidade. Neste contexto, o objetivo deste trabalho foi a aplicação de gráficos de controle, análise de correlação, estatística descritiva, testes de hipóteses e regressão linear múltipla na linha de abate de um abatedouro-frigorífico de aves para monitorar a variabilidade da absorção de água pelas carcaças de frango após a etapa de pré-resfriamento. Como resultado, verificou-se que o teor de absorção de água das carcaças de frango apresentou elevada variabilidade, sendo que 10% (8/80) das carcaças apresentaram absorção de água superior ao limite de 8% definido pela legislação brasileira. Do total de 16 variáveis de entrada analisadas, as mais impactantes no teor de absorção de água foram o “tempo de retenção da carcaça no pré-chiller” e o “tempo de espera da carcaça após a etapa de gotejamento”. Entretanto, o modelo de regressão obtido apresentou baixa correlação (R²=0,16) que foi associada à elevada variabilidade da variável-resposta. Os resultados da estatística descritiva demonstraram que as variáveis de entrada também apresentaram elevada variabilidade, com coeficiente de variação entre 7,95 e 63,5%. Verificou-se, pela análise dos gráficos de controle de medida individual e da amplitude móvel, que 15 das 16 variáveis de entrada se apresentaram fora de controle estatístico assim como a variável-resposta. Baseado no fluxograma e na descrição das etapas da linha de abate, previamente realizados, atribuiu-se à falta de padronização na condução das etapas e de procedimentos para o controle de qualidade das operações na linha de abate como fatores relevantes que poderiam estar associados à presença de causas especiais no processo. Concluiu-se que para reduzir a elevada variabilidade das variáveis e eliminar as causas especiais presentes são necessários ajustes operacionais para, dessa forma, obter um processo mais estável e mais uniforme garantindo o padrão de qualidade das carcaças de frango em relação ao teor de absorção de água.

Caracterização molecular, formação de biofilme e susceptibilidade a antimicrobianos de isolados de E. coli de aderência difusa Afa/Dr e não Afa/Dr

A Escherichia coli de aderência difusa (DAEC), um patotipo diarreiogênico de E. coli, corresponde a um grupo heterogêneo sem marcador de virulência comum a todos os isolados e de papel controverso na diarreia infantil. O objetivo deste estudo foi caracterizar genotipica e fenotipicamente amostras de DAEC, portadoras e não portadoras de adesinas Afa/Dr, isoladas de crianças com e sem diarreia. Em 70 amostras de DAEC, PCR foi realizado para pesquisa de genes descritos em DAEC, EAEC ou UPEC, que codificam: (i) oito adesinas fimbriais e afimbriais (fimH, papC, sfa, aggA, aafA, agg3A, aidA/aah, afaC); (ii) cinco toxinas (pet, astA, set1A, sat, hlyA); (iii) três proteínas captadoras/receptora de ferro (irp2, iucA, chuA/shuA); (iv) invasina (daaD) e; antígeno 43 (agn43). Ensaio de formação de biofilme foi realizado a partir da bactéria cultivada em caldo Luria-Bertani e inoculada em placas de poliestireno com DMEM suplementado com 0,4% glicose. A leitura da densidade ótica (DO490) foi realizada após coloração com safranina. Soroaglutinação para 23 antígenos O (Probac do Brasil) foi realizada em 50% das DAEC. Método de difusão de disco foi realizado para testar a suscetibilidade a 13 antimicrobianos. A presença de pelo menos um gene que codifica adesinas, toxinas, proteínas captadoras/receptora de ferro, invasina ou antígeno 43 foram encontrados em 58,6%, 51,4%, 80%, 48,6% e 57,1%, respectivamente, com os genes fimH, irp2, agn43, iucA, chuA/shuA, presentes em mais de 50% das amostras. Gene afaC+ (PCR) e/ou sonda afaBC+ (hibridização de colônias) classificou 50% das DAEC como Afa/Dr, sendo pet, sat, irp2, iucA, chuA/shuA e agn43 significantes nessas amostras (p<0,05). Do total das DAEC, 44,3% foram formadoras de biofilme, igualmente distribuídas entre as Afa/Dr e não Afa/Dr, e nenhum gene foi associado com esse fenótipo. Sorologia de 35 amostras evidenciou os seguintes sorogrupos: 1 O29, 2 O125, 2 O127 e 7 O86. Todas as O86 foram de DAEC Afa/Dr. Maiores frequências de resistência antimicrobiana foram encontradas para ampicilina (55,7%), sulfametoxazol/trimetoprim (35,7%) e tetraciclina (28,6%) e o perfil resistente/intermediário para amoxicilina/ácido clavulânico, ampicilina, sulfametoxazol/trimetoprim foi significante nas DAEC Afa/Dr, assim como a multi-droga resistência (p<0,05). Em conclusão, observou-se: (i) alta frequência de fimH e pet e presença de agn43, até então não descrito em DAEC, em frequências similares àquelas encontradas em EAEC, UPEC e EAEC/UPEC, respectivamente; (ii) que as amostras de DAEC Afa/Dr e não Afa/Dr constituíram grupos com perfis genéticos diferenciados entre si; (iii) poucos sorogrupos foram encontrados entre as DAEC; (iv) frequências de resistência menores quando comparado com as poucas descrições em DAEC, sugerindo uma menor pressão seletiva da população do presente estudo e; (v) amostras de DAEC Afa/Dr podem representar um importante reservatório de genes de resistência a antimicrobianos, além de diversos fatores de virulência.