RESUMO
There is ongoing discussion about patient-specific implants (PSI) to reconstruct orbital defects. Although PSI offer excellent clinical outcome, they are expensive. Subsequently, their routine application is not indicated. The purpose of this study was to estimate the frequency of implant malposition and revision procedures after primary orbital repair with preformed plates and to identify cases where primary use of PSI would help to prevent revision surgery. All patients included in the study were operated on for orbital fractures at the Royal London Hospital between August 2017 and July 2018. Selection criteria included adult patients treated for orbital fractures with a titanium plate. Revision was planned in symptomatic patients presenting with clear implant malposition. Seventy-nine patients with 81 implants were included, 33 of whom had multiple orbital wall fractures (medial wall and floor or all four walls) and were summarised as group 2. Group 1 consisted of single orbital floor/medial wall fractures. The five patients for whom revision surgery was planned or undertaken because of radiological poorly positioned implants and substantial clinical symptoms all had multiple wall fractures. This finding was significant (p=0.006). The major reason for revision was a defect that was too large for the prescribed plate. Patients with large orbital defects needing surgical treatment are at risk of implant malposition. The orbital reconstruction with preformed plate evidences good outcome in single wall fractures. However, the risk of malposition increases massively with fracture size. We therefore postulate that in large, two-wall fractures, primary treatment with a PSI has to be considered.
Assuntos
Implantes Dentários , Fraturas Orbitárias , Procedimentos de Cirurgia Plástica , Adulto , Humanos , Londres , Órbita/cirurgia , Fraturas Orbitárias/diagnóstico por imagem , Fraturas Orbitárias/cirurgia , Titânio , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The live-attenuated yellow fever vaccine (YFV) is generally contraindicated in immunosuppressed patients. Our aim was to investigate if immunosuppressive therapy impairs the long-term protection against yellow fever virus in patients who had received YFV prior to the start of their immunosuppressive therapy. METHODS: Our study examined 35 healthy individuals and 40 immunosuppressed patients with autoimmune diseases or organ transplants. All individuals had received YFV prior to the onset of their immunosuppression. We analysed the long-term influence of the immunosuppressive therapy on the YFV protective immunity by measuring neutralising antibodies (NA) with the Plaque Reduction Neutralisation Test (PRNT). We assessed risk factors for a negative PRNT result (titre below 1: 10) and their influence on the magnitude of the NA. RESULTS: A median time interval of 21.1 years (interquartile range 14.4-31.3 years) after the YFV in all patients, a total of 35 immunosuppressed patients (88%) were seropositive (PRNT ≥ 1:10) compared to 31 patients (89%) in the control group. The geometric mean titres of NA did not differ between the groups. The duration of an underlying rheumatic disease was the only risk factor found for a lower magnitude of NA. An insufficient level of NA was found in nine subjects (12%) who had received a single dose of YFV (in one subject, the number of YFV doses was unknown). CONCLUSION: The use of an immunosuppressive drug started after the administration of the YFV did not affect long-term persistence of NA. A second dose of YFV may be necessary to secure long-term immunity.
Assuntos
Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Vacina contra Febre Amarela/imunologia , Febre Amarela , Anticorpos Antivirais , Humanos , Testes de Neutralização , Vacinação , Febre Amarela/prevenção & controle , Vírus da Febre AmarelaRESUMO
No disponible
Assuntos
Humanos , Pediatria/métodos , Cuidado da Criança/métodos , Cuidado da Criança/organização & administração , Atenção Primária à Saúde/métodos , Algoritmos , Saúde da Criança/normas , Saúde da Criança/tendênciasRESUMO
AIMS: VENTURE-AF is the first prospective randomized trial of uninterrupted rivaroxaban and vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) undergoing catheter ablation (CA). METHODS AND RESULTS: Trial size was administratively set at 250, the protocol-specified target. Events were independently and blindly adjudicated. We randomly assigned 248 NVAF patients to uninterrupted rivaroxaban (20 mg once-daily) or to an uninterrupted VKA prior to CA and for 4 weeks afterwards. The primary endpoint was major bleeding events after CA. Secondary endpoints included thromboembolic events (composite of stroke, systemic embolism, myocardial infarction, and vascular death) and other bleeding or procedure-attributable events. Patients were 59.5 ± 10 years of age, 71% male, 74% paroxysmal AF, and had a CHA2DS2-VASc score of 1.6. The average total heparin dose used to manage activated clotting time (ACT) was slightly higher (13 871 vs. 10 964 units; P < 0.001) and the mean ACT level attained slightly lower (302 vs. 332 s; P < 0.001) in rivaroxaban and VKA arms, respectively. The incidence of major bleeding was low (0.4%; 1 major bleeding event). Similarly, thromboembolic events were low (0.8%; 1 ischemic stroke and 1 vascular death). All events occurred in the VKA arm and all after CA. The number of any adjudicated events (26 vs. 25), any bleeding events (21 vs. 18), and any other procedure-attributable events (5 vs. 5) were similar. CONCLUSION: In patients undergoing CA for AF, the use of uninterrupted oral rivaroxaban was feasible and event rates were similar to those for uninterrupted VKA therapy. NAME OF THE TRIAL REGISTRY: Clinicaltrials.gov trial registration number is NCT01729871.
Assuntos
Fibrilação Atrial/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Ablação por Cateter/métodos , Inibidores do Fator Xa/administração & dosagem , Rivaroxabana/administração & dosagem , Vitamina K/antagonistas & inibidores , Antiarrítmicos/uso terapêutico , Ablação por Cateter/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Prospectivos , Veias Pulmonares/cirurgia , Recidiva , Reoperação , Método Simples-Cego , Resultado do TratamentoRESUMO
AIMS/HYPOTHESIS: A reliable method for in vivo quantification of pancreatic beta cell mass (BCM) could lead to further insight into the pathophysiology of diabetes. The glucagon-like peptide 1 receptor, abundantly expressed on beta cells, may be a suitable target for imaging. We investigated the potential of radiotracer imaging with the GLP-1 analogue exendin labelled with indium-111 for determination of BCM in vivo in a rodent model of beta cell loss and in patients with type 1 diabetes and healthy individuals. METHODS: The targeting of (111)In-labelled exendin was examined in a rat model of alloxan-induced beta cell loss. Rats were injected with 15 MBq (111)In-labelled exendin and single photon emission computed tomography (SPECT) acquisition was performed 1 h post injection, followed by dissection, biodistribution and ex vivo autoradiography studies of pancreatic sections. BCM was determined by morphometric analysis after staining with an anti-insulin antibody. For clinical evaluation SPECT was acquired 4, 24 and 48 h after injection of 150 MBq (111)In-labelled exendin in five patients with type 1 diabetes and five healthy individuals. The tracer uptake was determined by quantitative analysis of the SPECT images. RESULTS: In rats, (111)In-labelled exendin specifically targets the beta cells and pancreatic uptake is highly correlated with BCM. In humans, the pancreas was visible in SPECT images and the pancreatic uptake showed high interindividual variation with a substantially lower uptake in patients with type 1 diabetes. CONCLUSIONS/INTERPRETATION: These studies indicate that (111)In-labelled exendin may be suitable for non-invasive quantification of BCM. TRIAL REGISTRATION: ClinicalTrials.gov NCT01825148, EudraCT: 2012-000619-10.
Assuntos
Diabetes Mellitus Tipo 1/diagnóstico por imagem , Radioisótopos de Índio , Células Secretoras de Insulina/diagnóstico por imagem , Peptídeos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adolescente , Adulto , Animais , Diabetes Mellitus Tipo 1/sangue , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Ratos , Receptores de Glucagon/metabolismo , Fatores de Tempo , Adulto JovemRESUMO
Glutamic acid decarboxylase 65 (GAD) and proinsulin are major diabetes-associated autoantigens that drive autoreactive T cells. Altered peptide ligands (APL) have been proposed as reagents for the modification of autoimmune reactions. Here, we have prepared GAD-derived protease-resistant APL (prAPL) by cleavage site-directed modification. The resulting prAPL are resistant to lysosomal and serum proteases, bind with high-affinity to HLA-DRB1(*)0401 and have a prolonged half-life in the serum. GAD-derived prAPL significantly decreased the secretion of proinflammatory cytokines by a GAD-specific human T cell clone. Likewise, the production of IL-17, TNF-alpha, and secretion of IL-6 by peripheral blood lymphocytes from patients with type 1 diabetes mellitus (T1D) was reduced, when stimulated with both GAD and GAD-derived prAPL. Thus, prAPL with high affinity for HLA-DRB1(*)0401 mitigate the response of GAD-reactive human Th17 cells. The strategy of designing specific immunomodulatory protease-resistant altered peptide ligands provides the basis for novel avenues of therapeutic intervention.
Assuntos
Diabetes Mellitus Tipo 1/sangue , Interleucina-7/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Catepsinas/metabolismo , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Glutamato Descarboxilase/química , Humanos , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Espectrometria de Massas , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Peptídeo Hidrolases/metabolismo , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
The neuroleptic malignant syndrome (NMS) is a rare, but potentially lethal side effect of conventional and atypical antipsychotic drugs. We present a 62 years old male patient who was admitted to our institution because of sudden onset of mild hyperthermia, muscle rigidity, stupor, leucocytosis and massive rhabdomyolysis after 30 years uneventful treatment with clozapine. The medication with clozapine was suspended because of the suspicion of NMS. When the acute symptoms were abated, the treatment with clozapine was resumed again after 14 days. The very next day, the patient suffered again from raised body core temperature, leucocytosis, elevated serum creatine kinase and new catatonia. The therapy with clozapine was stopped definitively and benzodiazepines were administered assuming a relapse of an alleviated, probably reconvening NMS. Under the treatment with benzodiazepines the patient was free of symptoms even after 1 month. To our knowledge, the latency of 30 years between the beginning of the treatment with clozapine and the onset of NMS is the longest period in the literature. According to our case, the differential diagnosis of NMS is not always trivial and is therefore discussed.
Assuntos
Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Síndrome Maligna Neuroléptica/diagnóstico , Antipsicóticos/uso terapêutico , Temperatura Corporal/efeitos dos fármacos , Clozapina/uso terapêutico , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Rabdomiólise/induzido quimicamente , Esquizofrenia/tratamento farmacológicoRESUMO
BACKGROUND: Anti-tumor necrosis factor alpha (anti-TNF- alpha ) antibodies have been used for the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriasis arthritis. Such antibody therapies result in a severe interference with the patient's immune system. Increased rates of upper respiratory tract infection, reactivation of latent tuberculosis, and other systemic infectious diseases have been reported among patients receiving anti-TNF- alpha antibodies. METHODS: As a note of caution, we describe a 57-year-old woman who received therapy with anti-TNF- alpha antibodies for RA refractory to methotrexate. After almost 2 years of treatment, she developed a severe cytomegalovirus (CMV) retinitis of the right eye. RESULTS: Laboratory assays revealed an immune status with nearly total loss of the cellular immune response and partial reduction of the humoral immune response. Intravenous treatment with ganciclovir, followed by oral administration of valganciclovir, resulted in an ophthalmological remission. Cessation of immunosuppressive therapy led to partial immunological reconstitution in the patient. Six months after discontinuation of immunosuppressive therapy, CMV retinitis of the left eye occurred but was treated successfully with a second course of oral valganciclovir. CONCLUSION: In the light of this first reported case of a serious CMV infection following therapy with anti-TNF- alpha antibodies, CMV infection should be considered in symptomatic patients.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Retinite por Citomegalovirus/induzido quimicamente , Retinite por Citomegalovirus/imunologia , Fator de Necrose Tumoral alfa/imunologia , Anticorpos Monoclonais/imunologia , Antivirais/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/imunologia , Retinite por Citomegalovirus/complicações , Retinite por Citomegalovirus/tratamento farmacológico , Feminino , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Humanos , Infliximab , Pessoa de Meia-Idade , ValganciclovirAssuntos
Inibidores da Protease de HIV/uso terapêutico , HIV-1 , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Piridinas/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Sulfato de Atazanavir , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The role of CD8(+) T lymphocytes in chronic hepatitis C virus (HCV) infection and in liver injury with subsequent development of fibrosis and cirrhosis is poorly understood. To address this question, we performed a follow-up study including 27 chronically HCV-infected individuals. We determined clonality and phenotypes of circulating CD8(+) T cells employing TCRBV spectratyping. Antigen specificity was tested by rMHC-peptide tetramer staining and stimulation with recombinant HCV antigens. In addition, T-cell clonality and phenotypes were followed during the variable clinical response of interferon- (IFN) alpha treatment. We could demonstrate that CD8(+) T-cell expansions were significantly associated with liver fibrosis and cirrhosis. Likewise, increased oligoclonality of circulating CD8(+) T cells in chronic HCV infection was identified as an indicator for poor clinical response to IFN-alpha therapy. Moreover, we also found that IFN-alpha therapy enhanced the differentiation of CD8(+) T cells towards a late differentiation phenotype (CD28(-) CD57(+)). In cases of virus elimination the disappearance of expanded terminally differentiated CD8(+) cells was observed. Thus, this study identifies an association of clonal expansions of circulating CD8(+) T cells with liver pathology and provides a possible explanation for the fact that response to IFN-alpha therapy diminishes with the duration of infection.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Interferon-alfa/uso terapêutico , Cirrose Hepática/virologia , Adulto , Idoso , Antígenos CD28/análise , Linfócitos T CD4-Positivos/imunologia , Antígenos CD57/análise , Células Clonais , Feminino , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/genética , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/imunologia , Antígenos HLA-DR/análise , Hepatite C Crônica/complicações , Humanos , Memória Imunológica , Cirrose Hepática/patologia , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologiaRESUMO
Memory T cells of the CD4 lineage coordinate immune responses against pathogens via the antigen-induced secretion of potent effector cytokines. The efficacy of these responses is thought to depend on both the overall number of pathogen-specific memory T cells and the particular array of cytokines that these cells are programmed to secrete. It is unknown to what extent cellular immunity can be induced by Echinococcus multilocularis infection. To examine the immunological memory provided by the adaptive cellular immune system in control of the chronic-persisting infection, peripheral lymphocytes of patients with alveolar echinococcosis (AE) were studied ex vivo. Stimulation of memory cells was performed with E. multilocularis vesicular fluid, purified protein derivative as recall antigen and phytohemagglutinin. Cytomegalovirus latency served as disease control. Frequencies of circulating CD4(+) T cells secreting IFN-gamma, IL-2, tumor necrosis factor-alpha, IL-4, IL-5 and IL-10 were determined by both cytokine flow cytometry and ELISPOT assays. Most strikingly, in chronic AE the frequencies of E. multilocularis antigen-specific cells committed to T(h)1-cytokine production were low (mean 0.5% of CD4(+) T cells). However, an E. multilocularis-specific response of CD4(+) T cells at frequencies of >/=0.1% was detected in the majority of AE patients (68%). Low numbers of cells committed to T(h)1 cytokine secretion were invariably seen in patients with active and inactive disease. Interestingly, the number of specific CD4(+) memory T cells was not increased in cured AE patients after complete surgical removal of the metacestode. Hyporesponsiveness during the chronic helminth infection was E. multilocularis specific. Thus, our results demonstrate that antigen-specific memory function against E. multilocularis is markedly different from that against viral or bacterial pathogens. Whether the antigen-specific cellular hyporesponsiveness with impeded T(h)1 CD4(+) memory T cell generation is a cause or a result of the progressive metacestode activity remains to be determined.
Assuntos
Equinococose Hepática/imunologia , Hepatopatias/parasitologia , Células Th1/imunologia , Células Th1/parasitologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Doença Crônica , Citocinas/metabolismo , Echinococcus/imunologia , Feminino , Citometria de Fluxo , Humanos , Imunoensaio , Memória Imunológica/fisiologia , Hepatopatias/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
Most patients with alveolar echinococcosis are diagnosed at a late stage when the disease has advanced to unresectable hepatic lesions. These patients require lifelong therapy with benzimidazoles, the only medical treatment currently available. To date, no treatment option remains for patients with benzimidazole intolerance or treatment failure. Amphotericin B was recently shown to exert antiparasitic activity in vitro. Here, we report the efficacy of amphotericin B in human alveolar echinococcosis. In three patients with extensive disease and without further treatment options, disease progression had been documented over several months. They were treated with amphotericin B intravenously at a dose of 0.5 mg/kg of body weight three times per week. Follow-up parameters were physical examination, laboratory parameters, and imaging techniques. Amphotericin B treatment effectively halted parasite growth in all three patients. The antiparasitic effect was most evident by spontaneous closure of cutaneous fistulae in two patients and by constant size of parasitic lesions during treatment, as assessed radiologically. Metabolic activity in parasitic areas was visualized by positron emission tomography and significantly decreased during treatment. However, progressive affection of the heart in one patient could not be stopped. All patients currently continue on amphotericin B and have been treated for 25, 17, and 14 months, respectively. We introduce amphotericin B as salvage treatment for alveolar echinococcosis patients with intolerance or resistance to benzimidazoles, as it effectively suppresses parasite growth. Amphotericin B is not parasitocidal; therefore long-term treatment has to be anticipated.
Assuntos
Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Equinococose Hepática/tratamento farmacológico , Equinococose Pulmonar/tratamento farmacológico , Terapia de Salvação , Adolescente , Idoso , Animais , Equinococose Hepática/parasitologia , Equinococose Pulmonar/parasitologia , Echinococcus/crescimento & desenvolvimento , Feminino , Fluordesoxiglucose F18 , Gerbillinae , Humanos , Assistência de Longa Duração , Imageamento por Ressonância Magnética , Masculino , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão , Tomografia Computadorizada por Raios XRESUMO
Biphenyl-utilizing polychlorinated biphenyls (PCB)-degrading bacteria were isolated from sites highly contaminated by PCBs, and their degradation abilities were determined using GC for typical commercial PCB mixtures (Delor 103 and Delor 106). Out of twelve strains which utilized biphenyl as a sole source of carbon and energy, strains Pseudomonas alcaligenes KP2 and P. fluorescens KP12, characterized by the BIOLOG identification system and the NEFERM test, were shown to significantly co-metabolize the PCB mixture Delor 103. DNA-DNA hybridization was used to compare both strains with well-known PCB-degraders Burkholderia cepacia strain LB400 and Ralstonia eutropha strain H850. The strain KP12 employs the same meta-fission route for degradation of chlorobenzoates as a chlorobiphenyl degrader Pseudomonas cepacia P166. Both isolates KP2 and KP12 belong to different phylogenetic groups, which indicates that the same geographical location does not ensure the same ancestor of degradative enzymes. We confirmed that also highly chlorinated and the most toxic congeners, which are contained in commercial PCB mixtures, can be biotransformed by members of indigenous bacterial-soil community under aerobic conditions.
Assuntos
Bifenilos Policlorados/metabolismo , Pseudomonas/metabolismo , Microbiologia do Solo , Biodegradação Ambiental , Southern Blotting , Burkholderia cepacia/isolamento & purificação , Burkholderia cepacia/metabolismo , Cupriavidus necator/isolamento & purificação , Cupriavidus necator/metabolismo , República Tcheca , DNA Bacteriano/química , DNA Bacteriano/isolamento & purificação , Pseudomonas/genética , Pseudomonas/isolamento & purificação , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidadeRESUMO
Alveolar echinococcosis (AE) in humans is a chronic disease characterized by slowly expanding liver lesions. Cellular immunity restricts the spreading of the extracellular pathogen, but functional contributions of CD4(+) and CD8(+) T cells are not defined. Here we studied ex vivo the phenotype and function of circulating T-cell subsets in AE patients by means of flow cytometry, T-cell receptor spectratyping, and lymphocyte proliferation. AE patients with parasitic lesions displayed a significant increase of activation of predominantly CD8(+) T cells compared to healthy controls and AE patients without lesions. In vitro, proliferative T-cell responses to polyclonal stimulation with recall antigens and Echinococcus multilocularis vesicular fluid antigen were sustained during chronic persisting infection in all AE patients. Only in AE patients with parasitic lesions did T-cell receptor spectratyping reveal increased oligoclonality of CD8(+) but not CD4(+) T cells, suggesting a persistent antigenic drive for CD8(+) T cells with subsequent proliferation of selected clonotypes. Thus, our data provide strong evidence for an active role of CD8(+) T cells in AE.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Equinococose Hepática/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/imunologia , Doença Crônica , Células Clonais , Feminino , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , FenótipoRESUMO
Several aerobic co-cultures capable of co-metabolising polychlorinated biphenyls (PCBs) were acquired by cultivation on biphenyls (BP). The source of micro-organisms was PCB-contaminated soil taken from various sites in the Czech Republic. Several bacterial strains (Gram-negative rods) were isolated, and their capacity to degrade Delor 103 (a PCB mixture containing di- to hexachlorobiphenyls) was analysed. This study was focused on co-culture 319 and isolate 2. The growth parameters of both those cultures were studied on BP; for isolate number 2 the specific growth rate mu = 0.122 (h-1) was calculated. The degradation of the individual congeners was estimated and resulted in more than 50% of the degradation of nearly all congeners during a 2-week experiment. Toxicity of Delor 103 on the vitality of the cells was followed by using viable plate count. The viability of the tested strain was preserved in the 100 times higher Delor 103 concentration compared with conditions in degradation experiments.
Assuntos
Bactérias/metabolismo , Bifenilos Policlorados/metabolismo , Poluentes do Solo/metabolismo , Aerobiose , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Biodegradação Ambiental , Cinética , Pseudomonas/crescimento & desenvolvimento , Pseudomonas/isolamento & purificação , Pseudomonas/metabolismo , Microbiologia do SoloRESUMO
Hydrocarbone diamantane has been shown to be a specific substrate with a high affinity for the binding site of PB-inducible cytochrome P-450 2B1 (Hodek et al. 1988). Using a difference spectroscopy approach, a battery of diamantane analogues and diamantane oxygen containing derivatives were examined for their interaction with P-450 2B1 active site. Of the compounds (diamantane and its analogues, adamantane and triamantane) tested, diamantane had the lowest value of a spectral dissociation constant Ks = 0.5 mumol/l, indicating that diamantane was accommodated well to the cytochrome P-450 2B1, hence values of 0.46 nm and 0.66 nm for the width and length of the diamantane molecule, respectively, were used to describe of the dimensions the cytochrome P-450 binding site. Adamantane (Ks = 1.3 mumol/l) is relatively small and thus it binds loosely whereas triamantane (Ks = 4.3 mumol/l) is bulky enough to fit the binding site. This conclusion has been confirmed by spectral competition experiments as well as metabolic studies. Of all oxygen containing derivatives diamantane 1,6-dicarboxylic acid dimethylester only exhibited a pronounced ligand interaction with cytochrome P-450. Using molecular dimensions of this derivative the distance of 0.56 nm from the heme iron to the center of the substrate binding site was estimated.
Assuntos
Adamantano/análogos & derivados , Hidrocarboneto de Aril Hidroxilases , Sistema Enzimático do Citocromo P-450/química , Esteroide Hidroxilases/química , Adamantano/química , Adamantano/metabolismo , Aminopirina/metabolismo , Animais , Sítios de Ligação , Ligação Competitiva , Fenômenos Biofísicos , Biofísica , Sistema Enzimático do Citocromo P-450/metabolismo , Técnicas In Vitro , Cinética , Microssomos Hepáticos/enzimologia , Estrutura Molecular , Ratos , Ratos Wistar , Esteroide Hidroxilases/metabolismoRESUMO
We performed an assay to assess the polychlorinated biphenyl (PCB) degradative capability and congener specificity of aerobic microorganisms. Microbial strains were isolated and separated from different types of soils in the Czech Republic, and their PCB-degrading abilities were compared. An industrial mixture of PCB congeners ranging from dichloro- to hexachlorobiphenyl and representing various chlorination patterns was used throughout. The PCB degradative ability of microorganisms was determined by gas chromatography after 7 days of incubation. The degree of degradation was found to depend on the number of chlorine substituents.
RESUMO
In a cross-sectional study, 65 workers in the chemical industry with exposure to platinum salts were investigated with regard to the prevalence to allergic respiratory tract diseases. A respiratory questionnaire, a skin-prick test with K2PtCl6 and environmental allergens, determination of total IgE, platinum-specific IgE and histamine release in basophilic granulocytes and lung function tests were applied before and after a Monday shift and after a Friday shift. Work-related symptoms of respiratory allergy were present in 23% of all workers, but were significantly more frequent in the most exposed group in the platinum refinery (52.4%). Of all workers, 18.7% had a positive skin-prick test with platinum salt. As compared to the other workers, the workers with work-related symptoms of respiratory allergy had significantly more positive skin-prick tests (64.3%) and a higher total IgE and platinum-specific IgE; they did not, however, show higher histamine release. In the course of the week, a significant fall in lung function, namely in FEV1 and FEF25, was recorded in the group of workers with work-related symptoms.