RESUMO
Cyclodextrin glycosyltransferases (CGTases) are bacterial enzymes that catalyze starch conversion into cyclodextrins, which have several biotechnological applications including solubilization of hydrophobic compounds, masking of unpleasant odors and flavors in pharmaceutical preparations, and removal of cholesterol from food. Additionally, CGTases produce maltooligosaccharides, which are linear molecules with potential benefits for human health. Current research efforts are concentrated in the development of engineered enzymes with improved yield and/or particular product specificity. In this work, we analyzed the role of four residues of the CGTase from Paenibacillus barengoltzii as determinants of product specificity. Single mutations were introduced in the CGTase-encoding gene to obtain mutants A137V, A144V, L280A and M329I and the activity of recombinant proteins was evaluated. The residue at position 137 proved to be relevant for CGTase activity. Molecular dynamics studies demonstrated additionally that mutation A137V produces a perturbation in the catalytic site of the CGTase, which correlates with a 10-fold reduction in its catalytic efficiency. Moreover, this mutant showed increased production of maltooligosaccharides with a high degree of polymerization, mostly maltopentaose to maltoheptaose. Our results highlight the role of residue 137 as a determinant of product specificity in this CGTase and may be applied to the rational design of saccharide-producing enzymes.
Assuntos
Ciclodextrinas/biossíntese , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Mutagênese Sítio-Dirigida , Mutação , Oligossacarídeos/biossíntese , Paenibacillus/enzimologia , Sequência de Aminoácidos , Domínio Catalítico , Ciclização , Ciclodextrinas/metabolismo , Glucosiltransferases/química , Simulação de Dinâmica Molecular , Oligossacarídeos/metabolismo , Especificidade por SubstratoRESUMO
PURPOSE: The aim of the study is to compare the effects of continuous positive airway pressure (CPAP) on the nasal cavities of patients with obstructive sleep apnoea (OSA) and with or without allergic rhinitis (AR/nonAR). METHODS: This paper is a prospective, longitudinal study. Thirty-four consecutive CPAP treatment-adherent patients with OSA (17 AR and 17 nonAR) were evaluated before and 2 months after treatment, by means of clinical (otorhinolaryngological symptoms, daytime sleepiness, overall and rhinoconjunctivitis-specific quality of life), anatomical (otorhinolaryngological examination), functional (auditory function, tubal function, nasal airflow, and mucociliary clearance), and biological variables (nasal cytology). No humidifier or anti-allergy medicines were used during treatment. RESULTS: Before treatment, patients with AR presented a higher score, compared to nonAR in rhinitis symptoms (4.82 ± 2.53 vs. 0.93 ± 1.02, p = 0.000), otologic symptoms (2.06 ± 1.95 vs. 0.44 ± 0.72, p = 0.004), cutaneous/ocular symptoms (2.12 ± 2.17 vs. 0.65 ± 1.17, p = 0.052), immunoglobulin E (181.82 ± 126.09 vs. 66.13 ± 97.97, p = 0.004), and nasal neutrophils (14.42 ± 31.94 vs. 0.16 ± 0.39, p = 0.031). After treatment, nonAR and AR groups improved in daytime sleepiness (11.53 ± 4.60 vs. 7.53 ± 2.87, p = 0.000 and 13.76 ± 4.93 vs. 7.53 ± 4.41, p = 0.001) respectively and increased nasal neutrophil (0.16 ± 0.39 vs. 5.78 ± 9.43, p = 0.001 and 14.42 ± 31.94 vs. 79.47 ± 202.08, p = 0.035). The symptoms and quality of life improved in patients with AR. NonAR patients, significantly increase nasal dryness (1.65 ± 1.27 vs. 0.00, p = 0.002) and mucociliary clearance times (38.59 ± 24.90 vs. 26.82 ± 23.18, p = 0.016). CONCLUSIONS: CPAP produces inflammation with increased nasal neutrophil levels in AR and nonAR patients. Nevertheless, patients with AR observed an improvement in nasal symptoms and quality of life, whereas in patients without AR, a relevant worsening of nasal dryness and mucociliary transport was observed.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Rinite Alérgica/complicações , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de VidaRESUMO
Neuroendocrine small cell carcinoma is a malignant neoplasm that most frequently arises in the lung. Salivary gland involvement is rare, and the parotid is the main gland affected. We describe the fine-needle aspiration (FNA) cytology findings, the immunophenotypical study and the differential diagnosis of a small cell carcinoma that presented in the parotid of a 91-year-old man. The tumour was treated only with radiotherapy and presented a complete response, with no evidence of the disease after three years of follow-up. This is the first case reported in the literature with good outcome after exclusive irradiation.
Assuntos
Carcinoma de Células Pequenas/patologia , Neoplasias Parotídeas/patologia , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Carcinoma/patologia , Carcinoma de Células Pequenas/radioterapia , Diagnóstico Diferencial , Humanos , Imunofenotipagem , Linfoma/patologia , Masculino , Neoplasias Parotídeas/radioterapiaRESUMO
Skull-base metastases are very unfrequent. Occipital condyle syndrome (OCS) is usually underdiagnosed. Until now few cases have been reported in the literature. We present a 71-year-old woman with metastatic rectum adenocarcinoma, with right occipital headache and ipsilateral hypoglossal palsy, diagnosed by computed tomography and magnetic resonance imaging of OCS due to a skull-base metastasis and treated with radiation therapy.
Assuntos
Adenocarcinoma/patologia , Cefaleia/etiologia , Doenças do Nervo Hipoglosso/etiologia , Osso Occipital , Neoplasias Retais/patologia , Neoplasias da Base do Crânio/secundário , Idoso , Feminino , Humanos , Neoplasias da Base do Crânio/complicações , Neoplasias da Base do Crânio/radioterapia , SíndromeRESUMO
INTRODUCTION: Whole brain radiation therapy (WBRT) remains a recommended treatment for patients with brain metastases in terms of symptom palliation, especially when extracranial systemic disease is present. The aim of the study was to determine the clinical correlation between pre-existing leukoaraiosis and posterior leukoencephalopathy secondary to WBRT. METHODS AND MATERIALS: We retrospectively reviewed the results of WBRT treatment in 44 patients with melanoma brain metastases. The neuroimaging abnormalities of the white matter (T2-weighted MRI) were graded over time. RESULTS: From the 37 evaluable patients the mean age was 53 years old, 23 male and 14 female. Vascular risk factors were present in 22 patients (59.5%). The WBRT total dose was 20 Gy/5fr (n=21) and 30 Gy/10fr (n=16). Leukoaraiosis pre-WBRT was observed in 9/37 patients (24.3%) and leukoencephalopathy post-WBRT in 2/37 (5.4%). Univariate analysis of prognostic factors (sex, age and vascular risk factors) for leukoaraiosis was conducted observing statistically significant differences for patients with age>or=65 years old (p=0.003). Nineteen patients survived more than 3 months. Twelve patients (63.2%) suffered from vascular risk factors. Univariate analysis demonstrated previous leukoaraiosis as a prognostic factor for developing further leukoencephalopathy after WBRT (p=0.015). CONCLUSIONS: Radiation-induced leukoencephalopathy is greater in patients with pre-existing leukoaraiosis. Because of the potential of long-term survival in a small subset of patients with brain metastases and the risk of radiation-induced dementia, neurotoxicity reduction in patients with leukoaraiosis is an important goal of treatment.
Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Síndrome da Leucoencefalopatia Posterior/epidemiologia , Radioterapia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/complicações , Fracionamento da Dose de Radiação , Feminino , Humanos , Incidência , Leucoaraiose/diagnóstico , Masculino , Pessoa de Meia-Idade , Síndrome da Leucoencefalopatia Posterior/etiologia , Prognóstico , Lesões por Radiação/epidemiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Intramedullary spinal cord metastases (ISCM) are uncommon and present with rapidly progressing neurological deficits. The objective of this study was to determine the rate, duration of neurological response and survival after radiation therapy. We have retrospectively reviewed the clinical outcome of six cases with a diagnosis of ISCM from primary lung cancer, non-small cell (NSCLC) (n=3) and small cell (SCLC) (n=3). Total radiation dose ranged from 27 Gy/5 fr to 40 Gy/20 fr. Ambulation was preserved in 3 patients and partially recovered in one. Five out of the six patients (83%) showed improvement in neurological signs/symptoms with a mean duration of 17.2 days (max: 40 days; min: 6 days). Median survival time was 5 months (confidence interval (CI) 95%: 0-12) for NSCLC and 5 months (CI 95%: 4-6) for SCLC. Although radiation response rate is high, the interval free of neurological progression is very short. A therapeutic approach should be considered for each individual.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Pequenas/secundário , Neoplasias Pulmonares/patologia , Neoplasias da Medula Espinal/secundário , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/radioterapia , Vértebras Cervicais , Intervalo Livre de Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Paraplegia/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/complicações , Neoplasias da Medula Espinal/radioterapia , Vértebras Torácicas , Resultado do TratamentoRESUMO
This multicenter trial investigated the ability of the cytoprotective agent sucralfate and the antisecretory agent cimetidine to prevent ulcer relapses. Seventy-one patients with recently healed duodenal ulcer were included, randomly assigned to one of the two treatment groups, and administered sucralfate 2 g per day or cimetidine 400 mg per day for six months; the treatment period was followed by another six months of follow-up without treatment. The response to therapy was evaluated by systematic single-blind endoscopy controls during the sixth and the 12th months. Quantitative (42 percent relapse rate with sucralfate and 52 percent with cimetidine) as well as qualitative (20 percent silent relapses with sucralfate and 47 percent with cimetidine) differences were observed, although these could not be demonstrated to be statistically significant.