PubMed Health⌕ Search

Biomedical subjects

F Mendes

Publications and source records attributed to F Mendes.

9 recordsLinked to original sources

S-nitrosoglutathione increases cystic fibrosis transmembrane regulator maturation.

Endogenous S-nitrosoglutathione (GSNO) is known to increase the expression of certain proteins at concentrations present in the normal human airway. We hypothesized that GSNO would increase expression and maturation of the cystic fibrosis transmembrane conductance regulator (CFTR). Cells expressing DeltaF508 and wild type CFTR were exposed to GSNO and analyzed for expression and maturation by Western blot analysis. Physiologically relevant concentrations of GSNO resulted in dose- and time-dependent increases in expression. The GSNO-induced increases were eliminated by cycloheximide, suggesting a posttranscriptional effect. Unlike proteasome inhibitors, GSNO resulted in an increase CFTR maturation. The GSNO effect could be reversed by dithiothreitol and inhibited by acivicin, a gamma glutamyl transpeptidase inhibitor. These observations suggest that GSNO leads to maturation of mutated DeltaF508 CFTR, a process associated with restoration of CFTR function. Because endogenous levels of GSNO are low in the cystic fibrosis (CF) airway, these results raise the possibility that GSNO replacement therapy could be an effective treatment for CF.

Animals↗

Cystic fibrosis F508del patients have apically localized CFTR in a reduced number of airway cells.

Present state of knowledge, mostly based on heterologous expression studies, indicates that the cystic fibrosis transmembrane conductance regulator (CFTR) protein bearing the F508del mutation is misprocessed and mislocalized in the cytoplasm, unable to reach the cell surface. Recently, however, it was described that protein levels and localization are similar between F508del and wild-type CFTR in airway and intestinal tissues, but not in the sweat glands. In this study, we used immunocytochemistry with three different anti-CFTR antibodies to investigate endogenous CFTR expression and localization in nasal epithelial cells from F508del homozygous patients, F508del carriers, and non-CF individuals. On average, 300 cells were observed per individual. No significant differences were observed for cell type distributions among CF, carrier, and non-CF samples; epithelial cells made up approximately 80% to 95% of all cells present. CFTR was detected mostly in the apical region (AR) of the tall columnar epithelial (TCE) cells, ciliated or nonciliated. By confocal microscopy analysis, we show that the CFTR apical region-staining does not overlap with either anti-calnexin (endoplasmic reticulum), anti-p58 (Golgi), or anti-tubulin (cilia) stainings. The median from results with three antibodies indicate that the apical localization of CFTR happens in 22% of TCE cells from F508del homozygous patients with CF (n = 12), in 42% of cells from F508del carriers (n = 20), and in 56% of cells from healthy individuals (n = 12). Statistical analysis indicates that differences are significant among all groups studied and for the three antibodies (p < 0.05). These results confirm the presence of CFTR in the apical region of airway cells from F508del homozygous patients; however, they also reveal that the number of cells in which this occurs is significantly lower than in F508del carriers and much lower than in healthy individuals. These findings may have an impact on the design of novel pharmacological strategies aimed at circumventing the CF defect caused by the F508del mutation.

Cell Line↗

Intervertebral disc prosthesis. Results and prospects for the year 2000.

Presently, the kinematic disc prosthesis model (SB Charité) is the best disc replacement compromise, and is the basis of the evolution of the prosthetic concept at the dawning of the year 2000. Clinical results of a homogeneous series of 105 cases with a mean followup of 51 months show 79% of the patients had an excellent result and 87% returned to work, radiologically, these results correlated with restoration of a well balanced lordosis and with segmental mobility. Factors leading to failure are posterior facet arthritis, osteoporosis, structural deformities, and secondary facet pain. Two- and 3-dimensional numeric modeling enables one to study the total facet joint loading and the maximal local loading on the facet. Dissociation of the stiffness in pure rotation and stiffness in translation of the disc are the bases of the technologic improvement.

Activities of Daily Living↗

[Risk factors for cerebrovascular stroke in a cohort of hypertensive patients].

OBJECTIVES: To identify stroke risk factors in hypertensive patients and the probability of stroke in relation to those risk factors and follow-up. STUDY DESIGN: A cohort study (patients with high blood pressure). MATERIAL AND METHODS: 707 hypertensive patients were studied (Hypertension Register) in what concerns stroke incidence until 1992 (n = 126), considering one case per individual. The following variables were analysed: age, sex, body mass index (Quetelet), systolic and diastolic blood pressure, heart rate, types of hypertension (JNC-IV), left ventricular hypertrophy, changes in ST segment and T wave (Minnesota Code), fundi, angina pectoris, heart failure, central nervous (neurological) disturbances, antihypertensive treatment, smoking, serum potassium, serum sodium, blood urea, creatinine, uric acid, blood sugar, diabetes and cholesterol, in the initial record. Individually, in relation to the control of hypertension, the subjects were classified according to the casual recording of normal blood pressure, the absence of drug treatment, diastolic pressure > 114 mmHg and, at the end of 1992, according to survival, causes of death and follow-up. Stroke risk factors have been identified by multivariate analysis (Cox regression model). The survival probability (without stroke) was defined by Kaplan-Meier method. RESULTS: It was possible to maintain the epidemiological surveillance, from 1975 to 1992, of 598 cases. From those, 109 hypertensive patients were victims of at least one episode of non transient cerebral ischaemia, during their follow-up of 10.5 years. From the characteristics studied, only five were identified at risk factors. The adjusted relative risks and confidence intervals (95% CI) were the following: age: 1.08 (1.06-1.10); diastolic pressure > 114 mmHg: 1.96 (1.32-2.91); neurological disturbances 4.64 (2.99-7.2); diabetes: 2.57 (1.62-4.05) and left ventricular hypertrophy: 1.34 (1.13-1.58). CONCLUSIONS: As far as stroke is concerned: a) Age, diabetes, a casual measurement of diastolic blood pressure > 114 mmHg and left ventricular hypertrophy (electrocardiogram) were the risk factors identified; b) Prevention should include blood pressure and diabetes control, although this disease has shown more risk than a casual measurement of severe hypertension; c) Its occurrence, in this model, has only partly been explained, therefore it has become necessary to deepen the study of the risk profile.

Adult↗

[The course of care for cancer patients hospitalized in a central hospital].

Prevention and early diagnosis are considered the main tools to reduce the incidence and mortality from cancer. The authors studied prospectively 150 oncologic patients admitted to Santa Maria Hospital-Lisbon from April/92 to April/93, by personal interview, to analyze their assistance pathways from the appearance of first symptoms. We tried to define the role of the different medical assistance structures and the most important factors conditioning delay in diagnosis and therapeutics. The results show that primary care physicians were the first medical assistance in 56% of patients; 22% of the patients went to the Emergency Service of the Hospital for the first time. Duration of symptoms was less then 3 months in 74% of the population studied. Primary care physicians diagnosed neoplasia in 32% of the cases and prescribed symptomatic treatment in another 41%. The Emergency Service was the most efficient in diagnosis, providing rapid orientation in 91% of patients. In this population, 43% had their residence more than 30 km from Lisbon. Median age was less than 60 years. These results emphasize the fundamental role of Primary Care Physicians in the initial management of cancer patients and their responsibility in early diagnosis. They also suggest the need for the promotion of graduate education and courses designed for primary care physicians and the population.

Aged↗

[Hemorrheologic changes in the hypertensive elderly patient].

The aim of this work is to make a review of the papers about hemorheology and hypertension on the aged. The paucity of the works did not allow any conclusions. However, some of the drugs frequently used have tight links with hemorheology, which must be in our minds when dealing with old people.

Age Factors↗

[Indirect articular lymphography using Tc 99m-labeled Dextran in animals].

Looking for a standardization of the articular lymphoscintigraphy, an experimental research was conducted on 14 dogs injected in the ankle, with 2.5 mCi of 99m Tc-labeled dextran (P.M. = 70,000). Good scintigraphic images of the lymphatic system have been obtained. After having collected blood samples during the experimentation as well as aliquots of organs and of tissues, after the necropsy of the animal, it was verified that the 99m Tc-labeled dextran was useful for quantitative studies of the articular lymphatic drainage. The activities attained, in the drainage lymph nodes of injected articulation, are 152 times superior to those obtained in the kidney and one gramma of popliteal ganglion was 8929 times more active than one gramma of blood. The dextran 70,000, widely used in our clinical routine, can be injected to the human being, without any risk, and it may be the tracer which permits studies of the articular lymphatic drainage and the usage of the lymphoscintigraphy, already in expansion in many other Medicine branches, in the articular studies, nowadays.

Animals↗

Non-Hodgkin's lymphoma in a population with or at risk for acquired immunodeficiency syndrome: indications for intensive chemotherapy.

PURPOSE: An increased risk of malignancies, including Kaposi's sarcoma and non-Hodgkin's lymphoma, is found in patients infected with the human immunodeficiency virus type 1 (HIV-1). Treatment of such patients may be complicated by their underlying immunodeficiency, especially when aggressive regimens are used. Clinical presentation and treatment outcomes were assessed in 31 patients with non-Hodgkin's lymphoma who had or were at risk for infection with HIV-1 at a single community institution. PATIENTS AND METHODS: Lymphomas presented in advanced stages and involved extranodal sites. Twenty-six patients received therapy (two radiation, one surgery), and a total of 23 patients received chemotherapy. RESULTS: A 52 percent response rate was seen with the use of chemotherapy. A history of opportunistic infections, or Kaposi's sarcoma, or both impacted negatively on the ability to achieve a complete response. Sixty-four percent of the 11 patients who received an intensive chemotherapeutic regimen, MACOP-B (methotrexate, Adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin) had complete remissions. Overall median survival for 23 patients who received chemotherapy was seven months. Patients achieving complete responses had a median survival of 20 months. CONCLUSION: Our results support intensive chemotherapy for patients with lymphoma and HIV-1 infection.

Acquired Immunodeficiency Syndrome↗