139 resultados para Concomitant Methotrexate


Relevância:

10.00% 10.00%

Publicador:

Resumo:

Objectives: To examine the effects of triiodothyronine (T3), 17β-estradiol (E2), and tamoxifen (TAM) on transforming growth factor (TGF)-α gene expression in primary breast cancer cell cultures and interactions between the different treatments. Methods and results: Patients included in the study (no.=12) had been newly diagnosed with breast cancer. Fresh human breast carcinoma tissue was cut into 0.3-mm slices. These slices were placed in six 35-mm dishes on 2-ml organ culture medium. Dishes received the following treatments: dish 1: ethanol; dish 2: T3; dish 3: T3+TAM; dish 4: TAM; dish 5: E2; dish 6: E2+TAM. TGF-α mRNA content was normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA levels. All tissues included in this study were positive for estrogen receptor (ER) and thyroid hormone receptor expression. Treatment with T3 for 48 h significantly increased TGF-α mRNA levels compared to controls (15-fold), and concomitant treatment with TAM reduced expression to 3.4-fold compared to controls. When only TAM was added to the culture medium, TGF-α mRNA expression increased 5.3-fold, significantly higher than with all other treatment modalities. Conclusion: We demonstrate that TGF-α mRNA expression is more efficiently upregulated by T3 than E2. Concomitant treatment with TAM had a mitigating effect on the T3 effect, while E2 induced TGF-α upregulation. Our findings show some similarities between primary culture and breast cancer cell lines, but also some important differences: a) induction of TGF-α, a mitogenic protein, by TAM; b) a differential effect of TAM that may depend on relative expression of ER α and β; and c) supraphysiological doses of T3 may induce mitogenic signals in breast cancer tissue under conditions of low circulating E2. ©2008, Editrice Kurtis.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Purpose: This study evaluated the long-term effects of orthognathic surgery on subsequent growth of the maxillomandibular complex in the young cleft patient. Patients and Methods: We evaluated 12 young cleft patients (9 male and 3 female patients), with a mean age of 12 years 6 months (range, 9 years 8 months to 15 years 4 months), who underwent Le Fort I osteotomies, with maxillary advancement, expansion, and/or downgrafting, by use of autogenous bone or hydroxyapatite grafts, when indicated, for maxillary stabilization. Five patients had concomitant osteotomies of the mandibular ramus. All patients had presurgical and postsurgical orthodontic treatment to control the occlusion. Radiographs taken at initial evaluation (T1) and presurgery (T2) were compared to establish the facial growth vector before surgery, whereas radiographs taken immediately postsurgery (T3) and at longest follow-up (T4) were used to determine postsurgical growth. Each patient's lateral cephalograms were traced, and 16 landmarks were identified and used to compute 11 measurements describing presurgical and postsurgical growth. Results: Before surgery, all patients had relatively normal growth. After surgery, cephalograms showed statistically significant growth changes from T3 to T4, with the maxillary depth decreasing by -3.3° ± 1.8°, Sella-nasion-point A by -3.3° ± 1.8°, and point A-nasion-point B by -3.6° ± 2.8°. The angulation of the maxillary incisors increased by 9.2° ± 11.7°. Of 12 patients, 11 showed disproportionate postsurgical jaw growth. Maxillary growth occurred predominantly in a vertical vector with no anteroposterior growth, even though most patients had shown anteroposterior growth before surgery. The distance increased in the linear measurement from nasion to gnathion by 10.3 ± 7.9 mm. Four of 5 patients operated on during the mixed dentition phase had teeth that erupted through the cleft area. A variable impairment of postoperative growth was seen with the 2 types of grafting material used. No significant difference was noted in the effect on growth in patients with unilateral clefts versus those with bilateral clefts. The presence of a pharyngeal flap was noted to adversely affect growth, whereas simultaneous mandibular surgery did not. After surgery, 11 of 12 patients tended toward a Class III end-on occlusal relation. Conclusions: Orthognathic surgery may be performed on growing cleft patients when mandated by psychological and/or functional concerns. The surgeon must be cognizant of the adverse postsurgical growth outcomes when performing orthognathic surgery on growing cleft patients with the possibility for further surgery requirements. Performing maxillary osteotomies on cleft patients would be more predictable after completion of facial growth. © 2008 American Association of Oral and Maxillofacial Surgeons.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Autoimmune bullous dermatoses are diseases in which blisters and vesicles are the primary and fundamental types of skin lesion. Their classification is based on the location of the blister: intraepidermal and subepidermal. Patients produce autoantibodies against self-specific structures of the skin detectable by immunofluorescence techniques, immunoblotting and ELISA. Recent advances in molecular and cellular biology have brought to knowledge these self-antigens, against which patients are sensitized, and which are found in epidermis or in the dermo-epidermal junction. These are low incidence, but high morbidity diseases that may be fatal. The aim of this article is to review and describe the progress of four autoimmune vesiculobullous disorders: endemic pemphigus foliaceous (wild fire), pemphigus vulgaris, bullous pemphigoid and dermatitis herpetiformis. ©2009 by Anais Brasileiros de Dermatologia.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Background: Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases. Methods: In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ. Results: DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete. Conclusion: The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases. © 2009 Santos et al; licensee BioMed Central Ltd.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Verruciform xanthoma (VX) is a relatively rare benign lesion and oral predominantly, which occasionally affects skin and genital mucosa. It appears as a papule or single plaque showing a verrucous or papillomatous aspect, with variable color from reddish pink to gray. In majority of oral cases, it affects gingiva and alveolar mucosa such a solitary lesion. Histopathological findings are foamy histiocytes within elongated dermal papillae. Treatment consists of conservative excision surgery and recurrence is rare. A clinical case is reported, located in anterior gingiva, showing good prognosis, without recurrence. There was no concomitant oral lesion associated. Local trauma was the only possibility suggested to be related to etiology. No relevant alterations in laboratory exams (hemogram, total cholesterol, HDL, LDL, VLDL, glycose and glycolized hemoglobin) were found. The origin of the lesion remains unclear and investigation for possible associations with other lesions that could present greater risk of carcinogenesis is required. © Medicina Oral S.L.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

We report on the results of a double-blind, randomized, controlled clinical trial comparing two preparations of ethinylestradiol and cyproterone acetate in the treatment of women of reproductive age presenting menstrual irregularities of hyper-androgenic origin. After obtaining informed consent, subjects were randomized to a 4-month treatment period consisting of one daily dose of 0.035mg ethinylestradiol + 2mg cyproterone acetate. The treatment regimen cycle consisted of one pill, once daily for 21 days, followed by a 7-day pill-free period. We compared the efficacy of two presentations of the drug combination after each treatment cycle (Visits 2, 3, 4, and 5) in establishment and maintenance of menstrual regulation, intensity of menstrual flow, and dysmenorrhea, as well as a comparison of the two presentations in terms of Global Satisfaction and Drug Satisfaction assessments performed by the patients and the investigating physician. At each study visit, drug compliance and use of concomitant medications, as well as incidence, severity and duration of adverse events were recorded. A total of 86 subjects were randomized to treatment, with 43 subjects in each treatment group. At Visit 2 and each subsequent visit, all patients in both treatment groups reported an episode of withdrawal bleeding during the 7-day hormone-free period. We observed a statistically significant (p<0.0001) decrease in the incidence of dysmenorrhea at each study visit in relation to the pretreatment assessment. There was a significant reduction (p<0.0001) in the number of subjects reporting intermenstrual bleeding at each study visit in both treatment groups. Global Satisfaction scores by the patient and physician increased significantly at each successive study visit in both treatment groups. There were no clinically significant changes in vital signs, weight, and body mass index throughout the study period in either group. The number of subjects reporting adverse events at each visit did not vary between treatment groups. The combined oral contraceptive pill containing ethinylestradiol and cyproterone acetate was found to be both effective and safe in the menstrual irregularities of hyper-androgenic origin (amenorrhea, dysmenorrhea, and intermenstrual bleeding) assessed in this study. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

In the present communication, by using dielectric spectroscopy measurement, the correlations between Nanosized Barrier Layer Capacitance (NBLC) (Bueno et al. (2009) [7]) and the high frequency polaronic near-Debye dipolar relaxation found in CaCu3Ti4O12 compounds was discussed. The polaronic process was confirmed to be closely associated with the ultrahigh dielectric features of CaCu3Ti4O12 materials and its concomitant dielectric loss. Herein, the shift in relaxation frequency as a function of temperature was used for calculating the activation energy for hopping electronic conduction. The value obtained was 33 meV, an energy whose magnitude is compatible and confirmed the hypothesis of polaronic features for this high frequency dipolar relaxation process. Furthermore, it is shown that the nanosized barrier inferred from the NBLC model has a polaronic feature with dielectric permittivity exiting orthogonally to dielectric loss, a phenomenological pattern that contradicts the normally observed behavior for traditional dielectrics but explain the dielectric and conductivity feature of CaCu3Ti4O12 compounds. © 2010 Elsevier Ltd. All rights reserved.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Infertility represents one of the main long-term consequences of combination chemotherapy used for the treatment of breast cancer. Approximately 60%-65% of breast cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ tumors with respect to recurrence-free survival and overall survival, Presentation of the hypothesis: It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+ tumours) if they want to preserve their reproductive function. Testing the hypothesis: Assessment of ovarian reserve tests: follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume 6 months, and 1 year after the end of therapy with GnRHa/tamoxifen. The recurrence-free survival and overall survival should be analysed. Implications of the hypothesis: The major implication will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases. © Todos os direitos reservados a SBRA - Sociedade Brasileira de Reprodução Assistida.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Over the last decade, several studies were conducted on the gastrointestinal changes associated to chronic heart failure. This article presents a literature review on the physiopathology and clinical consequences of pathological digestive changes of heart failure patients. Structural and functional abnormalities of the gastrointestinal tract, such as edema of absorptive mucosa and intestinal bacterial overgrowth, have been leading to serious clinical consequences. Some of these consequences are cardiac cachexia, systemic inflammatory activation and anemia. These conditions, alone or in combination, may lead to worsening of the pre-existing ventricular dysfunction. Although currently there is no therapy specifically earmarked for gastrointestinal changes associated to heart failure, the understanding of digestive abnormalities is germane for the prevention and management of systemic consequences.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Context - Several paradoxical cases of infliximab-induced or-exacerbated psoriatic lesions have been described in the recent years. There is disagreement regarding the need to discontinue infliximab in order to achieve the resolution of these adverse cutaneous reactions specifically in inflammatory bowel disease (IBD) patients. Objective - To systematically review the literature to collect information on IBD patients that showed this adverse cutaneous reaction, focusing mainly on the therapeutic approach. Methods - A systematic literature review was performed utilizing Medline, Embase, SciELO and Lilacs databases. Published studies were identified, reviewed and the data were extracted. Results - Thirty-four studies (69 IBD patients) met inclusion criteria for review. There was inconsistency in reporting of some clinical and therapeutic aspects. Most patients included had Crohn's disease (89.86%), was female (47.83%), had an average age of 27.11 years, and no reported history of psoriasis (84.05%). The patients developed primarily plaque-type psoriasis (40.58%). There was complete remission of psoriatic lesions in 86.96% of IBD patients, existing differences in the therapeutic approaches; cessation of infliximab therapy led to resolution in 47.83% of cases and 43.48% of patients were able to continue infliximab therapy. Conclusion - As increasing numbers of IBD patients with psoriasis induced or exacerbated by infliximab, physicians should be aware of its clinical manifestations so that appropriate diagnosis and treatment are properly established. The decision whether to continue or discontinue infliximab should be individualized.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

l-Amino acid oxidases (LAAOs) are flavoenzymes that catalytically deaminate l-amino acids to corresponding α-keto acids with the concomitant production of ammonia (NH 3) and hydrogen peroxide (H 2O 2). Particularly, snake venom LAAOs have been attracted much attention due to their diverse clinical and biological effects, interfering on human coagulation factors and being cytotoxic against some pathogenic bacteria and Leishmania ssp. In this work, a new LAAO from Bothrops jararacussu venom (BjsuLAAO) was purified, functionally characterized and its structure determined by X-ray crystallography at 3.1å resolution. BjsuLAAO showed high catalytic specificity for aromatic and aliphatic large side-chain amino acids. Comparative structural analysis with prokaryotic LAAOs, which exhibit low specificity, indicates the importance of the active-site volume in modulating enzyme selectivity. Surprisingly, the flavin adenine dinucleotide (FAD) cofactor was found in a different orientation canonically described for both prokaryotic and eukaryotic LAAOs. In this new conformational state, the adenosyl group is flipped towards the 62-71 loop, being stabilized by several hydrogen-bond interactions, which is equally stable to the classical binding mode. © 2012 Elsevier Inc.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Objectives: To compare the oral prevalence and antimicrobial susceptibility of Candida spp., staphylococci, enterobacteriaceae, and pseudomonas spp.from ankylosing spondylitis (AS) patients receiving conventional and anti-TNF-α therapy. Methods: The study included 70 AS patients, diagnosed according to the modified New York criteria (1984). The volunteers were divided into 2 groups: a biological group (AS BioG) (n=35) (on anti-TNF-α therapy) and a conventional group (AS ConvG) (n=35). The control group (ContG) (n=70) was made up of healthy individuals matched for age, gender, and oral conditions. After clinical examination, oral rinse samples were collected and plated in specific culture media. The number of colony-forming units per milliliter (cfu/ml) was obtained, and isolates were identified using the API system. Antimicrobial susceptibility tests were performed according to the NCCLS guidelines. Prevalence and counts of microorganisms were statistically compared between the 3 groups, using the Mann-Whitney and Chi-square tests. Significance level was set at 5%. Results: In both the AS BioG and the AS ConvG, staphylococci counts were higher than that in the ContG (p<0.0001). Candida albicans and staphylococcus epidermidis were the most commonly found species in all the groups. Serratia marcescens and klebsiella oxytoca were more prevalent in the AS BioG and the AS ConvG, respectively. Two Candida isolates (2.8%) from the AS BioG and 5 (10.8%) from the AS ConvG were resistant to amphotericin B and 5-fluorocytosine. A low percentage of staphylococci isolates was resistant to amoxicillin, ciprofloxacin, and doxycycline. Conclusion: Higher counts of staphylococci were observed in both AS groups, regardless of the current therapy, age, sex, and oral conditions. Anti-TNF-α therapy could not be correlated with increased counts of microorganisms. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2012.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Background: Paradoxical cases of psoriatic lesions induced or exacerbated by anti-tumor necrosis factor (TNF)-α therapy have been reported more frequently in recent years, but data related to inflammatory bowel disease (IBD) are rare. A systematic literature review was performed to provide information about this adverse effect in patients with IBD who receive anti-TNF therapy. Methods: Published studies were identified by a search of Medline, Embase, Cochrane, SciELO, and LILACS databases. Results: A total of 47 studies (222 patients) fulfilled the inclusion criteria and were selected for analysis. Clinical and therapeutic aspects varied considerably among these reports. Of the 222 patients, 78.38% were diagnosed with Crohn's disease, and 48.20% were female. The mean patient age was 26.50. years, and 70.72% of patients had no history of psoriasis. Patients developed psoriasiform lesions (55.86%) more often than other types of psoriatic lesions, and infliximab was the anti-TNF-α therapy that caused the cutaneous reaction in most patients (69.37%). Complete remission of cutaneous lesions was observed in 63.96% of the cases. Conclusions: We found that psoriatic lesions occurred predominantly in adult patients with Crohn's disease who received infliximab and had no previous history of psoriasis. Most patients can be managed conservatively without discontinuing anti-TNF-α therapy. © 2012 European Crohn's and Colitis Organisation.