Metropolitan University of Santos
Sao Paulo, Brazil
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Fragoso Y.D.,Metropolitan University of Santos
Current Topics in Pharmacology | Year: 2015

Multiple sclerosis (MS) is a chronic, demyelinating, immune-mediated disease of the central nervous system. MS can lead to severe neurological disability and demands medical and pharmacological follow-up (both specific and symptomatic) as well as non-pharmacological treatments. MS can affect people of all ages and some patients have the disease onset before they reach the age of 18 years. This creates a limitation in their treatment. Although a very vigorous approach is needed in order to alter the disease course, no drugs have ever been studied in patients below the age of 18 years. When the disease is aggressive and the patient fails to respond to first-line immunomodulatory drugs, the therapeutic approach becomes very limited. Only observational studies are available to support the use of some medications in early-onset MS, and among these, natalizumab comes as an important therapeutic possibility. The present work summarizes data on natalizumab prescribed for patients before they completed 18 years of age, and reports on the efficacy and safety of this drug for this population. There are very few reports in the literature regarding natalizumab for children with MS, but they point towards a good safety profile and highly effective MS control with this therapeutic approach.

Shearer K.D.,University of Aberdeen | Fragoso Y.D.,University of Aberdeen | Fragoso Y.D.,Metropolitan University of Santos | Clagett-Dame M.,University of Wisconsin - Madison | McCaffery P.J.,University of Aberdeen
GLIA | Year: 2012

Retinaldehyde dehydrogenases (RALDH) catalyze the synthesis of the regulatory factor retinoic acid (RA). Cultured astrocytes express several of the RALDH enzyme family, and it has been assumed that this can be extrapolated to astrocytes in vivo. However, this study finds that few astrocytes in the rodent brain express detectable RALDH enzymes, and only when these cells are grown in culture are these enzymes upregulated. Factors controlling the expression of the RALDHs in cultured astrocytes were explored to determine possible reasons for differences between in vitro versus in vivo expression. Retinoids were found to feedback to suppress several of the RALDHs, and physiological levels of retinoids may be one route by which astrocytic RALDHs are maintained at low levels. In the case of RALDH2, in vivo reduction of vitamin A levels in rats resulted in an increase in astrocyte RALDH2 expression in the hippocampus. Other factors though are likely to control RALDH expression. A shift in astrocytic RALDH subcellular localization is a potential mechanism for regulating RA signaling. Under conditions of vitamin A deficiency, RALDH2 protein moved from the cytoplasm to the nucleus where it may synthesize RA at the site of the nuclear RA receptors. Similarly, in conditions of oxidative stress RALDH1 and RALDH2 moved from the cytoplasm to a predominantly nuclear position. Thus, the RALDHs have been revealed to be dynamic in their expression in astrocytes where they may maintain retinoid homeostasis in the brain. © 2012 Wiley Periodicals, Inc.

Fragoso Y.D.,Metropolitan University of Santos | Fragoso Y.D.,University of Aberdeen | Shearer K.D.,University of Aberdeen | Sementilli A.,Metropolitan University of Santos | And 2 more authors.
Brain Structure and Function | Year: 2012

Retinoic acid, the active form of the nutrient vitamin A, regulates several facets of neuronal plasticity in the hippocampus, including neurogenesis and synaptic strength, acting via specific retinoic acid receptors (RARs). Essential for conversion of vitamin A to retinoic acid is the enzyme retinaldehyde dehydrogenase (RALDH) and in the rodent hippocampus this is only present in the adjacent meninges where it must act as a locally released paracrine hormone. Little is known though about the expression of RALDHs and RARs in the human hippocampus. This study confirms that RALDH levels are very low in mouse neurons but, surprisingly, strong expression of RALDH protein is detected by immunohistochemistry in hippocampal neurons. The receptors RARα, β and γ were also detected, each receptor exhibiting differing subcellular locations implying their potential regulation of both transcription and non-genomic actions. These results imply an essential function of retinoic acid in the human hippocampus likely to include regulation of neuronal plasticity. © Springer-Verlag 2011.

Fragoso Y.D.,Metropolitan University of Santos
Expert Opinion on Drug Safety | Year: 2014

Introduction: Multiple sclerosis (MS) is a disease that mainly affects young adults who are of reproductive age. MS can lead to severe disability and is associated with worse prognosis in untreated patients. Although MS is not negatively affected by pregnancy itself, it may be a high-risk decision to leave a woman without treatment because she may get pregnant.Areas covered: This paper reviews the literature on pregnancies where the mother was exposed to glatiramer acetate. Few data are available on paternal exposure, but this does not seem to pose a problem due to the pharmacological characteristics of the drug. Only a limited amount of data from individual groups in the world is available in the literature.Expert opinion: TEVA Pharmaceuticals would need to open the database on pregnancy exposure to glatiramer acetate to allow for proper conclusions. Glatiramer acetate is a drug of low risk in pregnancy (category B in the FDA classification) and may be a safe option for the treatment of women of fertile age with MS. © 2014 Informa UK, Ltd.

Ferraz V.,Metropolitan University of Santos
Arthroscopy Techniques | Year: 2013

Whereas "anatomic" anterior cruciate ligament reconstruction may improve clinical results, the technique has introduced new technical challenges. The purpose of this technical note and video is to explore tips and tricks that improve femoral socket drilling with a retrograde reamer, bone-patellar tendon-bone graft passage, and interference screw fixation. The techniques for retrograde femoral socket drilling in an inside-out direction, bone-patellar tendon-bone graft passage, and interference screw fixation are described and demonstrated. Pitfalls, troubleshooting tips, and possible solutions are discussed. With the retrograde reamer, the femoral socket can be placed in the footprint of the anterior cruciate ligament with a longer and more vertical tunnel. By modifying the size of the patellar bone plug, graft passage is improved. With care and technique, interference screw fixation in the femoral socket over a guidewire is possible. © 2013 Arthroscopy Association of North America.

Branco L.P.,Metropolitan University of Santos
Journal of oral science | Year: 2013

The aim of the present study was to assess the relationship between temporomandibular joint disorder (TMJD) and headache in children and adolescents. A prospective cross-sectional cohort study was carried out involving 93 children and adolescents (6 to 14 years of age) at the outpatient service of a dental school. All participants underwent a clinical examination involving Axis 1 of the Research Diagnostic Criteria for Temporomandibular Disorders, along with a characterization of headache and an anthropometric evaluation. Statistical analysis involved the chi-squared test for quantitative variables and the Student's t-test, ANOVA and Tukey's test for quantitative data. An adjusted logistic regression model was used to determine significant associations among gender, age, TMJD and headache. Mild TMJD was identified in 35.8% of the sample and was not associated the presence of headache. Moderate TMJD was found in 25.8% of patients and severe TMJD was found in 11.8%; both forms of TMJD were associated with headache. A significant correlation was found between the intensity of TMJD and the risk of headache. The present findings demonstrate a positive correlation between TMJD and headache in children and adolescents, independently of gender and age.

Fragoso Y.D.,Metropolitan University of Santos | Brooks J.B.B.,Metropolitan University of Santos
Expert Review of Clinical Pharmacology | Year: 2015

Leflunomide modulates T-cell responses and induces a shift from the Th1 to Th2 subpopulation. This process results in a beneficial effect in diseases in which there is good evidence that T cells play a major role in both initiation and perpetuation of the inflammatory condition. Leflunomide has been successfully used for treating rheumatoid arthritis and psoriatic arthritis for many years. The active metabolite of leflunomide is teriflunomide, which has been approved for treating multiple sclerosis. Teriflunomide, just like the mother drug, inhibits dihydro-orotate dehydrogenase and synthesis of pyrimidine. The present review presents and discusses the safety profiles of leflunomide and teriflunomide, two drugs that are indeed the same, considering that much can be learned from the reported side effects of both. © Informa UK, Ltd.

Fragoso Y.D.,Metropolitan University of Santos
Arquivos de Neuro-Psiquiatria | Year: 2014

Potential environmental modifiable factors involved in multiple sclerosis (MS) include low adherence to treatment, smoking, obesity, low levels of liposoluble vitamins A and D, high consumption of salt, and a sedentary lifestyle. Chronic tobacco use, obesity, sedentarism and insufficient levels of these vitamins all contribute to maintenance of a proinflammatory state. It is unlikely that there will be noticeable improvement in the inflammatory condition of MS if stopping smoking, reducing weight, exercising, increasing vitamin levels are done in an isolated and erratic manner. Modification of each and every one of these environmental risk factors is likely to be an important approach in the management of MS. The present review presents the arguments for an association between these hazardous modifiable factors and the chronic inflammatory state observed in MS. © 2014, Arquivos de Neuro-Psiquiatria. All rights reserved.

Fragoso Y.D.,Metropolitan University of Santos
Current Drug Safety | Year: 2015

Natalizumab and alemtuzumab are monoclonal antibodies approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). A third monoclonal antibody, daclizumab, should soon become another alternative for RRMS therapy. A group of 26 doctors working at specific MS Units in seven different Latin American countries participated in the present study. All 26 neurologists had experience with natalizumab for the treatment of MS and were willing to discuss strategies for improving this treatment. Most neurologists had no confidence in starting a patient on natalizumab and alemtuzumab, which are new and efficient drugs approved by North American, European and most Latin American health agencies. The Latin American specialists felt they were not properly informed on daclizumab. Specific pharmacovigilance programs for each of these monoclonal antibodies were considered very important by the neurologists, who were also willing to discuss these therapeutic options with peers from other countries. © 2015 Bentham Science Publishers.

Brooks J.B.B.,Metropolitan University of Santos | Brooks J.B.B.,Rio de Janeiro State Federal University | Fragoso Y.D.,Metropolitan University of Santos
Arquivos de Neuro-Psiquiatria | Year: 2013

The blink reflex - a simple, non-invasive and inexpensive test - may be indicative of lesions or dysfunctions of the brainstem, and particularly assesses the trigeminal-facial arch. Results from alterations of the blink reflex in patients with headaches have provided controversial data. Method: Registration of the waves R1 and R2 (ipsilateral to the stimulus) and R2c (contralateral to the stimulus) by electroneuromyography. Results: A large number of controls (n=160) and patients with chronic migraine (n=160) were studied. No significant differences were observed between the two groups. Conclusion: It is possible that this relatively simple and primitive reflex is not affected unless there is significant damage to the brainstem.

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