Craniofaringioma cístico: quimioterapia intratumoral com interferon alfa

OBJECTIVE: To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha. METHOD: Nineteen patients with the diagnosis of cystic craniopharyngioma were treated with intratumoral chemotherapy with interferon alpha from January 2002 to April 2006. All patients underwent placement of an intracystic catheter connected to an Ommaya reservoir. Through this reservoir were made applications during chemotherapy cycles. Each cycle corresponded to application of 3,000,000 units of interferon alpha three times per week on alternate days totalizing 36,000,000 units. Response to treatment was evaluated by calculating the tumor volume on MRI control after one, three and six months after the end of each cycle. Patients who developed worsening of symptoms or who had insignificant reduction in tumor volume during follow-up underwent repeat cycle chemotherapy. RESULTS: Four patients received four cycles of chemotherapy, three patients received three cycles, six patients received two cycles and six patients received one. The lower percentage of reduction in tumor volume was 60% and the bigger reduction was 98.37%. Eleven patients had a reduction greater than 90%. Five patients had a tumor reduction between 75 and 90% and in three patients the tumors were reduced by less than 75%. No deaths occurred during treatment and side effects of interferon alpha were well tolerated. No treatment was discontinued. Follow-up after the last application ranged from one year and five months to three years and nine months. CONCLUSION: The intratumoral chemotherapy with interferon alpha decreases the volume of cystic craniopharyngiomas and so far can be considered a new therapeutic alternative.OBJETIVO: Avaliar se os craniofaringiomas císticos podem ser controlados com aplicações intratumorais de interferon alfa. MÉTODO: De janeiro de 2002 a abril de 2006, 19 pacientes foram submetidos à colocação de um cateter intracístico conectado a reservatório de Ommaya para aplicações intratumorais de ciclos de 36.000.000 de unidades de interferon alfa. A resposta ao tratamento foi avaliada pelo cálculo do volume tumoral na ressonância magnética de controle ao término de cada ciclo. RESULTADOS: Os pacientes receberam de um a quatro ciclos de quimioterapia. Onze pacientes apresentaram uma redução do volume tumoral maior que 90%; cinco pacientes apresentaram uma redução entre 75% e 90% e três pacientes uma redução menor de 75%. Não houve óbitos durante o tratamento e os efeitos colaterais do inferferon alfa foram bem tolerados. Nenhum tratamento foi interrompido. CONCLUSÃO: A quimioterapia intratumoral com interferon alfa diminui o volume dos craniofaringeomas císticos e pode ser considerada uma nova alternativa terapêutica.Federal University of São Paulo Department of Neurosurgery and Section of Pediatric NeurosurgeryFederal University of São Paulo Department of PediatricsFederal University of São Paulo Laboratory of Pediatric Oncology InstituteUNIFESP, Department of Neurosurgery and Section of Pediatric NeurosurgeryUNIFESP, Department of PediatricsUNIFESP, Laboratory of Pediatric Oncology InstituteSciEL

Brazilian consensus on guidelines for diagnosis and treatment for restless legs syndrome

The Consensus on restless legs syndrome is an effort of neurologists from several Brazilian states, which tirelessly reviewed the literature of recent years in search of evidence, both in regard to diagnosis and treatment, according to the Oxford Centre for Evidence-based Medicine.Serv Neurol & Neurocirurgia, Passo Fundo, RS, BrazilUniv São Paulo, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, SP, BrazilClin Carlos Bacelar, Rio de Janeiro, RJ, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilHosp Moinhos Vento, BR-90560030 Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Dept Neurol, São Paulo, BrazilHosp Israelita Albert Einstein, São Paulo, BrazilUniv Fed Alagoas, Fac Med, Maceio, AL, BrazilUniv Fed Pernambuco, Recife, PE, BrazilClin Rio Sono, Rio de Janeiro, RJ, BrazilUniv São Paulo, Fac Med, Hosp Clin, São Paulo, BrazilPontificia Univ Catolica Rio Grande do Sul, Porto Alegre, RS, BrazilUniv Brasilia, Fac Med, Brasilia, DF, BrazilHosp Clin Porto Alegre, Porto Alegre, RS, BrazilProSSono Ctr Med Sono, Ribeirao Preto, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol, São Paulo, BrazilWeb of Scienc

ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

<p>Abstract</p> <p>Background</p> <p>ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, <it>ADAM23</it>, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer.</p> <p>Methods</p> <p>First, we analysed <it>ADAM33 </it>expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR) treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP). Finally, <it>ADAM33 </it>promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test.</p> <p>Results</p> <p>The expression analysis of <it>ADAM33 </it>in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR) demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to <it>ADAM33 </it>promoter hypermethylation. Using MSP, we detected <it>ADAM33 </it>promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM); tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC) was 76.2% compared with 25.5% in invasive ductal carcinoma (IDC), and this difference was statistically significant (p = 0.0002).</p> <p>Conclusion</p> <p><it>ADAM33 </it>gene silencing may be related to the discohesive histological appearance of ILCs. We suggest that <it>ADAM33 </it>promoter methylation may be a useful molecular marker for differentiating ILC and IDC.</p

Preliminary experience with the use of ultra-low profile endografts

PURPOSE: We aimed to report a preliminary single-center experience of elective endovascular aortic repair (EVAR) using ultra-low profile (ULP) endografts of 14 F outer diameter. METHODS: Data of 67 consecutive patients who underwent EVAR using either Ovation (group A, n=30) or Incraft (group B, n=37) endografts were retrospectively analyzed. RESULTS: Aorto-iliac anatomy was significantly different between the two groups, as patients of group A had a greater thrombotic apposition on proximal aortic neck (thrombus thickness: 7.2\ub11 mm vs. 3.3\ub11.6 mm, P = 0.042; percentage of the circumference covered by thrombus: 45.2%\ub110.4% vs. 18.7%\ub110.6%, P = 0.0003), while patients of group B had a more angulated proximal neck in the coronal axis (35.9\ub0\ub16.4\ub0 vs. 16.7\ub0\ub15\ub0, P = 0.012). Procedural success was 93.3% and 97.3%, respectively, in groups A and B. One patient in group A required an immediate conversion to open surgery for persistent occlusion of both iliac limbs. Another patient required implantation of a conical endograft with a femoro-femoral right-to-left bypass for occlusion of the contralateral gate during the cannulation. In group B, one intraoperative type Ia endoleak was immediately corrected. Neither deaths nor major adverse events were recorded within 30-days. During a median follow-up of 15.2 months (range, 1-56.7 months) two type Ia endoleaks in group A required open conversion after 12.1 and 40.5 months, respectively. Three patients in group B required a reintervention after 30 days. Neither deaths nor aortic ruptures were recorded during follow-up. CONCLUSION: Both ULP endografts showed satisfying early and mid-term results

Gastroprotective and anti Helicobacter pylori activities of propolis

Helicobacter pylori (HP) determines the most common human infection overall. Important gastric diseases are associated with HP with percentage of correlation up to 90% (duodenal ulcer and gastric lymphoma). The complexity of the pathogenetic factors of HP has prompted research to identit/ "phytocomplexes" able to act on different mechanisms of HP pathogenesis [1]. Our group investigated propolis regarding its antibacterial activity and focusing the protection from oxidative stress and massive inflammatory response, key elements of the progression of HP gastric diseases related, scarcely considered in classic antibiotical therapies [21. We studied propolis marketed in ltaly: classic propolis dry extract, hydrodispersible propolis, water-soluble propolis and a new formulation of propolis (75% italian propolis dry extract, 15% green tea catechins, 10% grape seed procyanidins), 50% total polyphenols UV method standardized. The different chemical composition of samples determines different biological activity as evidenced by in vífro and in human cells assays [3,4,51. Propolis water solutions at different concentrations were tested. Results indicated that propolis has high radical scavenging capacity (lCso in DPPH test ranging from 8.2 to 65.4 ?g/mt) and protect cell membranes from oxidative stress. Antioxidant activitvity was directly proportional to the effectiveness against HP: the new propolis formulation MBC and MIC against HPcagt and HPcag is 0.250 mg/ mL Tests on human PBMC stimulated wíth LPS showed that all samples (conc. 200 pg/ml) exhibited anti-inflammatory activity respect to LPS group. This research clearly demonstrated that antioxidant properties of propolis preparatíons and effectively promote gastric protection acfing in different steps of HP pathogenesis. Keyvu,ords: Helicobacter pylori, propolis, anti-infl ammatory, antioxidant, gastroprotective References: [1] Molnar B, Galamb O, Sipos F, Leisztef K, Tulassay (2010) Z Dig Dis 28(4-5):604-608. [2] Calvino-Fernindez M, Pana-Cid T (2010) Rev Esp Enferm Dig 1O2:. 41-5O. [3] Biagi M, Miraldi E, Figura N, ciachetti D (2009) Nat Prod Commun 4(2):255-260. [4] Rapta P, Misík V, Srasko A, Vrébet I (1995) Free Radic Biol Med 18 (5):901-908. [5] Boyanova L, Gergova G, Nikolov R, Derejian S, Lazarova E, Katsarov N, Mitov l, I(rastev Z (2005) J Med Microbiol 54:481-483

Modification of Epigenetic Patterns in Low Birth Weight Children: Importance of Hypomethylation of the <i>ACE</i> Gene Promoter

There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (P0.001) in parallel with a higher ACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (PPPACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels.</p