Keratinocyte growth factor: a new mesothelial targeted therapy to reduce postoperative pericardial adhesions

Background: Several methods have been utilized to prevent pericardial and retrosternal adhesions, but none of them evaluated the mesothelial regenerative hypothesis. There are evidences that the mesothelial trauma reduces pericardial fibrinolytic capability and induces an adhesion process. Keratinocyte growth factor (KGF) has proven to improve mesothelial cells proliferation. This study investigated the influence of keratinocyte growth factor in reducing post-surgical adhesions. Methods: Twelve pigs were operated and an adhesion protocol was employed. Following a stratified randomization, the animals received a topical application of KGF or saline. At 8 weeks, intrapericardial adhesions were evaluated and a severity score was established. The time spent to dissect the adhesions and the amount of sharp dissection used, were recorded. Histological sections were stained with sirius red and morphometric analyses were assessed with a computer-assisted image analysis system. Results: The severity score was lower in the KGF group than in the control group (11.5 vs 17, p = 0.005). The dissection time was lower in the KGF group (9.2 +/- 1.4 min vs 33.9 +/- 9.2 min, p = 0.004) and presented a significant correlation with the severity score (r = 0.83, p = 0.001). A significantly less sharp dissection was also required in the KGF group. Also, adhesion area and adhesion collagen were significantly tower in the KGF group than in the control group. Conclusion: The simulation of pericardial cells with KGF reduced the intensity of postoperative adhesions and facilitated the re-operation. This study suggests that the mesothelial regeneration is the new horizon in anti-adhesion therapies. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Imunofenótipo e evolução de câncer de mama: comparação entre mulheres muito jovens e mulheres na pós-menopausa

OBJETIVO: avaliar características clínicas, patológicas e moleculares de carcinomas mamários em mulheres muito jovens em comparação a tumores de mulheres na pós-menopausa. MÉTODOS: foram selecionados 106 casos de câncer de mama de mulheres jovens e 130 casos de mulheres pós-menopausa. Foram analisados dados clínicos (idade ao diagnóstico, estadiamento, ocorrência de metástases, tempo de sobrevida global e livre de doença), anátomo-patológicos (tamanho do tumor, tipo e grau histológico do tumor primário) e marcadores moleculares (receptores de estrógeno e progesterona, HER2, p53, p63, citoqueratinas 5 e 14 e EGFR) com uso da imunoistoquímica empregando microarranjo de tecido. Foi analisada a relação entre as características clínico-patológicas, imunoistoquímicas e de sobrevidas global e livre de doença. RESULTADOS: as pacientes muito jovens apresentaram maior frequência de nuliparidade (p=0,03), maior diâmetro dos tumores (p<0,000), estadiamento clínico mais avançado (p=0,01), maior número de linfonodos positivos (p=0,001) e tumores pouco diferenciados (p=0,004). A maioria das pacientes jovens recebeu tratamento com quimioterapia (90,8%) e radioterapia (85,2%) e em menor proporção com tamoxifeno (31,5%), comparado às mulheres na pós-menopausa. Observamos baixa positividade para o receptor de estrógeno (49,1%; p=0,01) e alta positividade para a proteína HER2 (28,7%; p=0,03) nas mulheres jovens. O fenótipo triplo-negativo foi observado em 29,6% no grupo jovem e em 20% nas mulheres na pós-menopausa. Os tumores de fenótipo basal foram mais frequentes nas mulheres jovens (50%). As metástases sistêmicas ocorreram em 55,3% dos casos nas jovens e em 39,2% nas idosas. As sobrevidas global e livre de doença em cinco anos foram, respectivamente, 63 e 39% para as mulheres jovens e 75 e 67% para o grupo de mulheres na pós-menopausa. CONCLUSÕES: carcinomas mamários de mulheres muito jovens têm características clínicas, patológicas e moleculares mais agressivas quando comparadas às mulheres acima de 50 anos.

Evaluation of the dental structure loss produced during maintenance and replacement of occlusal amalgam restorations

The aim of this in vitro study was to evaluate four different approaches to the decision of changing or not defective amalgam restorations in first primary molar teeth concerning the loss of dental structure. Ditched amalgam restorations (n = 11) were submitted to four different treatments, as follows: Control group - polishing and finishing of the restorations were carried out; Amalgam group - the ditched amalgam restorations were replaced by new amalgam restorations; Composite resin group - the initial amalgam restorations were replaced by composite resin restorations; Flowable resin group - the ditching around the amalgam restorations was filled with flowable resin. Images of the sectioned teeth were made and the area of the cavities before and after the procedures was determined by image analysis software to assess structural loss. The data were submitted to ANOVA complemented by the Student Newman Keuls test (p < 0.05). The cavities in all the groups presented significantly greater areas after the procedures. However, the amalgam group showed more substantial dental loss. The other three groups presented no statistically significant difference in dental structure loss after the re-treatments. Thus, replacing ditched amalgam restorations by other similar restorations resulted in a significant dental structure loss while maintaining them or replacing them by resin restorations did not result in significant loss.

Alveolar osseous defect in rat for cell therapy: preliminary report

PURPOSE: To study were to reproduce an alveolar bone defect model in Wistar rats to be used for testing the efficacy of stem cell therapies. Additionally, we also aimed to determine the osteogenesis process of this osseous defect in the 1 month period post-surgery. METHODS: The animals were randomly divided into two groups of 7 animals each. A gingivobuccal incision was made, and a bone defect of 28 mm² of area was performed in the alveolar region. Animals were killed at 2 weeks after surgery (n=7) and 4 weeks after surgery (n=7). RESULTS: The average area of the alveolar defect at time point of 2 weeks was 22.27 ± 1.31 mm² and the average area of alveolar defect at time point of 4 weeks was 9.03 ± 1.17 mm². The average amount of bone formation at time point of 2 weeks was 5.73 ± 1.31 mm² and the average amount of bone formation at time point of 4 weeks was 19 ± 1.17 mm². Statistically significant differences between the amount of bone formation at 2 weeks and 4 weeks after surgery were seen (p=0.003). CONCLUSION: The highest rate of ossification occurred mostly from 2 to 4 weeks after surgery. This observation suggests that 4 weeks after the bone defect creation should be a satisfactory timing to assess the potential of bone inductive stem cells to accelerate bone regeneration in Wistar rats.

Eutaleola, a replacement name for the homonym Euteleia (Bryozoa: Pasytheidae)

Eutaleola nom. nov. is proposed as a replacement name for Euteleia Marcus, 1938 (Bryozoa: Cheilostomata), a secondary homonym of Euteleia Raffray, 1904 (Arthropoda: Coleoptera). Eutaleola is a monospecific genus of Pasytheida e, found in warm shallow waters on both sides of the Atlantic and in deeper waters of the eastern Pacific. Brazilian material of Eutaleola evelinae (Marcus, 1938) comb. nov. is described and illustrated.

Evaluation of the effects of ozone therapy in the treatment of intra-abdominal infection in rats

INTRODUCTION: The antibacterial effect of ozone (O3) has been described in the extant literature, but the role of O3 therapy in the treatment of certain types of infection remains controversial. OBJECTIVES: To evaluate the effect of intraperitoneal (i.p.) O3 application in a cecal ligation/puncture rat model on interleukins (IL-6, IL-10) and cytokine-induced neutrophil chemoattractant (CINC)-1 serum levels, acute lung injury and survival rates. METHODS: Four animal groups were used for the study: a) the SHAM group underwent laparotomy; b) the cecal ligation/puncture group underwent cecal ligation/puncture procedures; and c) the CLP+O2 and CLP+O3 groups underwent CLP+ corresponding gas mixture infusions (i.p.) throughout the observation period. IL-6, CINC-1 and IL-10 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Acute lung injury was evaluated with the Evans blue dye lung leakage method and by lung histology. P<0.05 was considered significant. RESULTS: CINC-1 was at the lowest level in the SHAM group and was lower for the CLP+O3 group vs. the CLP+O2 group and the cecal ligation/puncture group. IL-10 was lower for the SHAM group vs. the other three groups, which were similar compared to each other. IL-6 was lower for the SHAM group vs. all other groups, was lower for the CLP+O3 or CLP+O2 group vs. the cecal ligation/puncture group, and was similar for the CLP+O3 group vs. the CLP+O2 group. The lung histology score was lower for the SHAM group vs. the other groups. The Evans blue dye result was lower for the CLP+O3 group vs. the CLP+O2 group and the cecal ligation/puncture group but similar to that of the SHAM group. The survival rate for the CLP+O3 group was lower than for the SHAM group and similar to that for the other 2 groups (CLP and CLP+O2). CONCLUSION: Ozone therapy modulated the inflammatory response and acute lung injury in the cecal ligation/puncture infection model in rats, although there was no improvement on survival rates.

The Na+/glucose cotransporters: from genes to therapy

Glucose enters eukaryotic cells via two types of membrane-associated carrier proteins, the Na+/glucose cotransporters (SGLT) and the facilitative glucose transporters (GLUT). The SGLT family consists of six members. Among them, the SGLT1 and SGLT2 proteins, encoded by the solute carrier genes SLC5A1 and SLC5A2, respectively, are believed to be the most important ones and have been extensively explored in studies focusing on glucose fluxes under both physiological and pathological conditions. This review considers the regulation of the expression of the SGLT promoted by protein kinases and transcription factors, as well as the alterations determined by diets of different compositions and by pathologies such as diabetes. It also considers congenital defects of sugar metabolism caused by aberrant expression of the SGLT1 in glucose-galactose malabsorption and the SGLT2 in familial renal glycosuria. Finally, it covers some pharmacological compounds that are being currently studied focusing on the interest of controlling glycemia by antagonizing SGLT in renal and intestinal tissues.

Time- and concentration-dependent cytotoxicity of antibiotics used in endodontic therapy

OBJECTIVE: New drugs have to be assessed in endodontic therapy due to the presence of microorganisms resistant to therapeutic procedures. Thus, this study evaluated the time- and concentration-dependent cytotoxicity of different antibiotics used in endodontic therapy. MATERIAL AND METHODS: Human gingival fibroblasts were treated and divided into the following experimental groups: Group I - control; Group II - ciprofoxacin hydrochloride; Group III - clyndamicin hydrochloride; and Group IV - metronidazole. Each drug was used at concentrations of 5, 50, 150, and 300 mg/L for 24, 48, 72, and 96 h. Cytotoxicity was evaluated by the MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and spectrophotometric reading of ELISA plates. The results were analyzed by BioEstat 4.0 software using Kruskal-Wallis and Dunn's tests at a signifcance level of 5%. Cell viability was assessed for the different concentrations and times. RESULTS: All drugs presented dose-dependent cytotoxicity. Concentrations of 5 and 50 mgjL produced viable fibroblasts at all experimental times in all groups. CONCLUSIONS: Cell viability at 24 h was greater than in the other experimental times. Comparison between the same concentrations of antibiotics at different times showed that metronidazole presented the highest cell viability at 72 and 96 h compared to the other antibiotics, whereas clyndamicin hydrochloride showed higher cell viability at 72 h than ciprofoxacin hydrochloride.

The nutritional status of children and adolescents with HIV/AIDS on antiretroviral therapy

FAPESP n. 07/55777-9 e n. 07/50009-3

Fatores associados à obesidade global e à obesidade abdominal em mulheres na pós-menopausa

OBJETIVOS: avaliar a prevalência de obesidade global e obesidade abdominal, em mulheres pós-menopausa, segundo o grau de instrução, nível de atividade física, uso de terapia hormonal na menopausa (THM) e paridade. MÉTODOS: foram entrevistadas 157 mulheres na pós-menopausa, atendidas em dois ambulatórios públicos da cidade de São Paulo, São Paulo, Brasil. A obesidade foi determinada segundo o índice de massa corporal (IMC > 30,0) e segundo o percentual de gordura corporal (%GC > 37%). A obesidade abdominal foi determinada pela relação cintura-quadril (RCQ > 0,85). RESULTADOS: a prevalência de obesidade global foi 34,4% (segundo o IMC) e de 40,1% (segundo o %GC). A prevalência de obesidade abdominal foi de 73,8%. Grande parte das entrevistadas referiu até sete anos de instrução formal (47,8%), foi considerada sedentária ou insuficientemente ativa (52,3%) e nunca tinha utilizado THM oral ou tinha utilizado por menos de 12 meses (72,0%). Foi constatada maior prevalência de obesidade global no grupo de mulheres sedentárias ou insuficientemente ativas e no grupo de não usuárias de THM (p<0,05). Quanto à obesidade abdominal, fator de risco para doenças cardiovasculares (DCV), apenas o grau de instrução mostrou-se associado à RCQ (p<0,05). CONCLUSÕES: mulheres após a menopausa, fisicamente ativas e usuárias de THM exibiram menor prevalência de obesidade global, porém a prevalência de obesidade abdominal foi alta e ainda maior nas mulheres com menor grau de instrução

Selol-loaded magnetic nanocapsules: A new approach for hyperthermia cancer therapy

Polylactic-co-glycolic nanocapsules, loaded with nanosized magnetic particles and Selol (a selenium-based anticancer drug), were successfully prepared by the precipitation method. Maghemite (gamma-Fe(2)O(3)) nanoparticles were incorporated into the nanocapsules using a highly stable ionic magnetic fluid sample. The obtained nanocapsules presented no agglomeration, negative surface charge while revealing a narrow monomodal size distribution. All the nanocapsule formulations exhibited a good physical stability at 4 degrees C during 3 month storage period. The in vitro antitumoral activity of Selol-magnetic nanocapsules was assessed using a murine melanoma cell line. The influence of nanocapsules on cell viability was investigated by spectrophotometric assay. The results demonstrated that Selol-loaded magnetic nanocapsules (at 100 mu g/ml/5 x 10(9) particle/ml) showed antitumoral activity of 50% on melanoma cells (absence of magnetic field). These results clearly indicate that the loaded nanocapsules represent a novel and promising magnetic drug delivery system suitable for cancer treatment via the active drug and magnetohyperthermia. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3556950]

Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms

Background: Thyroid receptors, TRa and TR beta, are involved in important physiological functions such as metabolism, cholesterol level and heart activities. Whereas metabolism increase and cholesterol level lowering could be achieved by TR beta isoform activation, TRa activation affects heart rates. Therefore, beta-selective thyromimetics have been developed as promising drug-candidates for treatment of obesity and elevated cholesterol level. GC-1 [ 3,5-dimethyl-4-(4'-hydroxy- 3'-isopropylbenzyl)-phenoxy acetic acid] has ability to lower LDL cholesterol with 600-to 1400-fold more potency and approximately two-to threefold more efficacy than atorvastatin (Lipitor(C)) in studies in rats, mice and monkeys. Results: To investigate GC-1 specificity, we solved crystal structures and performed molecular dynamics simulations of both isoforms complexed with GC-1. Crystal structures reveal that, in TRa Arg228 is observed in multiple conformations, an effect triggered by the differences in the interactions between GC-1 and Ser277 or the corresponding asparagine (Asn331) of TR beta. The corresponding Arg282 of TR beta is observed in only one single stable conformation, interacting effectively with the ligand. Molecular dynamics support this model: our simulations show that the multiple conformations can be observed for the Arg228 in TR alpha, in which the ligand interacts either strongly with the ligand or with the Ser277 residue. In contrast, a single stable Arg282 conformation is observed for TR beta, in which it strongly interacts with both GC-1 and the Asn331. Conclusion: Our analysis suggests that the key factors for GC-1 selectivity are the presence of an oxyacetic acid ester oxygen and the absence of the amino group relative to T(3). These results shed light into the beta-selectivity of GC-1 and may assist the development of new compounds with potential as drug candidates to the treatment of hypercholesterolemia and obesity.

Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease

AIM: To establish the efficacy and safety of a 7-d therapeutic regimen using omeprazole, bismuth suticitrate, furazolidone and amoxicillin in patients with peptic ulcer disease who had been previously treated with other therapeutic regimens without success. METHODS: Open cohort study which included patients with peptic ulcer who had previously been treated unsuccessfully with one or more eradication regimens. The therapeutic regimen consisted of 20 mg omeprazole, 240 mg colloidal bismuth subcitrate, 1000 mg amoxicillin, and 200 mg furazolidone, taken twice a day for 7 d. Patients were considered as eradicated when samples taken from the gastric antrum and corpus 12 wk after the end of treatment were negative for Helicobacter pylori (H pylori) (rapid urease test and histology). Safety was determined by the presence of adverse effects. RESULTS: Fifty-one patients were enrolled. The eradication rate was 68.8% (31/45). Adverse effects were reported by 31.4% of the patients, and these were usually considered to be slight or moderate in the majority of the cases. Three patients had to withdraw from the treatment due to the presence of severe adverse effects. CONCLUSION: The association of bismuth, furazolidone, amoxicillin and a proton-pump inhibitor is a valuable alternative for patients who failed to respond to other eradication regimens. It is an effective, cheap and safe option for salvage therapy of positive patients. (C) 2008 The WJG Press. All rights reserved.

Factitious thyrotoxicosis induced by mesotherapy: A case report

Context: Mesotherapy consists of cutaneous injections of a mixture of compounds and has recently been used for cosmetic purposes to reduce local fat and cellulite. To date, several reports have described only local adverse events related to this therapy. We describe the first report of a female patient who developed thyrotoxicosis due to cosmetic mesotherapy with triiodothyroacetic acid in its formulation. Apart from mechanical rupture of the epidermal barrier, a disturbance of type III deiodinase activity or skin fibroblast paracrine function and vascular alterations related to simultaneously injected vasoactive compounds were observed. These findings could be related to thyroid hormone metabolite absorption and systemic consequences in the reported case. Conclusion: We describe factitious thyrotoxicosis induced by mesotherapy, to raise awareness of a systemic adverse effect resulting from this widespread cosmetic practice.

Short-term triple therapy with azithromycin for Helicobacter pylori eradication: Low cost, high compliance, but low efficacy

Background: The Brazilian consensus recommends a short-term treatment course with clarithromycin, amoxicillin and proton-pump inhibitor for the eradication of Helicobacter pylori ( H. pylori). This treatment course has good efficacy, but cannot be afforded by a large part of the population. Azithromycin, amoxicillin and omeprazole are subsidized, for several aims, by the Brazilian federal government. Therefore, a short-term treatment course that uses these drugs is a low-cost one, but its efficacy regarding the bacterium eradication is yet to be demonstrated. The study's purpose was to verify the efficacy of H. pylori eradication in infected patients who presented peptic ulcer disease, using the association of azithromycin, amoxicillin and omeprazole. Methods: Sixty patients with peptic ulcer diagnosed by upper digestive endoscopy and H. pylori infection documented by rapid urease test, histological analysis and urea breath test were treated for six days with a combination of azithromycin 500 mg and omeprazole 20 mg, in a single daily dose, associated with amoxicillin 500 mg 3 times a day. The eradication control was carried out 12 weeks after the treatment by means of the same diagnostic tests. The eradication rates were calculated with 95% confidence interval. Results: The eradication rate was 38% per intention to treat and 41% per protocol. Few adverse effects were observed and treatment compliance was high. Conclusion: Despite its low cost and high compliance, the low eradication rate does not allow the recommendation of the triple therapy with azithromycin as an adequate treatment for H. pylori infection.