Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research.

Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments

In vitro wear resistance of three types of polymethyl methacrylate denture teeth

The wear resistance of denture teeth is important to the longevity of removable prostheses of edentulous patients. The ability of denture teeth to maintain a stable occlusal relationship over time may be influenced by this property. The purpose of this in vitro study was to evaluate the wear resistance of polymethyl methacrylate (PMMA) denture teeth based on their chemical composition when opposed by a ceramic antagonist. The maxillary canines (n=10) of 3 PMMA denture teeth (Trubyte Biotone, cross-linked PMMA; Trilux, highly cross-linked IPN (interpenetrating polymer network)-PMMA; and Vivodent, highly cross-linked PMMA) were secured in an in vitro 2-body wear-testing apparatus that produced sliding contact of the specimens (4.5 cycles/s, sliding distance of 20 mm, under 37°C running water) against glazed or airborne particle abraded ceramic. Wear resistance was measured as height loss (mm) under 300 g (sliding force) after 100,000 cycles, using a digital measuring microscope. Mean values were analyzed by 2-way ANOVA and Tukey's test (a=0.05). The wear of Trubyte Biotone (0.93 ± 0.14 mm) was significantly higher than that of both other types of teeth tested against abraded ceramic (p<0.05). The Vivodent tooth (0.64 ± 0.17 mm) exhibited the best wear resistance among the denture teeth tested against airborne particle abraded ceramic. There were no statistically significant differences (p>0.05) in wear among the 3 denture teeth evaluated against glazed ceramic. Trilux and Vivodent teeth tested against either glazed or airborne particle abraded ceramic did not differ significantly from each other (p<0.05). All teeth showed significantly more wear against airborne particle abraded ceramic than against glazed ceramic (p<0.05). In conclusion, the three types of PMMA denture teeth presented significantly different wear resistance against the abraded ceramic. The high-strength PMMA denture teeth were more wear-resistant than the conventional PMMA denture tooth.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Geospatial analysis : a study about dengue

Objetivo: Descrever/analisar o espaço geográfico dos coeficientes de incidência de dengue segundo área urbana da Região Norte do município de Palmas/TO, Brasil. Métodos: Trata-se de um estudo analítico ecológico transversal, que avalia hipóteses de relações de causa (variáveis socioeconômicas e ambientais) e efeito (casos confirmados de dengue) simultaneamente. É ecológico, pois a unidade de observação passa de indivíduos para grupos de indivíduos, onde áreas geográficas foram usadas como unidades de análise (epidemiologia espacial). Resultados: Revelam que o número de casos de dengue registrados em Palmas (2011) aumentou 170% em relação ao ano anterior. Conclusão: Alertarmos para uma epidemia através dos dados apresentados. Assim, sugerimos a necessidade de alterações nas estratégias utilizadas atualmente e aprimoramento das ações de vigilância para controlar o vetor Aedes aegypti, reduzindo a infestação a níveis inferiores a 1%, e consequentemente, minimizar o impacto da doença na saúde da população.Objective: To describe/analyze the geographic space of the incidence rates according to the urban area. Method: This was an analytical cross-sectional ecological study to evaluate hypotheses of the relationships of cause (socioeconomic and environmental variables) and effect (confirmed cases of dengue) simultaneously. It was ecological, as the observation unit passed from individuals to groups of individuals, in which geographical areas were used as units of analysis (spatial epidemiology). Results: Revealed that the number of reported cases of dengue in Palmas (2011) increased 170% in relationship to the previous year. Conclusion: We call attention to an epidemic through the data presented. Thus, we suggest the need for changes in the strategies used today and enhancement of surveillance actions to control the mosquito Aedes aegypti, reducing the infestation to levels below 1%, and consequently to minimize the impact of the disease on the health of the population

Anatomopathological evaluation of uterine scars according to the type of surgical suture (experimental model)

PURPOSE: to compare macro and microscopically, surgical uterine sutures in female rabbits, after caesarean section utilizing separate, continuous and continuous anchored suture stitches. METHODS: three New Zealand female rabbits in their first pregnancy were used. The caesarean section was carried out at the 26th day of gestation and three incisions were performed in each uterus. The hysterorrhaphy was performed with a 00 Vicryl® thread, and a different suture technique was employed for each incision. Total hysterectomy and adnexectomy were done at the 60th day post-delivery with the preservation of eventual adhesions for the evaluation of the surgical scars. The extent of scar retraction, amount of fibrin deposit and the suture integrity were evaluated through macroscopy. For the evaluation through microscopy, hematoxylin eosin technique was used for cellular colorimetry, and Masson's trichrom to evidence collagen. The statistical non-parametric Friedman's test was employed for the matching hypothesis, and Fisher's exact test to verify the homogeneity of the techniques (level of significance: 5%). RESULTS: a total of 18 scars were obtained (six scars per suture). The following mean values were obtained for the longitudinal (0.5/0.4/0.5, p=0.069) and transversal retraction degrees (0.3/0.4/0.3, p=0.143) respectively for separate, continuous and continuous anchored suture techniques. All sutures presented regular fibrin deposit, no adhesions and integral absorption of the stitches. The mean value of the blood vessels (158.5/139.3/172.1; p=0.293), fibroblasts (351.6/345.8/354.3; p=0.311) and of collagen percentage (44.0/45.5/48.5; p=0.422) were calculated through microscopy, respectively for separate, continuous and continuous anchored suture techniques. CONCLUSIONS: the type of hysterorrhaphy technique of caesarean section in female rabbits did not generate any significant statistical difference in the macroscopic and microscopic parameters evaluated.OBJETIVO: comparar, macro e microscopicamente, cicatrizes uterinas pós-cesáreas, nas quais foram feitas suturas com pontos separados, contínuos e contínuos ancorados. MÉTODOS: utilizamos três coelhas prenhes, realizando parto cesáreo no 26º dia de prenhez, com três incisões em cada corno uterino. As histerorrafias foram realizadas com fio Vicryl® 00, com suturas distintas (pontos separados, sutura contínua e contínua ancorada). No 60º dia pós-parto, realizamos histerectomia total abdominal e anexectomia bilateral, para avaliação das cicatrizes cirúrgicas. Na macroscopia, avaliamos o grau de retração cicatricial (longitudinal e transversal), o depósito de fibrina, presença de aderências e integridade dos fios de sutura. Na microscopia, utilizamos coloração de hematoxilina-eosina, para contagem de vasos sangüíneos e fibroblastos, e a coloração do tricômio de Masson, para quantificação do colágeno. Para a análise comparativa das cicatrizes, utilizamos os testes de Friedman e exato de Fisher, adotando nível de significância de 5%. RESULTADOS: foram obtidas 18 cicatrizes, seis para cada tipo de sutura. Obtivemos as seguintes médias 0,5/0,4/0,5 (p=0,069) para os graus de retração longitudinal e 0,3/0,4/0,3 (p=0,143) para os graus de retração transversal, respectivamente para as suturas com pontos separados, contínuo e contínuo ancorado. Todas as suturas apresentaram depósito de fibrina regular, ausência de aderência e reabsorção integral dos fios. Na microscopia, apuramos a média de vasos sangüíneos (158,5/139,3/172,1; p=0,293), de fibroblastos (351,6/345,8/354,3; p=0,311) e da porcentagem de tecido colágeno (44,0/45,5/48,5; p=0,422), respectivamente para as suturas com pontos separados, contínuo e contínuo ancorado. CONCLUSÕES: a técnica de histerorrafia na cesárea de coelhas (pontos simples, sutura contínua e contínua ancorada) não determinou diferenças estatísticas significantes em relação aos parâmetros macroscópicos e microscópicos avaliados.Centro Universitário Lusíada Faculdade de Ciências MédicasHospital do Servidor Público EstadualUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de ObstetríciaUNIFESP, EPM, Depto. de ObstetríciaSciEL

Oral manifestations of celiac disease : a case report and review of the literature

Celiac disease is a chronic intestinal disease caused by intolerance to gluten associated with poor digestion and absorption of the majority of nutrients and vitamins, which may affect both developing dentition and oral mucosa. The aim of this study is to make a brief review of the literature about celiac disease and to report on a clinical case, showing the impact it may have on the general and oral health. A 39-year-old woman reported the presence of diarrhea, nauseas, flatulence, colic, difficulty with falling asleep, lack of appetite and loose of 18 Kg in the last two years. She also noted the appearance of symptomatic lesions in the mouth. These lesions had a mean duration of a month and occurred in any region of the oral mucosa, particularly on the tongue. Multiples ulcerations were found in the sublingual caruncula region, at the vestibular fornix and at the lingual apex. Topical treatment was instituted for the oral lesions with immediately relief of the symptoms. The diagnosis of celiac disease was established by means of medical clinical exam, biopsy of the small intestine, and by the presence of specific antibodies in the blood. The patient has been instructed to follow a gluten-free diet. Multiprofessional action with the involvement of a gastroenterologist and other health professionals, such as dentists, is important for diagnosing the disease and guiding the patient with celiac disease to achieve a good quality of life

Vulnerability and the bioethics through the experiences of illness

Background: Vulnerable people are relatively or absolutely incapable of protecting their own interests. Vulnerability is an anthropological attribute of human beings due to the simple fact of being alive. Brazilian society has long been established as a matter through the eyes of social scientists. In the name of it, the vulnerability in the doctor-patient context is now being a much-discussed issue. Purpose: This study aims to analyze the current studies regarding the insertion of vulnerability in the health issue, reflexively dealing with the ethical matters involved, as well as with the narratives’ insertion in this process. Methods: This article is based on data extracted from Scientific Electronic Library Online (Scielo) and on secondary data from textbooks about vulnerability, ethics, physician-patient relationship and narratives. Results and discussion: Doctors are faced with dilemmas in clinical practice: moral, ethical, legal, social, religious and economic. On these occasions, question their own values. By listening carefully to the stories of patients, health professionals broaden their perspectives, organize and integrate complex situations, which assists in conducting these difficult situations. Conclusion: Reflect the concept of vulnerability raises (re) think health practices, particularly in bringing to light the social experience of illness and hospitalization of the patient

Synthetic organotelluride compounds induce the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisiae

Background: Resistance to fluconazole, a commonly used azole antifungal, is a challenge for the treatment of fungal infections. Resistance can be mediated by overexpression of ABC transporters, which promote drug efflux that requires ATP hydrolysis. the Pdr5p ABC transporter of Saccharomyces cerevisiae is a well-known model used to study this mechanism of antifungal resistance. the present study investigated the effects of 13 synthetic compounds on Pdr5p.Results: Among the tested compounds, four contained a tellurium-butane group and shared structural similarities that were absent in the other tested compounds: a lateral hydrocarbon chain and an amide group. These four compounds were capable of inhibiting Pdr5p ATPase activity by more than 90%, they demonstrated IC50 values less than 2 M and had an uncompetitive pattern of Pdr5p ATPase activity inhibition. These organotellurides did not demonstrate cytotoxicity against human erythrocytes or S. cerevisiae mutant strains (a strain that overexpress Pdr5p and a null mutant strain) even in concentrations above 100 mu M. When tested at 100 mu M, they could reverse the fluconazole resistance expressed by both the S. cerevisiae mutant strain that overexpress Pdr5p and a clinical isolate of Candida albicans.Conclusions: We have identified four organotellurides that are promising candidates for the reversal of drug resistance mediated by drug efflux pumps. These molecules will act as scaffolds for the development of more efficient and effective efflux pump inhibitors that can be used in combination therapy with available antifungals.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)University of São Paulo through the NAP-CatSinQ (Research Core in Catalysis and Chemical Synthesis)Univ Fed Rio de Janeiro, CCS, Inst Microbiol Paulo Goes, Dept Microbiol Geral,Lab Bioquim Microbiana, Rio de Janeiro, RJ, BrazilUniv São Paulo, Inst Quim, Dept Quim Fundamental, São Paulo, BrazilInst Fed Educ Ciencia & Tecnol Rio de Janeiro IFR, Rio de Janeiro, RJ, BrazilUniversidade Federal de São Paulo UNIFESP, Inst Ciencias Ambientais Quim & Farmaceut, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Inst Ciencias Ambientais Quim & Farmaceut, São Paulo, BrazilFAPERJ: E-26/111.338/2013FAPESP: 2005/59572-7FAPESP: 2008/55401-1FAPESP: 2010/17228-6FAPESP: 2011/03244-2FAPESP: 2011/11613-8FAPESP: 2012/17093-9CNPq: 470360/2012-7Web of Scienc

Can we manage prophylactic therapy in COVID-19 patients to prevent severe illness complications?

Many patients with COVID-19 have thromboembolic complications that worsen their prognosis. Herein, the authors propose a modified version of the CHA2DS2-VASc score, including 1 point for COVID-19, so that prophylaxis to protect against thromboembolic events would be indicated before the condition becomes severe. The advantages of this modification would be prevention of the patient’s condition worsening due to thromboembolic problems and reduction of the likelihood of a need for intensive care and mechanical ventilation, reducing mortality.Many patients with COVID-19 have thromboembolic complications that worsen their prognosis. Herein, the authors propose a modified version of the CHA2DS2-VASc score, including 1 point for COVID-19, so that prophylaxis to protect against thromboembolic events would be indicated before the condition becomes severe. The advantages of this modification would be prevention of the patient’s condition worsening due to thromboembolic problems and reduction of the likelihood of a need for intensive care and mechanical ventilation, reducing mortality

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts