Effects of simvastatin in abdominal sepsis in rats

Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats. Methods: Twenty eigth Wistar rats weighing 285±12g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs berofe CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-α, IL-1β and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05. Results: It was demonstrated that serum TNF-α, IL-1β and IL-6 were respectively 364,8±42pg/mL; 46,3±18pg/mL and 28,4±13pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778,5±86pg/ml; 176,9±46pg/ ml; 133,6±21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts. Conclusion: These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats

Total gastrectomy with substitution of stomach by jejunal pouch with and without duodenal passage. Study in rats

A comparison was done between the F. Paulino jejunal pouch (FP) and a jejunal pouch (JP) as esophagusduodenum interpositional graft, for replacing the stomach after total gastrectomy. It was investigated the effect of the two procedures on esophagus histology, nutritional state and serum gastrin in rats. Methods: Male Wistar rats weighing 282±17g were randomly submitted to sham operation (S), FP and JP after total gastrectomy. After eight weeks the rats were killed with overdose of anesthetic and tissue was taken from the distal esophagus for histology. Serum levels of total proteins, albumin, iron, transferring, folate, cobalamine, calcium, as well as serum gastrin were determined. Survival was considered. Results: Fourty six rats were operated and thirty survived for eight weeks. Five (33.3%) died after FP and 11 (52.3%) after JP (p<0.05). Postoperative esophagitis occurred in 6 JP rats. At 8th week, no difference was observed on body weight when compared FP and JP rats (p>0.05). The JP rats had a significant decrease in serum albumin, glucose, transferrin, iron, folate and calcium, compared to sham (p<0.05). Serum gastrin, iron and calcium were significantly higher in JP rats than in FP rats (p<0.05). In FP rats, transferrin and cobalamine showed significant decrease comparing the preoperative with 8th week levels (p<0.05). Conclusion: F. Paulino pouch in rats had lower mortality than JP, and esophagitis was not detected in it. JP rats had serum gastrin, iron and calcium unaffected, possibly because of preservation of duodenal passage

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™- Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented

Efeito da sinvastatina na sepse abdominal de ratos diabéticos

Analisar se o pré-tratamento com sinvastatina em modelo experimental de sepse abdominal é benéfico em ratos diabéticos. Métodos: Cinquenta e seis ratos Wistar foram aleatoriamente distribuídos em: grupo não diabético (n-28) e grupo diabetes induzido por estreptozotocina (n=28). Sepse abdominal por ligadura e punção do ceco foi induzida em 14 ratos diabéticos e em 14 não diabéticos. Os demais 28 animais foram alocados em grupo sham. Os grupos de ratos com sepse e os sham (cada com sete animais) foram tratados com microemulsão oral de simvastatina (20 mg kg-1 day-1) e solução salina 0,9%, respectivamente. Sangue periférico foi usado para dosagem de TNFa, IL-1b, IL-6, proteína C reativa, procalcitonina, contagem de leucócitos e neutrófilos em todos os animais. A análise estatística foi realizada pela ANOVA e teste de Tukey, com p<0,05. Resultados: A sinvastatina reduziu a mortalidade nos ratos diabéticos. Os valores séricos de TNF-a, IL-1b, IL-6, proteína C reativa, procalcitonina, leucócitos e neutrófilos mostraram-se mais baixos nos ratos diabéticos e não diabéticos com sepse, tratados com sinvastatina, do que nos tratados com solução salina. Conclusão: A sinvastatina teve efeito antiinflamatório, que pode ter resultado em proteção contra a sepse em ratos diabéticos

Biodistribution of the Radiopharmaceutical Sodium Pertechnetate after Biliopancreatic Bypass with a Duodenal Switch

Study with the purpose to examine the effects of duodenal switch (DS), regularly performed in morbidly obese patients, on biodistribution of sodium pertechnetate in several organs of rats. There was no early or late mortality in either rats groups. The values of percent radioactivity per gram of tissue (%ATI/g), showed no significant difference in liver, stomach, small bowel, duodenum, kidney, heart, bladder, bone and brain, when compared the DS rats with sham and controls rats. A postoperative significant increase (p<0.05) in mean %ATI/g levels was observed in spleen, pancreas and muscle in group DS rats, as compared to group S and C rats. In the lung there was an increase and in thyroid a decrease in mean %ATI/g of DS rats, when compared to sham rats (p<0.05). In conclusion, the biliopancreatic diversion with duodenal switch in rats modified the biodistribution of sodium pertechnetate in thyroid, lung, pancreas, spleen and muscle

Simvastatin improves the healing of infected skin wounds of rats

This study explores the potential of the simvastatin to ameliorate inflammation and infection in open infected skin wounds of rats. Methods: Fourteen Wistar rats weighing 285±12g were used. The study was done in a group whose open infected skin wounds were treated with topical application of sinvastatina microemulsion (SIM, n=7) and a second group with wounds treated with saline 0.9 % (SAL, n=7). A bacteriological exam of the wounds fluid for gram positive and gram negative bacteria, the tecidual expression of TNFá and IL-1â by imunohistochemical technique, and histological analysis by HE stain were performed. Results: The expression of TNFa could be clearly demonstrated in lower degree in skin wounds treated with simvastatin (668.6 ± 74.7 ìm2) than in saline (2120.0 ± 327.1 ìm2). In comparison, wound tissue from SIM group displayed leukocyte infiltration significantly lower than that observed in SAL group (p<0.05). Culture results of the samples taken from wound fluid on fourth post treatment day revealed wound infection in only one rat of group simvastatin (SIM), where Proteus mirabilis, Escherchia coli and Enterobacter sp were isolated. In the rats whose wounds were treated with saline (SAL), polymicrobial infection with more than 100,000 CFU/g was detected in all the wounds. Conclusion: In addition to its antiinflammatory properties, the protective effects of simvastatin in infected open skin wounds is able to reduce infection and probably has antibacterial action. The potential to treat these wounds with statins to ameliorate inflammation and infection is promising

Effects of simvastatin in abdominal sepsis in rats

Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats. Methods: Twenty eigth Wistar rats weighing 285±12g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs berofe CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-α, IL-1β and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05. Results: It was demonstrated that serum TNF-α, IL-1β and IL-6 were respectively 364,8±42pg/mL; 46,3±18pg/mL and 28,4±13pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778,5±86pg/ml; 176,9±46pg/ ml; 133,6±21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts. Conclusion: These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats

Total gastrectomy with substitution of stomach by jejunal pouch with and without duodenal passage. Study in rats

A comparison was done between the F. Paulino jejunal pouch (FP) and a jejunal pouch (JP) as esophagusduodenum interpositional graft, for replacing the stomach after total gastrectomy. It was investigated the effect of the two procedures on esophagus histology, nutritional state and serum gastrin in rats. Methods: Male Wistar rats weighing 282±17g were randomly submitted to sham operation (S), FP and JP after total gastrectomy. After eight weeks the rats were killed with overdose of anesthetic and tissue was taken from the distal esophagus for histology. Serum levels of total proteins, albumin, iron, transferring, folate, cobalamine, calcium, as well as serum gastrin were determined. Survival was considered. Results: Fourty six rats were operated and thirty survived for eight weeks. Five (33.3%) died after FP and 11 (52.3%) after JP (p<0.05). Postoperative esophagitis occurred in 6 JP rats. At 8th week, no difference was observed on body weight when compared FP and JP rats (p>0.05). The JP rats had a significant decrease in serum albumin, glucose, transferrin, iron, folate and calcium, compared to sham (p<0.05). Serum gastrin, iron and calcium were significantly higher in JP rats than in FP rats (p<0.05). In FP rats, transferrin and cobalamine showed significant decrease comparing the preoperative with 8th week levels (p<0.05). Conclusion: F. Paulino pouch in rats had lower mortality than JP, and esophagitis was not detected in it. JP rats had serum gastrin, iron and calcium unaffected, possibly because of preservation of duodenal passage

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™- Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented

Os projectos comenius 1 nas escolas do Concelho de Silves: Contributo para a avaliação dos impactos percepcionados pelos professores-coordenadores, nas diferentes dimensões do processo educativo

Este estudo teve como principal objectivo ser um contributo para a compreensão e identificação dos impactos importantes que os Projectos Europeus, na área da Educação, no âmbito da sub-acção Comenius 1 - Parcerias entre Escolas, do Programa Sócrates, tiveram e têm na comunidade educativa do concelho de Silves. O estudo parte, assim, da seguinte questão de investigação: Quais são os impactos percepcionados pelos professores coordenadores dos projectos Comenius 1 nas diferentes dimensões do processo educativo? Neste sentido, estabeleceram-se as seguintes questões secundárias: • Como se construíram e implementaram estes Projectos nas Escolas? • De que forma é que estes Projectos foram integrados no desenho curricular da escola? • Quais foram as maiores dificuldades sentidas pelos responsáveis pelos Projectos na implementação dos mesmos? Através de uma metodologia qualitativa, foram realizadas entrevistas semi­estruturadas a cinco professores de escolas diferentes do Concelho de Silves e recorreu-se à análise documental e de testemunhos. Os resultados parecem indicar que a implementação deste tipo de projectos nas escolas deixa impactos em todos os intervenientes (na Escola, no Conselho Executivo, nos Professores da escola e das escolas parceiras, no Pessoal não Docente, na Comunidade Envolvente, na Família, no responsável pelo Projecto e nos alunos) e que, muitas vezes, esses impactos só se verificam a longo prazo. Verificamos também que a implementação destes projectos segue três princípios essenciais: a planificação, a realização e a avaliação sendo que as escolas tentam integrar os projectos no seu Projecto Educativo. As maiores dificuldades sentidas verificaram-se a nível da organização da escola, da carga burocrática inerente ao projecto e do pouco envolvimento e participação de alguns professores. Sugere-se que a Escola aposte cada vez mais na implementação deste tipo de projectos, pois estes podem contribuir para uma Escola mais democrática, mais flexível, com mais qualidade, mais motivadora e mais Europeia. ABSTRACT; The aim of this study was to understand and to identify the biggest impacts that the Community's education-related action programmes "Socrates" (namely Comenius 1) have in the School policy. So, the central question of this research was to find out, from the coordinators points of view, which were the most important impacts of the Comenius projects. This central question led to the formulation of the following three questions: a) How were the Comenius projects implemented at school? b) How were the Comenius projects integrated in school organisation and structure? c) Which were the difficulties coordinators had to face in order to organize and implement a Comenius project? Using a qualitative methodology, semi-structured interviews were held with five teachers from different schools in the region of Silves. The following instruments were used during the research: analysis of documents and interviews. The results of the research revealed that the Comenius projects have impacts (although they take a lot of time to be felt) on School, on School heads, on other teachers, on School staff, on the region, on parents, on coordinators and on pupils. They also revealed that the preparation, the activities and the evaluation are important moments to implement Comenius project and that all the projects are included in the School policy. The biggest difficulties had to do with the school organization, with the coordination work and with the lack of motivation and of participation of some colleagues. It is suggested that schools should implement more Comenius projects, because they can lead to a more democratic, flexible, motivating and European School.

Análisis crítico-jurídico del proceso a la orden del Temple, 1309-1312 (prolegómenos, disolución y repercusiones posteriores)

El proceso contra la orden del Temple ha sido calificado por algunos autores como el juicio más conocido de la Edad Media y uno de los más famosos y escandalosos de la historia de la Humanidad, junto a otros procesos célebres, como el llevado a cabo en Atenas contra Sócrates en el siglo cuarto A.C. y el celebrado en Galilea contra Jesús de Nazaret en el siglo primero. Además, es el proceso más antiguo de cuya instrucción existe una detallada documentación. En esta obra no sólo se hace un concienzudo análisis del proceso ordenado por Clemente V contra la orden del Temple, sino que se analizan las causas reales y las ficticias de la persecución, la orden de detención indiscriminada emitida por Felipe IV, con la colaboración necesaria del gran inquisidor de Francia, los artículos de cargo formulados por el papa y las presiones y tormentos a los que se les sometió por orden del papa y del gran inquisidor. También se realiza un análisis más somero y sucinto de los procesos contra las personas de los templarios llevados a cabo en los diferentes países de la Cristiandad donde estaba implantada la Orden, análisis que pone de manifiesto las triviales y anodinas declaraciones, en todo caso exculpatorias, expresadas por los templarios en los países en que no fueron sometidos a tortura. La obra se completa con un primer capítulo en el que, a partir de textos históricos, se trata de fijar la fecha de fundación de la Orden y se analizan las motivaciones que dieron lugar a su nacimiento de la Orden en el primer cuarto del siglo XII, y a la aprobación de la Regla en el Concilio de Vienne en 1128, circunstancia que es aprovechada para llevar a cabo un análisis de la Regla de Edimburgo, décima de las que se conocen en la actualidad, sacada a la luz por nosotros de su letargo de siglos en las estanterías de la Biblioteca Nacional de Escocia, y con un tercer capítulo dedicado al análisis de las repercusiones posteriores a la disolución, en el que se hace un especial hincapié en el juicio y condena de los dignatarios y en la situación de los templarios sobrevivientes, completándose el capítulo con un estudio sobre la sucesión y eventual continuidad de la Orden. La estructura expositiva de cada capítulo es la misma y consiste en una parte en la que en varios epígrafes se recogen los hechos históricos a los que se refiere a partir de la bibliografía que consideramos más rigurosa sobre la época histórica a que se refiere y un epígrafe final en el que se realiza el análisis crítico jurídico de los hechos más relevantes. Por último se incluye un capítulo de conclusiones con las más relevantes que, a nuestro juicio, se ponen de manifiesto tras el análisis crítico-jurídico de cada capítulo.

Desenvolvimento de nanosistemas farmacêuticos para terapia gênica

Gene therapy is one of the major challenges of the post-genomic research and it is based on the transfer of genetic material into a cell, tissue or organ in order to cure or improve the patient s clinical status. In general, gene therapy consists in the insertion of functional genes aiming substitute, complement or inhibit defective genes. The achievement of a foreigner DNA expression into a population of cells requires its transfer to the target. Therefore, a key issue is to create systems, vectors, able to transfer and protect the DNA until it reaches the target. The disadvantages related to the use of viral vectors have encouraged efforts to develop emulsions as non-viral vectors. In fact, they are easy to produce, present suitable stability and enable transfection. The aim of this work was to evaluate two different non-viral vectors, cationic liposomes and nanoemulsions, and the possibility of their use in gene therapy. For the two systems, cationic lipids and helper lipids were used. Nanoemulsions were prepared using sonication method and were composed of Captex® 355; Tween® 80; Spam® 80; cationic lipid, Stearylamine (SA) or 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) and water (Milli-Q®). These systems were characterized by average droplet size, Polidispersion Index (PI) and Zeta Potential. The stability of the systems; as well as the DNA compaction capacity; their cytotoxicity and the cytotoxicity of the isolated components; and their transfection capacity; were also evaluated. Liposomes were made by hydration film method and were composed of DOTAP; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), containing or not Rhodaminephosphatidylethanolamine (PE- Rhodamine) and the conjugate Hyaluronic Acid DOPE (HA-DOPE). These systems were also characterized as nanoemulsions. Stability of the systems and the influence of time, size of plasmid and presence or absence of endotoxin in the formation of lipoplexes were also analyzed. Besides, the ophthalmic biodistribution of PE-Rhodamine containing liposomes was studied after intravitreal injection. The obtained results show that these systems are promising non-viral vector for further utilization in gene therapy and that this field seems to be very important in the clinical practice in this century. However, from the possibility to the practice, there is still a long way

Evaluación del programa de ingeniería de sistemas de la Universidad Cooperativa de Colombia -Seccional Bogotá- mediante el modelo de evaluación CIPP

202 p.

Manos manchadas de sangre: los orígenes cristianos del mito antijudío del crimen ritual

La acusación antijudía del crimen o asesinato ritual gozó de una enorme popularidad en la Edad Media. A mediados del siglo XII, surgió de forma “espontánea” en diferentes lugares de la Europa medieval y dio lugar a infinidad de variantes. Su versión definitiva fue la del asesinato, preferentemente por crucifixión, de un niño cristiano a manos de los judíos con el fin de incorporar su sangre al pan ázimo. Sin embargo, su origen más remoto debe buscarse en la Antigüedad. De hecho, su más incipiente desarrollo puede encontrarse ya a comienzos del siglo V en el historiador cristiano Sócrates (Hist. Eccl., VII, 16), quien cuenta que hacia el año 415, en Inmestar (Siria), con motivo de las celebraciones de la fiesta de Purim, los judíos, embriagados por el vino, amarraron a un niño cristiano a una cruz y lo asesinaron. El relato de este hecho monstruoso plantea algunas dudas acerca de lo acontecido. Seguramente la historia sea falsa y se sitúe en el contexto de una ley del Codex Theodosianus del año 408 (XVI, 8, 18) que prohibía insultar a la Cruz durante la celebración de dicha festividad judía.

Malaria in gold-mining areas in Colombia

Gold-mining may play an important role in the maintenance of malaria worldwide. Gold-mining, mostly illegal, has significantly expanded in Colombia during the last decade in areas with limited health care and disease prevention. We report a descriptive study that was carried out to determine the malaria prevalence in gold-mining areas of Colombia, using data from the public health surveillance system (National Health Institute) during the period 2010- 2013. Gold-mining was more prevalent in the departments of Antioquia, Córdoba, Bolívar, Chocó, Nariño, Cauca, and Valle, which contributed 89.3% (270,753 cases) of the national malaria incidence from 2010-2013 and 31.6% of malaria cases were from mining areas. Mining regions, such as El Bagre, Zaragoza, and Segovia, in Antioquia, Puerto Libertador and Montelíbano, in Córdoba, and Buenaventura, in Valle del Cauca, were the most endemic areas. The annual parasite index (API) correlated with gold production (R2 0.82, p < 0.0001); for every 100 kg of gold produced, the API increased by 0.54 cases per 1,000 inhabitants. Lack of malaria control activities, together with high migration and proliferation of mosquito breeding sites, contribute to malaria in gold-mining regions. Specific control activities must be introduced to control this significant source of malaria in Colombia.