Os efeitos protetores da imunidade humoral são medidas por uma família de glicoproteínas chamadas anticorpos ou imunoglobulinas. As preparações de imunoglobulina G (IgG) utilizadas em nosso país são importantes. No Brasil, a primeira preparação de IgG foi obtida na Fundação Pró-Sangue Hemocentro de São Paulo em 1993. O presente estudo avaliou preparações de IgG obtidas de misturas de plasma humano de variadas procedências, inclusive a preparação obtida no Brasil. Foram avaliados os seguintes parâmetros: concentração protéica, distribuição das subclasses da IgG, atividade de anticorpos específicos e segurança quanto a agentes patogênicos transmissíveis pelo sangue. Em algumas preparações, a concentração protéica de IgG e a distribuição das suas subclasses estavam fora das especificações. As preparações apresentaram atividade de anticorpos específicos contra os vírus das hepatites A e B, do herpes simples, da rubéola, citomegalovírus; contra a bactéria Streptococcus pyogenes β-hemolítico do grupo A e contra o parasita Toxoplasma gondii. A qualidade de matéria-prima utilizada em algumas das preparações de IgG não foi adequada em função de reações positivas para anticorpos contra alguns agentes infecciosos, tais como HTLV I/II, HAV, HBV, HCV e Treponema pallidum. Esse estudo também mostrou a necessidade de se implantar urgente um programa abrangente para avalição das preparações de IgG a serem consumidas pela população brasileira. / A family of glicoproteins, which are called antibodies or immunoglobulins (IgG), mediates the protective effects of humoral immunity. In Brazil, the IgG for intravenous use are imported from other countries. The first Brazilian immunoglobulin G for therapheutic use was obtained from human plasma at the Fundação Pró-Sangue Hemocentro de São Paulo. The present study was carried out to evaluate different preparations of IgG, human plasmad-derived, include the preparation from Brazil. The protein concentration, IgG subclass distribution, specific antibody activities and safety regarding the main blood transmitted infectious diseases were analyzed. In some preparations, IgG protein concentration and subclass distribution were different from their specifications. Some preparations showed specific antibody activity against the following antigens: A and B hepatitis virus, rubella, herpes simplex virus, citomegalovirus, measles virus, Streptococcus pyogenes β-hemolytic group A and Toxoplasma gondii. The presence of antibodies against antigens such as HTLV I/II, HAV, HBV, HCV and Treponema pallidum has compromissed the quality guaranty of the material-source (plasma) used in some preparations. This study has also showed that a complete and effective program for the quality evaluation of IgG preparations used in Brazil is needed and should be urgently established

Os eventos adversos a medicamentos são comuns e provavelmente irão ocorrer em qualquer sistema, entretanto, é essencial identificar suas causas e tentar minimizar os riscos visando à segurança do paciente. O objetivo desse estudo foi analisar os eventos adversos a medicamentos em um hospital público do estado do Amazonas, com base nos relatos da equipe de enfermagem e propor estratégias à instituição para otimizar o sistema de medicamentos para a segurança do paciente. Um estudo do tipo descritivo, adotando-se a Técnica do Incidente Crítico como norteadora dos procedimentos metodológicos foi realizado com 15 enfermeiros, 09 auxiliares e 44 técnicos de enfermagem de um hospital de ensino de Manaus-AM. A análise dos dados constou da identificação e agrupamento das situações, comportamentos e consequências. A maioria dos profissionais entrevistados era do sexo feminino (89,7%), predominando a classe de idade de 31 a 35 anos (30,9%). Os resultados foram agrupados e categorizados em 47 situações, correspondentes a nove tipos de erros de medicação. Dos tipos de erros identificados pela equipe de enfermagem, os erros de diluição (23,4%), dose (14,9%), medicamentos não autorizados (14,9%), erro de via de administração (10,6%) e erro de paciente (8,5%) foram os mais frequentes. Com relação às categorias de comportamentos, estes foram distribuídos em função da percepção e comunicação do erro (36) e entre as consequências identificadas no estudo (103), 47 eram relacionadas aos pacientes e 56 aos profissionais de enfermagem. Os resultados apresentados indicam a necessidade de tomada imediata de iniciativas que minimizem essas situações e previna a ocorrência de futuros eventos adversos a medicamentos. / Adverse drug events are common and will probably occur in any system, however, it is essential to identify their causes and try to minimize the risks to patients\' safety. This descriptive study aimed to analyze adverse drug events at a public hospital in the state of Amazonas, based on the reports of the nursing team. The goal was to propose strategies for the institution to optimize the medication system for patient safety. The Critical Incident Technique guided the methodological procedures, carried out with 15 nurses, 09 nursing auxiliaries and 44 nursing technicians from a teaching hospital in Manaus, state of Amazonas. Data analysis consisted of identifying and grouping situations, behaviors and consequences. Most of the interviewed professionals were female (89.7%) from the age group of 31 to 35 (30.9%) years. Results of the studies were grouped and categorized into 47 situations, corresponding to nine types of medication errors. Of the types of errors identified by the nursing team, dilution errors (23.4%), dosing errors (14.9%), unauthorized medication (14.9%), wrong administration route (10.6%) and mistaken patient (8.5%) were the most frequent. The categories of behavior were distributed according to the perception and communication of error (36) and among the consequences identified in the study (103), of which 47 were related to patients and 56 to nursing professionals. The results indicate the need for immediate initiatives that minimize these situations and prevent the occurrence of future adverse drug events.

Os enfermeiros têm a responsabilidade ética, legal e profissional de promover uma assistência segura na administração de medicamentos. A aprendizagem da administração de medicamentos está centrada no conhecimento que os enfermeiros constroem em sua formação acadêmica e na vivência profissional. O objetivo deste trabalho foi compreender o significado da administração de medicamentos, pelo estudante de enfermagem nas suas primeiras experiências. Dada a natureza do problema, esta investigação utilizou uma abordagem qualitativa, tendo como referencial metodológico a Teoria Fundamentada nos Dados, à luz do Interacionismo Simbólico. Como estratégias para a coleta de dados foi utilizada a observação não-participante e entrevistas semi-estruturadas, tendo como sujeitos 13 estudantes de uma instituição pública de ensino superior, localizada no interior do Estado de São Paulo. Os dados foram coletados, organizados e analisados por meio da estratégia da análise comparativa constante. Os resultados revelaram que os estudantes de enfermagem, ao vivenciarem o processo da administração de medicamentos, experienciaram insegurança ao administrar medicamentos; evidenciando as categorias: não valorizando a execução de determinados procedimentos básicos e emergindo sentimentos de dúvida para \"ser Enfermeiro\" no contexto desta ação. Como condições causais do fenômeno despontam a vivência de situações de erros e a percepção de conhecimentos teórico-práticos insuficientes; e como estratégia de ação a importância do laboratório e do campo de prática para o aprendizado. As condições intervenientes que influenciaram a realização dessa ação foram: tendo apoio dos colegas, família e professor e tendo dificuldades no relacionamento com o cliente. Como conseqüências as categorias: despertando para a responsabilidade da \"ação\" de administrar medicamentos e despertando para a profissão: sentindo-se enfermeiro ao administrar medicamentos. Enfim, os estudantes de enfermagem participantes do estudo atribuíram o significado da administração de medicamento como uma atividade de ilimitado valor e responsabilidade, conduzindo-os a um despertar para a futura profissão. / Nurses have the ethical, legal and professional responsibility to promote safe care in medication administration. Learning about medication administration is centered on the knowledge that nurses develop during their academic education and professional experience. This work aimed at understanding the meaning of medication administration to nursing students during their first experiences. Due to the nature of the problem addressed, a qualitative approach was used according to the Grounded Theory, in the light of Symbolic Interactionism. Non-participant observation and semi-structured interviews were used as strategies for data collection from 13 subjects who were students at a public college in São Paulo state. Data were collected, organized and analyzed through the strategy of constant comparative analysis. The results showed that, during the process of medication administration, the nursing students experienced insecurity according to the following categories: not valuing the execution of basic procedures and with feelings of doubt \"about being a nurse\" emerging in the context of this action. The causes for the phenomenon were: experiencing situations of error and the perception that theoretical and practical knowledge was insufficient. As action strategies, the following must be cited: the importance of laboratory and practical activities for learning; as interventional conditions that would influence the performance of this action: having support from colleagues, relatives, teachers and having difficulties in the relationship with the client, and as consequences: awakening to the responsibility of the \"action\" of administering medication and awakening to the profession: feeling as a nurse when administering medication. Finally, the nursing students participating in the study attributed the meaning of medication administration as an activity of unlimited value and responsibility which leads them to the awakening to a future profession.

A vigabatrina (VGB) é um fármaco anticonvulsivante que apresenta apenas a forma farmacêutica sólida disponível para uso. Na área hospitalar, devido à ausência de medicamentos na forma farmacêutica líquida, são preparadas derivações a partir de comprimidos e cápsulas para adequar a administração da dose prescrita. No entanto, a falta de estudos de estabilidade podem comprometer a eficácia e segurança destas derivações. O objetivo deste trabalho foi analisar a estabilidade química de derivações de comprimidos de vigabatrina em condições de armazenamento sob diferentes temperaturas e variações na embalagem utilizada. A análise das derivações de VGB foi realizada através de cromatografia líquida de alta eficiência (CLAE). O método descrito na Farmacopeia Britânica (2016) foi covalidado quanto a especificidade, linearidade, precisão e exatidão. Amostras de derivação de VGB foram preparadas em triplicata e acondicionadas em frascos de vidro e de PET âmbar. Após, foram armazenadas sob três diferentes condições de temperatura: temperatura ambiente (15 a 30 °C), sob refrigeração (2 a 8 °C) e em estufa (40 °C). Foram coletadas amostras armazenadas nas diferentes embalagens a cada 7 dias, por um período de 35 dias para as amostras conservadas em temperatura ambiente e refrigerada. O mesmo procedimento foi realizado para as amostras conservadas em estufa, porém por um período de 28 dias Também foi analisado o pH das amostras em cada tempo de coleta. As derivações de VGB foram analisadas por CLAE e apresentaram variação dentro dos limites preconizados pela Farmacopeia Britânica 2016, até 21 dias para frascos de vidro e de PET âmbar para as temperaturas ambiente e refrigerada. As amostras de VGB conservadas em estufa, apresentaram redução acima de 10% após 7 dias de estudo. A menor variação de pH ocorreu em frasco de vidro âmbar armazenado sob refrigeração. O resultado deste estudo serve de referência no preparo de derivações de VGB para uso hospitalar, pois apresentou intervalo de tempo confiável e condições de armazenamento adequadas para sua utilização. Desta forma, os pacientes pediátricos que utilizam doses fracionadas ou pacientes em uso de sondas nasogástricas terão as derivações adequadamente preparadas, reduzindo o risco de erros de diluição e contaminação microbiológica, melhorando a eficácia e segurança terapêutica. / Vigabatrin (VGB) is an anticonvulsant drug that has only solid dosage form available for use. In hospital, due to lack of medicines in liquid dosage form, extemporaneous preparations are prepared from tablets and capsules to adapt the administration of the prescribed dose. However, the lack of stability studies may compromise the efficacy and safety of these preparations. The aim of this study was to analyze the chemical stability of VGB extemporaneous preparation from tablets at storage conditions in different temperatures and variations of packaging used. The analysis of VGB extemporaneous preparations were performed by high-performance liquid chromatography (HPLC). The method described in British Pharmacopoeia (2016) was co-validated for specificity, linearity, precision and accuracy. VGB extemporaneous preparations were prepared in triplicate and placed in amber glass and PET bottles, which were stored under three different conditions: at room temperature (15 to 30 °C), under refrigeration (2 to 8 °C), and oven (40 °C). Samples of preparations stored at room temperature and refrigeration were collected every 7 days along 35 days. The same was done for solutions kept at 40 °C, but for a period of 28 days. It was also analyzed the preparations pH for each sampling time VGB extemporaneous preparations were analyzed by HPLC and demonstrated variations within the limits of British Pharmacopoeia (2016) up to 21 days in amber glass and PET bottles at room and refrigerated temperatures. VGB content for preparations kept in oven decreased above 10% after 7 days of study. The lowest pH change occurred in amber glass bottle stored under refrigeration. Results of this study can be applied as a reference for VGB extemporaneous preparation in hospital, once it was demonstrated the reliability of storage time interval and proper conditions for the use. Thus, pediatric patients with fractionated doses or patients using nasogastric probe will have adequately prepared extemporaneous preparations, reducing the risk of dilution errors and microbiological contamination.

Chronic kidney disease (CKD) is growing global public health problem affecting 1 in 10 adults in developed countries and recognised as an important risk factor for cardiovascular disease (CVD) development. CVD is the main cause of death among CKD patients. Endothelial injury and dysfunction are critical steps in atherosclerosis, a major CVD. Oxidative stress (increased level of reactive oxygen species, ROS) has been associated with CVD development. Intravenous (IV) iron preparations are widely used in the management of CKD mediated anaemia, and have been associated with increased oxidative stress and cellular dysfunction. This study examined the effect of pharmacologically-relevant concentrations of IV Venofer (iron sucrose) or IV Ferinject (Ferric carboxymaltose, FCM) on primary human umbilical vein endothelial cell (HUVEC) activation/damage and on intracellular ROS generation as well as studying the potential mechanisms responsible. Data from TUNEL assay and Annexin V-FITC/PI staining showed that, IV FCM had no effect, but IV iron sucrose increased HUVEC apoptosis at 24hr. IV iron sucrose inhibited cell proliferation and reduced cell viability. Both compounds induced EC activation through sustained activation of p38 MAPK and up-regulation of ICAM-1 and VCAM-1. Additionally, the compounds induced significant increase in total ROS and superoxide anion production, which was attenuated by the anti-oxidant N-acetylcysteine (NAC). P38 MAPK showed up-regulation of pro-apoptotic protein Bax and down-regulation of antiapoptotic Bcl-2 protein in HUVEC treated with IV iron sucrose and p38 inhibition reversed these effects. In summary, these results suggest that IV iron sucrose causes more severe EC injury than IV FCM. However, both IV iron preparations induced intracellular ROS and superoxide anion generation in HUVEC leading to EC activation/dysfunction, providing a potential explanation for vascular damage in CKD patients.

Resin-based composite for Class IV restoration is a conservative alternative for maxillary incisor fracture. Little is known about the effect of lingual margin configurations on the longevity of these restorations. This in vitro experiment compared the mean fracture strength among four lingual margin configurations (butt joint, 45° bevel, 60° bevel and chamfer) for Class IV resin-based composite restorations. A total sample size of n=100 human extracted lower incisors were selected, then the teeth were randomly assigned to one of the four lingual margin configuration groups (n=25) and restored with resin-based composite. After thermocycling (5000 cycles, 5°C-55°C with 30 seconds dwell time), they were subjected to inter-incisal static load (135° angulation) until failure (N). Failure mode was determined. In vitro fracture strength was compared among the four groups using one-way ANOVA at alpha=0.05. Mean standard deviation of fracture strength and frequency distribution of failure modes were reported. Results revealed no significant effect on the fracture strength for the type of lingual margin configurations (F(3,96)=0.13; p=0.9435). The data showed that 71% of failure modes resulted in complete tooth fracture (intact restoration), 11% in total adhesive failure, 7% in adhesive only facial, 6% in total cohesive, 4% in cohesive only facial, 1% in avulsion. Fischer’s exact test revealed no statistically significant association (p>0.05) between the margin configurations and failure modes. Within the limitations of this study, it can be concluded that any of the four lingual margin configurations are acceptable in Class IV preparation in terms of fracture strength under static load.

RNR Polymerase I (RNA Pol I) is a “factory” that orchestrate the transcription of ribosomal rRNA for constructing ribosomes as a primary workshop for protein translation to sustain cell growth. Misregulation of RNA Pol I can cause uncontrolled cell proliferation, which leads to the development of cancer. Yeast (Saccharomyces cerevisiae) is a valuable model system to study RNA Pol I. Recently, the X-ray crystal structure of the yeast homologue of RNA Pol I was elucidated, offering the structural basis to selectively target this transcriptional machinery. The approach to selective RNA Pol I targeting was to disrupt the interaction between a specific transcription factor, RRN3 that bind distinct regions of RNA Pol I. For this purpose, a recombined plasmid was designed to carry human rDNA plus its promoter as target together with a selection marker gene. Therefore, this plasmid could not only introduce the target gene into the yeast (host), but also facilitate the passage of this target gene into a stable yeast strain. In this project, one uracil deficient yeast strain of YBR140C was transformed with the recombined yeast integrative plasmid of pHmrDNA-YIPlac211-TG1. This is a recombined plasmid containing not only the human rDNA but also the URA3 gene as a selection marker. PCR amplification of the human ribosomal DNA was indicative of successful integration of the human ribosomal DNA into the genome of the two yeast strains. Virtual screening using a library of 700 FDA-approved compounds was docked into the RRN3-RNA Pol I complex to identify small molecule disruptors of the RRN3-RNA Pol I as a selective strategy. Using growth assays, gel electrophoresis and transcriptional assays, we identified cerivastatin sodium as a lead virtual hit. The result implicates cerivastatin sodium as a selective RNA Pol I inhibitor worthy of further development with potential as targeted anticancer therapeutic.

Glaucoma is the leading cause of blindness in the United States accounting for 9-12% of all cases of blindness. Currently, the front line treatment for glaucoma are prostaglandins that may have to be taken up to several times a day. Even with proper treatment, roughly 11% of the patients using the treatment are non-compliant and lose their vision. In this project, ForSight Laboratories has developed a pharmaceutical drug delivering implant with the capability of sustaining long-term release of a prostaglandin as a new way to treat the condition. This project reports the product development of a polymer drug matrix with a controlled release in order to better treat glaucoma. Accompanying product development, a mathematical model was created in order to strengthen the understanding of the dosage profile and to predict long term dosages.

<p>I och med Försvarsmaktens omställning till insatsförsvar med internationella åtaganden har sannolikheten för att marina förband ska nyttjas för väpnad strid ökat markant. Med detta följer ett än större behov av att kunna hantera sådana prövningar. I den här uppsatsen provas idealtypsanalys som metod att mäta korvetten HMS Stockholms effektivitet ur ett organisationsteoretiskt perspektiv. Idealtypen, referensfartyget ”HMS Excellence”, skapas genom att använda 7s modellen (Waterman et al.) för att åskåda organisationen och resultat från den Amerikanska studien <em>”Excellence in the Surface Navy”</em> (Gullickson & Chenette) som indikatorer för effektivitet. Genom att presentera intervjudata från HMS Stockholm i samma dimensioner skapas ett underlag för analys.</p><p>Resultaten från uppsatsen visar att HMS Stockholm är ett effektivt stridsfartyg med vissa organisatoriska brister vars orsak kan spåras till intensiteten i pågående insatsförberedelser. Vidare visar analysen att 7s modellen har potential att vara ett användbart verktyg för att optimera ett stridsfartygs organisation samt som en komponent i idealtypsanalys.</p> / <p>Because of the Swedish Armed Forces reformation from an operational defense force to a rapid action force with international commitments the odds of naval units being involved in armed confrontation has distinctively increased. This leads to an even greater need for battle readiness. In this thesis ideal type analysis is tried as a method to assess the efficiency of the Swedish warship HMS Stockholm from an organization theoretical perspective. The ideal case, a reference war ship named HMS Excellence, is created by combining results from Gullickson & Chenettes study <em>Excellence in the Surface Navy, </em>with the 7s framework. HMS Stockholm is presented in the same manner combining interview data with the 7s framework. The difference between the ideal case and empirical case is used as a measurement of HMS Stockholm´s efficiency.</p><p>The author concludes that HMS Stockholm is an effective organization with an occasional weakness in the systems dimension due to the intensity of deployment preparations. Also, the author argues for ideal type analysis, using the 7s framework, as a tool to optimize deployment preparations and the 7s framework as a tool to optimize war ship organizations.</p>

I och med Försvarsmaktens omställning till insatsförsvar med internationella åtaganden har sannolikheten för att marina förband ska nyttjas för väpnad strid ökat markant. Med detta följer ett än större behov av att kunna hantera sådana prövningar. I den här uppsatsen provas idealtypsanalys som metod att mäta korvetten HMS Stockholms effektivitet ur ett organisationsteoretiskt perspektiv. Idealtypen, referensfartyget ”HMS Excellence”, skapas genom att använda 7s modellen (Waterman et al.) för att åskåda organisationen och resultat från den Amerikanska studien ”Excellence in the Surface Navy” (Gullickson &amp; Chenette) som indikatorer för effektivitet. Genom att presentera intervjudata från HMS Stockholm i samma dimensioner skapas ett underlag för analys. Resultaten från uppsatsen visar att HMS Stockholm är ett effektivt stridsfartyg med vissa organisatoriska brister vars orsak kan spåras till intensiteten i pågående insatsförberedelser. Vidare visar analysen att 7s modellen har potential att vara ett användbart verktyg för att optimera ett stridsfartygs organisation samt som en komponent i idealtypsanalys. / Because of the Swedish Armed Forces reformation from an operational defense force to a rapid action force with international commitments the odds of naval units being involved in armed confrontation has distinctively increased. This leads to an even greater need for battle readiness. In this thesis ideal type analysis is tried as a method to assess the efficiency of the Swedish warship HMS Stockholm from an organization theoretical perspective. The ideal case, a reference war ship named HMS Excellence, is created by combining results from Gullickson &amp; Chenettes study Excellence in the Surface Navy, with the 7s framework. HMS Stockholm is presented in the same manner combining interview data with the 7s framework. The difference between the ideal case and empirical case is used as a measurement of HMS Stockholm´s efficiency. The author concludes that HMS Stockholm is an effective organization with an occasional weakness in the systems dimension due to the intensity of deployment preparations. Also, the author argues for ideal type analysis, using the 7s framework, as a tool to optimize deployment preparations and the 7s framework as a tool to optimize war ship organizations.