Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic cell death in the substantia nigra pars compacta (SNc) and dopamine (DA) depletion in the striatum. Current pharmacological treatments are aimed at the replacement of striatal DA via the administration of levodopa. While this therapy is beneficial initially, long-term treatment is associated with significant side effects, and disease progression continues. The present experiments investigate neuroprotective and neurotransplantation strategies as alternatives to palliative pharmacologic treatments. The optimal therapeutic approach to neurodegenerative diseases would be to protect against cell death and prevent disease progression. PD is well-suited for such neuroprotective strategies as primarily one cell population is affected in this disorder. Neurotrophic factors (NTFs) have been identified which support dopaminergic neuronal survival in vitro. In the present studies, the neuroprotective effects of the neurotrophin brain-derived neurotrophic factor (BDNF) have been evaluated in a 1-methyl-4-phenylpyridinium (MPP+) model of substantia nigra (SN) degeneration. BDNF-secreting fibroblasts were implanted dorsal to the SN prior to the infusion of the mitochondrial complex I inhibitor MPP+. Subsequent histological analysis demonstrated that BDNF is able to attenuate MPP+ induced dopaminergic cell loss in the SNc. Moreover, neurochemical evaluation demonstrated that BDNF is able to enhance DA levels in the remaining SN neurons in this same paradigm. The cause of cell death in neurodegenerative diseases likely involves the interaction of mitochondrial impairment, excitotoxicity, and oxidative stress. In order to evaluate the mechanism of NTF-mediated protection, the ability of nerve growth factor (NGF) to attenuate the production of the oxidant peroxynitrite was evaluated in a model of mitochondrial impairment. NGF was found to decrease the production of 3-nitrotyrosine, the product of peroxynitrite mediated tyrosine nitration. Thus, NTF-mediated neuroprotection may act in part by decreasing reactive oxygen species and oxidative stress. At present, neuroprotective therapies are not clinically available. An alternate therapeutic approach to PD is the replacement of striatal DA and reconstruction of synaptic circuitry via the intrastriatal transplantation of fetal dopaminergic neurons. Current transplantation protocols using human fetal tissue are constrained by limited tissue availability. In order to investigate an alternate cell source for the treatment of PD, fetal porcine dopaminergic neurons were implanted into the DA depleted striatum of 6-OHDA lesioned rats. Amphetamine-induced rotational recovery was monitored, and graft survival was evaluated 19 weeks after grafting. In immunosuppressed rats, porcine dopaminergic neurons were found to attenuate rotational deficits and extensively reinnervate the host striatum. The neuroprotective effects of BDNF suggest that NTFs may be important mediators of dopaminergic neuronal survival and function in the adult brain. However, several conditions including appropriate dosage and delivery need to be determined before clinical applications may be achieved. As an alternative to neuroprotection, neurotransplantation not only restores striatal DA but also reconstructs the synaptic circuitry of the basal ganglia. The finding that porcine dopaminergic neurons survive with in adult host brain, reinnervate the DA depleted striatum, and mediate functional recovery suggests that porcine DA neurons may serve as an alternate cell source for transplantation in PD.

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.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A equivalÃncia farmacÃutica entre dois medicamentos relaciona-se à comprovaÃÃo de que ambos contÃm o mesmo fÃrmaco na mesma dosagem e forma farmacÃutica, o que pode ser avaliado por meio de testes in vitro. No Brasil, os medicamentos alopÃticos sÃo divididos em trÃs categorias quanto ao registro junto à AgÃncia Nacional de VigilÃncia SanitÃria: medicamentos novos, medicamentos similares e medicamentos genÃricos. A legislaÃÃo atual dispÃe que para o registro de novos medicamentos genÃricos e similares à necessÃria a comprovaÃÃo da equivalÃncia farmacÃutica e a bioequivalÃncia em relaÃÃo ao medicamento de referÃncia. Produtos registrados antes de 2003 tÃm um perÃodo de adaptaÃÃo garantido, de modo que os resultados dos testes de equivalÃncia farmacÃutica e perfil de dissoluÃÃo sejam incluÃdos ao seu registro atà 2014. O Programa FarmÃcia Popular do Brasil à uma nova polÃtica de AssistÃncia FarmacÃutica, dentro do Sistema Ãnico de SaÃde que tem como objetivo facilitar o acesso da populaÃÃo aos medicamentos considerados bÃsicos e essenciais, diminuindo assim, o impacto dos preÃos dos medicamentos no orÃamento familiar. O objeivo deste trabalho foi avaliar a EquivalÃncia FarmacÃutica de comprimidos de Captopril 25 mg e Cloridrato de Propranolol 40 mg comercializados no Programa FarmÃcia Popular do Brasil, comparando-o com medicamentos de ReferÃncia e GenÃrico, visando discutir a importÃncia da qualidade dos medicamentos para a saÃde pÃblica. Realizaram-se testes fÃsicos e fÃsico-quÃmicos como: identificaÃÃo, determinaÃÃo de peso, desintegraÃÃo, dureza, friabilidade, teor, uniformidade de conteÃdo, pureza e perfil de dissoluÃÃo, segundo a FarmacopÃia Brasileira, 4a ediÃÃo. Os resultados indicaram uma baixa dureza nos comprimidos de cloridrato de propranolol da FarmÃcia Popular. Os perfis de dissoluÃÃo, analisados por ANOVA e teste de Tukey demonstraram diferenÃas significativas (p<0,001) entre os perfis de dissoluÃÃo da FarmÃcia popular em relaÃÃo ao GenÃrico e ReferÃncia nos tempos avaliados dos dois fÃrmacos em estudo. Compararam-se os perfis de dissoluÃÃo dos comprimidos da FarmÃcia Popular com os medicamentos ReferÃncia e GenÃrico atravÃs da EficiÃncia de DissoluÃÃo (ED%). A extensÃo do fÃrmaco dissolvido do medicamento FarmÃcia Popular foi significativamente menor (P < 0,001) do que o ReferÃncia para Captopril e Propranolol. O Captopril da FarmÃcia Popular, apesar de ter cumprido as exigÃncias da legislaÃÃo, foi reprovado no ensaio de ED%. Portanto, os comprimidos de Cloridrato de Propranolol e Captopril da FarmÃcia Popular nÃo foram considerados equivalentes farmacÃuticos em relaÃÃo aos medicamentos ReferÃncia e GenÃrico. / The pharmaceutical equivalence between two medicines is based on the confirmation that both contain the same active drug on the same dosage and dosage form, wich is assessed by in vitro tests. In Brazil, the National Health Surveillance Agency defines that allopathic medicines can be registered in three categories: innovator, generic and similar drugs. The actual legislation determines that to register new generic and similar medicines it is necessary to prove its pharmaceutical equivalence and bioequivalence with a reference drug. Products registered before 2003 have until 2014 to present these equivalence results. The Popular Pharmacy Program in Brazil is a new strategy of pharmaceutical assistance of the Health Sistem with the purpose to facilitate the populationâs access to medicines considered basic and essential, lowering the price impact of these medicines in the family budgets. The objective of this study was to assess the pharmaceutical equivalence of captopril 25 mg and propranolol hydrochloride 40 mg tablets sold in the Popular Pharmacy Program in Brazil, comparing them to a reference and generic drug, debating the importance of the quality of drugs for the public health. Physical and physicochemical tests such as identification, weight variation, disintegration, hardness, friability, purity, dosage, content uniformity, and dissolution profile, were performed according to the Brazillian Pharmacopeia 4th edition. The results showed a low hardness of propranolol hydrochloride tablets originated from the Popular Pharmacy Program. The dissolution profiles analised by analysis of variance (ANOVA) and Tukey test demonstrated significant differences between the dissolution profiles of both drugs originated from the Popular Pharmacy Program and their respective reference and generic drugs (p<0,001). The dissolution profiles were compared by the Dissolution Efficiency method. The extention of the active drug dissolved from the Popular Pharmacy medicine was significantly lower than the dissolution from the reference and generic drugs (P < 0,001) for both captopril and propranolol hydrochloride. Even though captopril would fulfill the requirements of the National Health Surveillance Agency to be considered equivalent, it was not approved on the dissolution efficiency test. Therefore, the assessed tablets originated from the Popular Pharmacy Program in Brazil were not considered pharmaceutical equivalents when compared to their respective reference and generic drugs.

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.

Recent pharmaceutical developments have investigated using supramolecular nanoparticles in order to increase the bioavailability and solubility of drugs delivered in various methods. Modification of the carbohydrate cyclodextrin increases the ability to encapsulate hydrophobic pharmaceutical molecules by forming a carrier with a hydrophobic core and hydrophilic exterior. Guest molecules are commonly added to these inclusion complexes in order to add stability and further increase targeting abilities of the carriers. One such guest molecule is adamantine combined with a poly(ethylene glycol) chain. Vesicles are formed by hydrating a thin film of amphiphilic cyclodextrin and guest molecules in buffer solution that mimics physiological conditions. The solution is subject to freeze-thaw cycles and extrusion, and the complexes are separated out via size exclusion chromatography. Dynamic Light Scattering instrumentation is used to observe the particle size distribution. Cargo release can be observed in fluorescent dye-loaded vesicles by addition of a membrane-cleaving agent under a fluorimeter instrument. Future work involving this drug delivery technology includes synthesizing a chemically sensitive guest that will cleave in the presence of an intra-cellular anti-oxidant, and finally observing the uptake of these vesicles into live cells and testing the delivery of cargo in vitro under physiological conditions.

No description available.

The Rational Drug Use Training Project is a district-oriented programme designed to improve rational drug use among primary health care prescribers in the South African public sector. This thesis describes the development of the project and details the initial implementation study in 3 facilities in Region B of KwaZulu-Natal. This was a small before-after study, with no control. There were three components: 1. A series of easily collectable drug use indicators, adapted from those developed by WHO/INRUD. These allow primary health care staff to monitor their prescribing patterns in a district or facility. Ninety sets of prescribing indicators were collected as a baseline at 3 facilities in KwaZulu-Natal in December 1996, by the district trainers and the Rational Drug Use Training Project staff. The process was repeated in March 1997, after the training intervention, by the district trainers alone. 2. The intervention was a 2-day training workshop in rational drug use. This is problem-based and trained on-site in primary health facilities. Training was done by 8 district trainers from Region B who were taught to present the workshop by the Rational Drug Use Training Project staff. The workshop covers principles of prescribing, use of standard treatment guidelines, principles of clinic stock management and principles of good dispensing. Staff are encouraged to develop their self-learning skills through questioning, and seeking answers to clinical and drug related queries. 3. A set of resources, including texts, treatment guidelines and information centres, to provide quality, safe and unbiased drug information, are made accessible to staff at primary care level. These are available by post, telephone or e-mail. The Primary Care Medicines Resource Centre at the University of Durban-Westville was developed as a result of this study. Significant improvements in prescribing habits were noticed after the study. There was an increase in the percentage of drugs prescribed by their generic names (p=0.000); an increase in the number of medications adequately labelled (p=0.0132); a decrease in the cost of prescriptions (p=0.0134); and a decrease in the number of prescriptions that did not follow standard treatment guidelines at all for that diagnosis (p=0.0109). The Mann-Whitney U- test was used for statistical analysis. There were no significant changes in the average number of drugs per prescription; the percentage of drugs from the Essential Drugs List; and the number of prescriptions that completely followed standard treatment guidelines. Qualitative feedback was favourable too. This was a difficult study to undertake. The staff and funding organisation, Health Systems Trust, fell outside of the provincial health structure and met resistance at that level. Regional politics shaped the programme's design. District trainers needed for the cascade approach were not available. District staff remained entrenched in a traditional health hierarchy and found it difficult to function as a team. The will of district prescribing staff to learn was low. Rational drug use training is only one of a number of essential elements of in-service training urgently needed by these staff. Despite these problems, quantitative and qualitative success was shown. The Training Manual, developed in support of the training, has been in demand. The Primary Care Medicines Resource Centre is growing. Primary care prescribers have been motivated to monitor their own practices and manage their own clinic stock. The project is a successful example of multi-disciplinary and institutional collaboration. The Rational Drug Use Training Project has expanded to eight other health districts in 1997. A list of criteria, such as the need for a district trainer, have been set. These must be met by the district before training will commence. The project is a resource for Initiative for Sub-District Support, a joint district development programme of Health System Trust and the Department of Health. Most expansion in 1998 will be through this initiative. The difficulties encountered and achievements made during this small study will be used to support, and hopefully strengthen, the development of the primary health care oriented district health system, so urgently needed by the South African population.

The growing prevalence of antibiotic-resistant bacteria is a global health crisis that threatens the effectiveness of antibiotics in medical treatment. Increases in the number of antibiotic-resistant bacteria and a drop in the pharmaceutical development of novel antibiotics have combined to form a situation that is rapidly increasing the likelihood of a post-antibiotic era. The development of antibiotics with novel enzymatic targets is critical to stall this growing crisis. In silico methods of molecular modeling and drug design were utilized in the development of novel tryptamine analogs as potential antibiotics through their inhibition of the bacterial enzyme tryptophan synthase. Following the creation of novel tryptamine analogs, the molecules were analyzed in silico to determine their binding affinity to human MAOB and the E. coli α-subunit, E. coli β2-dimer and the M. tuberculosis β2-dimer of tryptophan synthase. Ten tryptamine analogs displayed significant increases in tryptophan synthase binding affinity and show promise as potential antibiotics and antibiotic adjuvants. Further in silico modeling determined that the binding sites of the tryptamine analogs were similar to wild-type tryptamine in the E. coli β2-dimer, the M. tuberculosis β2-dimer and human MAOB, while the analogs’ binding sites to the E. coli α-subunit differed. Although no tryptamine analogs increased tryptophan synthase binding affinity while decreasing human MAOB binding affinity, related increases in MAOB binding affinity warrants further research into the analogs’ potentials as MAO inhibitors. Given the increases in tryptophan synthase binding affinity and similar β2-dimer binding sites, a provisional patent was filed on the ten identified tryptamine analogs. Moving forward, we recommend the synthesis of the ten identified tryptamine analogs. Following synthesis, further research should be conducted to determine the in vitro and in vivo antibiotic properties of the ten tryptamine analogs.

No Brasil, poucos estudos investigaram a prevalência de medicamentos potencialmente inapropriados (MPIs) em idosos ambulatoriais. Este estudo visa determinar a prevalência de MPIs prescritos para estes pacientes, identificando os mais comumente envolvidos e verificando se a idade, o sexo e o número de medicamentos estão relacionados à prescrição de tais medicamentos. Foram coletadas prescrições de 3070 pacientes idosos (60 anos) em banco de dados, provenientes dos ambulatórios de Geriatria e Clínica Geral de um hospital universitário de atenção terciária em São Paulo-Brasil entre fevereiro e maio de 2008, que foram divididas de acordo com o sexo e faixa etária (60-69; 70-79 e 80). Os critérios de Beers versão 2003 foram utilizados para a avaliação de MPIs. A maior parte da casuística foi composta por mulheres em ambos os ambulatórios (66,6% na Clínica Geral e 77,7% na Geriatria). Os pacientes da Clínica Geral apresentaram média de idade de 71,3 anos e os da Geriatria, 80,1 anos. Na Clínica Geral a prevalência média de prescrição de MPIs foi de 37,6% e na Geriatria de 26,9%, sendo que em ambos as mulheres de 60-69 foram as que apresentaram a maior prevalência destes medicamentos. Os MPIs mais prescritos nos dois ambulatórios foram o carisoprodol, a fluoxetina e a amitriptilina, sendo que houve diferenças nos perfis de prescrições entre homens e mulheres. A chance de uso de MPI no sexo feminino é maior que no masculino (p<0,001); a chance de uso de MPI na faixa de 70-79 anos é menor que na faixa de 60-69 anos (p=0,030), assim como na faixa de 80 (p=0,024). Estas conclusões não dependem do ambulatório (p=0,164).O efeito de ambulatório depende do número de medicamentos (p=0,009). Se o número de medicamentos é < 9 a chance de uso de MPI na Clínica Geral é maior que na Geriatria (p=0,041). Quando o número de medicamentos é 7 ou 8, a chance de uso de MPI é maior do que quando são prescritos 1-4 medicamentos (p<0,001), nos dois ambulatórios (p=0,098). Quando são usados 9 medicamentos, a chance de uso de MPI depende do ambulatório (p=0,044). Na Geriatria, a chance de uso de um MPI é 8,2 vezes a RC na categoria 1-4 medicamentos; enquanto que na Clínica Geral a razão de chances é 4,6. As prevalências de MPIs encontradas foram semelhantes ao relatado na literatura e estão correlacionadas ao sexo feminino. A chance de prescrição de MPIs foi menor em pacientes com 70 anos; observou-se que se o número de medicamentos for <9, a chance de uso de MPI na Clínica Geral é maior que na Geriatria, porém, se o número de medicamentos for 9 não há diferença entre as chances de uso de MPI nos dois ambulatórios / In Brazil, few studies have investigated the prevalence of potentially inappropriate medications (PIMs) among elderly outpatients. This study aimed to determine the prevalence of PIMs prescribed to such patients, identify the medications most commonly involved and investigate whether age, sex and number of medications are related to the prescription of such medications. Prescriptions issued to 3,070 elderly patients (60 years) were gathered from a database. These patients were attended at the geriatric and general clinical outpatient services of a tertiary-level university hospital in São Paulo, Brazil, between February and May 2008. They were divided according to sex and age group (60- 69; 70-79; and 80 years). The Beers criteria (2003 version) were used to evaluate PIMs. The majority of the sample comprised women, at both outpatient services (66.6% in the general clinic and 77.7% in geriatrics). The mean age of the general clinical patients was 71.3 years and the mean for the geriatric patients was 80.1 years. At the general clinic, the mean prevalence of prescriptions of PIMs was 37.6%, and it was 26.9% at the geriatric clinic. At both outpatient services, women aged 60-69 years presented the highest prevalence of such medications. The PIMs most prescribed at the two outpatient services were carisoprodol, fluoxetine and amitriptyline, and there were differences in the prescription profiles between the men and women. The chances of using PIMs were greater for the women than for the men (p < 0.001). The chances of using PIMs in the 70-79 years group were lower than in the 60-69 years group (p = 0.030), and likewise for the group 80 years (p = 0.024). These conclusions were independent of the outpatient service (p = 0.164). The outpatient effect depended on the number of medications (p = 0.009). If the number of medications was < 9, the chances of using PIMs at the general clinic were greater than the chances at the geriatric clinic (p = 0.041). When the number of medications was 7 or 8, the chances of using PIMs were greater than when prescribed 1-4 medications (p < 0.001), at both outpatient services (p = 0.098). When 9 medications were used, the chances of using PIMs depended on the outpatient service (p = 0.044). At the geriatric clinic, the chances of using PIMs were 8.2 times greater than the chances in the category of 1-4 medications; while at the general clinic, the odds ratio was 4.6. The prevalence of PIMs encountered was similar to what has been reported in the literature, and it correlated with female sex. The chances of being prescribed PIMs were lower among patients 70 years. If the number of medications was < 9, the chances of using PIMs at the general clinic were greater than the chances at the geriatric clinic. However, if the number of medications was 9, there was no difference in the chances of using PIMs between the two outpatient services

Cisplatin is a chemotherapy drug effective against several forms of cancer, but can also cause serious side-effects, including nephrotoxicity and ototoxicity. Curcumin, a natural plant compound, can increase cisplatin’s anti-cancer activity and counteract cisplatin’s deleterious effect on the auditory and renal systems. Unfortunately, curcumin exhibits poor bioavailability, which has promoted interest in the development of synthetic curcumin analogs (curcuminoids) that are soluble, target cancer, and do not cause side effects. This study investigated whether the curcuminoid (3E,5E)-3,5-bis[(2-fluorophenyl) methylene]-4-piperidinone (EF-24) increases the anti-cancer effects of cisplatin against a human ovarian cancer cell line (A2780) and its cisplatin-resistant counterpart (A2780cis), while preventing cisplatin-mediated side effects in a human kidney cell line (HEK-293T) and a mouse auditory hybridoma cell line (HEI-OC1). The effect of cisplatin and EF-24 on cellular viability was measured using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. The expression and activity of signal transduction proteins in several apoptotic pathways was measured using caspase luminescence assays. Reactive oxygen species (ROS) production was also measured using flow cytometry. Our data suggest that cisplatin and EF-24 are effective against ovarian cancer cell lines, but both compounds may also have adverse effects on auditory and renal cells. This project provides relevant information that may improve our understanding of how these compounds function in different tissues, facilitating improved cancer treatment and circumvention of side effects commonly associated with cisplatin treatment.