Antidiabetic and hypolipidemic potential of Campomanesia xanthocarpa seed extract obtained by supercritical CO2 / Potencial Antidiabético e hipolipidêmico do extrato das sementes de Campomanesia xanthocarpa obtido por CO2 supercrítico

Abstract Campomanesia xanthocarpa, a plant belonging to the Myrtaceae family, is popularly known as gabiroba. Leaves of gabiroba has been popularly used to treat various diseases, including inflammatory, renal, and digestive, among others. Additionally, studies have shown an effect to reduce blood cholesterol levels. The aim of this study was to evaluate the antihyperglycemic and hypolipidemic effects of Campomanesia xanthocarpa seed extract in hyperglycemic rats. The results showed that 400 mg/kg of seed extract was able to decrease blood glucose levels and to increase the muscular and hepatic glycogen content as well as to inhibit the sucrase and maltase activity. At doses of 200 mg/kg and 800 mg/kg, the activity of these enzymes was also reduced. In the lipid profile 400 mg/kg produced a decrease in total and LDL cholesterol serum levels; and with 200 mg/kg there was an increase in HDL cholesterol levels. The extract did not present hepatic and renal toxic effects at the different doses tested. The results suggest that the treatment with Campomanesia xanthocarpa seeds extract is useful in reducing glycemia, total cholesterol and LDL levels with potential adjuvant therapeutic in the treatment of diabetes and hypercholesterolemia, however, additional pharmacological and toxicological studies are still required.

Resumo Campomanesia xanthocarpa, planta pertencente à família Mirtaceae, é popularmente conhecida como gabiroba. Folhas da gabiroba são popularmente usadas para tratar de doenças inflamatórias, renais, digestivas entre outras. Além disso, estudos têm mostrado um efeito redutor dos níveis de colesterol. O objetivo deste estudo foi avaliar os efeitos anti-hiperglicêmico e hipolipidêmico do extrato de sementes de Campomanesia xanthocarpa em ratos hiperglicêmicos. Os resultados mostraram que 400 mg/kg do extrato da semente foi capaz de reduzir os níveis de glicose sanguínea e aumentar o conteúdo de glicogênio hepático e muscular, bem como inibir a atividade da maltase e sacarase. Na dose de 200 mg/kg e 800 mg/kg, a atividade das enzimas também foi reduzida. No perfil lipídico, 400 mg/kg produziu uma redução nos níveis séricos de colesterol total e LDL e com 200 mg/kg houve um aumento nos níveis de colesterol HDL. O extrato não apresentou efeitos tóxicos hepáticos e renais nas doses testadas. Os resultados sugerem que o tratamento com o extrato de Campomanesia xanthocarpa é eficaz na redução da glicemia, de colesterol total e LDL com potencial para tratamento adjuvante do diabetes e hipercolesterolemia, no entanto estudos farmacológicos e toxicológicos adicionais são necessários.

Antidiabetic and hypolipidemic potential of Campomanesia xanthocarpa seed extract obtained by supercritical CO2.

Campomanesia xanthocarpa, a plant belonging to the Myrtaceae family, is popularly known as gabiroba. Leaves of gabiroba has been popularly used to treat various diseases, including inflammatory, renal, and digestive, among others. Additionally, studies have shown an effect to reduce blood cholesterol levels. The aim of this study was to evaluate the antihyperglycemic and hypolipidemic effects of Campomanesia xanthocarpa seed extract in hyperglycemic rats. The results showed that 400 mg/kg of seed extract was able to decrease blood glucose levels and to increase the muscular and hepatic glycogen content as well as to inhibit the sucrase and maltase activity. At doses of 200 mg/kg and 800 mg/kg, the activity of these enzymes was also reduced. In the lipid profile 400 mg/kg produced a decrease in total and LDL cholesterol serum levels; and with 200 mg/kg there was an increase in HDL cholesterol levels. The extract did not present hepatic and renal toxic effects at the different doses tested. The results suggest that the treatment with Campomanesia xanthocarpa seeds extract is useful in reducing glycemia, total cholesterol and LDL levels with potential adjuvant therapeutic in the treatment of diabetes and hypercholesterolemia, however, additional pharmacological and toxicological studies are still required.

Antioxidant activity, antibacterial and inhibitory effect of intestinal disaccharidases of extracts obtained from Eugenia uniflora L. Seeds.

The use of medicinal plants for disease prevention, treatment and cure is an ancient practice used by humanity, and many plants species are used in bioprospecting research. In this context, its stands out Eugenia uniflora L., populary known as pitangueira and belongs to the Myrtaceae family, with a wide geographic distribution and native of Brazil. In view of the therapeutic qualities of the plant and the lack of the studies on its seeds, the present study had as objective to evaluate the phytochemical profile of the extracts of Eugenia uniflora L. seeds, from different solvents, as well as their antibacterial activity, antioxidant and its inhibitory effect of intestinal disaccharidases. Results showed a high content of phenolic compounds and total flavonoids, thus characterizing antioxidant activity, also highlighting the best bacteriostatic action for the Gram positive strain of Staphylococcus aureus in the ethanolic fraction. Regarding the disaccharidases, a strong inhibitory action was observed for all concentrations, evidencing a antihyperglycemic potential. The present research allowed to concluded that Eugenia uniflora L. seeds have promising biological activities for the industrial sector, but a more detailed investigation is needed regarding their bioactive compounds.

Antioxidant activity, antibacterial and inhibitory effect of intestinal disaccharidases of extracts obtained from Eugenia uniflora L. seeds / Atividade antioxidante, antibacteriana e efeito inibidor de dissacaridases intestinais de extratos obtidos das sementes de Eugenia uniflora L

The use of medicinal plants for disease prevention, treatment and cure is an ancient practice used by humanity, and many plants species are used in bioprospecting research. In this context, its stands out Eugenia uniflora L., populary known as pitangueira and belongs to the Myrtaceae family, with a wide geographic distribution and native of Brazil. In view of the therapeutic qualities of the plant and the lack of the studies on its seeds, the present study had as objective to evaluate the phytochemical profile of the extracts of Eugenia uniflora L. seeds, from different solvents, as well as their antibacterial activity, antioxidant and its inhibitory effect of intestinal disaccharidases. Results showed a high content of phenolic compounds and total flavonoids, thus characterizing antioxidant activity, also highlighting the best bacteriostatic action for the Gram positive strain of Staphylococcus aureus in the ethanolic fraction. Regarding the disaccharidases, a strong inhibitory action was observed for all concentrations, evidencing a antihyperglycemic potential. The present research allowed to concluded that Eugenia uniflora L. seeds have promising biological activities for the industrial sector, but a more detailed investigation is needed regarding their bioactive compounds.

A utilização de plantas com fins medicinais para prevenção, tratamento e cura de doenças é uma prática antiga utilizada pela humanidade, sendo que muitas espécies vegetais são usadas para a pesquisa da bioprospecção. Neste contexto, destaca-se a Eugenia uniflora L., conhecida popularmente como pitangueira e pertencente à família Myrtaceae, com ampla distribuição geográfica e nativa do Brasil. Diante das qualidades terapêuticas da planta e a falta de estudos sobre suas sementes, o presente trabalho teve como objetivo avaliar o perfil fitoquímico dos extratos das sementes de Eugenia uniflora L. a partir de diferentes solventes, bem como sua atividade antibacteriana, antioxidante e seu efeito inibidor de dissacaridases intestinais. Os resultados mostraram um alto teor de compostos fenólicos e flavonóides totais, caracterizando a atividade antioxidante, destacando também a melhor ação bacteriostática para a cepa Gram positiva de Staphylococcus aureus na fração etanólica. Em relação às dissacaridases, uma forte ação inibitória foi observada para todas as concentrações, evidenciando um potencial anti-hiperglicêmico. A presente pesquisa permitiu concluir que as sementes de Eugenia uniflora L. apresentam atividades biológicas promissoras para o setor industrial, mas é necessária uma investigação mais detalhada de seus compostos bioativos.

Antioxidant activity, antibacterial and inhibitory effect of intestinal disaccharidases of extracts obtained from Eugenia uniflora L. Seeds

Abstract The use of medicinal plants for disease prevention, treatment and cure is an ancient practice used by humanity, and many plants species are used in bioprospecting research. In this context, its stands out Eugenia uniflora L., populary known as pitangueira and belongs to the Myrtaceae family, with a wide geographic distribution and native of Brazil. In view of the therapeutic qualities of the plant and the lack of the studies on its seeds, the present study had as objective to evaluate the phytochemical profile of the extracts of Eugenia uniflora L. seeds, from different solvents, as well as their antibacterial activity, antioxidant and its inhibitory effect of intestinal disaccharidases. Results showed a high content of phenolic compounds and total flavonoids, thus characterizing antioxidant activity, also highlighting the best bacteriostatic action for the Gram positive strain of Staphylococcus aureus in the ethanolic fraction. Regarding the disaccharidases, a strong inhibitory action was observed for all concentrations, evidencing a antihyperglycemic potential. The present research allowed to concluded that Eugenia uniflora L. seeds have promising biological activities for the industrial sector, but a more detailed investigation is needed regarding their bioactive compounds.

Resumo A utilização de plantas com fins medicinais para prevenção, tratamento e cura de doenças é uma prática antiga utilizada pela humanidade, sendo que muitas espécies vegetais são usadas para a pesquisa da bioprospecção. Neste contexto, destaca-se a Eugenia uniflora L., conhecida popularmente como pitangueira e pertencente à família Myrtaceae, com ampla distribuição geográfica e nativa do Brasil. Diante das qualidades terapêuticas da planta e a falta de estudos sobre suas sementes, o presente trabalho teve como objetivo avaliar o perfil fitoquímico dos extratos das sementes de Eugenia uniflora L. a partir de diferentes solventes, bem como sua atividade antibacteriana, antioxidante e seu efeito inibidor de dissacaridases intestinais. Os resultados mostraram um alto teor de compostos fenólicos e flavonóides totais, caracterizando a atividade antioxidante, destacando também a melhor ação bacteriostática para a cepa Gram positiva de Staphylococcus aureus na fração etanólica. Em relação às dissacaridases, uma forte ação inibitória foi observada para todas as concentrações, evidenciando um potencial anti-hiperglicêmico. A presente pesquisa permitiu concluir que as sementes de Eugenia uniflora L. apresentam atividades biológicas promissoras para o setor industrial, mas é necessária uma investigação mais detalhada de seus compostos bioativos.

Antidiabetic and hypolipidemic potential of Campomanesia xanthocarpa seed extract obtained by supercritical CO2

Abstract Campomanesia xanthocarpa, a plant belonging to the Myrtaceae family, is popularly known as gabiroba. Leaves of gabiroba has been popularly used to treat various diseases, including inflammatory, renal, and digestive, among others. Additionally, studies have shown an effect to reduce blood cholesterol levels. The aim of this study was to evaluate the antihyperglycemic and hypolipidemic effects of Campomanesia xanthocarpa seed extract in hyperglycemic rats. The results showed that 400 mg/kg of seed extract was able to decrease blood glucose levels and to increase the muscular and hepatic glycogen content as well as to inhibit the sucrase and maltase activity. At doses of 200 mg/kg and 800 mg/kg, the activity of these enzymes was also reduced. In the lipid profile 400 mg/kg produced a decrease in total and LDL cholesterol serum levels; and with 200 mg/kg there was an increase in HDL cholesterol levels. The extract did not present hepatic and renal toxic effects at the different doses tested. The results suggest that the treatment with Campomanesia xanthocarpa seeds extract is useful in reducing glycemia, total cholesterol and LDL levels with potential adjuvant therapeutic in the treatment of diabetes and hypercholesterolemia, however, additional pharmacological and toxicological studies are still required.

Resumo Campomanesia xanthocarpa, planta pertencente à família Mirtaceae, é popularmente conhecida como gabiroba. Folhas da gabiroba são popularmente usadas para tratar de doenças inflamatórias, renais, digestivas entre outras. Além disso, estudos têm mostrado um efeito redutor dos níveis de colesterol. O objetivo deste estudo foi avaliar os efeitos anti-hiperglicêmico e hipolipidêmico do extrato de sementes de Campomanesia xanthocarpa em ratos hiperglicêmicos. Os resultados mostraram que 400 mg/kg do extrato da semente foi capaz de reduzir os níveis de glicose sanguínea e aumentar o conteúdo de glicogênio hepático e muscular, bem como inibir a atividade da maltase e sacarase. Na dose de 200 mg/kg e 800 mg/kg, a atividade das enzimas também foi reduzida. No perfil lipídico, 400 mg/kg produziu uma redução nos níveis séricos de colesterol total e LDL e com 200 mg/kg houve um aumento nos níveis de colesterol HDL. O extrato não apresentou efeitos tóxicos hepáticos e renais nas doses testadas. Os resultados sugerem que o tratamento com o extrato de Campomanesia xanthocarpa é eficaz na redução da glicemia, de colesterol total e LDL com potencial para tratamento adjuvante do diabetes e hipercolesterolemia, no entanto estudos farmacológicos e toxicológicos adicionais são necessários.

Could cytokine levels in the peri-implant crevicular fluid be used to distinguish between healthy implants and implants with peri-implantitis? A systematic review.

BACKGROUND AND OBJECTIVE: Despite investigative efforts to identify the levels of different types of cytokines in the peri-implant crevicular fluid (PICF), the efficacy of these biomarkers in assisting the diagnosis of peri-implantitis is still undetermined. This systematic review aimed to answer the following question: "Could cytokine levels in the PICF be used to distinguish between healthy implants and implants with peri-implantitis?" MATERIAL AND METHODS: This review was conducted and reported in accordance with the PRISMA statement. The MEDLINE and EMBASE databases were searched from 1990 up to and including March 2015, using MeSH terms and other keywords. Additional publications were searched using a hand search of reference lists of relevant studies. Titles and abstracts were screened and papers that fulfilled eligibility criteria were assessed. RESULTS: Out of 1212 titles, 18 studies reporting the levels of nine different cytokines were included. Proinflammatory cytokines [interleukin (IL)-1ß, IL-6, IL-12, IL-17 and tumor necrosis factor-α) were the cytokines studied most commonly, followed by anti-inflammatory cytokines (IL-4 and IL-10), osteoclastogenesis-related cytokines (RANKL) and chemokines (IL-8). Nine studies reported statistically significantly higher levels of proinflammatory cytokines in the PICF of implants with peri-implantitis than in the PICF of healthy implants. Most studies did not find any significant differences in the PICF levels of anti-inflammatory cytokines and RANKL between healthy implants and implants with peri-implantitis. IL-8 was the only chemokine studied and its levels did not differ significantly between healthy and diseased implants. The studies differed greatly in the manner in which they reported the results (e.g. concentrations or total amounts) and in the exclusion of confounders, such as smoking. CONCLUSION: The results of this systematic review indicate moderate evidence in the literature to support that implants with peri-implantitis present higher levels of proinflammatory cytokines in the PICF than do healthy implants. Evidence regarding the PICF levels of anti-inflammatory cytokines, osteoclastogenesis-related cytokines and chemokines as possible predictors of peri-implantitis is too limited.

Shorter myotomy on the gastric site (≤2.5 cm) provides adequate relief of dysphagia in achalasia patients.

The right length of the myotomy on the gastric side for esophageal achalasia is still a debated issue. We aimed to investigate the final outcome after classic myotomy (CM) as compared with a longer myotomy on the gastric side (LM) in two cohorts of achalasia patients. Forty-four achalasia patients who underwent laparoscopic Heller-Dor were considered; patients with a sigmoid-shaped esophagus were excluded. Symptoms were scored using a detailed questionnaire for dysphagia, regurgitation, and chest pain. Barium swallow, endoscopy, and esophageal manometry were performed before and 6 months after the surgical treatment; 24-hour pH-monitoring was also performed 6 months after the procedure. CM was defined as a gastric myotomy length in the range of 1.5-2.0 cm, while LM was 2.5-3 cm in length. The surgical treatment (CM or LM) was adopted in two consecutive cohorts. Treatment failure was defined as a postoperative symptom score >10th percentile of the preoperative score (i.e. >8). Of the 44 patients representing the study population, 20 had CM and 24 had LM. The patients' demographic and clinical parameters (age, sex, symptom score, duration of symptoms, esophageal diameter, and manometric pattern) were similar in the two groups. The median follow up was 24 months (interquartile range 12-39). One patient in each group was classified as a treatment failure. After the treatment, there was a significant decrease in both groups' symptom score, and resting and residual pressure (P < 0.01), with no statistically significant differences between the two groups in terms of postoperative symptom score, resting and residual pressure, or total and abdominal lower esophageal sphincter length and esophageal diameter. Extending the length of the myotomy on the gastric side does not seem to change the final outcome of the laparoscopic Heller-Dor procedure.

Autism and esophageal achalasia in childhood: a possible correlation? Report on three cases.

Chronic gastrointestinal symptoms are commonly reported in autistic patients. Dysphagia is often present, and it is generally related to behavioral eating disorders. The association between autism and esophageal achalasia has not been described in literature yet. We report our experience with three cases of autistic children we recently treated for esophageal achalasia. In the first case (a 14-year-old male), achalasia was diagnosed with barium swallow and esophageal manometry and was successfully treated with three pneumatic endoscopic dilatations (follow-up: 3 years). In the second case (a 12-year-old female), achalasia was diagnosed with barium swallow and esophageal manometry and was treated with Heller myotomy after two unsuccessful pneumatic endoscopic attempts (follow-up: 3 months). In the last case, a 15-year-old male underwent barium swallow and endoscopy that confirmed achalasia. He was treated with Heller myotomy, and he is asymptomatic at a 6-month follow-up. To our knowledge, this is the first report of a possible association between autism and esophageal achalasia. Because of the rarity of both diseases, their association in the same patient is unlikely to be casual even if speculation on their common etiology is impossible at present. This finding needs further confirmation, but it is sufficient, in our opinion, to indicate proper evaluation with barium swallow and/or manometry in any autistic children with eating difficulty.

Photo-elastic investigation of influence of dental implant shape and prosthetic materials to patterns of stress distribution.

AIM: Occlusal loading has to be considered a key factor influencing bone resorption due to the stress transmitted to surrounding tissues by the implant-abutment structure. The aim of this study was to evaluate, through a photo-elastic investigation, the patterns of tensions distribution of two different implant shapes, which were cylindrical and conical. METHODS: A 100N load was applied to two implant-abutment structures (with and without a metal-ceramic crown) incorporated in photo-elastic resin. Modification in light refraction were recorded and analyzed through a computerized software. Measurements of stripe extension and position were evaluated. RESULTS: Stress distribution around tapered implant was evaluated to be more uniform than in cylindrical one which demonstrated a high stress concentration at the more cervical region and in the apical region. The presence of a metal-ceramic crown caused an increase in tensions at the implant-resin interface. CONCLUSION: Conical implants distributed stresses to a larger and well-defined volume of resin and this can cause a decrease of forces acting at the interface. This could be due to the "wedge effect" of this fixture shape which could be considered superior in terms of stress distribution than cylindrical one.

Estrogen signaling in testicular cells.

Aromatase transforms irreversibly androgens into estrogens and is present in the endoplasmic reticulum of various tissues including the mammalian testis. In rat all testicular cells except peritubular cells express aromatase. Indeed in adult rat germ cells (pachytene spermatocytes and round spermatids) we have demonstrated the presence of a functional aromatase (transcript, protein and biological activity) and the estrogen output is equivalent to that of Leydig cells. In addition in the adult rat, transcripts of aromatase vary according to the germ cell type and to the stages of seminiferous epithelium. By contrast with the androgen receptors mainly localized in somatic cells, estrogen receptors (ERs) are described in most of the testicular cells including germ cells. Moreover, besides the presence of high affinity ERα and/or ERß, a rapid membrane effect has been recently reported and we demonstrated that GPR30 (a transmembrane intracellular estrogen receptor) is expressed in adult rat pachytene spermatocytes. Therefore estrogens through both GPR30 and ERα are able to activate the rapid EGFR/ERK/c-jun signaling cascade, which in turn triggers an apoptotic mitochondrial pathway involving an increase in Bax expression and a concomitant reduction of cyclin A1 and B1 gene levels. In another study in round spermatids of adult rat we have shown that the rapid membrane effect of estradiol is also efficient in controlling apoptosis and maturation / differentiation of these haploid germ cells. In man the presence of a biologically active aromatase and of estrogen receptors has been reported in Leydig cells, but also in immature germ cells and ejaculated spermatozoa. Thus the role of estrogen (intracrine, autocrine and / or paracrine) in spermatogenesis (proliferation, apoptosis, survival and maturation) and more generally, in male reproduction is now evidenced taking into account the simultaneous presence of a biologically active aromatase and the widespread distribution of estrogen receptors especially in haploid germ cells.

Age- and cell-related gene expression of aromatase and estrogen receptors in the rat testis.

Spermatogenesis is a complex and coordinated process leading to the formation of spermatozoa. This event, which is under the control of numerous endocrine and paracrine factors, seems to also be controlled by estrogens which exert their effects via nuclear estrogen receptors (ESRs) ESR1 and ESR2. Estrogens are synthesized by aromatase which is biologically expressed in the rat testis. The objective of our study was to clarify the gene expression patterns of aromatase and ESRs according to age and in the two compartments of the adult rat testis. In the adult, transcripts of aromatase vary according to the germ cell type and to the stages of seminiferous epithelium, a maximum being observed at stage I. The ESR1 gene is highly expressed in the adult testis and in stages from VIIc-d to XIV. Moreover, both ESR mRNA levels are higher in purified round spermatids than in pachytene spermatocytes, suggesting a putative role of estrogens in the haploid steps of spermatogenesis. The variability of the results in the expression of both ESRs led us to explore the putative presence of variants in the rat testis. Concerning ESR1, we have shown the presence of the full-length form and of one isoform with exon 4 deleted. For ESR2, besides the wild type, three isoforms were observed: one with exon 3 deleted, another with an insertion of 54 nucleotides, and the last one with both modifications. Therefore, the stage-regulated expression of aromatase and ESR1 genes in the rat testis suggests a likely role of estrogens in spermatogenesis.

Triagem laboratorial para a pesquisa de anticoagulante lúpico (AL) em pacientes atendidos no Hospital Universitário de Florianópolis, SC / Laboratory triage for lupic anticoagulant (LA) research in patients attended at Hospital Universitario de Florianopolis, SC

Os anticorpos anticoagulante lúpico (AL) são inibidores adquiridos que reagem contra fosfolípides in vitro, promovendo o prolongamento dos testes de coagulação fosfolípides dependentes. Clinicamente, as complicações tromboembólicas constituem se em manifestações comuns em pacientes portadores de anticorpos antifosfolípides. O presente trabalho teve por objetivo realizar a triagem laboratorial para a pesquisa do anticorpo anticoagulante lúpico em pacientes com trombofilia a esclarecer, atendidos no Hospital Universitário de Santa Catarina. Foram avaliados 238 pacientes do sexo masculino e feminino, de fevereiro abril de 2004. Am¨¦dia de idade foi de 48 anos (variando de 15 a 73 anos). O anticoagulante lúpico (AL) foi detectado por três testes de triagem (tempo de tromboplastina parcial ativada (TTPA), tempo de coagulação do kaolim (KCT) e do veneno de víbora de Russel diluído(dRVVT).A prevalência de AL foi de 7,6% (12 do sexo feminino e 6 do sexo masculino). Das 238 amostras, 15 foram positivas para o KCT, quando as amostras foram testadas para o dRVVT observou-se que 17 amostras apresentaram resultados positivos. No total, 13 amostras apresentaram-se positivas para ambos os testes. De acordo com os resultados, obtidos podemos sugerir que os pacientes estudados apresentam em sua maioria anticorpos direcionados contra a protrombina e/ou alfa2-glicoproteína I.

The lupic anticoagulant antibodies (LA) are acquired inhibitors which may react against phospholipids in vitro promoting the stretching of phospholipids-dependent coagulation tests Clinically, the tromboembolic complications are common manifestations in patients with anti-phospholipids antibodies. This work aims to develop a laboratory triage for the research of lupic anticoagulant antibodies in patients with non-clear cases of trombophilia attended at Hospital Universit¨¢rio de Santa Catarina. A total of 238 patients, males and females, were evaluated in the period comprehended between February and April, 2004. The average age of the patients was 48 years (ranging from 15 to 73 years). Lupic anticoagulant was detected by means of three triage tests (partial active tromboplastine time (KPTT), kaolin coagulation time (KCT) and Dilute Russell¡¯s Viper Venom time (dRVVT). The prevalence of LA was equal to 7.6 % (12 females and 6 males). Fifteen out of 238 samples were tested positive by KCT. The analysis of the samples by dRVVT resulted in 17 positive diagnosis. A total of 13 samples presented positive results in both tests. According to the results obtained, it can be suggested that the patients evaluated presented in the majority of cases anti-bodies directed against protrombine and/or alpha2-glycoprotein I.

Communicating quality of life information to cancer patients: a study of six presentation formats.

PURPOSE: To determine which formats for presenting health-related quality of life (HRQL) data are interpreted most accurately and are most preferred by cancer patients. Patients often want a great deal of information about cancer treatments, including information relevant to HRQL. Clinical trials provide methodologically sound HRQL data that may be useful to patients. PATIENTS AND METHODS: In a multicenter study, 198 patients with previously treated cancer participated in a structured interview. Participants judged HRQL information presented in one textual and five graphical formats. Outcome measures included the accuracy of patients' interpretations and ease-of-use and helpfulness ratings for each format. RESULTS: Correct interpretations ranged from 85% to 98% across formats (F = 10.3, P < .0001) with line graphs of mean HRQL scores over time being interpreted correctly most often. Older patients and less-educated patients were less likely to interpret graphs accurately (F = 7.3, P = .008; and F = 10.6, P = .001, respectively), but all groups were most accurate on simple line graphs. Multivariate analysis revealed that format type, participant age and education were independent predictors of accuracy rates. Patients' ratings also varied across formats both for ease of understanding scores (F = 12.1, P < .0001) and for helpfulness scores (F = 13.2, P < .0001), with line graphs being rated highest on both outcomes. CONCLUSION: Patients generally prefer a simple linear representation of group mean HRQL scores, and can accurately interpret data presented in this format more than 98% of the time irrespective of their age group and educational level. The findings have important implications for the communication of clinical trial HRQL results.

Cancer patients' preferences for communicating clinical trial quality of life information: a qualitative study.

Health-related quality of life (HRQL) is a prevalent outcome measure in clinical trials, but it is not known how best to communicate HRQL results to new patients with cancer. The purpose was to explore cancer patients' attitudes toward, and preferences for, 10 visual and written formats for communicating HRQL information. Using standardized qualitative methods, six focus groups were held (two groups in each of three cancer centres) with patients who had completed treatment for cancer at least 6 months earlier. Groups were stratified according to patients' education. To ensure consistency across centres, group moderators used the same detailed guide, training video, and props. Three investigators independently coded the resulting transcripts. Participants also rated each of the 10 presentation formats as to their perceived usefulness. Fourteen men and 19 women with a variety of cancer diagnoses participated; 13 (39%) participated in the three lower-education groups and 20 (61%) in the three higher-education groups. We found that simple formats (simple graphs or written text) were generally preferred to more complex graphical information, regardless of educational level. The same format was rated favourably by the highest proportion of participants in both the high (85%) and low (85%) education level groups. Individual patients, however, varied as to which visual format they most preferred. Patients did not wish to receive HRQL information out of context or without explanation. We conclude that cancer patients desire HRQL information, but vary in their preferences for its communication. Simple formats are generally preferred.

In vivo and in vitro effect of imipramine and fluoxetine on Na+,K+-ATPase activity in synaptic plasma membranes from the cerebral cortex of rats.

The effects of in vivo chronic treatment and in vitro addition of imipramine, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake inhibitor, on the cortical membrane-bound Na+,K+-ATPase activity were studied. Adult Wistar rats received daily intraperitoneal injections of 10 mg/kg of imipramine or fluoxetine for 14 days. Twelve hours after the last injection rats were decapitated and synaptic plasma membranes (SPM) from cerebral cortex were prepared to determine Na+,K+-ATPase activity. There was a significant decrease (10%) in enzyme activity after imipramine but fluoxetine treatment caused a significant increase (27%) in Na+,K+-ATPase activity compared to control (P<0.05, ANOVA; N = 7 for each group). When assayed in vitro, the addition of both drugs to SPM of naive rats caused a dose-dependent decrease in enzyme activity, with the maximal inhibition (60-80%) occurring at 0.5 mM. We suggest that a) imipramine might decrease Na+,K+-ATPase activity by altering membrane fluidity, as previously proposed, and b) stimulation of this enzyme might contribute to the therapeutic efficacy of fluoxetine, since brain Na+,K+-ATPase activity is decreased in bipolar patients.

In vivo and in vitro effect of imipramine and fluoxetine on Na+, K+-ATPase activity in synaptic plasma membranes from the cerebral cortex of rats

The effects of in vivo chronic treatment and in vitro addition of imipramine, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake inhibitor, on the cortical membrane-bound Na+,K+-ATPase activity were studied. Adult Wistar rats received daily intraperitoneal injections of 10 mg/kg of imipramine or fluoxetine for 14 days. Twelve hours after the last injection rats were decapitated and synaptic plasma membranes (SPM) from cerebral cortex were prepared to determine Na+,K+-ATPase activity. There was a significant decrease (10 percent) in enzyme activity after imipramine but fluoxetine treatment caused a significant increase (27 percent) in Na+,K+-ATPase activity compared to control (P<0.05, ANOVA; N = 7 for each group). When assayed in vitro, the addition of both drugs to SPM of naive rats caused a dose-dependent decrease in enzyme activity, with the maximal inhibition (60-80 percent) occurring at 0.5 mM. We suggest that a) imipramine might decrease Na+,K+-ATPase activity by altering membrane fluidity, as previously proposed, and b) stimulation of this enzyme might contribute to the therapeutic efficacy of fluoxetine, since brain Na+,K+-ATPase activity is decreased in bipolar patients

Differences of ropivacaine and bupivacaine relevant to antiinflammatory activity, platelet aggregation and antioxidant activity in vitro.

Ropivacaine and bupivacaine affect the in vitro growth of rat fibroblasts and monkey kidney Vero cells with bupivacaine generally showing the stronger effect. Up to 3 mM concentration the two anesthetics affect the expression of genes differently for CD2, CD3 gamma, CD40L, IL-2, IL-2R alpha, IL-2R beta, IL-2R gamma, IL-4, and IL-4R during activation of human lymphocytes, with bupivacaine showing the higher effect. Human platelet aggregation is inhibited by the two anesthetics which also show an antioxidant effect on lipid peroxidation of rat liver microsomes. In both cases bupivacaine seems more active than ropivacaine.

Enzymatic dopamine peroxidation in substantia nigra of human brain.

The main metabolic pathway affected in Parkinson's disease is that of dopamine oxidation and melanin formation in substantia nigra which involves both oxidative and reductive enzymes. The cyclic nature of the biosynthetic pathway from dopamine to melanin implies that a derangement at any of the steps may result in the disappearance of melanin. Possible pathogenetic events such as oxidative stress have therefore no clearcut interpretation since they may be both cause or consequence of the disease. This paper documents the existence of a peroxidase converting dopamine to dopaminochrome in the presence of hydrogen peroxide in the substantia nigra of autopsied human brain. The activatory effect of dopaminochrome on a purified peroxidase is shown, together with the inhibitory effect of dopaminochrome-derived melanin and the activatory effect of melanin/Fe. The toxic effect of dopaminochrome on murine neuroblastoma cells cultured in vitro is demonstrated together with the inhibition of dopaminochrome melanization induced by acetylcholine in vitro.

Toxicity of dopamine and dopaminochrome on cultured cells.

Cultured rat fibroblasts, monkey kidney tumor cells (line Vero) and murine neuroblastoma cells were exposed to dopamine or dopaminochrome in the presence and absence of ascorbic acid. Ascorbic acid is able to potentiate the toxicity of both dopamine and dopaminochrome for all the tested cells. The toxicity of dopaminochrome was higher than that of dopamine. There is a correlation between toxicity and levels of bioreductive defenses of the cells, e.g. DT-diaphorase (NAD(P)H:quinone oxidoreductase EC 1.6.99.2) and glutathione. In general, tumor cells have lower defenses and seem to be more sensitive to the toxic action.