Real-World Evidence of Ribociclib Plus Aromatase Inhibitors as First-Line Treatment in Advanced Breast Cancer: The BrasiLEEira Study.

PURPOSE: Cyclin inhibitors plus endocrine therapy represent the reference standard for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer (ABC). Efficacy results on hard end points such as overall survival come from well-designed randomized clinical trials (RCTs). However, a limitation of RCTs is the low external results validity, and their extrapolation to a broader population may not be appropriate. Real-world studies can overcome these limitations, also increasing the reliability of RCTs. MATERIALS AND METHODS: The BrasiLEEira was an observational, longitudinal, retrospective, multicenter study to evaluate the effectiveness and safety of ribociclib plus nonsteroidal aromatase inhibitors in Brazilian women age 18 years or older with HR+/HER2- ABC. The study was approved by the institutional review boards of all 11 hospitals. Data were collected anonymously from medical records using an electronic case report form designed by an independent academic research organization, which conducted the study considering all recommendations of international guidelines. The primary end point was 1-year progression-free survival (PFS) rate. Secondary end points included mortality, dose reduction, and safety. RESULTS: The mean age of 76 patients was 57 years, and 28.9% were Black/Brown. The most prevalent comorbidity was arterial hypertension (34.7%). About 26.0% had endocrine-resistant disease, and 54.1% had more than three metastatic sites. The PFS rate was 77.6%. Three patients died (3.9%). Dose reductions occurred in 37.7% of patients. The most common adverse event was neutropenia (68.4%). CONCLUSION: The high-quality evidence from the BrasiLEEira study corroborates the RCTs' findings, expanding its validity to a broader spectrum and underrepresented population who may benefit from ribociclib treatment.

Alpha 1-acid glycoprotein is upregulated in severe COVID-19 patients and decreases neutrophil NETs in SARS-CoV-2 infection.

Orosomucoid, or alpha-1 acid glycoprotein (AGP), is a major acute-phase protein expressed in response to systemic injury and inflammation. AGP has been described as an inhibitor of neutrophil migration on sepsis, particularly its immunomodulation effects. AGP's biological functions in coronavirus disease 2019 (COVID-19) are not understood. We sought to investigate the role of AGP in severe COVID-19 infection patients and neutrophils infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Epidemiological data, AGP levels, and other laboratory parameters were measured in blood samples from 56 subjects hospitalized in the ICU with SARS-CoV-2 infection. To evaluate the role of AGP in NETosis in neutrophils, blood samples from health patients were collected, and neutrophils were separated and infected with SARS-CoV-2. Those neutrophils were treated with AGP or vehicle, and NETosis was analyzed by flow cytometry. AGP was upregulated in severe COVID-19 patients (p<0.05). AGP level was positively correlated with IL-6 and C-reactive protein (respectively, p=0.005, p=0.002) and negatively correlated with lactate (p=0.004). AGP treatment downregulated early and late NETosis (respectively, 35.7% and 43.5%) in neutrophils infected with SARS-CoV-2 and up-regulated IL-6 supernatant culture expression (p<0.0001). Our data showed increased AGP in COVID-19 infection and contributed to NETosis regulation and increased IL-6 production, possibly related to the Cytokine storm in COVID-19.

Cytokine storm in individuals with severe COVID-19 decreases endothelial cell antioxidant defense via downregulation of the Nrf2 transcriptional factor.

The cytokine storm in SARS-CoV-2 infection contributes to the onset of inflammation and target-organ damage. The endothelium is a key player in COVID-19 pathophysiology and it is an important target for cytokines. Considering that cytokines trigger oxidative stress and negatively impact endothelial cell function, we sought to determine whether serum from individuals with severe COVID-19 decreases endothelial cells' main antioxidant defense, i.e., the antioxidant transcriptional factor Nrf2. Human umbilical vein endothelial cells (HUVECs) were incubated with serum from patients with severe COVID-19 at different time points and the effects on redox balance and Nrf2 activity were determined. Serum from individuals with COVID-19 increased oxidant species, as indicated by higher DHE (dihydroethydine) oxidation, increased protein carbonylation, and induced mitochondrial reactive oxygen species (ROS) generation and dysfunction. Serum from patients with COVID-19, but not serum from healthy individuals, induced cell death and diminished nitric oxide (NO) bioavailability. In parallel, Nrf2 nuclear accumulation and the expression of Nrf2-targeted genes were decreased in endothelial cells exposed to serum from individuals with COVID-19. In addition, these cells exhibited higher expression of Bach-1, a negative regulator of Nrf2 that competes for DNA binding. All events were prevented by tocilizumab, an IL-6 receptor blocker, indicating that IL-6 is key to the impairment of endothelial antioxidant defense. In conclusion, endothelial dysfunction related to SARS-CoV-2 infection is linked to decreased endothelial antioxidant defense via IL-6-dependent mechanisms. Pharmacological activation of Nrf2 may decrease endothelial cell damage in individuals with severe COVID-19.NEW & NOTEWORTHY We demonstrate that endothelial cell dysfunction in SARS-CoV-2-infected individuals is linked to decreased activity of the major antioxidant system regulator, the Nrf2 transcription factor. We provide evidence that this phenomenon relies on IL-6, an important cytokine involved in the pathophysiology of COVID-19. Our data support the view that Nrf2 activation is a potential therapeutical strategy to prevent oxidative stress and vascular inflammation in severe cases of COVID-19.

Inhibition of IL-6 signaling prevents serum-induced umbilical cord artery dysfunction from patients with severe COVID-19.

Coronavirus disease 2019 (COVID-19) infection has a negative impact on the cytokine profile of pregnant women. Increased levels of proinflammatory cytokines seem to be correlated with the severity of the disease, in addition to predisposing to miscarriage or premature birth. Proinflammatory cytokines increase the generation of reactive oxygen species (ROS). It is unclear how interleukin-6 (IL-6) found in the circulation of patients with severe COVID-19 might affect gestational health, particularly concerning umbilical cord function. This study tested the hypothesis that IL-6 present in the circulation of women with severe COVID-19 causes umbilical cord artery dysfunction by increasing ROS generation and activating redox-sensitive proteins. Umbilical cord arteries were incubated with serum from healthy women and women with severe COVID-19. Vascular function was assessed using concentration-effect curves to serotonin in the presence or absence of pharmacological agents, such as tocilizumab (antibody against the IL-6 receptor), tiron (ROS scavenger), ML171 (Nox1 inhibitor), and Y27632 (Rho kinase inhibitor). ROS generation was assessed by the dihydroethidine probe and Rho kinase activity by an enzymatic assay. Umbilical arteries exposed to serum from women with severe COVID-19 were hyperreactive to serotonin. This effect was abolished in the presence of tocilizumab, tiron, ML171, and Y27632. In addition, serum from women with severe COVID-19 increased Nox1-dependent ROS generation and Rho kinase activity. Increased Rho kinase activity was abolished by tocilizumab and tiron. Serum cytokines in women with severe COVID-19 promote umbilical artery dysfunction. IL-6 is key to Nox-linked vascular oxidative stress and activation of the Rho kinase pathway.

Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients.

In the present study, the levels of serum and airway soluble chemokines, pro-inflammatory/regulatory cytokines, and growth factors were quantified in critically ill COVID-19 patients (total n=286) at distinct time points (D0, D2-6, D7, D8-13 and D>14-36) upon Intensive Care Unit (ICU) admission. Augmented levels of soluble mediators were observed in serum from COVID-19 patients who progress to death. An opposite profile was observed in tracheal aspirate samples, indicating that systemic and airway microenvironment diverge in their inflammatory milieu. While a bimodal distribution was observed in the serum samples, a unimodal peak around D7 was found for most soluble mediators in tracheal aspirate samples. Systems biology tools further demonstrated that COVID-19 display distinct eccentric soluble mediator networks as compared to controls, with opposite profiles in serum and tracheal aspirates. Regardless the systemic-compartmentalized microenvironment, networks from patients progressing to death were linked to a pro-inflammatory/growth factor-rich, highly integrated center. Conversely, patients evolving to discharge exhibited networks of weak central architecture, with lower number of neighborhood connections and clusters of pro-inflammatory and regulatory cytokines. All in all, this investigation with robust sample size landed a comprehensive snapshot of the systemic and local divergencies composed of distinct immune responses driven by SARS-CoV-2 early on severe COVID-19.

MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients.

Respiratory symptoms are one of COVID-19 manifestations, and the metalloproteinases (MMPs) have essential roles in the lung physiology. We sought to characterize the plasmatic levels of matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9) in patients with severe COVID-19 and to investigate an association between plasma MMP-2 and MMP-9 levels and clinical outcomes and mortality. MMP-2 and MMP-9 levels in plasma from patients with COVID-19 treated in the ICU (COVID-19 group) and Control patients were measured with the zymography. The study groups were matched for age, sex, hypertension, diabetes, BMI, and obesity profile. MMP-2 levels were lower and MMP-9 levels were higher in a COVID-19 group (p < 0.0001) compared to Controls. MMP-9 levels in COVID-19 patients were not affected by comorbidity such as hypertension or obesity. MMP-2 levels were affected by hypertension (p < 0.05), but unaffected by obesity status. Notably, hypertensive COVID-19 patients had higher MMP-2 levels compared to the non-hypertensive COVID-19 group, albeit still lower than Controls (p < 0.05). No association between MMP-2 and MMP-9 plasmatic levels and corticosteroid treatment or acute kidney injury was found in COVID-19 patients. The survival analysis showed that COVID-19 mortality was associated with increased MMP-2 and MMP-9 levels. Age, hypertension, BMI, and MMP-2 and MMP-9 were better predictors of mortality during hospitalization than SAPS3 and SOFA scores at hospital admission. In conclusion, a significant association between MMP-2 and MMP-9 levels and COVID-19 was found. Notably, MMP-2 and MMP-9 levels predicted the risk of in-hospital death suggesting possible pathophysiologic and prognostic roles.

Potentially hazardous waste produced at home.

BACKGROUND: The purpose of this study was to identify the sources of waste generation household consisting of biological material and to investigate the knowledge presented by those responsible for the generation of waste in the home environment on the potential health risk human and environmental. METHOD: It is a quantitative survey performed in Parque Capuava, Santo André (SP). The questionnaire was administered by the community employers and nursing students during the consultation with nursing supervision through interview question/answer. The exclusion criteria were patients who were not in the area served by the Basic Health Unit which covers the area of Pq Capuava. The sample was consisted of 99 persons and the data collection a questionnaire was used. RESULTS: We observed that 63.3% of people said to use disposables, with the majority (58.7%) of these use the public collection as the final destination of these materials. It was reported that 73.7% of those surveyed reported having knowledge about the risk of disease transmission. Public awareness of the importance of proper packaging and disposal of potentially hazardous household waste may contribute significantly to the preservation of human and environmental health and this procedure can be performed and supervised by professional nurses. CONCLUSION: We suggest implementation of workshops for community health workers and the general population in order to enhance their knowledge about the storage and disposal of potentially infectious waste generated at home, thereby reducing the potential risk of disease transmission by improper management.

Quality of essential drugs in tropical countries: evaluation of antimalarial drugs in the Brazilian Health System.

INTRODUCTION: The emergence of drug resistance is one of the main problems concerning malaria treatment. The use of counterfeit and/or substandard antimalarial drugs can contribute to the development of parasite resistance. Thus, the aim of this study was to evaluate the quality of antimalarial drugs distributed in Brazil. METHODS: Samples containing chloroquine phosphate, mefloquine hydrochloride, primaquine phosphate, and quinine sulfate tablets were delivered to the Rio de Janeiro central storeroom (CENADI), state storerooms (SS), and Basic Health Units (BHUs) in the north region of Brazil - a total of 10 sample sets. After 5 months of storage, the samples were collected, and in vitro quality control analyses according to official and published methods were performed. RESULTS: Inadequate drug storage conditions were found in two SS and in all BHUs evaluated. There were no quality deviations found in the chloroquine samples. The quinine samples exhibited weight variation above the allowed limits. The primaquine samples were found to have packaging deficiency. The release of mefloquine in samples from some regions showed a statistically significant difference when compared with the CENADI samples. CONCLUSIONS: It is important to periodically evaluate the quality and storage conditions of essential drugs. The quality deviations found with the primaquine and quinine samples are not related to storage conditions and must be addressed urgently. The decreased mefloquine release from tablets is related to formulation problems or influenced by inadequate storage conditions, prompting further investigation. Even with the mentioned problems, the samples would probably not contribute to resistant parasite selection.

Quality of essential drugs in tropical countries: evaluation of antimalarial drugs in the Brazilian Health System / Qualidade de medicamentos essenciais em países tropicais: avaliação de medicamentos antimaláricos no Sistema de Saúde do Brasil

INTRODUCTION: The emergence of drug resistance is one of the main problems concerning malaria treatment. The use of counterfeit and/or substandard antimalarial drugs can contribute to the development of parasite resistance. Thus, the aim of this study was to evaluate the quality of antimalarial drugs distributed in Brazil. METHODS: Samples containing chloroquine phosphate, mefloquine hydrochloride, primaquine phosphate, and quinine sulfate tablets were delivered to the Rio de Janeiro central storeroom (CENADI), state storerooms (SS), and Basic Health Units (BHUs) in the north region of Brazil - a total of 10 sample sets. After 5 months of storage, the samples were collected, and in vitro quality control analyses according to official and published methods were performed. RESULTS: Inadequate drug storage conditions were found in two SS and in all BHUs evaluated. There were no quality deviations found in the chloroquine samples. The quinine samples exhibited weight variation above the allowed limits. The primaquine samples were found to have packaging deficiency. The release of mefloquine in samples from some regions showed a statistically significant difference when compared with the CENADI samples. CONCLUSIONS: It is important to periodically evaluate the quality and storage conditions of essential drugs. The quality deviations found with the primaquine and quinine samples are not related to storage conditions and must be addressed urgently. The decreased mefloquine release from tablets is related to formulation problems or influenced by inadequate storage conditions, prompting further investigation. Even with the mentioned problems, the samples would probably not contribute to resistant parasite selection.

INTRODUÇÃO: O aparecimento de resistência aos medicamentos é um dos maiores problemas do tratamento da malária. O uso de medicamentos falsos e/ou de má qualidade pode contribuir para o desenvolvimento de resistência no parasita. Este estudo tem por objetivo avaliar a qualidade dos medicamentos antimaláricos distribuídos no Brasil. MÉTODOS: Amostras contendo comprimidos de difosfato de cloroquina, cloridrato de mefloquina, difosfato de primaquina e sulfato de quinina foram enviadas ao almoxarifado central na Cidade do Rio de Janeiro (CENADI), almoxarifados estaduais (SS) e Unidades Básicas de Saúde (UBS) nos estados da região norte do Brasil, totalizando dez amostras. Após cinco meses de armazenamento, as amostras foram coletadas e analisadas segundo métodos oficiais e da literatura. RESULTADOS: Foram encontradas condições inadequadas de armazenamento de medicamentos em duas SS e em todas as UBS avaliadas. Não foram encontrados problemas de qualidade com as amostras de cloroquina. As amostras de quinina apresentaram variação de peso acima dos limites permitidos. Amostras de primaquina foram encontradas com problemas na embalagem. A cedência de mefloquina de comprimidos, em algumas regiões, apresentou diferença estatisticamente significativa quando comparada com a amostra do CENADI. CONCLUSÕES: É importante avaliar, periodicamente, a qualidade e as condições de armazenamento de medicamentos essenciais. Desvios de qualidade encontrados com as amostras de primaquina e quinina não estão relacionados às condições de armazenamento e devem ser corrigidos urgentemente. O decréscimo na cedência de mefloquina dos comprimidos está relacionado com a formulação ou foi influenciada por condições de armazenamento inadequadas, necessitando de uma investigação posterior. Apesar dos problemas mencionados, as amostras provavelmente não contribuiriam para a seleção de parasitas resistentes.

Development and validation of an HPLC method for mefloquine hydrochloride determination in tablet dosage form.

A simple HPLC method for determination of mefloquine hydrochloride in tablets was developed and validated. The separation was carried out on an Xterra RP18 (250 x 4.6 mm id, 5 pm particle size) analytical column. The mobile phase was 0.05 M monobasic potassium phosphate buffer (pH 3.5)-methanol (40 + 60, v/v). The flow rate and wavelength were set to 1 mL/min and 283 nm, respectively. The method was specific for mefloquine hydrochloride in the presence of hydrolytic, oxidative, and photolytic degradation products. It was also linear, precise, accurate, and robust, being suitable for routine QC analyses and stability studies. The developed HPLC method was compared to a previously described spectrophotometric method.

Avaliação da enurese noturna em crianças com distúrbios respiratórios obstrutivos (DRO) durante o sono, antes e após adenotonsilectomia / Nocturnal enuresis in children with obstructive breathing disorders during sleep, before and after adenotonsilectomy

Introdução: Distúrbios respiratórios obstrutivos (DRO) são frequentes em crianças e têm como sua principal causa a hipertrofia das tonsilas. A enurese noturna tem sido associada aos DRO, causando assim importante impacto psicossocial. Objetivo: Avaliar a associação entre enurese e DRO em crianças e sua possível melhora após adenoidectomia e/ou tonsilectomia. Métodos: Foram estudadas 138 crianças do Ambulatório de Distúrbios do Sono, com idade entre 5 e 12 anos, com indicação de adeno e/ou tonsilectomia por DRO. Foram analisadas variáveis como: sexo, idade e presença de enurese. As crianças foram reavaliadas três a seis meses após o tratamento cirúrgico. Resultado: Dentre as 138 crianças, 31 (22,5%) apresentavam enurese noturna. Houve predomínio na faixa etária de cinco a sete anos, com distribuição igual entre os gêneros. Houve melhora da enurese em 21 (67,7%) dos pacientes após o procedimento cirúrgico, em sete (70%) das dez crianças nas quais persistiu a enurese, também houve persistência dos roncos. Conclusão: A enurese noturna é frequente em crianças com DRO e pode ter melhora após tratamento da causa da obstrução respiratória, sugerindo interação entre SAOS e enurese noturna.

Comparison of the estrogenic potencies of standardized soy extracts by immature rat uterotrophic bioassay.

Soy phytoestrogens, isoflavones, are a primary class of plant-based estrogen alternatives being sold over the counter nowadays. Genistein, daidzein and glycitein are the major isoflavones found in soybeans, as aglycones and glycosides. Each isoflavone shows distinctive estrogenic activity and pharmacokinetics. Soy dry extracts, employed as pharmaceutical raw material for manufacturing isoflavone supplements, are standardized to contain 40% of total isoflavones, but the amount of each isoflavone is highly diverse. The influence of these compositional differences on the estrogenic potency of soy extracts was evaluated by uterotrophic bioassay. Five commercial samples of standardized soy dry extract, homogeneously suspended in arachis oil, were administered per os in serial doses (125-4150 mg/kg bw/day) to immature female rats for 3 days. Soy extract samples with considerable diversity in isoflavone composition revealed different estrogenic potencies. Our results indicate a need of standardization of the individual isoflavone content in soy extracts.

Determinação de daidzeína, genisteína e gliciteína em cápsulas de isoflavonas por cromatografia em camada delgada (CCD) e cromatografia líquida de alta eficiência (CLAE) / Determination of daidzein, genistein and glycitein in isoflavone capsules by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC)

A utilização de produtos naturais e suplementos contendo extratos secos de isoflavonas aumentou na última década, devido, principalmente, aos efeitos benéficos atribuídos a estes compostos no alívio dos sintomas da menopausa. Genisteína, daidzeína e gliciteína são as agliconas mais abundantes nos extratos de soja, ocorrendo também como glicosídeos. Tendo em vista seus usos, não existe ainda na literatura uma definição da quantidade mínima de cada uma das agliconas que os extratos ou cápsulas de isoflavonas devem ter, e também não existe um método oficial para o controle de qualidade dos mesmos. O presente trabalho apresenta um método por CCD para análise qualitativa das três agliconas e de seus glicosídeos em extratos e cápsulas de isoflavonas, antes e após hidrólise ácida. A análise quantitativa das cápsulas de isoflavonas, realizada por cromatografia líquida de alta eficiência (CLAE), revelou grandes variações nos teores das três agliconas, após hidrólise ácida. Os teores variaram da seguinte forma, nos 18 lotes de cápsulas avaliados: daidzeína (13,34 a 76,20 mg/cápsula), genisteína (0,61 a 27,18 mg/cápsula) e gliciteína (0,49 a 8,80 mg/cápsula).

The use of herbal products and supplements based on isoflavone dry extracts has increased considerably in the last decade, mainly due to beneficial effects to relief of the menopausal symptoms credited to those compounds. Genistein, daidzein and glycitein are the most abundant isoflavone aglycones found in soy extract, where they also occur as glycosides. Concerning their uses, there is neither standardization regarding the minimum content of each aglycone in the extracts or capsules, nor an official method to the quality control of these products. The present work presents a TLC method for qualitative analysis of the three aglycones and their glycosides in extracts and capsules of isoflavones, before and after acid hydrolysis. The quantitative analysis of the isoflavone capsules, carried out by high performance liquid chromatography (HPLC), showed high variation in the content of the three aglycones, after acid hydrolysis. The contents varied in the following way, in the 18 batches of evaluated capsules: daidzein (13.34 to 76.20 mg/capsule), genistein (0.61 to 27.18 mg/capsule) and glycitein (0.49 to 8.80 mg/capsule).

Teste de dissolução para avaliação de liberação de glibenclamida em comprimidos / Glibenclamide dissolution test for drug release evaluation in tablets

A glibenclamida (GLIB) ou gliburida, é um hipoglicemiante oral de segunda geração, da classe das sulfoniluréias, usado sob a forma de comprimidos para tratamento do diabetes mellitus. Variações no tratamento podem ocorrer, devido à baixa solubilidade do fármaco em comprimidos. A comparação de várias formulações de comprimidos piloto com comprimidos do medicamento referência (Daonil®, glibenclamida 5 mg comprimidos, Aventis Pharma Ltda.) foi avaliada por meio do desenvolvimento de um teste de dissolução sem adição de solventes orgânicos ou tensoativos no meio, que mostrou ser discriminativo para as diferentes formulações farmacêuticas propostas. A quantificação de GLIB foi realizada por meio de cromatografia líquida de alta eficiência em fase reversa (CLAE-FR), método previamente validado. A partir de vários ensaios de perfil de dissolução testados comparativamente àquele de comprimidos do medicamento referência, verificou-se o potencial de determinada formulação proposta (f1 4,04 and f2 69,35) como candidata a medicamento genérico no mercado brasileiro.

Glibenclamide (GLIB) or glyburide, a second-generation hypoglycemic agent is used per oral as tablets for the treatment of diabetes mellitus. Much variabilility in the treatment may occur because of the low drug aqueous solubility in tablets dosage forms. This work reports the comparison of several pilot formulation batches with the commercial reference drug dosage form (Daonil®, glibenclamide 5 mg per tablet, Aventis Pharma Ltda.). A feasible dissolution test, developed with no use of organic solvents or surfactants in the medium, showed to be discriminative regarding to different formulations tested. GLIB quantitation was performed by a previously validated reverse-phase high performance liquid chromatography (RP-HPLC). Among several dissolution profiles compared with that of a commercial reference, a potential for a generic candidate was evident (f1 4.04 and f2 69.35) for a proposed solid dosage formulation in the Brazilian market.

Efavirenz related compounds preparation by hydrolysis procedure: setting reference standards for chromatographic purity analysis.

A simple procedure for obtaining and purifying two degradation products of efavirenz (amino alcohol and quinoline derivatives) from drug substance hydrolysis is described. These impurities are known to exhibit very different UV absorbance properties from those of the parent compound, making determination using a quantitation factor (QF) inaccurate. The obtained hydrolysis products were characterized by physicochemical methods to assure identity, purity and strength. Quinoline derivative was of high purity degree (100%) and amino alcohol was 98.74% pure. Both were set as reference standards in chromatographic related compounds test for efavirenz drug substance and tablets analyses.

Etiology and incidence facial fractures in children and adults.

UNLABELLED: Facial trauma has presented an increasing occurrence in the last four decades, due especially to the growth of accidents with automobiles as well as to the urban violence. Both of which continue being the main cause of such traumas. AIM: To evaluate the features of the population victim of facial trauma as to gender, age, occupation, origin, type of fracture and its cause. DESIGN STUDY: retrospective clinical with transversal cohort. MATERIAL AND METHOD: Retrospective study consulting hospital registers of 513 patients victims of the facial trauma. RESULTS: There was a higher incidence of facial trauma on men (84,9%), white (82,7) and with an average age of 29. Regarding occupation, the trauma was mostly occurred to students (16,6%) and Masons (11,2%). The jaw was the most affected place (35%), followed by zygoma (24%) and by the nose (23%), though most patients presented a single facial fracture (82,5%). Among the causes, accidents with automobiles (28,3%), aggression (21%) and accidental fall s (19,5%) were the most common. CONCLUSIONS: Accidents with automobiles continue being the main cause of facial trauma, especially of multiple fractures due to the great transmission of kinetic energy.

Dissolution test for lamivudine tablets: optimization and statistical analysis.

A comparison of different methods for dissolution test used by five different manufacturer laboratories of lamivudine tablets is made, evaluated, and discussed. Dissolution medium (water and hydrochloric acid pH 1.2), apparatus (paddles and baskets) and time (30 and 60 min) were analyzed. The determination was accomplished by spectrophotometry at 270 nm. Analysis of variance (ANOVA) factorial design 5 x 2 x 2 x 2 with six repetitions, with post hoc multiple comparisons between means conducted by Duncan test at 0.05 significance level was used. After the comparative analysis of the results, optimal dissolution conditions were determined as follows: water as dissolution medium, paddles at the stirring speed of 50 rpm as apparatus and time of 30 min. The method was applied to the dissolution test of samples from eleven batches of tablets, produced by five different laboratories.

Development and validation of a RP-HPLC method for quantification of isoflavone aglycones in hydrolyzed soy dry extracts.

Isoflavones are widely used as an alternative treatment to hormone replacement therapy and also for prevention of several chronic diseases, including cancers. Genistein, daidzein and glycitein are the most abundant isoflavone aglycones found in soy extracts, where they also occur as glycosides. This paper describes the development and validation of an isocratic reversed-phase HPLC (RP-HPLC) method for the analysis of isoflavone aglycones, released after acid hydrolysis of soy dry extracts, used as pharmaceutical raw material. The quantification was carried out in a C(18) endcapped column, using a mobile phase composed of 0.1% acetic acid and methanol (52:48), at a flow rate of 1.0 ml/min and diode array detection (DAD) at 254 nm. The method showed to be linear (r(2)>0.99), precise (R.S.D.<2%), accurate (recovery of 98.88% for daidzein and 98.12% for genistein), robust and specific.