Neurological manifestation of Brazilian spotted fever in childhood.

Rocky Mountain Spotted Fever is a rickettsial disease caused by the bacteria Rickettsia rickettsii. In Brazil, the disease is known as Brazilian spotted fever (BSF), being the most significant tick-borne disease in the country. Among the affected patients, only 5% of cases occur in children aged one to nine years. Typical symptoms of the disease are fever, rash, headache and digestive symptoms. Neurological manifestations such as seizures, aphasia and hemiparesis have been described in few patients. This study aimed to describe the case of an infant diagnosed with BSF who presented severe signs of neurological manifestation.

Neurological manifestation of Brazilian spotted fever in childhood

ABSTRACT Rocky Mountain Spotted Fever is a rickettsial disease caused by the bacteria Rickettsia rickettsii. In Brazil, the disease is known as Brazilian spotted fever (BSF), being the most significant tick-borne disease in the country. Among the affected patients, only 5% of cases occur in children aged one to nine years. Typical symptoms of the disease are fever, rash, headache and digestive symptoms. Neurological manifestations such as seizures, aphasia and hemiparesis have been described in few patients. This study aimed to describe the case of an infant diagnosed with BSF who presented severe signs of neurological manifestation.

Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming Pseudomonas aeruginosa lung infection on ciprofloxacin free pulmonary and epithelial lining fluid concentrations.

We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0-24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection.

Neuro-COVID-19 With or Without the Multisystem Inflammatory Syndrome (MIS-C): A Single-Center Study : COVID-19: Neurologic Manifestations in Children.

This study evaluates the range of neurological manifestation in children with COVID-19 (neuro-COVID-19) both with and without the multisystem inflammatory syndrome (MIS-C) and the persistence of symptoms after hospital discharge. The study was conducted as a prospective study of children and adolescents under 18 years of age who were admitted to a children's hospital for infectious diseases from January 2021 to January 2022. The children had no previous neurological or psychiatric disorders. Out of the 3021 patients evaluated, 232 were confirmed to have COVID-19 and 21 of these patients (9%) showed neurological manifestations associated with the virus. Of these 21 patients, 14 developed MIS-C, and 7 had neurological manifestations unrelated to MIS-C. There was no statistical difference regarding the neurological manifestations during hospitalization and outcomes between patients with neuro-COVID-19 who had or did not have MIS-C, except for seizures that occurred more frequently in patients with neuro-COVID-19 without MIS-C (p-value = 0.0263). One patient died, and 5 patients still had neurological or psychiatric manifestations at discharge, which persisted for up to 7 months. The study highlights that SARS-CoV-2 infection can affect the central and peripheral nervous system, particularly in children and adolescents with MIS-C, and that it is crucial to be vigilant for long-term adverse outcomes, as the neurological and psychiatric effects of COVID-19 in children are emerging during an important stage of brain development.

Haemophilus influenzae Serotype a as a Cause of Meningitis in Children in Brazil.

BACKGROUND: Since the introduction of Haemophilus influenzae type b vaccines, invasive disease due to Haemophilus influenzae serotype a (Hia) has been reported with increasing frequency. METHODS: This study is based on hospital-based surveillance for Hia meningitis over a 5-year period. RESULTS: Thirty-five patients with H. influenzae meningitis were hospitalized and 12 were serotype a. Hia was detected in blood and cerebrospinal fluid by culture or reverse transcription polymerase chain reaction. Patients' median age was 10 months, 7 (58%) boys and 5 (41%) girls. Ten (83%) children had received at least 1 vaccine dose against Haemophilus influenzae type b. All patients were treated with ceftriaxone for a median period of 11 days. The main complications described were empyema in 5 (41%) and seizures in 3 (25%) patients. Two (16.6%) patients died due to cerebral damage and shock. CONCLUSIONS: Invasive disease due to Hia affecting young children accounts for considerable morbidity and mortality.

A patent review of antibiofilm fungal drugs (2002-present).

Fungal biofilms, such as Candida albicans biofilms, are capable of surviving in hostile environments owing to their remarkable ability to adhere to surfaces and their tolerance to chemical interventions. Currently, therapeutic treatment options are few, making these biofilm-based infections problematic particularly due to their great tolerance to conventional antimicrobial drugs, thus causing serious health and economic problems. Therefore, the development of new drugs and antibiofilm specific therapies for the prevention and treatment of antifungal to eradicate biofilms are needed. This study was aimed at carrying out a patent review analysis to identify the innovation trends, and to explore the latest antifungal drugs and the specific therapeutic strategies available for the treatment of fungal biofilms. The present patent review was carried out using the Espacenet database, using the key words "biofilm and antifungal," from 2002 to December 2019. Through this review, it was possible to identify that most of the patent contents refer to new synthetic drugs derived from natural products and associations thereof with existing antifungal drugs. Methods and biomaterials for the treatment and prevention of fungal biofilms, mainly for C. albicans biofilms, which is the most isolated and studied fungal species, were also disclosed. The lack of scientific and technical information on the biofilm eradication subject is remarkable and further confirmed by the small number of patents identified in this survey.

Avaliação do estado nutricional e da dieta de crianças e adolescentes com síndrome de down / Evaluación del estado nutricional y de la dieta de niños y adolescentes con síndrome de down / Evaluation of nutritional status and diet of children and adolescents with down syndrome

RESUMO Introdução: As crianças com síndrome de Down (SD) podem apresentar maior incidência de neofobia e de seletividade alimentar, sobrepeso e obesidade. A alimentação saudável e equilibrada é de suma importância para o crescimento adequado dessas crianças. Objetivo: Avaliar a adequação dos componentes da dieta e o estado nutricional de crianças e adolescentes com síndrome de Down em seguimento no ambulatório de pediatria genética do Hospital das Clínicas de Botucatu. Método: Estudo clínico descritivo transversal, com coleta de dados clínicos e avaliação nutricional, realizadopor meio de dados antropométricos e recordatório alimentar para avaliação da dieta. Análise estatística dos testes de Qui-quadrado e de Tukey. Resultados: Foram incluídos 35 crianças e dois adolescentes. Os diagnósticos nutricionais foram 2,7% de magreza, 81,1% de eutrofia, 8,1% de obesidade e 8,1% em risco ou sobrepeso. Houve excesso de ingestão de lipídeos naqueles com sobrepeso e obesidade, e a dieta deficiente em fibras foi prevalente a partir do primeiro ano de vida, bem como excesso de calorias e adequação de ferro e zinco. Entre os dois adolescentes, predominou a dieta com déficits em macro e micronutrientes, exceto em vitamina C e colesterol. Conclusões: A dieta com excesso de calorias, carboidratos e lipídios, como tambémcom déficit de fibras, aponta uma alimentação pouco balanceada entre crianças e adolescentes com SD, principalmente após o primeiro ano de vida, apesar do seu adequado estado nutricional.

RESUMEN Introducción: los niños consíndrome de Down (SD) pueden presentar mayor incidencia de neofobia yde selectividad alimentaria, sobrepeso y obesidad. La alimentación saludabley equilibradaes de gran importancia para el crecimiento adecuado de estos niños. Objetivo: la adecuación de los componentes de la dieta yel estado nutricional de niños y adolescentes con síndrome de Downasistidosen la clínica médica depediatría genética delHospital das Clínicas de Botucatu. Método: estudio clínico descriptivo transversal, con recolección de datos clínicos yevaluación nutricional, realizado medianteindicadores antropométricos y recordatorio alimentario para la evaluación de la dieta. Análisis estadísticode laspruebas de ji-cuadrado y de Tukey. Resultados: fueron incluidos 35niños ydos adolescentes. Los diagnósticos nutricionales fueron 2,7% de delgadez, 81,1% de eutrofia, 8,1% de obesidady8,1% en riesgo o sobrepeso. Hubo exceso de ingestión delípidosenaquellos con sobrepeso y obesidad, yla dieta deficiente en fibrasfueprevalentea partir del primer año de vida, así como exceso de calorías y adecuación de hierro y zinc. Entre los dos adolescentes, predominóla dieta con déficits en macro y micronutrientes, excepto en vitamina C y colesterol. Conclusiones: la dieta con exceso de calorías, carbohidratosylípidos, como tambiéncondéficit de fibras, señala una alimentación poco balanceada entre niños y adolescentes con SD, principalmente trasel primer año de vida, apesar de su adecuado estado nutricional.

ABSTRACT Introduction: Children with Down syndrome (DS) may have a prevalence of neophobia and food selectivity, overweight, and obesity. A healthy and balanced diet is of utmost importance for the proper growth of these children. Objective: To evaluate the adequacy of diet components and the nutritional status of children and adolescents with Down syndrome followed up at the outpatient care of genetic pediatrics, Hospital das Clínicas de Botucatu. Method: A cross-sectional descriptive clinical study, with a collection of clinical data and nutritional assessment, using anthropometric data and dietary records to evaluate the diet. Statistical analysis of the Chi-square and Tukey tests were performed. Results: A total of 35 children and two adolescents were included. Nutritional diagnoses were 2.7% lean, 81.1% eutrophic, 8.1% obese, and 8.1% at risk or overweight. There was an excess of lipid intake in overweight and obese children, and a fiber-deficient diet was prevalent since the first year of age, as well as extra calories and adequate iron and zinc intake. Among the two adolescents, a diet with deficits in macro and micronutrients, except for vitamin C and cholesterol, stood out. Conclusions: A diet with an excess of calories, carbohydrates, and lipids, as well as a fiber-deficient diet, indicates an unbalanced diet among children and adolescents with DS, especially after one year of age, despite their adequate nutritional status.

Ocular manifestations of COVID-19: a literature review.

Coronavirus disease 2019 (COVID-19) caused by the highly pathogenic SARS-Cov-2 virus, was declared as a pandemic by the World Health Organization (WHO) in March 2020. Its main clinical manifestations are related to airway involvement; however, there is extrapulmonary impairment in some cases. Given this context, this literature review aims to identify the ophthalmological conditions caused by infection with the novel coronavirus. Although ocular findings do not include the standard clinical presentation of the disease, there are reports of some ophthalmological changes in COVID-19 patients, and conjunctivitis is the most common among these.

Ocular manifestations of COVID-19: a literature review

SUMMARY Coronavirus disease 2019 (COVID-19) caused by the highly pathogenic SARS-Cov-2 virus, was declared as a pandemic by the World Health Organization (WHO) in March 2020. Its main clinical manifestations are related to airway involvement; however, there is extrapulmonary impairment in some cases. Given this context, this literature review aims to identify the ophthalmological conditions caused by infection with the novel coronavirus. Although ocular findings do not include the standard clinical presentation of the disease, there are reports of some ophthalmological changes in COVID-19 patients, and conjunctivitis is the most common among these.

RESUMO A doença do coronavírus 2019 (COVID-19) causada pelo vírus, altamente patogênico, Sars-Cov-2, foi declarada como uma pandemia pela Organização Mundial da Saúde (OMS) em março de 2020. As principais manifestações clínicas se relacionam com o acometimento da via aérea; no entanto, há em alguns casos comprometimento extrapulmonar. Perante esse contexto, esta revisão de literatura objetiva identificar as condições oftalmológicas resultantes da infecção pelo novo coronavírus. Apesar de os achados oculares não contemplarem o quadro clínico padrão da doença, há relatos de algumas alterações oftalmológicas em pacientes com COVID-19 positivo, sendo a conjuntivite a mais comum entre estas.

In vitro evaluation of Pseudomonas aeruginosa chronic lung infection models: Are agar and calcium-alginate beads interchangeable?

Animal models of chronic lung infection with P. aeruginosa (PA) are useful tools to improve antibiotic (ATB) treatment. Two main models based on the pulmonary instillation of PA embedded in agar or calcium-alginate beads are currently used. However, these two polymers used to prepare the beads have different properties; for example, agar is a neutral polysaccharide while alginate is anionic. We hypothesized that the effect of an ATB on PA entrapped in agar or calcium-alginate beads depends on its physicochemical properties, including charge, and concentration. To test this hypothesis, PAs were entrapped in agar or calcium-alginate beads dispersed in a growth medium containing either tobramycin (TOB), selected as a cationic ATB, or ciprofloxacin (CIP) selected as a neutral zwitterionic ATB. In vitro, time-kill curves evaluating the efficacy of ATBs over time were performed by measuring the light emitted by a bioluminescent PA for 42 h in the presence of ATB concentrations ranging from 0 to 100 times the MIC. In the presence of CIP, time-kill curves obtained with PA trapped in agar or calcium-alginate beads were comparable, whatever the CIP concentration used. In the presence of TOB, a clear difference was observed between the kill curves obtained with PA embedded in agar or calcium-alginate beads. While PA trapped within agar displayed the same susceptibility than the planktonic one, it was unresponsive to TOB for concentrations up to 1-fold MIC when trapped in calcium-alginate. At 10-fold the TOB's MIC, the luminescence emitted by PA01 in the agar beads was reduced by 95% after 40 h, whereas it returned to the same initial value for PA01 trapped in alginate-based beads. The reduction in TOB efficiency was even greater when alginate-based beads were dispersed in a mucus-simulating medium. These results show that the agar and alginate beads models can be interchangeable only for uncharged ATB, such as CIP, but not for cationic ATB, like TOB. In vitro experiments performed in this study could be a quick way to evaluate the effect of each model on a given ATB before performing animal experiments.

Semimechanistic Pharmacodynamic Modeling of Aztreonam-Avibactam Combination to Understand Its Antimicrobial Activity Against Multidrug-Resistant Gram-Negative Bacteria.

Aztreonam-avibactam (ATM-AVI) is a promising combination to treat serious infections caused by multidrug-resistant (MDR) pathogens. Three distinct mechanisms of action have been previously characterized for AVI: inhibition of ATM degradation by ß-lactamases, proper bactericidal effect, and enhancement of ATM bactericidal activity. The aim of this study was to quantify the individual contribution of each of the three AVI effects. In vitro static time-kill studies were performed on four MDR Enterobacteriaceae with different ß-lactamase profiles. ß-Lactamase activity was characterized by measuring ATM concentrations over 27 hours. Data were analyzed by a semimechanistic pharmacodynamics modeling approach. Surprisingly, even though AVI prevented ATM degradation, the combined bactericidal activity was mostly explained by the enhancement of ATM effect within clinical range of ATM (5-125 mg/L) and AVI concentrations (0.9-22.5 mg/L). Therefore, when selecting a ß-lactamase inhibitor for combination with a ß-lactam, its capability to enhance the ß-lactam activity should be considered in addition to the spectrum of ß-lactamases inhibited.

Reassessing the dosing of cefoxitin prophylaxis during major abdominal surgery: insights from microdialysis and population pharmacokinetic modelling.

OBJECTIVES: Cefoxitin is frequently used for surgical antibiotic prophylaxis (SAP). Using microdialysis, we evaluated whether the currently recommended dosing regimen is appropriate to maintain cefoxitin subcutaneous tissue concentrations above the MIC for pathogens involved in abdominal surgical site infection. METHODS: Data from eight patients undergoing major abdominal surgery were analysed using population pharmacokinetic modelling, and Monte Carlo simulations were conducted to determine the PTA for aerobic and anaerobic pathogens. ClinicalTrials.gov: NCT02703857. RESULTS: Only 2.3% and 47.4% of the simulated patients maintained cefoxitin subcutaneous concentrations above the MIC breakpoint for anaerobic (MIC = 16 mg/L) and aerobic (MIC = 8 mg/L) pathogens, respectively. New simulations with administration of a loading dose followed by a constant infusion of cefoxitin were conducted and demonstrate that, notwithstanding using the same total dose per unit of time, continuous infusion of cefoxitin can cover aerobes in 96.6% of the simulated patients, but remains insufficient for anaerobic bacteria. CONCLUSIONS: The recommended dosing regimen of cefoxitin is insufficient for covering the usual bacteria during abdominal surgery. Administration of a loading dose followed by a constant infusion should be considered for aerobic bacteria and cefoxitin should be avoided as SAP for anaerobic bacteria.

Population pharmacokinetic modeling to establish the role of P-glycoprotein on ciprofloxacin distribution to lung and prostate following intravenous and intratracheal administration to Wistar rats.

Ciprofloxacin (CIP) is indicated for clinical treatment of urinary and respiratory tract infections. Poor infection site penetration and consequent insufficient exposure to the antimicrobial agent may be the reason for some therapeutic failures. Ciprofloxacin is reported as a substrate for efflux transporters, such as P-glycoprotein, which could be related to the presence of sub-therapeutic drug concentration at the infection site. In the present work we evaluated CIP pharmacokinetics (PK) in plasma and lung and prostate tissues of Wistar rats after intravenous (i.v.) and intratracheal (i.t.) dosing (7 mg/Kg) in the presence and absence of P-gp inhibitor tariquidar (TAR, 15 mg/Kg). Microdialysis was applied to determine free tissue concentration-time profiles and the obtained data were analyzed by non-compartmental and population PK (popPK) analysis. A sequential strategy was used to develop the popPK model: characterization of CIP PK in tissues (Tissue model) was performed subsequently to CIP PK modeling in plasma (Plasma model). Two and three compartmental models were used to simultaneously characterize plasma concentrations after i.t. and i.v. dosing; the distribution model was developed by separating the central compartment into venous and arterial compartment and by adding lung and prostate; TAR was identified as a significant covariate for clearance and volume of distribution of central compartment as well as for inter-compartmental clearance. Our results indicate an impact of P-gp on plasma PK, likely by acting on renal active secretion of CIP. Regarding CIP exposure in lung and prostate tissues, our results suggest a complex interplay between drug transporters; P-gp inhibition by TAR was likely counterbalanced by the activity of other efflux/influx transporters, which could not be fully characterized by our model.

Abordagem dinâmica das complicações do diabetes mellitus e da hipertensão arterial quando negligenciadas: um relato de experiência / A dynamic approach on the complications of Diabetes Mellitus and Hypertension when neglected: an experience report

Introdução: O Diabetes Mellitus atinge cerca de quatorze milhões de pessoas e um em cada quatro brasileiros vive perante risco de morte por causa da Hipertensão Arterial Sistêmica. Parte desse resultado é decorrente, principalmente, de fatores de risco modificáveis, como o consumo excessivo de sódio e de carboidratos e a inatividade física. Objetivo: Relatar a experiência de uma abordagem dinâmica e interativa sobre as consequências da diabetes e hipertensão quando não tratadas, de forma a impactar e fazer com que parte dos usuários do Núcleo de Apoio a Saúde da Família, no bairro Santa Lúcia, em Maceió, desenvolvam o autocuidado. Metodologia: Como recurso metodológico, foi realizada uma conversação acerca dessas doenças crônicas, utilizando-se de pinturas corporais a fim de demonstrar as complicações dessas doenças no organismo. Resultados: Essa atividade se mostrou efetiva ao incentivar o grupo alvo a colocar em prática as formas de prevenção apresentadas, incluindo a prática de atividades físicas e a reeducação alimentar. Conclusão: Tendo em vista os resultados apresentados e a excelente participação e interação do grupo, acreditamos que essa ação teve uma importante função social, uma vez que torna o público atingido o sujeito ativo frente a sociedade e que enriquece a formação dos futuros profissionais da área da saúde (AU).

Introduction: According to data from Nacional Health Search, the Diabetes Mellitus reaches approximately fourteen million people and one in each four brazilians live under life risk because of Systemic Arterial Hypertension. Part of this result is mainly due to modifiable risk factors, like the excessive consume of sodium and carbohydrates and the physical inactivity. Objective: Exploring in a dinamic and interactive way, the consequences of the Diabetes and Arterial Hypertension when not treated in a way to impact and make that part of Family Health Support Center (Núcleo de Apoio a Saúde da Família) users , in Santa Lúcia neighborhood, in Maceió, develop the self-care. Methodology: As methodological resource, was performed a conversation about these chronic diseases, using body paintings to demonstrate the complications of these ones in the organism. Results: This activity showed itself effective on encouraging the reached group to put in practice the ways of prevention presented, including the practice of physical activities and the nutritional education. Conclusion: In view of the results presented and the excellent participation and interaction of the group, we believe that this action had an important social function, once that makes the target audience the active subject against society and enriches the formation of the future health area professionals (AU).

Population Pharmacokinetic Modeling as a Tool To Characterize the Decrease in Ciprofloxacin Free Interstitial Levels Caused by Pseudomonas aeruginosa Biofilm Lung Infection in Wistar Rats.

Biofilm formation plays an important role in the persistence of pulmonary infections, for example, in cystic fibrosis patients. So far, little is known about the antimicrobial lung disposition in biofilm-associated pneumonia. This study aimed to evaluate, by microdialysis, ciprofloxacin (CIP) penetration into the lungs of healthy and Pseudomonas aeruginosa biofilm-infected rats and to develop a comprehensive model to describe the CIP disposition under both conditions. P. aeruginosa was immobilized into alginate beads and intratracheally inoculated 14 days before CIP administration (20 mg/kg of body weight). Plasma and microdialysate were sampled from different animal groups, and the observations were evaluated by noncompartmental analysis (NCA) and population pharmacokinetic (popPK) analysis. The final model that successfully described all data consisted of an arterial and a venous central compartment and two peripheral distribution compartments, and the disposition in the lung was modeled as a two-compartment model structure linked to the venous compartment. Plasma clearance was approximately 32% lower in infected animals, leading to a significantly higher level of plasma CIP exposure (area under the concentration-time curve from time zero to infinity, 27.3 ± 12.1 µg · h/ml and 13.3 ± 3.5 µg · h/ml in infected and healthy rats, respectively). Despite the plasma exposure, infected animals showed a four times lower tissue concentration/plasma concentration ratio (lung penetration factor = 0.44 and 1.69 in infected and healthy rats, respectively), and lung clearance (CLlung) was added to the model for these animals (CLlung = 0.643 liters/h/kg) to explain the lower tissue concentrations. Our results indicate that P. aeruginosa biofilm infection reduces the CIP free interstitial lung concentrations and increases plasma exposure, suggesting that plasma concentrations alone are not a good surrogate of lung concentrations.

Lapachol, a compound targeting pyrimidine metabolism, ameliorates experimental autoimmune arthritis.

BACKGROUND: The inhibition of pyrimidine biosynthesis by blocking the dihydroorotate dehydrogenase (DHODH) activity, the prime target of leflunomide (LEF), has been proven to be an effective strategy for rheumatoid arthritis (RA) treatment. However, a considerable proportion of RA patients are refractory to LEF. Here, we investigated lapachol (LAP), a natural naphthoquinone, as a potential DHODH inhibitor and addressed its immunosuppressive properties. METHODS: Molecular flexible docking studies and bioactivity assays were performed to determine the ability of LAP to interact and inhibit DHODH. In vitro studies were conducted to assess the antiproliferative effect of LAP using isolated lymphocytes. Finally, collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA) models were employed to address the anti-arthritic effects of LAP. RESULTS: We found that LAP is a potent DHODH inhibitor which had a remarkable ability to inhibit both human and murine lymphocyte proliferation in vitro. Importantly, uridine supplementation abrogated the antiproliferative effect of LAP, supporting that the pyrimidine metabolic pathway is the target of LAP. In vivo, LAP treatment markedly reduced CIA and AIA progression as evidenced by the reduction in clinical score, articular tissue damage, and inflammation. CONCLUSIONS: Our findings propose a binding model of interaction and support the ability of LAP to inhibit DHODH, decreasing lymphocyte proliferation and attenuating the severity of experimental autoimmune arthritis. Therefore, LAP could be considered as a potential immunosuppressive lead candidate with potential therapeutic implications for RA.

Population Pharmacokinetic Modeling of Etoposide Free Concentrations in Solid Tumor.

PURPOSE: This study aimed to determine free etoposide (ETO) concentrations in two regions of Walker-256 (W256) solid tumor using microdialysis and to establish a population pharmacokinetic (popPK) model to describe simultaneously free tumor and total plasma concentrations. METHODS: W256 tumor-bearing Wistar rats received ETO 10 or 20 mg/kg i.v. bolus. Free ETO concentrations were sampled from central and peripheral regions of the tumor via CMA/20 probes for up to 7 h, whereas blood samples were collected via carotid artery cannulation. Total plasma and free tumor concentration-time profiles were analyzed by non-compartmental approach using WinNonlin® v. 5.3. PopPK modeling was conducted using MONOLIX v.4.3.3. RESULTS: ETO penetration was higher in the periphery (61 ± 15% and 61 ± 29%) than in tumor center (34 ± 6% and 28 ± 11%) following 10 and 20 mg/kg doses, respectively (ANOVA, α = 0.05). A 4-compartment model fitted ETO concentration-time profiles in all sampling compartments. CONCLUSIONS: The popPK model allowed the simultaneous fitting of plasma and tumor concentrations and a better understanding of ETO distribution in solid tumors. ETO plasma concentrations are not a good surrogate for tumoral exposure, emphasizing the importance of knowing intratumoral concentrations to predict drug response.

Validation of a sensitive HPLC/fluorescence method for assessment of ciprofloxacin levels in plasma and prostate microdialysate samples from rats.

Chronic bacterial prostatitis treatment consists of broad-spectrum antibiotic therapy for long periods of time. Drug penetration into the prostate makes the treatment a challenged. Ciprofloxacin is one of the most prescribed drugs for this treatment. A liquid chromatography with fluorescence detection method was developed and validated for determining ciprofloxacin concentrations in two different matrices: plasma and prostate microdialysate. Ciprofloxacin was separated on a C18 column eluted with a mobile phase constituted of a mixture of 0.4% aqueous triethylamine:methanol:acetonitrile (75:15:10, v/v/v) and 0.4% aqueous triethylamine:acetonitrile (88:12, v/v) for microdialysate and plasma samples, respectively. Linearity was obtained over a concentration range of 5-1000 ng/mL (microdialysate) and 10-2000 ng/mL (plasma), with coefficients of determination ≥0.9956. Precision was determined from the analysis of six quality control samples and showed RSD values <11.1 and 7.4% for intra and inter-assay precision, respectively. The accuracy ranged from 85.6 to 114.3%. The method was applied to a preliminary pharmacokinetic study to investigate ciprofloxacin concentrations in prostate, sampled by microdialysis, and plasma after a 7 mg/kg intravenous dose to Wistar rats. The method showed high sensitivity using only protein precipitation as plasma sample clean-up and was successfully applied to investigate ciprofloxacin prostate penetration.

Importância e bases de um programa de controle e prevenção de infecçãoem unidade de terapia intensiva geral / Relevance and basis of a program of control and prevention of infection in general intensive care

Introdução: as Unidades de Terapia Intensiva (UTI) são destinadas a monitorização e suporte avançado de vida, utilizando tecnologia avançada e recursos invasivos que favorecem dois desfechos inoportunos: infecção e iatrogenia. Objetivo: avaliar a importância e as bases de um Programa de Controle e Prevenção de Infecção Hospitalar, a fim de criarambiente seguro e integrado à atividade profissional diária. Métodos: realizada sistematização dos processos essenciais usados em UTI por intermédio de revisão bibliográfica e com base na legislação vigente, com o fim de propor métricas para avaliação dos resultados das medidas instituídas. Conclusão: o processo de prevenção e controle das infecçõesem UTI depende da vigilância epidemiológica, da análise das melhorias a serem implantadas, da criação de protocolos, do treinamento e do desenvolvimento da equipe, bem como da reavaliação contínua dos resultados e da divulgação para toda a equipe.

Introduction: the Intensive Care Units (UTI) are aimed at monitoring and advancedlife support, using advanced technology and invasive resources that favor two unwelcomingoutcomes: infection and iatrogeny. Objective: to evaluate the importance andfoundations of a Program for the Control and Prevention of Hospital Infection in order tocreate a safe and integrated environment into the daily professional activity. Methods:the systematization of key processes used in the UTI was evaluated through a literaturereview and based on the current legislation in order to propose metrics to evaluate theresults from imposed measures. Conclusion: the process of prevention and control ofUTI infections depends on the epidemiological surveillance, analysis of improvements tobe implemented, creation of protocols, training and staff development, ongoing reviewof results, and dissemination of information to the entire team.

Trombose de seios venosos em criança com síndrome nefrótica: relato de caso e revisão da literatura / Venous sinus thrombosis in a child with nephrotic syndrome: a case report and literature review

A síndrome nefrótica associa-se a um estado de hipercoagulabilidade, apresentando risco aumentado de complicações tromboembólicas. A trombose dos seios venosos cerebrais é uma complicação rara da síndrome nefrótica, com poucos casos descritos na literatura, mas com diagnósticos cada vez mais frequentes. A verdadeira incidência pode estar subestimada, uma vez que muitos eventos são assintomáticos ou não são diagnosticados a tempo. Descrevemos aqui o caso de uma criança do sexo masculino, de 2 anos e 10 meses, com síndrome nefrótica, que apresentou, na evolução, cefaleia, crises epilépticas e rebaixamento sensorial, com o diagnóstico de trombose do seio sagital superior e transverso. Foi realizada revisão da literatura internacional por meio de estratégia de busca definida, nas bases de dados PubMed, SciELO e Lilacs, utilizando os termos “nephrotic syndrome” e “cerebral sinovenous thrombosis”. O diagnóstico de trombose venosa deve ser considerado em qualquer paciente com síndrome nefrótica que manifeste sinais e sintomas neurológicos, destacando que a suspeita clínica precoce tem relação com um desfecho favorável.

Nephrotic syndrome is associated with a hypercoagulable state and an increased risk of thromboembolic complications. Cerebral venous sinus thrombosis is a rare complication of nephrotic syndrome, with few cases described in the literature, although the disease may be under-diagnosis. The true incidence of cerebral venous sinus thrombosis may be underestimated because many events are asymptomatic or are not diagnosed in time. Here, we describe the case of a male child, 2 years and 10 months old, with nephrotic syndrome presenting with headache, epileptic seizures and sensory inhibition who was diagnosed with superior sagittal and transverse sinuses thrombosis. An international literature review was performed with a defined search strategy in the PubMed, SciELO and Lilacs databases using the terms ‘nephrotic syndrome’ and ‘cerebral sinovenous thrombosis’. The diagnosis of venous thrombosis should be considered in any patient with nephrotic syndrome who presents with neurological signs and symptoms, as early clinical diagnosis promotes favorable outcomes.