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Abstract When using the reverse-transcription quantitative polymerase chain reaction (RT-qPCR) technique for quantitative assessment of microRNA (miRNA) expression, normalizing data using a stable endogenous gene is essential; however, no universally adequate reference gene exists. Therefore, in this study, we aimed to determine, via the RNA-Seq technique, the most adequate endogenous normalizer for the expression assessment of plasma miRNAs in patients with coronavirus disease 2019 (COVID-19). Two massive sequencing procedures were performed (a) to identify differentially expressed miRNAs between patients with COVID-19 and healthy volunteers (n = 12), and (b) to identify differentially expressed miRNAs between patients with severe COVID-19 and those with mild COVID-19 (n = 8). The endogenous normalizer candidates were selected according to the following criteria: (1) the miRNA must have a fold regulation = 1; (2) the miRNA must have a p-value > 0.990; and (3) the miRNAs that were discovered the longest ago should be selected. Four miRNAs (hsa-miR-34a-3p, hsa-miR-194-3p, hsa-miR-17-3p, and hsa-miR-205-3p) met all criteria and were selected for validation by RT-qPCR in a cohort of 125 patients. Of these, only hsa-miR-205-3p was eligible endogenous normalizers in the context of COVID-19 because their expression was stable between the compared groups.

Abstract In Brazil, the judicialization of public health for access to medications has resulted in significant challenges to the management of public policies, especially at the municipal level. To evaluate the profile of drug litigations against the Campinas municipal health system from 2017 to 2021, this study analyzed the characteristics of litigants, medicine dispensation, and the timing of court decisions. A quantitative, analytical, and comparative cross-sectional study was conducted using data on the dispensation of 506 types of medications and 493 court cases. The analysis included sociodemographic, procedural, medical–sanitary, and pharmaceutical assistance management variables. The time of court decisions was assessed using the Kruskal‒Wallis test complemented by the Dunn test. The plaintiffs were predominantly adults, females, and self-declared students, and some cases involved nonresidents. Most of the lawsuits were represented by private lawyers, gratuitousness of justice and with decisions favorable to the plaintiff. However, only 43% of the patients obtained a preliminary injunction or early tutelage. The median time needed for a court decision from the date of case filing was 12 days until the granting of a preliminary injunction or early tutelage and 6.5 months until a judgment or dismissal without a decision on the merits. Approximately 32.4% of the medications dispensed by the judicial pharmacy already belonged to the list of the Brazil’s Unified Health System in 2020; 46.3% were prescribed by their generic name; 75.5% had therapeutic equivalents, and 94.9% had marketing authorization from the Brazilian National Health Surveillance Agency. Judicialization in Campinas is an alternative way of accessing medications, but it is time-consuming and benefits only a small portion of the population (0.068%). The characteristics of the plaintiffs and judicialized medicines highlight the need to review health policies to promote equitable and efficient access to essential treatments for the population.

Abstract Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recent research has demonstrated how epigenetic mechanisms regulate the host–virus interactions in COVID-19. It has also shown that microRNAs (miRNAs) are one of the three fundamental mechanisms of the epigenetic regulation of gene expression and play an important role in viral infections. A pilot study published by our research group identified, through next-generation sequencing (NGS), that miR-4433b-5p, miR-320b, and miR-16–2-3p are differentially expressed between patients with COVID-19 and controls. Thus, the objectives of this study were to validate the expression of these miRNAs using quantitative real-time polymerase chain reaction (qRT-PCR) and to perform in silico analyses. Patients with COVID-19 (n = 90) and healthy volunteers (n = 40) were recruited. MiRNAs were extracted from plasma samples and validated using qRT-PCR. In addition, in silico analyses were performed using mirPath v.3 software. MiR-320b was the only miRNA upregulated in the case group com-pared to the control group. The in silico analyses indicated the role of miR-320b in the regulation of the KITLG gene and consequently in the inflammatory process. This study confirmed that miR-320b can distinguish patients with COVID-19 from control participants; however, further research is needed to determine whether this miRNA can be used as a target or a biomarker.

Gefitinib is a selective inhibitor of the epidermal growth factor receptor that is used to treat advanced and metastatic non-small cell lung cancer (NSCLC). Dermatological adverse reactions are most commonly associated with gefitinib treatment. The cause of adverse reactions in individuals is multifactorial. Pharmacogenetics is an effective tool to detect such adverse reactions. This case report describes a female patient with NSCLC who was administered gefitinib at a dose of 250 mg/day. However, due to severe adverse dermatological reactions, the treatment was interrupted for 15 d and antibiotic therapy was administered to manage the skin rashes, maculopapular rashes, and hyperpigmentation. Treatment adherence was adequate, and no drug interactions were detected. A pharmacogenetic analysis revealed homozygosity in the ATP-binding cassette (ABC)-B1 rs1128503 (c.1236A>G), heterozygosity in ABCG2 rs2231142 (c.421G>T) and rs2622604 (c.-20+614T>C), and a non-functional variant of the cytochrome P450 family 3, subfamily A, member 5 (CYP3A5). The relationship between altered genetic variants and the presence of adverse reactions induced by gefitinib is still controversial. Overall, this case report highlights the importance of continuing to study pharmacogenetics as predictors of adverse drug reactions.

Introduction: The standard treatment for head and neck squamous cell carcinoma (HNSCC) is cisplatin chemoradiotherapy. One of the main treatment adverse reactions is nephrotoxicity, for which there is currently no adequate specific and sensitive biomarker. Thus, this study aimed to evaluate the use of microRNAs (miRNAs) as renal biomarker candidates.Methods: This was a retrospective cohort study. Nephrotoxicity was assessed through blood samples collected before and 5 days (D5) after chemotherapy. MiRNAs were extracted from urine samples collected at baseline and D5, and RNA sequencing identified miRNAs differentially expressed between participants with and without cisplatin-induced nephrotoxicity.Results: A total of 49 participants were included (n = 49). A significant difference was seen between the two groups for traditional renal markers (serum creatinine and creatinine clearance) and for the acute kidney injury (AKI) categories. Among the six miRNAs evaluated as biomarkers, four were upregulated (hsa-miR-6729-5p, hsa-miR-1238-5p, hsa-miR-4706, and hsa-miR-4322) and two were downregulated (hsa-miR-6805-5p and hsa-miR-21-5p), but only hsa-miR-6805-5p had a significant difference (p < 0.0001). Its receiver operating characteristic curve revealed excellent specificity (0.920) for its expression fluctuation assessment, while its absolute expression in D5 showed greater sensitivity (0.792).Conclusion: So, the integrated use of these two parameters seems to be an interesting approach for AKI.

The microRNA (miRNA) expression profile by qRT-PCR depends directly on the most appropriate normalization strategy adopted; however, currently there is no universally adequate reference gene. Therefore, this study aimed to determine, considering RNA-Seq results, the most adequate endogenous normalizer for use in the relative quantification of urine miRNAs from head and neck cancer patients, treated with cisplatin chemoradiotherapy. The massive sequencing was performed to identify the miRNAs differentially expressed between the group with cisplatin nephrotoxicity (n = 6) and the one without (n = 6). The candidate endogen normalizer was chosen according to four criteria: (1) the miRNA must be expressed in most samples; (2) the miRNA must have a fold change value between 0.99 and 1.01; (3) the miRNA must have a p-value ≥ 0.98; and (4) the miRNA must not be commented on by the final GeneGlobe (Qiagen, Hilden, Germany) analysis. Four miRNAs met all the criteria (hsa-miR-363-5p, hsa-miR-875-5p, hsa-miR-4302, and hsa-miR-6749-5p) and were selected for validation by qRT-PCR in a cohort of 49 patients (including the 12 sequencing participants). Only hsa-miR-875-5p was shown to be an adequate normalizer for the experimental condition under investigation, as it exhibited invariant expression between the two groups.

Abstract Background No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. Methods We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity. Results MiR-3168 (p = 1.98 × 10− 8), miR-4718 (p = 4.24 × 10− 5), and miR-6125 (p = 6.60 × 10− 5) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00–1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03–2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98–3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61–0.93) with sensitivity of 66.76 and specificity of 79.49. Conclusions We have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.

Cisplatin (DDP) is a well-known anticancer drug used for the treatment of numerous human cancers in solid organs, including bladder, breast, cervical, head and neck squamous cell, ovarian, among others. Its most important mode of action is the DNA-platinum adducts formation, inducing DNA damage response, silencing or activating several genes to induce apoptosis; these mechanisms result in genetics and epigenetics modifications. The ability of DDP to induce tumor cell death is often challenged by the presence of anti-apoptotic regulators, leading to chemoresistance, wherein many patients who have or will develop DDP-resistance. Cancer cells resist the apoptotic effect of chemotherapy, being a problem that severely restricts the successful results of treatment for many human cancers. In the last 30 years, researchers have discovered there are several types of RNAs, and among the most important are non-coding RNAs (ncRNAs), a class of RNAs that are not involved in protein production, but they are implicated in gene expression regulation, and representing the 98% of the human genome non-translated. Some ncRNAs of great interest are long ncRNAs, circular RNAs, and microRNAs (miRs). Accumulating studies reveal that aberrant miRs expression can affect the development of chemotherapy drug resistance, by modulating the expression of relevant target proteins. Thus, identifying molecular mechanisms underlying chemoresistance development is fundamental for setting strategies to improve the prognosis of patients with different types of cancer. Therefore, this review aimed to identify and summarize miRs that modulate chemoresistance in DDP-resistant in the top five deadliest cancer, both in vitro and in vivo human models.

Cisplatin is associated with dose-limiting nephrotoxicity, and the timely detection of acute kidney injury (AKI) can affect morbimortality. Therefore, this study aimed to investigate the tools for monitoring renal function in AKI. This was a retrospective, cohort study. Cisplatin-treated patients with head and neck cancer were included. Nephrotoxicity was assessed using serum creatinine, estimated creatinine clearance, serum electrolytic alterations, and plasma kidney injury molecule-1 (KIM-1). The toxicity severity was classified according to Common Terminology Criteria for Adverse Events (CTCAE), and AKI was classified by Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN). A total of 81 participants were included, of whom only 32 did not have AKI. Almost 90% of participants had a decreased estimated glomerular filtration rate five (D5) days after chemotherapy. The AKI estimate differs between AKIN and RIFLE; more participants were diagnosed by the RIFLE at D5, 19.5% versus 2.4% by AKIN, and fifteen had a discordance between these classifications. All laboratory markers showed significant changes on D5. KIM-1 appeared a possible biomarker when considering CTCAE or AKIN classifications (p < 0.05 on D5), but not when RIFLE classification was used (p = 0.0780). Further studies may seek to understand the profiles of different biomarkers together.

Abstract The protective antioxidant activity of acetylcysteine (NAC) against toxicity due to cisplatin has been reported in experimental models; however, its efficacy in patients has not been elucidated. The aim of this study was to investigate the possible protective effect of NAC on cisplatin‐induced toxicity and the effect of NAC on clinical response and oxidative stress in patients treated for head and neck cancer. This was a randomized, double‐blind, placebo‐controlled trial conducted in patients receiving high‐dose cisplatin chemotherapy concomitant to radiotherapy. Patients were randomly assigned to groups and received: (a) 600 mg NAC syrup, orally once daily at night for 7 consecutive days or (b) placebo, administered similarly to NAC. Nephro‐, oto‐, hepato‐, myelo‐, and gastrointestinal toxicities, clinical responses, and plasma and cellular markers of oxidative stress were evaluated. Fifty‐seven patients were included (n = 28, NAC arm; and n = 29, placebo arm). A high prevalence of most types of toxicities was observed after cisplatin chemotherapy; however, the parameters were similar between the two groups. There was a predominance of partial response to treatment. In the cellular and plasmatic oxidative stress analyses, minor differences were observed. Overall, there was no statistically significant difference between the groups for all outcomes. These findings show that low‐dose oral NAC does not protect patients with head and neck cancer from cisplatin‐induced toxicities and oxidative stress. The antitumor efficacy of cisplatin was apparently not impaired by NAC.

Cisplatin (cis-diamminedichloroplatinum (II), DDP) is an antineoplastic agent widely used in the treatment of solid tumors because of its extensive cytotoxic activity. However, the main limiting side effect of DDP use is nephrotoxicity, a rapid deterioration in kidney function due to toxic chemicals. Several studies have shown that epigenetic processes are involved in DDP-induced nephrotoxicity. Noncoding RNAs (ncRNAs), a class of epigenetic processes, are molecules that regulate gene expression under physiological and pathological conditions. MicroRNAs (miRNAs) are the most characterized class of ncRNAs and are engaged in many cellular processes. In this review, we describe how different miRNAs regulate some pathways leading to cell death by apoptosis, specifically the intrinsic apoptosis pathway. Accordingly, many classes of natural products have been tested for their ability to prevent DDP-induced apoptosis. The study of epigenetic regulation for underlying cell death is still being studied, which will allow new strategies for the diagnosis and therapy of this unwanted disease, which is presented as a side effect of antineoplastic treatment.

Abstract Background Leukocytoclastic vasculitis is typically mediated by deposition of immune complexes and is related to many causes, including medication. To the best of our knowledge, leukocytoclastic vasculitis related to cisplatin has not yet been described in the scientific literature. Case presentation We report a rare case of leukocytoclastic vasculitis after the first cycle of high-dose cisplatin chemotherapy in a patient with larynx carcinoma. A 48-year-old Caucasian man with larynx carcinoma received a high-dose of cisplatin monochemotherapy (100 mg/m2 every 21 days), along with 70 Gy of radiotherapy divided into 35 sessions, as a therapeutic schedule. Twelve days after the first chemotherapy administration and after 8 sessions of radiotherapy (total of 16 Gy), the patient presented with acute onset of palpable purpura in the lower limbs. The patient was hospitalized for 10 days, and during this period, he underwent several examinations to rule out infectious, autoimmune, and neoplastic disorders. A skin biopsy showed leukocytoclastic vasculitis with a positive pattern for IgM and C3, as detected through direct immunofluorescence. Twenty-five days after cisplatin administration, the chemotherapy regimen was changed to carboplatin AUC 5, and the episodes of purpura ceased, reinforcing the hypothesis of an adverse reaction to cisplatin. Conclusions Cisplatin can induce leukocytoclastic vasculitis and clinicians should be aware of this potential effect for better case management and diagnosis.

The purpose of this systematic review was to map out and summarize scientific evidence on dysregulated microRNAs (miRNAs) that can be possible biomarkers or therapeutic targets for cisplatin nephrotoxicity and have already been tested in humans, animals, or cells. In addition, an in silico analysis of the two miRNAs found to be dysregulated in the majority of studies was performed. A literature search was performed using eight databases for studies published up to 4 July 2021. Two independent reviewers selected the studies and extracted the data; disagreements were resolved by a third and fourth reviewers. A total of 1002 records were identified, of which 30 met the eligibility criteria. All studies were published in English and reported between 2010 and 2021. The main findings were as follows: (a) miR-34a and miR-21 were the main miRNAs identified by the studies as possible biomarkers and therapeutic targets of cisplatin nephrotoxicity; (b) the in silico analysis revealed 124 and 131 different strongly validated targets for miR-34a and miR-21, respectively; and (c) studies in humans remain scarce.

Background: Highly active antiretroviral therapy (HAART) is complex and many factors contribute to a patient’s response to initial therapy including adherence, drug effectiveness, and tolerance. Close HAART follow-up is needed, particularly when there are concurrent therapies such as prophylactic antibiotics and medications for the treatment of comorbidities. Objective: To assess the effectiveness of pharmacist intervention in reducing drug related problems in HIV/AIDS outpatients (intervention group) and in improving clinical parameters in the intervention group compared to the control group. Methods: We conducted a prospective controlled intervention study with patients paired by gender and initial T CD4+ lymphocyte (CD4) count. HIV-infected patients of a public outpatient service were enrolled for the study by consecutive and convenience sampling. Patients selected for the study were divided into a control group and an intervention group. Both groups were followed for one year; however, only the intervention group received pharmaceutical care. The primary outcome was the drug related problem (DRP) analysis for the intervention group. Secondary outcomes were CD4 count and viral load evaluation for both groups. Results: There was a total of 143 patients enrolled in this study, with 53 (37.06%) patients in the control group and 90 (62.94%) patients in the intervention group. A total of 202 pharmacist interventions with 193 pharmacist-patient and 9 pharmacist-physician interventions were proposed. After one year of pharmaceutical care, a reduction of 38.43% between the initial and final DRP was found (p = 0.0001). The most common DRPs found were related to medication safety. The intervention group showed a mean increase of 84% for the CD4 count in comparison with that observed in the control group. The viral load was not significantly different between the final and initial mean values for both groups. Conclusion: Pharmacist appointments enabled identification, prevention, and solving of drug related problems, especially those related to drug safety. Also, pharmacist interventions improved adherence and increased HAART effectiveness as suggested by the higher elevation in the CD4 count seen in the intervention group in comparison with the control group.

A administração de medicamentos por sonda enteral é prática hospitalar comum. Frequentemente estes medicamentos são utilizados off label, tendo portanto uma falta de informações técnicas coesas dos fabricantes e literatura, o que dificulta a escolha do medicamento e da forma farmacêutica mais adequada. Objetivos: Analisar informações disponíveis sobre o uso de medicamentos por tubos de nutrição, a sua coerência e recomendações gerais. Métodos: Levantamento de medicamentos sólidos orais mais consumidos em unidade de terapia intensiva de um hospital particular de São Paulo, e informações técnicas obtidas de diferentes fontes literárias usadas por este. Resultados: Foram analisadas 89 apresentações, dentre as quais 27 apresentaram informações contraditórias para o uso e 14 apresentaram informações incoerentes sobre farmacocinética. Conclusões: A interpretação das informações disponíveis, frequentemente insuficientes quali- e quantitativamente, é fundamental para a escolha do medicamento mais adequado pela equipe de cuidados ao paciente. Através deste trabalho foi possível reunir informações de diversas literaturas, destacando incoerências e recomendações de modo objetivo e sistemático, demonstrando a necessidade de mais estudos científicos na utilização destes medicamentos, para que o uso seja melhor embasado e que as fontes de pesquisa sejam padronizadas.

Objetivos: demonstrar a influência das intervenções farmacêuticas (IFs) na evolução clínica e na economia dos pacientes HIV positivos de um hospital universitário no interior do estado de São Paulo. Métodos: os pacientes foram separados aleatoriamente em grupo controle (GC; n=26) e grupo intervenção (GI; n=26). O GI recebeu acompanhamento farmacoterapêutico por meio de método próprio baseado no método PWDT e, foram realizadas IFs durante 1 ano com este grupo. A análise da evolução clínica foi baseada na identificação, resolução e prevenção de problemas farmacoterapêuticos (PFTs) e nos resultados dos exames de hemoglobina (Hb), CD4 e carga viral (CV); os aspectos econômicos foram avaliados por meio dos custos de consultas médicas, atendimentos da enfermagem, exames laboratoriais, procedimentos e internação no hospital. Resultados: noventa e uma IFs foram realizadas durante 1 ano no GI. PFTs diminuíram aproximadamente 16%. Depois de 1 ano, as variações de Hb e CD4 foram estatisticamente significativas para o GI (95% e 90% de confiança, respectivamente); 50% do GC e 77,78% do GI tiveram CV

Objetivos: O objetivo deste estudo foi avaliar a existência de interações medicamentosas potenciais teóricas em prescrições feitas na Unidade de Terapia Intensiva (UTI) de um hospital da rede pública de saúde (Hospital de Clínicas – UNICAMP), quantificá-las e classificá-las quanto ao seu grau de severidade, traçando com isso um perfil das prescrições deste setor. Métodos: No período de janeiro a junho de 2011 foram avaliadas prescrições de 195 pacientes, todos maiores de 18 anos, internados por mais de 24 horas na UTI adulto do HC. Resultados: Foram prescritos no período avaliado 172 diferentes tipos de medicamentos, média de 12,9 ± 4,3 por prescrição. Entre as prescrições avaliadas 88,2% apresentaram interações medicamentosas potenciais teóricas, obtendo-se uma média por prescrição de 4,7± 4,9. As 915 IMPT observadas nas prescrições foram classificadas, utilizando a base de dados Micromedex®, em contra-indicadas (20), maiores (257), moderadas (516) e menores (122), e sinalizadas à equipe médica de acordo com a sua severidade e necessidade de manejo clínico. Conclusão: Este estudo colabora com o delineamento do perfil da farmacoterapia utilizada em terapia intensiva, demonstrando que há nela uma elevada incidência de interações medicamentosas potenciais em prescrições. Ressalta-se com ele a necessidade de atuação do farmacêutico clínico nesta área, a fim de contribuir com a equipe multidisciplinar na redução de riscos provenientes da terapia medicamentosa.

Cisplatin is an antineoplastic drug used for the treatment of many solid tumors. Among its various side effects, nephrotoxicity is the most detrimental. In recent years, epigenetic regulation has emerged as a modulatory mechanism of cisplatin-induced nephrotoxicity, involving non-coding RNAs, DNA methylation and histone modifications. These epigenetic marks alter different signaling pathways leading to damage and cell death. In this review, we describe how different epigenetic modifications alter different pathways leading to cell death by apoptosis, autophagy, necroptosis, among others. The study of epigenetic regulation is still under development, and much research remains to fully determine the epigenetic mechanisms underlying cell death, which will allow leading new strategies for the diagnosis and therapy of this disease.

The aim of the present study was to quantify drug interactions in prescriptions for women undergoing supportive therapy in an oncology setting at a women’s hospital in Brazil and compare the information provided by different databases regarding these drug interactions. A convenience sample was selected of prescriptions for patients diagnosed with breast or gynecological tumors hospitalized in the clinical oncology and surgery wards from April to June 2009. DRUGDEX/Micromedex (Thomson Micromedex) was the main database used for the identification of drug interactions and was compared with two other databases: Drugs.com and Lexicomp. The search was performed by inputting all drug combinations found in the prescriptions in Micromedex and Drugs.com. All interactions identified and classified by Micromedex and/or Drugs.com as of major severity were then checked in Lexicomp. A total of 152 interactions were identified by Micromedex (61 major, 69 moderate and 22 minor). In Drugs.com, 614 interactions were identified (85 major, 464 moderate and 65 minor). Forty-four were classified as major drug interactions in at least one of the databases: 30 in Micromedex, 26 in Drugs. com and 14 in Lexicomp. The present findings reveal discrepancies among the three databases analyzed. Thus, standardization should be proposed. Moreover, both the pharmacist and multidisciplinary team should perform a critical analysis of prescriptions to promote safe practices in the use of medications and minimize potential complications caused by drug interactions.

Efforts to diminish the transmission of infections include programs in which disinfectants play a crucial role. Hospital surfaces and medical devices are potential sources of cross contamination, and each instrument, surface or area in a health care unit can be responsible for spread of infection. The decimal reduction time was used to study and compare the behavior of selected strains of microorganisms. The highest D-values for various bacteria were obtained for the following solutions: (i) 0.1% sodium dichloroisocyanurate (pH 7.0) - E. coli and A. calcoaceticus (D = 5.9 min); (ii) sodium hypochlorite (pH 7.0) at 0.025% for B. stearothermophilus (D = 24 min), E. coli and E. cloacae (D = 7.5 min); at 0.05% for B. stearothermophilus (D = 9.4 min) and E. coli (D = 6.1 min). The suspension studies were an indication of the disinfectant efficacy on a surface. The data in this study reflect the formulations used and may vary from product to product. The expected effectiveness from the studied formulations shows that the tested agents can be recommended for surface disinfection as stated in present guidelines and emphasize the importance and need to develop routine and novel programs to evaluate product utility.Esforços para diminuir o risco de transmissões de infecções incluem programas nos quais os desinfetantes desempenham papel crucial. As superfícies de materiais médico-hospitalares, se não estiverem diretamente ligados à transmissão de doenças, podem contribuir, potencialmente, para uma contaminação cruzada secundária. Cada instrumento ou superfície do estabelecimento do ambiente de saúde que entra em contato com um paciente é um disseminador potencial de infecção. Para estudar e comparar o comportamento dos microrganismos selecionados foram realizados ensaios de determinação do tempo de redução decimal. Os maiores valores D determinados, foram: (i) 0,1% dicloroisocianurato de sódio (NaDCC) (pH 7.0) - E. coli e A. calcoaceticus (D = 5,9 min); (ii) hipoclorito de sódio (pH 7,0) à 0,025% para B. stearothermophilus (D = 24 min), E. coli e E. cloacae (D = 7,5 min); e à 0,05% para B. stearothermophilus (D = 9,4 min) e E. coli (D = 6,1 min). Este estudo estabelece que as suspensões estudadas são indicação da eficácia de desinfecção recomendada pela legislação, mas os resultados podem variar de produto para produto. Para desinfecção de mãos clorexidina pode ser utilizada, pois apresentou valores D baixos. Para desinfecção de nível intermediário de equipamentos e instrumentos recomenda-se a utilização de NaDCC, devido à estabilidade e baixo efeito corrosivo para equipamentos e materiais. Glutaraldeído, apesar de muito aceito para processos esterilizantes, tem eficácia comparável a soluções de formaldeído.

Cholesterol oxides are atherogenic and can affect the activity of diverse important enzymes for the lipidic metabolism. The effect of 7β-hydroxycholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestan-3β,5α,6β-triol,5,6β-epoxycholesterol, 5,6α-epoxycholesterol and 7α-hydroxycholesterol on esterification of cholesterol by lecithin:cholesterol acyl transferase (LCAT, EC 2.3.1.43) and the transfer of esters of cholesterol oxides from high density lipoprotein (HDL) to low density lipoproteins (LDL) and very low density lipoproteins (VLDL) by cholesteryl ester transfer protein (CETP) was investigated. HDL enriched with increasing concentrations of cholesterol oxides was incubated with fresh plasma as source of LCAT. Cholesterol and cholesterol oxides esterification was followed by measuring the consumption of respective free sterol and oxysterols. Measurements of cholesterol and cholesterol oxides were done by gas-chromatography. 14C-cholesterol oxides were incorporated into HDL2 and HDL3 subfractions and then incubated with fresh plasma containing LCAT and CETP. The transfer of cholesterol oxide esters was followed by measuring the 14C-cholesterol oxide-derived esters transferred to LDL and VLDL. All the cholesterol oxides studied were esterified by LCAT after incorporation into HDL particles, competing with cholesterol by LCAT. Cholesterol esterification by LCAT was inversely related to the cholesterol oxide concentration. The esterification of 14C-cholesterol oxides was higher in HDL3 and the transfer of the derived esters was greater from HDL2 to LDL and VLDL. The results suggest that cholesterol esterification by LCAT is inhibited in cholesterol oxide-enriched HDL particles. Moreover, the cholesterol oxides-derived esters are efficiently transferred to LDL and VLDL. Therefore, we suggest that cholesterol oxides may exert part of their atherogenic effect by inhibiting cholesterol esterification on the HDL surface and thereby disturbing reverse cholesterol transport.Os óxidos de colesterol são aterogênicos e podem afetar a atividade de diversas enzimas importantes para o metabolismo lipídico. Este estudo investigou o efeito dos óxidos 7β-hidroxicolesterol, 7-cetocolesterol, 25-hidroxicolesterol, colestan-3β,5α,6β-triol, 5,6β-epoxicolesterol, 5,6α-epoxicolesterol e 7α-hidroxicolesterol na esterificação do colesterol por ação da lecitina colesterol aciltransferase (LCAT, EC 2.3.1.43) e a posterior transferência dos óxidos esterificados da lipoproteína de alta densidade (HDL) para as lipoproteínas de baixa densidade (LDL) e muito baixa densidade (VLDL) mediada pela proteína de transporte de éster de colesterol (CETP). Para atingir os objetivos, HDL enriquecida com concentrações crescentes de óxidos de colesterol foi incubada com plasma fresco pobre em lipoproteínas, como fonte de LCAT; posteriormente a esterificação do colesterol e dos óxidos de colesterol foi medida pelo consumo do colesterol livre e dos óxidos livres presentes na HDL. As determinações de colesterol e dos óxidos de colesterol foram realizadas por cromatografia gasosa. 14C-óxidos de colesterol foram incorporados nas subfrações HDL2 e HDL3 e posteriormente incubados com plasma fresco, contendo LCAT e CETP. A transferência dos ésteres de óxidos de colesterol foi medida e quantificada pela presença desses ésteres na LDL e VLDL. Todos os óxidos de colesterol estudados foram esterificados pela LCAT após incorporação nas partículas de HDL e competiram com a esterificação do colesterol nativo. A esterificação do colesterol pela LCAT foi inversamente relacionada à concentração de óxidos de colesterol. A esterificação dos óxidos de colesterol foi maior na HDL3 e a transferência desses ésteres foi maior a partir da HDL2 para a LDL e VLDL. Estes resultados indicam que a esterificação do colesterol pela LCAT é inibida nas partículas de HDL enriquecidas com óxidos de colesterol e que os ésteres de óxidos de colesterol são eficientemente transferidos para a LDL e VLDL. Portanto, sugere-se que os óxidos de colesterol exercem parte de seu efeito aterogênico pela inibição da esterificação do colesterol na superfície da HDL, causando um distúrbio no transporte reverso do colesterol, além de aumentar o potencial aterogênico da LDL e VLDL.

Due to the growing number of outbreaks of infection in hospital and nurseries, it becomes essential to set up a sanitation program that indicates that the appropriate chemical agent was chosen for application in the most effective way. Validating the effectiveness of decontamination and disinfection is an important and often challenging task. In order to study and compare the behavior of selected microorganisms, they were submitted to minimal inhibitory concentration (MIC). The MIC intervals, which reduced bacteria populations over 6 log10, were: 59 to 156 mg/L of quaternary ammonium compounds (QACs); 63 to 10000 mg/L of chlorhexidine; 1375 to 3250 mg/L of glutaraldehyde; 39 to 246 mg/L of formaldehyde; 43750 to 87500 mg/L of ethanol; 1250 to 6250 mg/L of iodine in polyvinyl-pyrolidone complexes, 150 to 4491 mg/L of chlorine-releasing-agents (CRAs) and 469 to 2500 mg/L of hydrogen peroxide. Chlorhexidine showed non inhibitory activity over germinating spores. A. calcoaceticus showed resistance to the majority of the agents tested, followed by E. cloacae and S. marcescens.Devido ao número crescente de surtos de infecção hospitalar, torna-se proeminente o estabelecimento de um programa de sanitização que liste os agentes químicos a serem empregados e o modo de aplicação mais efetivo. Validação da eficácia de descontaminação é uma tarefa ao mesmo tempo importante e desafiadora. Para estudar e comparar o comportamento dos microrganismos selecionados foram realizados ensaios de concentração inibitória mínima (CIM). A CIM capaz de reduzir o bioburden inicial (>6 log10) foi: 59 - 156 mg/L de quartenários de amônia; 63 - 10000 mg/L de clorexidina, 1375 - 3250 mg/mL de glutaraldeído, 39 - 246 mg/L de formaldeído, 43750 - 87500 mg/L de etanol 1250 - 6250 mg/L de PVPI, 150 - 4491 mg/L de compostos liberadores de cloro e 469 -2500 mg/L de peróxido de hidrogênio.

Lipid peroxidation and lipid-derived oxidized products have been implicated in the pathogenesis of a variety of human diseases. To clarify the role of oxidative stress in essential hypertension and hypercholesterolemia the in vitro oxidative susceptibility of LDL, the antioxidant status and the lipid peroxide content of blood plasma were examined in hypercholesterolemic (HC), hypertensive (H), hypercholesterolemic/hypertensive (HH) and normolipidemic/normotensive subjects (N). Plasma ascorbate and lipid-soluble antioxidants were lower, while LDL oxidizability, CE-OOH and TL-OOH were higher in H, HC, and HH groups than in the N group. No difference was observed among groups for PL-OOH and isoprostanes. In summary, the results show that: 1) lipid- and water-soluble antioxidants are lower in hypercholesterolemic and hypertensive patients as compared to normal subjects, whereas the lipid peroxide content and the LDL susceptibility to oxidation were higher; 2) total cholesterol, LDL-cholesterol, apoB and CE-OOH were negatively correlated with the content of a-tocopherol; 3) there was a positive correlation between the content of lipid-soluble antioxidants and the resistance of LDL to oxidation; and 4) CE-OOH and TL-OOH were positively correlated with total cholesterol and LDL-cholesterol.