Modern Approaches to Mouse Genome Editing Using the CRISPR-Cas Toolbox and Their Applications in Functional Genomics and Translational Research.

Mice have been used in biological research for over a century, and their immense contribution to scientific breakthroughs can be seen across all research disciplines, with some of the main beneficiaries being the fields of medicine and life sciences. Genetically engineered mouse models (GEMMs), along with other model organisms, are fundamentally important research tools frequently utilised to enhance our understanding of pathophysiology and biological mechanisms behind disease. In the 1980s, it became possible to precisely edit the mouse genome to create gene knockout and knock-in mice, although with low efficacy. Recent advances utilising CRISPR-Cas technologies have considerably improved our ability to do this with ease and precision, while also allowing the generation of desired genetic variants from single nucleotide substitutions to large insertions/deletions. It is now quick and relatively easy to genetically edit somatic cells which were previously more recalcitrant to traditional approaches. Further refinements have created a 'CRISPR toolkit' that has expanded the use of CRISPR-Cas beyond gene knock-ins and knockouts. In this chapter, we review some of the latest applications of CRISPR-Cas technologies in GEMMs, including nuclease-dead Cas9 systems for activation or repression of gene expression, base editing and prime editing. We also discuss improvements in Cas9 specificity, targeting efficacy and delivery methods in mice. Throughout, we provide examples wherein CRISPR-Cas technologies have been applied to target clinically relevant genes in preclinical GEMMs, both to generate humanised models and for experimental gene therapy research.

Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets.

BACKGROUND: Invasive lobular carcinoma (ILC) accounts for 10-15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable mechanism underlying enhanced human epidermal growth factor 2 (HER2) activity. We tested the hypothesis that therapeutically targetable ERBB2/3 mutations in primary ILC of the breast associate with poor survival outcome in large public datasets. METHODS: We performed in silico comparison of ERBB2 non-amplified cases of ER+ stage I-III primary ILC (N = 279) and invasive ductal carcinoma (IDC, N = 1301) using METABRIC, TCGA, and MSK-IMPACT information. Activating mutations amenable to HER2-directed therapy with neratinib were identified using existing functional data from in vitro cell line and xenograft experiments. Multivariate analysis of 10-year overall survival (OS) with tumor size, grade, and lymph node status was performed using a Cox regression model. Differential gene expression analyses by ERBB2 mutation and amplification status was performed using weighted average differences and an in silico model of response to neratinib derived from breast cancer cell lines. RESULTS: ILC tumors comprised 17.7% of all cases in the dataset but accounted for 47.1% of ERBB2-mutated cases. Mutations in ERBB2 were enriched in ILC vs. IDC cases (5.7%, N = 16 vs. 1.4%, N = 18, p < 0.0001) and clustered in the tyrosine kinase domain of HER2. ERBB3 mutations were not enriched in ILC (1.1%, N = 3 vs. 1.8%, N = 23; p = 0.604). Median OS for patients with ERBB2-mutant ILC tumors was 66 months vs. 211 months for ERBB2 wild-type (p = 0.0001), and 159 vs. 166 months (p = 0.733) for IDC tumors. Targetable ERBB2 mutational status was an independent prognostic marker of 10-year OS-but only in ILC (hazard ratio, HR = 3.7, 95% CI 1.2-11.0; p = 0.021). Findings were validated using a novel ERBB2 mutation gene enrichment score (HR for 10-year OS in ILC = 2.3, 95% CI 1.04-5.05; p = 0.040). CONCLUSIONS: Targetable ERBB2 mutations are enriched in primary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.

Synthesis of micellar-like terpolymer nanoparticles with reductively-cleavable cross-links and evaluation of efficacy in 2D and 3D models of triple negative breast cancer.

Triple negative or basal-like breast cancer (TNBC) is characterised by aggressive progression, lack of standard therapies and poorer overall survival rates for patients. The bad prognosis, high rate of relapse and resistance against anticancer drugs have been associated with a highly abnormal loss of redox control in TNBC cells. Here, we developed docetaxel (DTX)-loaded micellar-like nanoparticles (MLNPs), designed to address the aberrant TNBC biology through the placement of redox responsive cross-links designed into a terpolymer. The MLNPs were derived from poly(ethyleneglycol)-b-poly(lactide)-co-poly(N3-α-ε-caprolactone) with a disulfide linker pendant from the caprolactone regions in order to cross-link adjacent chains. The terpolymer contained both polylactide and polycaprolactone to provide a balance of accessibility to reductive agents necessary to ensure stability in transit, but rapid micellar breakdown and concomitant drug release, when in breast cancer cells with increased levels of reducing agents. The empty MLNPs did not show any cytotoxicity in vitro in 2D monolayers of MDA-MB-231 (triple negative breast cancer), MCF7 (breast cancer) and MCF10A (normal breast epithelial cell line), whereas DTX-loaded reducible crosslinked MLNPs exhibited higher cytotoxicity against TNBC and breast cancer cells which present high intracellular levels of glutathione. Crosslinked and non-crosslinked MLNPs showed high and concentration-dependent cellular uptake in monolayers and tumour spheroids, including when assessed in co-cultures of TNBC cells and cancer-associated fibroblasts. DTX loaded crosslinked MLNPs showed the highest efficacy against 3D spheroids of TNBC, in addition the MLNPs also induced higher levels of apoptosis, as assessed by annexin V/PI assays and increased caspase 3/7 activity in MDA-MB-231 cells in comparison to cells treated with DTX-loaded un-crosslinked MLNP (used as a control) and free DTX. Taken together these data demonstrate that the terpolymer micellar-like nanoparticles with reducible crosslinks have high efficacy in both 2D and 3D in vitro cancer models by targeting the aberrant biology, i.e. loss of redox control of this type of tumour, thus may be promising and effective carrier systems for future clinical applications in TNBC.

Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age.

Multi-cohort analysis demonstrated that cytoplasmic cyclin E expression in primary breast tumors predicts aggressive disease. However, compared to their younger counterparts, older patients have favorable tumor biology and are less likely to die of breast cancer. Biomarkers therefore require interpretation in this specific context. Here, we assess data on cytoplasmic cyclin E from a UK cohort of older women alongside a panel of >20 biomarkers. Between 1973 and 2010, 813 women ≥70 years of age underwent initial surgery for early breast cancer, from which a tissue microarray was constructed (n = 517). Biomarker expression was assessed by immunohistochemistry. Multivariate analysis of breast cancer-specific survival was performed using Cox's proportional hazards. We found that cytoplasmic cyclin E was the only biological factor independently predictive of breast cancer-specific survival in this cohort of older women (hazard ratio (HR) = 6.23, 95% confidence interval (CI) = 1.93-20.14; p = 0.002). At ten years, 42% of older patients with cytoplasmic cyclin E-positive tumors had died of breast cancer versus 8% of negative cases (p < 0.0005). We conclude that cytoplasmic cyclin E is an exquisite marker of aggressive tumor biology in older women. Patients with cytoplasmic cyclin E-negative tumors are unlikely to die of breast cancer. These data have the potential to influence treatment strategy in older patients.

Interrupções de atividades de enfermeiros: contribuições para a segurança do paciente e do profissional / Interrupciones de actividades de los enfermeros: contribuciones para la seguridad del paciente y del profesional / Interruptions of nursing activities: contributions to patient and professional safety

Resumo Objetivo Classificar atividades realizadas por enfermeiros, identificar interrupções e verificar fatores humanos e ambientais associados às interrupções. Métodos Estudo observacional realizado com amostra composta por 25 enfermeiros que trabalham em unidades pediátricas ou de adultos, cirúrgicas ou de terapia intensiva de um hospital universitário. Resultados Observamos 2.295 atividades, a maioria classificada como assistência indireta ao paciente (38,6%) e assistência direta ao paciente (22,5%). Setecentos e dezenove (31,3%) atividades interrompidas foram identificadas, com média de 1,6 interrupções na mesma atividade, totalizando 1.180 interrupções. Houve maior número de interrupções durante o cuidado indireto (44,7%), e suas principais fontes foram equipe de enfermagem (43,3%) e médicos e residentes (16,5%). O número de indivíduos nas unidades (profissionais e familiares/acompanhantes), a proporção de pacientes em alta dependência e o número de profissionais de saúde influenciaram o número de interrupções. Conclusão Houve interrupções em todos os tipos de atividades realizadas pelos enfermeiros, mesmo naquelas caracterizadas como intervenções à beira do leito, o que pode comprometer a segurança do paciente.

Resumen Objetivo Clasificar actividades realizadas por enfermeros, identificar interrupciones y verificar factores humanos y ambientales asociados a las interrupciones. Métodos Estudio observacional realizado con muestra compuesta por 25 enfermeros que trabajan en unidades pediátricas o de adultos, quirúrgicas o de cuidados intensivos de un hospital universitario. Resultados Observamos 2.295 actividades, la mayoría clasificada como atención indirecta al paciente (38,6%) y atención directa al paciente (22,5%). Se identificaron 719 (31,3%) actividades interrumpidas, con un promedio de 1,6 interrupciones de la misma actividad, totalizando 1.180 interrupciones. Hubo mayor número de interrupciones durante el cuidado indirecto (44,7%) y sus principales fuentes fueron el equipo de enfermería (43,3%) y médicos y residentes (16,5%). El número de individuos en las unidades (profesionales y familiares/acompañantes), la proporción de pacientes de alta dependencia y el número de profesionales de la salud influyeron en el número de interrupciones. Conclusión Hubo interrupciones en todos los tipos de actividades realizadas por los enfermeros, inclusive en aquellas caracterizadas como intervenciones a pie de cama, lo que puede comprometer la seguridad del paciente.

Abstract Objective To classify activities performed by nurses, to identify interruptions and to verify human and environmental factors associated with interruptions. Methods Observational study conducted with a sample comprising 25 nurses working in pediatric or adult, surgical or intensive care units of a university hospital. Results We observed 2,295 activities, most of them were classified as indirect patient care (38.6%) and direct patient care (22.5%). Seven hundred and nineteen (31.3%) interrupted activities were identified, with mean of 1.6 interruptions in the same activity, thus totaling 1,180 interruptions. There was greater number of interruptions during the indirect care (44.7%), and their main sources were the nursing (43.3%), and the physicians and residents (16.5%) staffs. The number of individuals in the units (staff and family/visitors), the proportion of patients under high-dependency, the number of healthcare and allied professionals influenced the number of interruptions. Conclusion There were interruptions in all types of activities performed by the nurses, even in those characterized as bedside interventions, which can jeopardize patient safety.

Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor-γ (PPARγ) are disrupted by retinal disease-associated mutations.

Photoreceptor-specific nuclear receptor (PNR/NR2E3) and Tailless homolog (TLX/NR2E1) are human orthologs of the NR2E group, a subgroup of phylogenetically related members of the nuclear receptor (NR) superfamily of transcription factors. We assessed the ability of these NRs to form heterodimers with other members of the human NRs representing all major subgroups. The TLX ligand-binding domain (LBD) did not appear to form homodimers or interact directly with any other NR tested. The PNR LBD was able to form homodimers, but also exhibited robust interactions with the LBDs of peroxisome proliferator-activated receptor-γ (PPARγ)/NR1C3 and thyroid hormone receptor b (TRb) TRß/NR1A2. The binding of PNR to PPARγ was specific for this paralog, as no interaction was observed with the LBDs of PPARα/NR1C1 or PPARδ/NR1C2. In support of these findings, PPARγ and PNR were found to be co-expressed in human retinal tissue extracts and could be co-immunoprecipitated as a native complex. Selected sequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPARγ LBD associated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPARγ complex formation. Wild-type PNR, but not a PNR309G mutant, was able to repress PPARγ-mediated transcription in reporter assays. In summary, our results reveal novel heterodimer interactions in the NR superfamily, suggesting previously unknown functional interactions of PNR with PPARγ and TRß that have potential importance in retinal development and disease.

Mir-190b negatively contributes to the Trypanosoma cruzi-infected cell survival by repressing PTEN protein expression.

Chagas disease, which is caused by the intracellular protozoan Trypanosoma cruzi, is a serious health problem in Latin America. The heart is one of the major organs affected by this parasitic infection. The pathogenesis of tissue remodelling, particularly regarding cardiomyocyte behaviour after parasite infection, and the molecular mechanisms that occur immediately following parasite entry into host cells are not yet completely understood. Previous studies have reported that the establishment of parasitism is connected to the activation of the phosphatidylinositol-3 kinase (PI3K), which controls important steps in cellular metabolism by regulating the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate. Particularly, the tumour suppressor PTEN is a negative regulator of PI3K signalling. However, mechanistic details of the modulatory activity of PTEN on Chagas disease have not been elucidated. To address this question, H9c2 cells were infected with T. cruzi Berenice 62 strain and the expression of a specific set of microRNAs (miRNAs) were investigated. Our cellular model demonstrated that miRNA-190b is correlated to the decrease of cellular viability rates by negatively modulating PTEN protein expression in T. cruzi-infected cells.

Mir-190b negatively contributes to the Trypanosoma cruzi- infected cell survival by repressing PTEN protein expression

Chagas disease, which is caused by the intracellular protozoanTrypanosoma cruzi, is a serious health problem in Latin America. The heart is one of the major organs affected by this parasitic infection. The pathogenesis of tissue remodelling, particularly regarding cardiomyocyte behaviour after parasite infection, and the molecular mechanisms that occur immediately following parasite entry into host cells are not yet completely understood. Previous studies have reported that the establishment of parasitism is connected to the activation of the phosphatidylinositol-3 kinase (PI3K), which controls important steps in cellular metabolism by regulating the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate. Particularly, the tumour suppressor PTEN is a negative regulator of PI3K signalling. However, mechanistic details of the modulatory activity of PTEN on Chagas disease have not been elucidated. To address this question, H9c2 cells were infected with T. cruzi Berenice 62 strain and the expression of a specific set of microRNAs (miRNAs) were investigated. Our cellular model demonstrated that miRNA-190b is correlated to the decrease of cellular viability rates by negatively modulating PTEN protein expression in T. cruzi-infected cells.

Interruptions of nurses' activities and patient safety: an integrative literature review.

OBJECTIVES: to identify characteristics related to the interruption of nurses in professional practice, as well as to assess the implications of interruptions for patient safety. METHOD: integrative literature review. The following databases were searched: Pubmed/Medline, LILACS, SciELO and Cochrane Library, using the descriptors interruptions and patient safety. An initial date was not established, but the final date was December 31, 2013. A total of 29 papers met the inclusion criteria. RESULTS: all the papers included describe interruptions as a harmful factor for patient safety. Data analysis revealed three relevant categories: characteristics of interruptions, implications for patient safety, and interventions to minimize interruptions. CONCLUSION: interruptions favor the occurrence of errors in the health field. Therefore, there is a need for further studies to understand such a phenomenon and its effects on clinical practice.

Interruptions of nurses' activities and patient safety: an integrative literature review / Interrupções de atividades de enfermeiros e a segurança do paciente: revisão integrativa da literatura / Interrupciones de actividades de enfermeros y la seguridad del paciente: revisión integradora de la literatura

OBJECTIVES: to identify characteristics related to the interruption of nurses in professional practice, as well as to assess the implications of interruptions for patient safety. METHOD: integrative literature review. The following databases were searched: Pubmed/Medline, LILACS, SciELO and Cochrane Library, using the descriptors interruptions and patient safety. An initial date was not established, but the final date was December 31, 2013. A total of 29 papers met the inclusion criteria. RESULTS: all the papers included describe interruptions as a harmful factor for patient safety. Data analysis revealed three relevant categories: characteristics of interruptions, implications for patient safety, and interventions to minimize interruptions. CONCLUSION: interruptions favor the occurrence of errors in the health field. Therefore, there is a need for further studies to understand such a phenomenon and its effects on clinical practice. .

OBJETIVOS: identificar características relacionadas à interrupção de enfermeiros em sua prática profissional, bem como avaliar as implicações para a segurança do paciente. MÉTODO: foi realizada revisão de literatura do tipo integrativa, com busca nas bases de dados Pubmed/Medline, LILACS, SciELO e Biblioteca Cochrane, utilizando os descritores interruptions e patient safety. A data inicial não foi limitada e a data final foi 31 de dezembro de 2013, identificando-se 29 artigos que atenderam aos critérios de inclusão. RESULTADOS: todos os artigos revisados descreveram a interrupção como fator prejudicial à segurança do paciente. A análise destes estudos revelou três categorias relevantes: características da interrupção, implicações da interrupção para a segurança do paciente e intervenções para minimizar as interrupções. CONCLUSÃO: a interrupção favorece a ocorrência de erros na saúde. Assim, notou-se necessidade de novas pesquisas para compreender tal fenômeno e seus efeitos na prática clínica. .

OBJETIVOS: identificar características relacionadas a la interrupción que sufren los enfermeros en su práctica profesional, así como evaluar las implicaciones para la seguridad del paciente. MÉTODO: fue realizada una revisión de literatura de tipo integradora, con búsqueda en las bases de datos Pubmed/Medline, LILACS, SciELO y Biblioteca Cochrane, utilizando los descriptores interruptions y patient safety. La fecha inicial no fue limitada y la fecha final fue 31 de diciembre de 2013, se identificaron 29 artículos que atendieran a los criterios de inclusión. RESULTADOS: todos los artículos revisados describieron la interrupción como un factor perjudicial a la seguridad del paciente. El análisis de estos estudios reveló tres categorías relevantes: características de la interrupción, implicaciones de la interrupción para la seguridad del paciente e intervenciones para minimizar las interrupciones. CONCLUSIÓN: la interrupción favorece la ocurrencia de errores en la salud. Así, se notó la necesidad de realizar nuevas investigaciones para comprender ese fenómeno y los efectos del mismo en la práctica clínica. .

A novel function for CUGBP2 in controlling the pro-inflammatory stimulus in H9c2 cells: subcellular trafficking of messenger molecules.

Accumulating evidence demonstrates that chronic inflammation plays an important role in heart hypertrophy and cardiac diseases. However, the fine-tuning of cellular and molecular mechanisms that connect inflammatory process and cardiac diseases is still under investigation. Many reports have demonstrated that the overexpression of the cyclooxygenase-2 (COX-2), a key enzyme in the conversion of arachidonic acid to prostaglandins and other prostanoids, is correlated with inflammatory processes. Increased level of prostaglandin E2 was also found in animal model of left ventricle of hypertrophy. Based on previous observations that demonstrated a regulatory loop between COX-2 and the RNA-binding protein CUGBP2, we studied cellular and molecular mechanisms of a pro-inflammatory stimulus in a cardiac cell to verify if the above two molecules could be correlated with the inflammatory process in the heart. A cellular model of investigation was established and H9c2 was used. We also demonstrated a regulatory connection between COX-2 and CUGBP2 in the cardiac cells. Based on a set of different assays including gene silencing and fluorescence microscopy, we describe a novel function for the RNA-binding protein CUGBP2 in controlling the pro-inflammatory stimulus: subcellular trafficking of messenger molecules to specific cytoplasmic stress granules to maintain homeostasis.

[Hydrogen potential of antibiotic solutions subjected to environmental conditions: a preliminary trial]. / Potencial hidrogeniônico de soluções de antibióticos submetidas a condições ambientais: ensaio preliminar.

This experimental study was performed to assess the hydrogen potential (pH) of the antimicrobials ceftriaxone sodium, vancomycin hydrochloride, metronidazole, penicillin G potassium, and amikacin sulphate, following reconstitution, diluted with NaCl 0.9% (SF) and glucose solution 5% (GS), at eight different time intervals and under the normal daily conditions of lighting and temperature within the hospital unit (no air conditioning). The objective of this study was to verify the changes in the acid-base behavior of the solutions, which indicate chemical instability and can be associated with complications during intravenous therapy. Of the 186 analyzed pH values, there were no variations greater than 1.0 and no physical alterations visible to the naked eye. All solutions had a pH less than 7, and there were no significant differences for clinical practice regarding the diluent. The mean pH values after dilution with SF and GS for vancomycin hydrochloride, metronidazole, and amikacin sulphate are a risk factor for the development of intravenous complications due to their extreme acidity.

Potencial hidrogeniônico de soluções de antibióticos submetidas a condições ambientais: ensaio preliminar / Hydrogen potential of antibiotic solutions subjected to environmental conditions: a preliminary trial / Potencial de hidrógeno de soluciones de antibióticos sometidas a condiciones ambientales: ensayo preliminar

Estudo experimental para aferição do potencial hidrogeniônico (pH) dos antimicrobianos ceftriaxona sódica, cloridrato de vancomicina, metronidazol, penicilina G potássica e sulfato de amicacina, após reconstituição, diluição com NaCl 0,9% (SF) e soro glicosado 5% (SG), em oito momentos distintos e sob condições cotidianas de luminosidade e temperatura ambiente de unidade hospitalar não climatizada. O objetivo deste estudo foi verificar alterações no comportamento ácido-básico das soluções, indicativas de instabilidade química ou relacionadas a complicações da terapia intravenosa. Nos 186 valores de pH analisados, não foram identificadas variações maiores que 1,0 valor nem alterações físicas visíveis a olho nu. Todas as soluções tiveram pH menor que 7 e não houve diferença considerável para a prática clínica segundo o diluente. As médias dos valores de pH após a diluição em SF e SG, do cloridrato de vancomicina, metronidazol e sulfato de amicacina constituem fator de risco para o desenvolvimento de complicações intravenosas devido a sua extrema acidez.

This experimental study was performed to assess the hydrogen potential (pH) of the antimicrobials ceftriaxone sodium, vancomycin hydrochloride, metronidazole, penicillin G potassium, and amikacin sulphate, following reconstitution, diluted with NaCl 0.9% (SF) and glucose solution 5% (GS), at eight different time intervals and under the normal daily conditions of lighting and temperature within the hospital unit (no air conditioning). The objective of this study was to verify the changes in the acid-base behavior of the solutions, which indicate chemical instability and can be associated with complications during intravenous therapy. Of the 186 analyzed pH values, there were no variations greater than 1.0 and no physical alterations visible to the naked eye. All solutions had a pH less than 7, and there were no significant differences for clinical practice regarding the diluent. The mean pH values after dilution with SF and GS for vancomycin hydrochloride, metronidazole, and amikacin sulphate are a risk factor for the development of intravenous complications due to their extreme acidity.

Estudio experimental de contraste del potencial de hidrógeno (pH) de antimicrobianos ceftriaxona sódica, clorhidrato de vancomicina, metronidazol, penicilina G potásica y sulfato de amikacina, luego de reconstitución, dilución con NaCl 0,9% (SF) y suero glucosado 5% (SG), en ocho momentos distintos, bajo condiciones normales de luminosidad y temperatura de unidad hospitalaria no climatizada. Objetivó verificar alteraciones del comportamiento ácido-básico de las soluciones, indicativas de inestabilidades químicas o relacionadas a complicaciones de terapia intravenosa. En 186 pH analizados, no se identificaron variaciones mayores a 1,0 valor, ni alteraciones físicas a simple vista. Todas las soluciones tuvieron pH menor a 7, no hubo diferencia considerable para la práctica clínica según el diluyente. Los promedios de valor de pH luego de dilución en SF y SG para clorhidrato de vancomicina, metronidazol y sulfato de amikacina constituyen factor de riesgo para desarrollo de complicaciones intravenosas debido a su extrema acidez.

Hydrogen-ion potential of antibiotics according to the environment factors temperature and luminosity.

The objective of this experimental study was to measure the pH of antibiotics administered by intravenous infusion--ceftriaxone sodium, vancomycin hydrochloride, metrodinazole, penicillin G potassium and amikacin sulfate--after reconstitution with sterile water and dilution with NaCl 0.9% or dextrose 5% in water, according to temperature and luminosity of the environment. The results showed that variation in the drugs' pH was less than 1.0 value and that some antibiotics remained acidic after dilution and maintained this chemical profile in all situations studied, suggesting that the studied environmental factors did not change the solutions' acid base characteristic. Some pH values measured characterize risk for the development of chemical phlebitis and infiltration, and it is important for clinical practice to emphasize the profile of intravenous solutions of antibiotics, considering method of dilution, and time to infusion.

Hydrogen-ion potential of antibiotics according to the environment factors temperature and luminosity / Potencial hidrogeniônico de antimicrobianos, segundo os fatores ambientais temperatura e luminosidade / Potencial hidrogenionico de antimicrobianos, según los factores ambientales de temperatura y luminosidad

The objective of this experimental study was to measure the pH of antibiotics administered by intravenous infusion - ceftriaxone sodium, vancomycin hydrochloride, metrodinazole, penicillin G potassium and amikacin sulfate - after reconstitution with sterile water and dilution with NaCl 0.9 percent or dextrose 5 percent in water, according to temperature and luminosity of the environment. The results showed that variation in the drugs' pH was less than 1.0 value and that some antibiotics remained acidic after dilution and maintained this chemical profile in all situations studied, suggesting that the studied environmental factors did not change the solutions' acid base characteristic. Some pH values measured characterize risk for the development of chemical phlebitis and infiltration, and it is important for clinical practice to emphasize the profile of intravenous solutions of antibiotics, considering method of dilution, and time to infusion.

O objetivo deste estudo experimental foi medir o pH dos antibióticos de administração intravenosa ceftriaxona sódica, cloridrato de vancomicina, metronidazol, penicilina G potássica e sulfato de amicacina, após reconstituição com água destilada e diluição com NaCl 0,9 por cento, ou soro glicosado 5 por cento, considerando a influência da temperatura e luminosidade ambientais, assim como do tempo de exposição, no comportamento químico desses fármacos. Os resultados demonstraram variações que não ultrapassaram 1,0 valor de pH e que alguns antimicrobianos, eminentemente ácidos após a diluição, mantiveram esse comportamento em todas as situações estudadas, não sugerindo a influência de fatores ambientais no comportamento químico das soluções. Como alguns valores de pH encontrados podem contribuir para o desenvolvimento de flebite química e infiltração, é importante enfatizar para a prática clínica em saúde, a necessidade de conhecer as características das soluções de infusão intravenosa, considerando tipo de diluição e tempo de infusão.

El objetivo de este estudio experimental fue medir el pH de los antibióticos de administración intravenosa ceftriaxona sódica, clorhidrato de vancomicina, metronidazol, penicilina G potásica y sulfato de amikacina, después de reconstitución con agua destilada y dilución con NaCl a 0,9 por ciento, o suero glucosado a 5 por ciento, considerando la influencia de la temperatura y luminosidad ambientales, así como el tiempo de exposición, en el comportamiento químico de esos fármacos. Los resultados demostraron variaciones que no ultrapasaron 1,0 (valor de pH) y que algunos antimicrobianos, eminentemente ácidos después de la dilución, mantuvieron ese comportamiento en todas las situaciones estudiadas, no sugiriendo la influencia de factores ambientales en el comportamiento químico de las soluciones. Considerando que algunos valores de pH encontrados pueden contribuir para el desarrollo de flebitis química e infiltración, es importante enfatizar que para la práctica clínica en salud, existe la necesidad de conocer las características de las soluciones de infusión intravenosa, considerando el tipo de dilución y el tiempo de infusión.