RESUMO
Plasmonic nanoparticles (NPs), predominantly gold (AuNPs), are easily internalised into cells and commonly employed as nanosensors for reporter-based and reporter-free intracellular SERS applications. While AuNPs are generally considered non-toxic to cells, many biological and toxicity studies report that exposure to NPs induces cell stress through the generation of reactive oxygen species (ROS) and the upregulated transcription of pro-inflammatory genes, which can result in severe genotoxicity and apoptosis. Despite this, the extent to which normal cellular metabolism is affected by AuNP internalisation remains a relative unknown along with the contribution of the uptake itself to the SERS spectra obtained from within so called 'healthy' cells, as indicated by traditional viability tests. This work aims to interrogate the perturbation created by treatment with AuNPs under different conditions and the corresponding effect on the SERS spectra obtained. We characterise the changes induced by varying AuNP concentrations and medium serum compositions using biochemical assays and correlate them to the corresponding intracellular reporter-free SERS spectra. The different serum conditions lead to different extents of nanoparticle internalisation. We observe that changes in SERS spectra are correlated to an increasing amount of internalisation, confirmed qualitatively and quantitatively by confocal imaging and ICP-MS analysis, respectively. We analyse spectra and characterise changes that can be attributed to nanoparticle induced changes. Thus, our study highlights a need for understanding condition-dependent NP-cell interactions and standardisation of nanoparticle treatments in order to establish the validity of intracellular SERS experiments for use in all arising applications.
Assuntos
Ouro/química , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , Técnicas Biossensoriais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/toxicidade , Microscopia Confocal , Análise de Componente Principal , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: To evaluate the effectiveness of nurse-led telephone follow-up (TFU) for patients with stage-I endometrial cancer. DESIGN: Multicentre, randomised, non-inferiority trial. SETTING: Five centres in the North West of England. SAMPLE: A cohort of 259 women treated for stage-I endometrial cancer attending hospital outpatient clinics for routine follow-up. METHODS: Participants were randomly allocated to receive traditional hospital based follow-up (HFU) or nurse-led TFU. MAIN OUTCOME MEASURES: Primary outcomes were psychological morbidity (State Trait Anxiety Inventory, STAI-S) and patient satisfaction with the information provided. Secondary outcomes included patient satisfaction with service, quality of life, and time to detection of recurrence. RESULTS: The STAI-S scores post-randomisation were similar between groups [mean (SD): TFU 33.0 (11.0); HFU 35.5 (13.0)]. The estimated between-group difference in STAI-S was 0.7 (95% confidence interval, 95% CI -1.9 to 3.3); the confidence interval lies above the non-inferiority limit (-3.5), indicating the non-inferiority of TFU. There was no significant difference between groups in reported satisfaction with information (odds ratio, OR 0.9; 95% CI 0.4-2.1; P = 0.83). Women in the HFU group were more likely to report being kept waiting for their appointment (P = 0.001), that they did not need any information (P = 0.003), and were less likely to report that the nurse knew about their particular case and situation (P = 0.005). CONCLUSIONS: The TFU provides an effective alternative to HFU for patients with stage-I endometrial cancer, with no reported physical or psychological detriment. Patient satisfaction with information was high, with similar levels between groups. TWEETABLE ABSTRACT: ENDCAT trial shows effectiveness of nurse-led telephone follow-up for patients with stage-I endometrial cancer.
Assuntos
Neoplasias do Endométrio/enfermagem , Papel do Profissional de Enfermagem , Ambulatório Hospitalar , Pacientes Ambulatoriais , Satisfação do Paciente , Qualidade de Vida , Telefone , Neoplasias do Endométrio/epidemiologia , Inglaterra/epidemiologia , Feminino , Seguimentos , Humanos , Estadiamento de Neoplasias , Pacientes Ambulatoriais/estatística & dados numéricos , Telefone/estatística & dados numéricos , Recursos HumanosRESUMO
Cenicriviroc, a dual CCR2/CCR5 antagonist, is being evaluated for treatment of nonalcoholic steatohepatitis and liver fibrosis (CENTAUR; NCT02217475). As it is metabolized by the liver, cenicriviroc was investigated in hepatic-impaired participants for pharmacokinetic changes. Participants with mild-to-moderate hepatic impairment (HI) (Child-Pugh class A (N = 7) or B (N = 8)) and matched controls (N = 15) received cenicriviroc 150 mg once daily for 14 days. Serial blood samples were obtained on Days 1 and 14. Safety, tolerability, and effects on CCR2/CCR5 ligands, cytokines, and bacterial translocation biomarkers were evaluated. Cenicriviroc exposures were increased by moderate HI (AUC0-τ 55%, Cmax 29% higher) but were not with mild HI (AUC0-τ 38%, Cmax 40% lower). Cenicriviroc was well tolerated. Rapid and potent CCR2/CCR5 blockade was observed, not associated with increases in hepatic inflammation or bacterial translocation biomarkers. Study findings suggest that cenicriviroc 150 mg can be used in patients with mild-to-moderate HI.
Assuntos
Imidazóis/efeitos adversos , Imidazóis/farmacocinética , Hepatopatias/tratamento farmacológico , Receptores CCR2/antagonistas & inibidores , Receptores CCR5/metabolismo , Translocação Bacteriana/efeitos dos fármacos , Biomarcadores/metabolismo , Estudos de Casos e Controles , Citocinas/metabolismo , Demografia , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Flagelina/metabolismo , Humanos , Imidazóis/administração & dosagem , Imidazóis/sangue , Mediadores da Inflamação/metabolismo , Intestinos/efeitos dos fármacos , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Permeabilidade/efeitos dos fármacos , Sulfóxidos , Fatores de TempoRESUMO
There is conflicting evidence in the published literature regarding the effects of clomiphene citrate (CC) on endometrial development and its impact on conception. CC is an anti-oestrogen that is commonly used in assisted reproduction to induce ovulation for a range of conditions. The setting was the Reproductive Medicine department at the Royal Blackburn Hospital (RBH). This retrospective cohort study set out to assess the relationship between endometrial thickness (EMT) as measured by trans-vaginal ultrasound scan and pregnancy rates in 81 sub-fertile women treated with CC and to review some of the current literature. Using analysis of logistic regression, the results showed a 14% increase in the odds of conception for each millimetre increase in EMT when the confounding variables of age, basal follicle-stimulating hormone level and body mass index were corrected for. There is good evidence of a positive relationship between greater EMT (within normal limits) and the probability of success. EMT on its own cannot thus far be used to estimate the probability of conception, rather it seems that changes on a microscopic level give better clues to endometrial quality. Taking into account the limitations of patient selection and some missing data, this study should be viewed as a pilot for future investigation.
Assuntos
Clomifeno/uso terapêutico , Endométrio/patologia , Fármacos para a Fertilidade Feminina/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Endométrio/efeitos dos fármacos , Antagonistas de Estrogênios , Feminino , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/patologia , Modelos Logísticos , Síndrome do Ovário Policístico/complicações , Gravidez , Taxa de Gravidez , Estudos RetrospectivosRESUMO
In the event of unexpectedly finding an ovarian cyst at the time of laparoscopy, serum CA 125 assay is helpful in deciding the subsequent management of the cyst. It is unclear, however, when the CA 125 should be checked. There has been some debate as to the effect of laparoscopy on the level of CA 125 and whilst it is widely accepted that laparotomy will increase the level of CA 125 the effects of laparoscopy have not been investigated until now. Pre and post operative CA 125 levels were measured in 20 patients undergoing simple laparoscopic surgery. Analysis of the results indicate that simple laparoscopic procedures have an insignificant effect on serum CA 125 levels checked in the immediate post operative period.
Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Cistos Ovarianos/sangue , Cistos Ovarianos/cirurgia , Feminino , Humanos , Laparoscopia , Valor Preditivo dos TestesRESUMO
PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following intranasal administration in healthy male subjects and in Viagra-responsive erectile dysfunction (ED) patients. Erectile response was assessed by RigiScan trade mark in healthy subjects without visual sexual stimulation (VSS) and in Viagra-responsive ED patients with VSS. In healthy subjects, mean C(max) and AUC((0-t)) increased in a dose-dependent manner. Median T(max) was 0.50 h and mean t(1/2) ranged from 1.85 to 2.09 h. In both studies, an erectile response induced by PT-141 administration was statistically significant, compared to placebo, at doses greater than 7 mg, with the onset of the first erection occurring in approximately 30 min. PT-141 was safely administered and well tolerated in both studies. A maximum-tolerated dose was not identified. Flushing and nausea were the most common adverse events reported in both studies and no clinically significant changes in vital signs, laboratory tests, ECGs, or physical exams were observed. Based upon its erectogenic potential and tolerability profile, PT-141 is a promising candidate for further evaluation as a treatment for male ED.
Assuntos
Disfunção Erétil/tratamento farmacológico , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/farmacocinética , Receptores de Melanocortina/agonistas , Administração Intranasal , Adolescente , Adulto , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/efeitos dos fármacos , Peptídeos Cíclicos/efeitos adversos , Placebos , Índice de Gravidade de Doença , Resultado do Tratamento , alfa-MSHAssuntos
Descolamento Prematuro da Placenta/complicações , Coagulação Intravascular Disseminada/complicações , Histerotomia , Hemorragia Uterina/cirurgia , Adulto , Coagulação Intravascular Disseminada/terapia , Feminino , Morte Fetal , Humanos , Transfusão de Plaquetas , Gravidez , Segundo Trimestre da Gravidez , Hemorragia Uterina/etiologiaRESUMO
Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021-39-4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non-neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote.
Assuntos
Carcinógenos/farmacologia , Creosoto/farmacologia , Neoplasias/induzido quimicamente , Animais , Antidiarreicos/farmacologia , Peso Corporal/efeitos dos fármacos , Testes de Carcinogenicidade , Carcinógenos/química , Creosoto/química , Comportamento Alimentar/efeitos dos fármacos , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Neoplasias/mortalidade , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Sons Respiratórios/efeitos dos fármacos , Salivação/efeitos dos fármacos , Taxa de SobrevidaAssuntos
Atitude do Pessoal de Saúde , Parto Obstétrico/métodos , Tocologia , Feminino , Humanos , GravidezAssuntos
Sinusite Maxilar/etiologia , Sinusite Maxilar/cirurgia , Micoses/diagnóstico , Micoses/cirurgia , Adulto , Doença Crônica , Endoscopia/métodos , Feminino , Seguimentos , Humanos , Sinusite Maxilar/patologia , Micoses/complicações , Micoses/patologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
The life expectancy of women with cystic fibrosis has doubled in the last 20 years. A major implication of this is the advent of previously unseen reproductive health problems. We review the management problems presented by these women throughout their reproductive lives, including pregnancy.
Assuntos
Fibrose Cística/complicações , Medicina Reprodutiva , Anticoncepção , Feminino , Humanos , Trabalho de Parto , Período Pós-Parto , Gravidez , Resultado da GravidezRESUMO
Systemically administered fluorescein (F) is rapidly transformed to the fluorescent metabolite fluorescein glucuronide (FG). Little is known about how diseases can influence the synthesis or disposition of FG. We studied F and FG in the plasma ultrafiltrate of 75 people who were normal or had diabetes, retinitis pigmentosa, or idiopathic rhegmatogenous retinal detachment. F and FG were determined by high-performance liquid chromatography. The concentration of FG was comparable to F 1 h after an intravenous injection of F, both in normal subjects and in patients with retinitis pigmentosa, which suggests that FG may not be an important contributor to the vitreous fluorescence at that time. At later times FG substantially exceeded F. The concentration of FG was significantly higher in diabetics than in the other groups 14 h after an oral dose of F. Accordingly, the possible effect of disease on plasma dye concentrations should be considered in studies measuring F by fluorescence hours after systemic F administration, since this could influence the intraocular fluorescence irrespective of any alteration in ocular function.
Assuntos
Oftalmopatias/sangue , Fluoresceínas/sangue , Adulto , Humor Aquoso/fisiologia , Diabetes Mellitus/sangue , Oftalmopatias/fisiopatologia , Feminino , Fluoresceína , Fluorometria , Humanos , Masculino , Descolamento Retiniano/sangue , Retinose Pigmentar/sangue , UltrafiltraçãoRESUMO
We used a novel approach to cost-justify clinical pharmacy services on a general surgery team in nine diagnosis-related group cases. The clinical pharmacist monitored nine patients longitudinally on a general surgery team from admission to discharge and intervened in their therapeutic management. Each recommendation was analyzed for rationale, acceptance, perceived impact on quality and/or cost of patient care, whether self-initiated or solicited, and impact on patient outcome. Types of recommendations and outcomes were categorized by process and outcome measurement criteria. Total cost avoidance per patient was calculated using costs of drug therapy, laboratory tests, and length of stay. Accounting for cost of clinical pharmacy services, net cost avoidance per patient was calculated. The clinical pharmacist made 101 recommendations on nine patients. Physicians accepted 82 percent of the recommendations; 77 percent of the recommendations were self-initiated and 23 percent were solicited. Recommendations had a perceived impact on cost, quality, or both at 13, 31, and 56 percent, respectively. Most recommendations (79 percent) brought patient therapy to a level of conformance with current standards of practice as documented in the medical literature. Recommendations that potentially preserved a major organ function by preventing drug-induced toxicity or the exacerbation of existing problems constituted 16 percent of the total. None of the accepted recommendations adversely affected patient outcome and 23 percent directly resulted in a measurable positive outcome in patient care. A total of four hospital days was potentially saved for two cases. Based on objective outcome criteria, a 1.9-day increase in therapeutic control was documented per patient.(ABSTRACT TRUNCATED AT 250 WORDS)