RESUMO
Correction for 'Emerging pollutants in the Esmeraldas watershed in Ecuador: discharge and attenuation of emerging organic pollutants along the San Pedro-Guayllabamba-Esmeraldas rivers' by A. Voloshenko-Rossin et al., Environ. Sci.: Processes Impacts, 2015, 17, 41-53, https://doi.org/10.1039/C4EM00394B.
RESUMO
Doxorubicin is a clinical benchmark drug, which is applied in the treatment of numerous cancers. Known for its accumulation in the nucleus and ability to intercalate into DNA, it targets quickly dividing i.e. hypermitotic cells. Through this mechanism, it could be an ideal structural motif for a new class of imaging agents, given that the new entity approximates the in vitro profile of the parent drug. Here we describe design, synthesis and biological activity of a small array of Doxorubicin-metalloconjugates (M = (99m)Tc, Re). We demonstrate that the conjugates preferably accumulate in the nuclear compartment, tightly bind to DNA and retain an appreciable cytotoxicity. Moreover, the Re conjugates effectively act as inhibitors of the human Topoisomerase II enzyme, which is the widely accepted mechanism of action of the parent drug. Since the conjugates effectively mimic the in vitro behavior of native Doxorubicin, the (99m)Tc compounds are prospective imaging agents.
Assuntos
Doxorrubicina , Compostos Organometálicos , Tecnécio , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Diagnóstico por Imagem , Doxorrubicina/química , Doxorrubicina/farmacologia , Células HeLa , Humanos , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Tecnécio/química , Tecnécio/farmacologia , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologiaRESUMO
Fungal infections are a group of diseases spread all over the world with an extremely high morbidity. Worryingly, although several pathogenic fungi were found to develop resistance towards traditional therapy, research towards the discovery of novel antimycotic agents is very limited. Considering the promising results obtained with the ferrocene-based drug candidates Ferroquine and Ferrocifen as antimalarial and anticancer drug candidates, respectively, we envisaged derivatizing the organic scaffold of a new broad-spectrum fungicide, namely sedaxane, with a ferrocenyl moiety in order to obtain new metal-based antifungal agents. The new ferrocenyl sedaxane derivatives called herein Sedaxicenes (, and ) were characterized using different analytical techniques and the structures were confirmed by X-ray crystallography. As expected for antimycotic agents, , and were found to have a low or even no toxicity towards human cells (IC50 > 100 µM). Interestingly, while the parent drug did not display any mycotoxicity (EC50 > 100 µM), complex was found to have some antifungal activity with an IC50 value of 43 µM under the same experimental conditions. In order to investigate the possible redox-mediated mode of action of , we synthesized the ruthenocene analogue of , namely . Ruthenocene is known to have a completely different electrochemical behaviour from ferrocene although both the compounds are isostructural. As anticipated, complex was found to induce an increase of the reactive oxygen species level in S. cerevisiae, contrary to its analogue and to the parent compound sedaxane.
Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Compostos Ferrosos/química , Compostos Ferrosos/farmacologia , Antifúngicos/síntese química , Antifúngicos/toxicidade , Linhagem Celular Tumoral , Desenho de Fármacos , Compostos Ferrosos/síntese química , Compostos Ferrosos/toxicidade , Humanos , Metalocenos , Modelos Moleculares , Conformação Molecular , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismoRESUMO
Water quality characteristics and emerging organic pollutants were sampled along the San Pedro-Guayllabamba-Esmeraldas River and its main water pollution streams in the summer of 2013. The annual flow rate of the stream is 22 000 Mm(3) y(-1) and it collects the wastewater of Quito-Ecuador in the Andes and supplies drinking water to the city of Esmeraldas near the Pacific Ocean. The most persistent emerging pollutants were carbamazepine and acesulfame, which were found to be stable along the San Pedro-Guayllabamba-Esmeraldas River, whereas the concentration of most other organic emerging pollutants, such as caffeine, sulfamethoxazole, venlafaxine, O-desmethylvenlafaxine, and steroidal estrogens, was degraded to a large extent along the 300 km flow. The mass rate of the sum of cocaine and benzoylecgonine, its metabolite, was increased along the stream, which may be attributed to coca plantations and wild coca trees. This raises the possibility of using river monitoring as an indirect way to learn about changes in coca plantations in their watersheds. Several organic emerging pollutants, such as venlafaxine, carbamazepine, sulphamethoxazole, and benzoylecgonine, survived even the filtration treatment at the Esmeraldas drinking water system, though all except for benzoylecgonine are found below 20 ng L(-1), and are therefore not likely to cause adverse health effects. The research provides a way to compare drug consumption in a major Latin American city (Quito) and shows that the consumption of most sampled drugs (carbamazepine, venlafaxine, O-desmethylvenlafaxine, sulphamethoxazole, ethinylestradiol) was below their average consumption level in Europe, Israel, and North America.
Assuntos
Monitoramento Ambiental , Compostos Orgânicos/análise , Rios/química , Poluentes Químicos da Água/análise , Cidades , EquadorRESUMO
The stereoselectivity of R,S-venlafaxine and its metabolites R,S-O-desmethylvenlafaxine, N-desmethylvenlafaxine, O,N-didesmethylvenlafaxine, N,N-didesmethylvenlafaxine and tridesmethylvenlafaxine was studied in three processes: (i) anaerobic and aerobic laboratory scale tests; (ii) six wastewater treatment plants (WWTPs) operating under different conditions; and (iii) a variety of wastewater treatments including conventional activated sludge, natural attenuation along a receiving river stream and storage in operational and seasonal reservoirs. In the laboratory and field studies, the degradation of the venlafaxine yielded O-desmethylvenalfaxine as the dominant metabolite under aerobic and anaerobic conditions. Venlafaxine was almost exclusively converted to O-desmethylvenlafaxine under anaerobic conditions, but only a fraction of the drug was transformed to O-desmethylvenlafaxine under aerobic conditions. Degradation of venlafaxine involved only small stereoisomeric selectivity. In contrast, the degradation of O-desmethylvenlafaxine yielded remarkable S to R enrichment under aerobic conditions but none under anaerobic conditions. Determination of venlafaxine and its metabolites in the WWTPs agreed well with the stereoselectivity observed in the laboratory studies. Our results suggest that the levels of the drug and its metabolites and the stereoisomeric enrichment of the metabolite and its parent drug can be used for source tracking and for discrimination between domestic and nondomestic wastewater pollution. This was indeed demonstrated in the investigations carried out at the Jerusalem WWTP.
Assuntos
Cicloexanóis/química , Cicloexanóis/metabolismo , Poluentes Químicos da Água/metabolismo , Aerobiose , Biodegradação Ambiental , Cromatografia Líquida de Alta Pressão , Succinato de Desvenlafaxina , Laboratórios , Oxirredução , Esgotos/química , Estereoisomerismo , Espectrometria de Massas em Tandem , Cloridrato de Venlafaxina , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/químicaRESUMO
The cystic variant of renal oncocytoma was defined by Ogden et al. (1986), who described a single case. A further case is described in the present communication, with notes on the clinical presentation, aspiration cytology, and histology of the surgical specimen. Follow-up over 3 years has been uneventful.
Assuntos
Adenoma/patologia , Neoplasias Renais/patologia , Doenças Renais Policísticas/patologia , Adenoma/cirurgia , Epitélio/patologia , Humanos , Rim/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Doenças Renais Policísticas/cirurgiaRESUMO
Thirty-eight patients with metastatic renal-cell carcinoma (RCC) and 1 patient with a second primary RCC were treated with coumarin and cimetidine. Patients received 400 mg cimetidine p.o. daily and after 1 week 100 mg coumarin p.o. daily in addition until tumour progression. Two complete remission (30 and 50+ months) and 3 partial remissions (14, 13.8 months) could be achieved. Problems regarding possibly spontaneous regressions and comparable results of other treatment in RCC are discussed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Cimetidina/administração & dosagem , Cumarínicos/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
The diagnostic value of different laboratory methods in detecting Chlamydia trachomatis infections in high risk groups was analysed. The efficiency of a direct specimen test was compared with serology (IgG and IgM ELISA) and culture in L929 cells, stained either with fluorescein conjugated monoclonal antibodies or with iodine. Patients (no. = 1041) with localized genital infections attending a STD clinic, sexual contacts and patients with ascending infections from urological and gynecological clinics were examined. Chlamydia trachomatis was detected in 225 patients: 210 (93.3%) were reactive in the direct test (smears stained with monoclonal antibodies), whereas culture missed only 5 (sensitivity 97.8%) when stained by the same method. Cultures stained with iodine produced the lowest recovery rate (73.8%), but this rate increased to 80.9% when a second passage was performed. In addition the prevalence of Neisseria gonorrhoeae, Mycoplasma hominis, Ureaplasma urealyticum, Candida albicans and Trichomonas vaginalis was investigated. In patients with non-gonococcal urethritis (no. = 331) and cervicitis (no. = 353), Chlamydia trachomatis was isolated in 32.3% and 12.8% respectively. However, this pathogen could be isolated in only 3 (15.8%) out of 19 patients with epididymitis and 15 (14%) out of 107 patients with adnexitis, although 66.7% and 93.3% respectively had specific IgG antibodies. Specific IgM could by detected with a sandwich ELISA in patients with adnexitis (46.7%), epididymitis (33.3%), cervicitis (22.2%), non-gonococcal urethritis (14%) and in the sexual partners of patients with genital infections (35.7%). The direct specimen test with monoclonal antibodies is the method of choice for the diagnosis of a C. trachomatis infection in patients with urethritis and cervicitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Infecções por Chlamydia/diagnóstico , Anticorpos Monoclonais , Técnicas Bacteriológicas , Chlamydia trachomatis/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Feminino , Masculino , Coloração e RotulagemRESUMO
The aim of the present study was to examine the effects of combined sedation and analgesia during extracorporeal shockwave lithotripsy using the Dornier lithotriptor HM III. We used a combination of a benzodiazepin derivatives with an opioid. We tested the dosage of drugs needed in relation to the length of treatment, the size of the stone and the overall energy output of the lithotriptor. In addition, continuous records were made of the patient's blood pressure and the oxygen saturation in the blood, with and without oxygen insufflation. Our results show that sedation combined with analgesia is a reasonable and useable alternative to general or regional anaesthesia for extracorporeal lithotripsy.
Assuntos
Anestesia por Condução , Hipnóticos e Sedativos/administração & dosagem , Cálculos Renais/terapia , Litotripsia , Quimioterapia Combinada , Feminino , Flunitrazepam/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Oxigênio/sangue , Pirinitramida/administração & dosagemRESUMO
Cholecystolithiasis is a good example to show the economic effects of using ultrasonography consequently as one of the first diagnostic procedures. In this way it is possible to reduce the examination costs about 50% for the out-patient as well as for the diagnosis during the hospital stay.
Assuntos
Colelitíase/diagnóstico , Ultrassonografia/economia , Colelitíase/cirurgia , Controle de Custos , Diagnóstico Diferencial , Humanos , Estudos RetrospectivosRESUMO
In the past 50 years 2210 patients suffering from induratio penis plastica were admitted to our department. In 69% of the cases an improvement could be observed within 18 months after radium moulage therapy. By improving radium protection the therapy may now be performed without any significant exposure of the testes. A 15 year old patient is the youngest case reported in world literature. Trend analyses show a case shift towards the senium.
Assuntos
Braquiterapia/instrumentação , Induração Peniana/radioterapia , Rádio (Elemento)/uso terapêutico , Adolescente , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Modelos AnatômicosRESUMO
Percutaneous sclerotherapy of the spermatic vein has become a very efficacious and safe treatment and is also a real alternative to surgery.