RESUMO
Cancer mice models are critical for immune-oncology research; they provide conditions to explore tumor immunoenviroment aiming to advance knowledge and treatment development. Often, research groups breed their own mice colonies. To assess the effect of C57BL/6 mice breeding nuclei in prostate cancer development and intratumoral macrophage populations, an isotransplantation experiment was performed. C57BL/6J mice from two breeding nuclei (nA and nB) were employed for prostate adenocarcinoma TRAMP-C1 cell implantation; tumor growth period and intratumoral macrophage profile were measured. BL/6nB mice (54%) showed tumor implantation after 69-day growth period while BL/6nA implantation reached 100% across tumor growth period (28 days). No difference in total macrophage populations was observed between groups within several tumoral regions; significantly higher M2 macrophage profile was observed in tumor microenvironments from both mice groups. Nevertheless, BL/6nB tumors showed around twice the population of M1 profile (11-27%) than BL6nA (4-15%) and less non-polarized macrophages. The M1:M2 average ratio was 1:8 for group A and 1:4 for B. Our results demonstrate different tumor progression and intratumoral macrophage populations among mice from the same substrain. Data obtained in this study shows the relevance of animal source renewal for better control of murine cancer model variables.
Assuntos
Modelos Animais de Doenças , Progressão da Doença , Macrófagos , Camundongos Endogâmicos C57BL , Neoplasias da Próstata , Microambiente Tumoral , Animais , Neoplasias da Próstata/patologia , Masculino , Camundongos , Macrófagos/imunologia , Linhagem Celular TumoralRESUMO
Milk is a liquid food that possesses an important quantity of highly bioavailable macronutrients. In addition, it is readily accessible, as well as relatively inexpensive. Given that the knowledge of physicians about nutrition and food composition is deficient, in general, many of the dietary interventions recommended in diverse clinical settings lack a scientific basis. The aim of the present review was to produce a technical opinion that serves as a frame of reference to best sustain recommendations for consuming milk and dairy products as daily nutrition in the adult and older adult. The effects of milk and dairy products during the pediatric stage are not addressed in the present work. The Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Gerontología y Geriatría jointly discussed and analyzed topics dealing with the legal designation of milk, the classification and nutritional profile of cow's milk, its nutritional characteristics, its consumption in the adult, intolerance to cow's milk, and associations of milk consumption with digestive tract alterations and other conditions. Finally, certain aspects of milk consumption in the older adult and its relation to overall health are briefly discussed.
Assuntos
Laticínios , Leite , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Bovinos , Consenso , Fenômenos Fisiológicos do Sistema Digestório , Saúde , Humanos , México , Hipersensibilidade a Leite , Estado NutricionalRESUMO
In this work, the presence of 20 pharmaceuticals in wastewater from Colombia is investigated. Several widely consumed compounds have been detected in wastewater samples from different origins and geographical areas in Colombia. The studied pharmaceuticals included antibiotics, analgesics and anti-inflammatories, cholesterol lowering statin drugs, lipid regulators, and anti-depressants. The investigated samples were urban wastewater collected during one whole week before (influent) and after treatment (effluent) in the wastewater treatment plants (WWTPs) of Bogotá and Medellin. Raw wastewater from the Hospital of Tumaco and from the city of Florencia were also collected. Analyses performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed that most of the target analytes were present in all the wastewater samples. The highest concentrations (up to 50⯵g/L) corresponded to acetaminophen, but several antibiotics, such as azithromycin, ciprofloxacin and norfloxacin, and antihypertensive drugs, such as losartan and valsartan, were commonly present in influent wastewater (IWW) at levels above 1⯵g/L. Moreover, the treatment applied in WWTPs seemed to not efficiently remove the compounds under study, because most pharmaceuticals were also present in effluent wastewater (EWW) at concentrations close to those of the IWW. Special emphasis was made in this work on the quality of data reported, performing a detailed study of quality control (QC) samples. The analytical approach used -direct injection of 5-fold diluted samples without any additional treatment - is simpler and faster than the commonly applied solid phase extraction (SPE). The use of 12 isotope-labelled internal standards ensured the satisfactory correction of matrix effects for the corresponding analytes. For the remaining 8 compounds, no drastic matrix effects were observed, and only four compounds (cloxacillin, doxycycline, losartan, tetracycline) presented QC recoveries near or slightly below 60%, revealing ionization suppression, particularly in the IWW. Data on the occurrence of pharmaceuticals reported in this paper are the basis for current studies that aim to develop efficient systems for the degradation/removal of these compounds from the aquatic environment.
Assuntos
Preparações Farmacêuticas/análise , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/análise , Cromatografia Líquida de Alta Pressão , Cidades , Colômbia , Monitoramento Ambiental , Extração em Fase Sólida , Espectrometria de Massas em TandemRESUMO
The aim of this study was to determine the prevalence and risk factors for human papillomavirus (HPV) infection in the Southern region of the State of Bahia, evaluating the performance of alternative complementary methods for cervical lesion detection. Cervical samples from women who attended healthcare units were collected and diagnosed by visual inspection, cervical cytology and nested polymerase chain reaction (PCR). Moreover, hemi-nested PCR was performed to detect different HPV genotypes. The prevalence of HPV infection was 47·7%, with genotype 16 detected in most cases. Infection was associated with dyspareunia and bleeding (P < 0·001, odds ratio (OR) 5·6, 95% confidence interval (CI) 2·815-11·14) and hormonal contraceptive use (P = 0·007, OR 2·33, 95% CI 1·25-4·34). There was a positive correlation between positive PCR and positive visual inspection, cervical cytology and symptoms reported. Furthermore, visual inspection was twice as specific, and had a greater positive predictive value than cytology. We showed a high prevalence of HPV infection in Southern Bahia, with HPV 16 being the most common type, and visual inspection being most effective at detecting HPV lesions, corroborating the suggestion that it can be applied in routine gynecologic examinations for low-income populations.
Assuntos
Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Colo do Útero/citologia , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Pobreza , Prevalência , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: The purpose of this study was to determine the accuracy of manual semi-automated and volumetric measurements to assess prostate cancer volume on multiparametric magnetic resonance imaging (MP-MRI) using whole-mount histopathology for validation. MATERIALS AND METHODS: We evaluated 30 consecutive men (median age, 65.7 years; interquartile range [IQR], 61.5-70.9 years) with a median prostatic specific antigen of 8.5ng/dL (IQR, 5.5-10.5ng/dL), who underwent MP-MRI before radical prostatectomy. Index tumor volume was determined prospectively and independently on the basis of MRI and whole-mount section volumetric assessment using the maximum histologic diameter (MHD) and the histologic volume (HV). The MRI index tumor volume was determined by two independent radiologists using a single measurement of the maximum tumor dimension (MTD), a simplified MR ellipsoid volume (MREV) calculation and a MR region of interest volume (MROV) segmentation displayed by a commercially available OsiriX®. MTD was compared to MHD, whereas MREV and MROV were compared to HV. RESULTS: Thirty index lesions (median HV, 1.514 cm3; IQR, 0.05-3.780 cm3) were analyzed. The MREV, MROV and HD were significantly correlated with each other (r>0.5). Inter-observer agreement for measurements was good for each method (r>0.780). The MTD was the best predictor of maximum histologic diameter (r=0.980 and 0.791) and had an excellent inter-variability correlation (P<0.0001). CONCLUSION: Prostate cancer histologic volume can be assessed using MREV or MROV with a good accuracy and low inter-observer variability. MTD has the lowest inter-observer variability and provides best degrees of correlation with MHD. MTD should be used on MRI for selecting and following patients for active surveillance and staging before focal treatment of prostate cancer.
Assuntos
Imageamento por Ressonância Magnética , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Carga Tumoral , Idoso , Automação , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Male germ cells undergo different processes within the female reproductive tract to successfully fertilize the oocyte. These processes are triggered by different extracellular stimuli leading to activation of protein phosphorylation. Protein kinase C (PKC) is a key regulatory enzyme in signal transduction mechanisms involved in many cellular processes. Studies in boar sperm demonstrated a role for PKC in the intracellular signaling involved in motility and cellular volume regulation. Experiments using phorbol 12-myristate 13-acetate (PMA) showed increases in the Serine/Threonine phosphorylation of substrates downstream of PKC in boar sperm. In order to gain knowledge about those cellular processes regulated by PKC, we evaluate the effects of PMA on boar sperm motility, lipid organization of plasma membrane, integrity of acrosome membrane and sperm agglutination. Also, we investigate the crosstalk between PKA and PKC intracellular pathways in spermatozoa from this species. The results presented here reveal a participation of PKC in sperm motility regulation and membrane fluidity changes, which is probably associated to acrosome reaction and to agglutination. Also, we show the existence of a hierarchy in the kinases pathway. Previous works on boar sperm suggest a pathway in which PKA is positioned upstream to PKC and this new results support such model.
Assuntos
Proteína Quinase C/metabolismo , Espermatozoides/enzimologia , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/enzimologia , Masculino , Fosforilação/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Suínos , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
The Sentinel Distributed Database (SDD) is a large database of patient-level medical and prescription records, primarily derived from insurance claims and electronic health records, and is sponsored by the U.S. Food and Drug Administration for drug safety assessments. In this chart validation study, we report on the positive predictive value (PPV) of inpatient ICD-9-CM acute ischemic stroke (AIS) administrative diagnosis codes (433.x1, 434.xx, and 436) in the SDD.As part of an assessment of the risk of thromboembolic adverse events following treatment with intravenous immune globulin (IGIV), charts were obtained for 131 potential post-IGIV AIS cases. Charts were abstracted by trained nurses and then adjudicated by stroke experts using pre-specified diagnostic criteria.Case status could be determined for 128 potential AIS cases, of which 34 were confirmed. The PPVs for the inpatient AIS diagnoses recorded in the SDD were 27% overall [95% confidence interval (95% CI): 19-35], 60% (95% CI: 32-84) for principal-position diagnoses, 42% (95% CI: 28-57) for secondary diagnoses, and 6% (95% CI: 2-15) for position-unspecified diagnoses (which in the SDD generally originate from separate physician claims associated with an inpatient stay).Position-unspecified diagnoses were unlikely to represent true AIS cases. PPVs for principal and secondary inpatient diagnosis codes were higher, but still meaningfully lower than estimates from prior chart validation studies. The low PPVs may be specific to the IGIV user study population. Additional research is needed to assess the validity of AIS administrative diagnosis codes in other study populations within the SDD.
Assuntos
Isquemia Encefálica/diagnóstico , Hospitalização , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Classificação Internacional de Doenças , Acidente Vascular Cerebral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Bases de Dados Factuais , Registros Eletrônicos de Saúde , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estados Unidos , Adulto JovemRESUMO
Some studies of polymorphisms in prostate cancer (PCa) analyze individuals in a uniform manner, regardless of genetic ancestry. However, PCa aggressiveness differs between subjects of African descent and those of European extraction. Thus, genetic ancestry analysis may be used to detect population stratification in case-control association studies. We genotyped 11 ancestry informative markers to estimate the contributions of African, European, and Amerindian ancestries in a case-control sample of 213 individuals from Bahia State, Northeast Brazil, including 104 PCa patients. We compared this data with self-reported ancestry and the stratification of cases by PCa aggressiveness according to Gleason score. A larger African genetic contribution (44%) was detected among cases, and a greater European contribution (61%) among controls. Self-declaration data revealed that 74% of PCa patients considered themselves non-white (black and brown), and 41.3% of controls viewed themselves as white. Our data showed a higher degree of European ancestry among fast-growing cancer cases than those of intermediate and slow development. This differs from many previous studies, in which the prevalence of African ancestry has been reported for all grades. Differences were observed between degrees of PCa aggressiveness in terms of genetic ancestry. In particular, the greater European contribution among patients with high-grade PCa indicates that a population's genetic structure can influence case-control studies. This investigation contributes to our understanding of the genetic basis of tumor aggressiveness among groups of different genetic ancestries, especially admixed populations, and has significant implications for the assessment of inter-population heterogeneity in drug treatment effects.
Assuntos
População Negra/genética , Etnicidade/genética , Genoma Humano , Neoplasias da Próstata/genética , Idoso , Brasil , Estudos de Casos e Controles , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Pigmentação/genética , População Branca/genéticaRESUMO
The increasing use of organophosphorus pesticides in agricultural practices over the past few years has generated a number of environmental problems; these compounds tend to bioaccumulate through food chains showing high levels of toxicity triggering potential health risk for species that are exposed to these substances. In this research were used the Soxhlet and solid phase micro extraction in headspace (HS-SPME) methods for the extraction of organophosphorus pesticides in agricultural cattle soils and bovine milk, respectively. The presence of demeton-S-methylsulfon was determined at concentrations between 272.9 and 1793.3 ppm in cropland and 12.9 ppm in cow milk. Native soil bacteria were isolated showing degrading capacity of these pesticides, Bacillus sp and Pantoea agglomerans which gave results of degradation of 73.5% and 68.6 %, respectively, in the concentration of chlorpyrifos, showing that these microorganisms are a possible solution for improving soils contaminated by this class of pesticides.
El incremento en el uso de pesticidas organofosforados en las prácticas agrícolas a través de los últimos años, ha generado una serie de problemas ambientales. Estos compuestos tienden a bioacumularse a través de las cadenas tróficas presentando altos niveles de toxicidad desencadenando potenciales riesgos para la salud de las especies que son expuestas a este tipo de sustancias. En esta investigación se usaron los métodos de extracción soxhlet y micro extracción en fase sólida en espacio de cabeza (HS-SPME) para la extracción de pesticidas organofosforados en suelos de cultivo y leche de ganado bovino, respectivamente. Se determinó la presencia de demetón-S-metilsulfón en concentraciones entre 272.9 y 1793.3 ppm en los suelos de cultivo y 12.9 ppm en leche de vaca. Se aislaron bacterias nativas de suelo con capacidad degradadora de estos pesticidas, Bacillus sp y Pantoea agglomerans, obteniéndose resultados de degradación del compuesto organofosforado, clorpirifos de 73.5% y 68.67%, respectivamente, evidenciando que estos microorganismos son una posible solución para el mejoramiento de suelos contaminados por esta clase de pesticidas.