RESUMO
The therapeutic effect of tacrolimus against ulcerative colitis (UC) is correlated with its trough blood concentration. Conventionally, oral tacrolimus for the treatment of UC is initiated under fasting conditions; once the symptoms improve, food intake is resumed. Tacrolimus blood concentration decreases with food intake compared with that under fasting conditions. The aim of this study was to explore the characteristics of patients with UC whose tacrolimus blood concentrations tended to decrease after food initiation. Medical data of 13 patients with UC and treated with tacrolimus were retrospectively obtained. The participant characteristics associated with the changes in tacrolimus blood concentrations after food initiation were analyzed using regression analysis based on the rate of decrease in the concentration/dose (C/D) ratio after food initiation. Single regression analysis showed that the number of days required from tacrolimus initiation to food resumption (P = 0.0071) and individual differences in the increase in tacrolimus blood concentration after administration (P = 0.0247) were significantly associated with the rate of decrease in the C/D ratio after food initiation. Furthermore, multiple regression analysis showed a significant effect of the number of days to food resumption (P = 0.0004) and individual differences in the increase in tacrolimus blood concentration after administration (P = 0.0012). The results suggest that the degree of change in blood tacrolimus concentration after food initiation may be related to the severity of the symptoms and pathology of UC. Early identification of participant characteristics may help control tacrolimus blood concentration fluctuations after food initiation.
Assuntos
Colite Ulcerativa , Imunossupressores , Tacrolimo , Humanos , Tacrolimo/sangue , Tacrolimo/farmacocinética , Tacrolimo/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/sangue , Feminino , Masculino , Imunossupressores/sangue , Imunossupressores/farmacocinética , Imunossupressores/administração & dosagem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Regressão , Administração Oral , Adulto Jovem , Jejum , Idoso , Ingestão de AlimentosRESUMO
In this study, we examined patients who received liposomal amphotericin B (L-AMB) to determine the risk factors associated with nephrotoxicity before and during L-AMB treatment. In this retrospective, single-center, observational cohort study, we examined 37 patients who received L-AMB treatment between April 2018 and December 2019. Nephrotoxicity was observed in 11 (29.7%) patients. We focused on the baseline albumin level and body surface area (BSA) before L-AMB treatment. Univariate analysis showed that the BSA and baseline albumin levels in patients with nephrotoxicity were significantly higher than those in patients without nephrotoxicity. Moreover, univariate analysis showed that albumin supplementation was significantly associated with the frequency of nephrotoxicity during L-AMB treatment. Multiple logistic regression analysis revealed the following independent risk factors for nephrotoxicity before or during L-AMB treatment: baseline albumin level (odds ratio [OR] = 16.000; 95% CI 1.480-172.000; P = 0.022) and albumin supplementation (OR = 40.800; 95% CI 2.210-753.000; P = 0.013). In conclusion, we identified baseline albumin level and albumin supplementation as novel risk factors for L-AMB-induced nephrotoxicity.
Assuntos
Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Nefropatias/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Albuminas/metabolismo , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
In this study, we investigated a highly hydrated gel phantom with electrical anisotropy that can be used at 18.375 MHz to 23.625 MHz. This is one of the frequency bands used for human body communication. To achieve the communication, the electrical characteristics of the quadriceps femoris muscle of the rat were measured immediately after sacrifice. These were used to obtain an indicator of electrical characteristics to be satisfied by the phantom. Electrical anisotropy was realized by adding carbon fiber to the phantom and controlling its direction. We were able to develop a high hydrated gel phantom for human body communication with a maximum error of 8.1% assuming its use at 18.735 MHz to 23.625 MHz.
Assuntos
Anisotropia , Eletricidade , Corpo Humano , Imagens de Fantasmas , Animais , Géis , Humanos , RatosRESUMO
It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of immune responses towards a T helper type 1 (Th1) or Th2 milieu. In this study, we attempted to generate LCs from murine bone marrow cells and elicit a Th1- or Th2-prone immune response through the LCs after stimulation with Th1 or Th2 adjuvant. LCs were generated from murine bone marrow cells using granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and transforming growth factor (TGF)-ß, and were obtained as I-A(d) positive cells. Mice were primed with Th1/Th2 adjuvant- and ovalbumin (OVA)-pulsed LCs and then given a booster injection of OVA 2 days later via the hind footpad. Five days after the OVA injection, the cytokine response in the draining popliteal lymph nodes was investigated by reverse transcription-polymerase chain reaction (RT-PCR) flow cytometry and enzyme-linked immunosorbent assay (ELISA). The generated LCs expressed typical LC surface markers, E-cadherin and Langerin, and were classified accordingly as LC-like dendritic cells (LDCs). Administration of Th1 adjuvant, cytosine-phosphate-guanosine (CpG)-DNA- and OVA-pulsed LDCs into the hind footpads of mice induced a Th1-prone immune response, as represented by up-regulation of IFN-γ production and down-regulation of IL-4 production in the lymph node cells. Conversely, Th2 adjuvant, histamine-pulsed LDCs induced a Th2-prone immune response, as represented by up-regulation of IL-4 production and down-regulation of IFN-γ production. These results suggest that LDCs may be used as a substitute for LCs and have the ability to induce the development of Th1 and Th2 cells in vivo. Our experimental system would therefore be useful for screening of inhibitors of Th1/Th2 differentiation in order to control allergic disease.
Assuntos
Células de Langerhans/citologia , Células Th1/imunologia , Equilíbrio Th1-Th2 , Células Th2/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Antígenos de Superfície/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Caderinas/metabolismo , Diferenciação Celular/imunologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Interferon gama/biossíntese , Interleucina-4/biossíntese , Interleucina-4/farmacologia , Células de Langerhans/imunologia , Lectinas Tipo C/metabolismo , Linfonodos/imunologia , Linfonodos/metabolismo , Lectinas de Ligação a Manose/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Th1/citologia , Células Th2/citologia , Fator de Crescimento Transformador beta/farmacologiaRESUMO
INTRODUCTION: Social anxiety disorder is believed to be a stress-induced disease. Although it can be inferred from the symptoms during attacks that there exists some abnormality of autonomic nervous system in any of the stress systems in social anxiety disorder, little evidence has been reported. This study focused on comparing the reactivity of 2 stress systems, the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis in patients with social anxiety disorder. METHODS: 32 patients with the generalized type of social anxiety disorder were compared with 80 age- and gender-matched controls. We collected saliva samples from patients and controls before and after electrical stimulation to measure the concentrations of salivary alpha-amylase (sAA) and salivary cortisol. Profile of Mood State (POMS) and State-Trait Anxiety Inventory (STAI) scores and Heart Rate Variability (HRV) were also determined following stimulation. RESULTS: SAA in patients displayed a significantly higher level at baseline and a significantly larger response to electrical stimulation as compared to controls, whereas no group differences were seen in any HRV. Neither within-subject nor group differences were seen in salivary cortisol levels. CONCLUSIONS: These results suggest that SAD patients displayed enhanced ANS (but not HPA axis) activity vs. healthy controls.
Assuntos
Transtornos de Ansiedade/metabolismo , Hidrocortisona/metabolismo , alfa-Amilases/metabolismo , Adulto , Transtornos de Ansiedade/enzimologia , Transtornos de Ansiedade/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Estudos de Casos e Controles , Estimulação Elétrica , Feminino , Frequência Cardíaca/fisiologia , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Nervo Mediano/fisiologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Saliva/metabolismoRESUMO
WHAT IS KNOWN AND OBJECTIVE: Calcium channel blockers (CCBs), which have been widely used for the treatment of hypertension and angina pectoris, decrease lower oesophageal sphincter pressure and, as a result, can exacerbate gastrointestinal disease. In a previous study, increased risk of exacerbation of gastrointestinal disease among elderly patients following treatment with CCBs was identified. The prevalence of gastrointestinal diseases has increased in elderly patients, and it is possible that treatment with CCBs may have undesirably influenced this increase. The change in risk of gastrointestinal disease can be estimated by analysing changes in the prescription of antisecretory drugs as an outcome of exacerbation of gastrointestinal disease caused by CCBs. METHODS: It was hypothesized that patients who were prescribed CCBs would also change their use of antisecretory drugs. From September 2005 to August 2009, a dynamic retrospective cohort study was performed at five community pharmacies in Nagasaki, Japan, to assess alteration of antisecretory drug therapy following treatment with CCBs. Correlations with alterations of antisecretory drug therapy were determined by the Cox proportional hazards model. RESULTS AND DISCUSSION: The proposed study included 260 patients who were prescribed CCBs and 155 controls. During the study period, 53 patients were prescribed CCBs and 13 controls altered their antisecretory drug therapy; the hazard ratio was 2·22 (95% CI 1·25-4·26). WHAT IS NEW AND CONCLUSION: Calcium channel blocker treatment of patients with gastrointestinal disease was associated with alteration in frequency of prescription and an increase in dosage of antisecretory drugs. For clinical management of hypertension, alternative antihypertensive drugs may be considered for patients with gastrointestinal diseases. Further studies are required to determine the influence of CCB therapy on gastroesophageal diseases, suggested by the increase in use of antisecretory drugs.
Assuntos
Bloqueadores dos Canais de Cálcio/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Hipertensão/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos de Coortes , Serviços Comunitários de Farmácia/estatística & dados numéricos , Relação Dose-Resposta a Droga , Feminino , Fármacos Gastrointestinais/administração & dosagem , Gastroenteropatias/fisiopatologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
In the mature rat parotid gland, myoepithelial cells (MEC) invest intercalated ducts, but not acini. During postnatal development, however, these cells differentiate around both intercalated ducts and acini, then translocate to only intercalated ducts during weaning. Previously, we found that thyroxine (T(4)) accelerates translocation of cells with small secretory granules from acini into intercalated ducts and the number of apoptotic cells increased tremendously with high doses. We present here additional analysis of the effects of T(4) on developing rat parotid gland, namely, the distribution of MEC and the proliferation of parenchymal cells. Beginning at age four days, pups were given daily subcutaneous injections of low, medium, and high doses of T(4) or vehicle or no injection. At ages 4, 7, 10, and 15 days, glands were excised and processed for light microscopy. Sections were double-immunostained with antibodies against proliferating cell nuclear antigen (PCNA) and actin, and counterstained with hematoxylin. Proliferative activity was assessed via PCNA histochemistry and MEC were identified using actin histochemistry. MEC in the T(4) groups invested mostly acini at 15 days in vehicle/normal glands and mostly intercalated ducts after 10 days in the T(4) groups. The proliferative activity of acinar cells and MEC in vehicle/normal glands declined progressively with age and T(4) increased the rate of this decline in the MEC in a dose-dependent manner. We conclude that T(4) accelerates the translocation of MEC from acini to intercalated ducts and that an important mechanism is the more rapid decline in the proliferative activity of MEC than in acinar cells in the T(4) groups. Some of the decline in the proliferative activity of all cells in the high and medium dose T(4) groups after seven days may have been due to dose-related thyroxine toxicity.
Assuntos
Epitélio/efeitos dos fármacos , Células Musculares/efeitos dos fármacos , Glândula Parótida/efeitos dos fármacos , Glândula Parótida/crescimento & desenvolvimento , Tiroxina/farmacologia , Actinas/análise , Animais , Animais Recém-Nascidos , Anticorpos , Diferenciação Celular , Células Epiteliais/química , Epitélio/química , Feminino , Histocitoquímica , Células Musculares/química , Músculo Liso/química , Glândula Parótida/química , Antígeno Nuclear de Célula em Proliferação/análise , Ratos , Ratos Sprague-Dawley , Vesículas Secretórias/química , Organismos Livres de Patógenos EspecíficosRESUMO
Aging is thought to be a risk factor to develop vulnerability of the neuroendocrine system, including the hypothalamic-pituitary-adrenal (HPA) axis, and dysregulation of this axis characterized by dexamethasone (DEX)-mediated negative feedback resistance is sometimes observed in elderly humans and animals. However, the influence of aging on the feedback system including an involvement of the brain is not fully understood. In the present study, we examined the suppressive effects of DEX by the systemic injection or the intracranial infusion into the prefrontal cortex (PFC), hippocampus, and hypothalamus on circulating corticosterone levels, and compared between young (3-month-old) and aged (24-month-old) rats. Moreover, we examined expression levels of glucocorticoid receptors (GRs) and their translocation from the cytoplasm to the nucleus using immunohistochemical and Western immunoblot techniques in the pituitary in addition to three brain regions. When DEX was injected systemically, the suppressive response was significantly enhanced in aged rats, compared with young rats. When DEX was infused into three brain regions, the suppressive response to DEX was abolished in aged rats. The immunohistochemical analysis revealed that the number of GR positive cells in the PFC, hippocampus, and hypothalamus was decreased, but that in the pituitary was increased, in aged rats, compared with young rats. The Western immunoblot analysis confirmed these results. Thus, basal expression levels of GRs in three brain regions were decreased, but those in the pituitary were increased, in aged rats. After the injection or infusion of DEX, the translocation of GRs in three brain regions was reduced, but that in the pituitary was enhanced, in aged rats. These results suggest that aging in rats enhances the feedback ability at the systemic level, which mainly involves the pituitary, but it attenuates the ability in the brain. These mechanisms may underlie the vulnerable neuroendocrine systems associated with aging.
Assuntos
Envelhecimento/fisiologia , Encéfalo/metabolismo , Retroalimentação Fisiológica/fisiologia , Regulação da Expressão Gênica/fisiologia , Glucocorticoides/metabolismo , Fatores Etários , Análise de Variância , Animais , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Contagem de Células , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Corticosterona/sangue , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Retroalimentação Fisiológica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Masculino , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Radioimunoensaio/métodos , Ratos , Ratos Endogâmicos F344 , Receptores de Glucocorticoides/metabolismoRESUMO
This Letter studies the relationship between the elastic constants and the microstructure of nanocrystalline diamond thin films deposited by the chemical vapor deposition method doping various concentration of N2 gas. The elastic constants were measured by resonant ultrasound spectroscopy and picosecond laser ultrasounds. The increase of N2 gas decreases the diagonal elastic constants, but increases the off-diagonal elastic constants. The micromechanics calculation can explain this unusual elastic behavior, and it predicts thin graphitic phases at grain boundaries.
RESUMO
Section of motor nerve fibers (axotomy) elicits a variety of morphofunctional responses in the motoneurons in the motor nuclei. Later than the fifth post-operational day after section of the facial nerve, synapse elimination occurs in the facial motoneuron pool, leading to gradual abolishment of synaptic input-driven activities of the axotomized motoneurons. However, it remains unknown how the amount of synaptic input changes during this period between the axotomy and the synaptic elimination. Here we examined a hypothesis that axotomy of the motoneurons itself modifies the synaptic inputs to the motoneurons. One day after axotomy, the postsynaptic currents, mostly mediated by non-N-methyl-D-aspartic acid (non-NMDA) receptors, recorded from the axotomized facial motoneurons in the acute slice preparations of the rats were of higher frequency and larger amplitude than those in the intact motoneurons. This difference was not observed after the third post-operational day and appeared earlier than the changes in the electrophysiological properties and increase in the number of dead neurons in the axotomized motor nucleus. The larger postsynaptic current frequency of the axotomized motoneurons was observed both in the absence and in the presence of tetrodotoxin citrate, suggesting that increased excitability and facilitated release underlie the postsynaptic current frequency increase. These results suggest that synaptic re-organization occurs in the synapses of motoneurons at an early stage following axotomy.
Assuntos
Tronco Encefálico/citologia , Traumatismos do Nervo Facial/fisiopatologia , Neurônios Motores/fisiologia , Transmissão Sináptica/fisiologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Fatores Etários , Animais , Animais Recém-Nascidos , Axotomia/métodos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Lateralidade Funcional , Imuno-Histoquímica/métodos , Técnicas In Vitro , Masculino , Potenciais da Membrana/fisiologia , Neurônios Motores/efeitos dos fármacos , Técnicas de Patch-Clamp/métodos , Ratos , Ratos Wistar , Bloqueadores dos Canais de Sódio/farmacologia , Estilbamidinas/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/efeitos da radiação , Sinaptofisina/metabolismo , Tetrodotoxina/farmacologia , Fatores de TempoRESUMO
St. John's Wort (Hypericum perforatum, SJW) has been used as a herbal medicine for the treatment of depression in oral doses of 900-1050 mg/day in humans. However, the ingestion of SJW was reported to cause interactions with drugs. In the present study, we examined the effects of SJW treatment on the induction of drug transporters and enzymes in rats. An immunoblot analysis was performed to quantify the expression of the transporters and enzymes. SJW was given at a dose of 400 mg/kg/day, since it was reported that 400 mg/kg/day is antidepressant effective dose in rats. When SJW was administered for 10 days, the amounts of multidrug resistance protein 2 (MRP2), glutathione S-transferase-P (GST-P) and cytochrome P450 1A2 (CYP1A2) in the liver were increased to 304%, 252% and 357% of controls, respectively, although the amounts of P-glycoprotein and multidrug resistance protein 1 were not changed. Under the same conditions, an increase of MRP2 in the kidney was not observed. The increase in the levels of each protein was maximal at 10 days after SJW treatment and lasted for at least 30 consecutive days. These results suggest that SJW induces hepatic MRP2, GST-P and CYP1A2 overexpressions, and thus, it could affect drug metabolism, conjugation and disposition.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Proteínas de Transporte/biossíntese , Citocromo P-450 CYP1A2/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/biossíntese , Hypericum/química , Administração Oral , Animais , Interações Medicamentosas , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Extratos Vegetais/farmacologia , Ratos , Ratos WistarRESUMO
In vitro studies demonstrated that the accumulation of 2-deoxy-D-glucose was reduced in multidrug resistant cell lines. In animal study, it has been suggested that 2-[18F]fluoro-2-deoxy-D-glucose (FDG) may be a marker for multidrug resistance (MDR). The aim of this clinical study was to compare MDR characteristics by immunohistochemical assay with FDG uptake and investigate whether FDG is a marker for MDR in patients with untreated lung cancer. Forty-seven patients with 49 untreated lung cancers, who had undergone both preoperative FDG PET imaging and thoracotomy, were enrolled in this study. Before surgery, FDG PET was performed 40 min after injection, and standardized uptake values (SUVs) were obtained. Patients were classified into low-SUV (< or = 5) and high-SUV (> 5) groups. After surgery, the expression of P-glycoprotein (Pgp) was investigated by immunohistochemistry, and the lung cancer FDG uptake was analysed for possible association with Pgp expression. The strong intensity of Pgp immunoreactivity was seen only in the low-SUV group. The percentage of the Pgp positive area was significantly lower in the high-SUV group (21.7 +/- 13.4%) than in the low-SUV group (44.1 +/- 29.7%) (P = 0.015). In the high-SUV group, the percentage of Pgp positive area did not exceed 50%. In lung adenocarcinoma, the intensity of Pgp immunoreactivity and the percentage of Pgp positive area increased with degree of cell differentiation, while FDG uptake decreased with degree of cell differentiation. Bronchioloalveolar carcinoma, in particular, showed overexpression of Pgp and modest uptake of FDG. In conclusion, Pgp expression was found to be inversely related to FDG uptake in untreated lung cancer. Pgp expression correlated with the degree of cell differentiation in adenocarcinomas, whilst FDG uptake was inversely related to cell differentiation. FDG may be an in vivo marker for MDR in patients with untreated lung cancer.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Biomarcadores Tumorais/metabolismo , Resistência a Múltiplos Medicamentos , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Adenocarcinoma Bronquioloalveolar/diagnóstico por imagem , Adenocarcinoma Bronquioloalveolar/metabolismo , Adenocarcinoma Bronquioloalveolar/patologia , Adenocarcinoma Bronquioloalveolar/cirurgia , Idoso , Idoso de 80 Anos ou mais , Divisão Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
For the first time, four different methods to determine the degree of molecular orientation from polarized Raman spectroscopy measurements are compared. The great influence of molecular orientation on the properties of polymers has driven the development of multiple experimental techniques and procedures. This study is based on the C(1)-C(4) ring stretching vibration of poly(propylene terephthalate) (PPT) at 1614 cm(-1). It is shown that simply ratioing the band intensity obtained with the polarization parallel and perpendicular to the unique axis of the sample provides a good qualitative method to observe the evolution of orientation in a series of similar samples. To quantitatively compare the degree of orientation one needs to utilize a more complex method yielding the second- and fourth-order parameters of the orientation distribution function (P(2) and P(4), respectively). To date, most studies have been based on the assumption of a cylindrically symmetric polarizibility tensor. It is shown that this assumption is highly questionable although this method has been used fairly successfully in the past. This method results in orientation parameters that are clearly different from those obtained with the two more complex procedures. The most complex method, both theoretically and experimentally, requires the most measurements per sample. Major problems have occurred when trying to calculate the desired parameters, in particular for samples with high birefringence. These problems are related to experimental complexities occurring for measurements when the samples are tilted with respect to the polarization direction of the incident light. These measurements are replaced by a simple determination of depolarization ratio in the third method. This method assumes that the depolarization ratio is independent of changes in molecular orientation and structure. It was found that this assumption is not correct. Thus, the most complex method is the method of choice to quantitatively determine the second- and fourth-order parameters of the orientation distribution function, unless one has knowledge of the depolarization ratio of each sample being studied. That knowledge permits the use of an experimentally simpler method to obtain the desired parameters.
Assuntos
Materiais Biocompatíveis/química , Poliésteres/química , Análise Espectral Raman/métodos , Algoritmos , Birrefringência , Teste de Materiais/métodos , Estrutura MolecularRESUMO
OBJECTIVE: In order to elucidate the effects of radiation on centrosome hyperamplification (CH), we examined the centrosome duplication cycle in KK47 bladder cancer cells following irradiation. METHODS: KK47 cells were irradiated with various doses of radiation and were examined for CH immunostaining for gamma-tubulin. RESULTS: Nearly all control cells contained one or two centrosomes, and mitotic cells displayed typical bipolar spindles. The centrosome replication cycle is well regulated in KK47. Twenty-four hours after 5-Gy irradiation, approximately 80% of irradiated cells were arrested in G2 phase, and at 48 h after irradiation, 56.9% of cells contained more than two centrosomes. Laser scanning cytometry performed 48 h after irradiation showed the following two pathways: (1) unequal distribution of chromosomes to daughter cells, or (2) failure to undergo cytokinesis, resulting in polyploidy. With mitotic collection, M-phase cells with CH could be divided into G1 cells with micronuclei and polyploidal cells. Fluorescence in situ hybridization analysis showed clear signs of chromosomal instability (CIN) at 48 h after irradiation. The present study had two major findings: (1) continual duplication of centrosomes occurred in the cell cycle-arrested cells upon irradiation, leading to centrosome amplification; (2) cytokinesis failure was due to aberrant mitotic spindle formation caused by the presence of amplified centrosomes. Abnormal mitosis with amplified centrosomes was detected in the accumulating G2/M population after irradiation, showing that this amplification of centrosomes was not caused by failure to undergo cytokinesis, but rather that abnormal mitosis resulting from amplification of centrosomes leads to cytokinesis block. CONCLUSION: These results suggest that CH is a critical event leading to CIN following exposure to radiation.
Assuntos
Centrossomo/efeitos da radiação , Instabilidade Cromossômica/efeitos da radiação , Amplificação de Genes/efeitos da radiação , Mitose/efeitos da radiação , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/radioterapia , Western Blotting , Linhagem Celular Tumoral/efeitos da radiação , Humanos , Hibridização in Situ Fluorescente , Marcação In Situ das Extremidades Cortadas , Citometria de Varredura a Laser , Poliploidia , Tubulina (Proteína)/análise , Neoplasias da Bexiga Urinária/químicaRESUMO
A new method has been developed to determine an orientation-independent Raman scattered intensity based on various polarized Raman measurements. The equivalent term in infrared spectroscopy is the structural absorbance, which has existed for many years. As with the structural absorbance, the calculated Raman intensity allows one to observe spectral changes that are due uniquely to morphological changes in a set of different samples in the presence of orientation differences. The full theoretical development is presented, followed by an example based on a set of polymer fibers processed under different conditions leading to different morphologies and degrees of molecular orientation.
Assuntos
Algoritmos , Cristalização/métodos , Modelos Moleculares , Polietilenotereftalatos/química , Polietilenotereftalatos/classificação , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Espectral Raman/métodos , Anisotropia , Simulação por Computador , Microscopia de Polarização/métodos , Conformação Molecular , Polietilenotereftalatos/análiseRESUMO
OBJECTIVE: Chromosomal instability (CIN) is a common feature of malignant tumors. Centrosome hyperamplification (CH) occurs frequently in human cancers, and may be a contributing factor in CIN. In this study, we investigated the relationship between CH and CIN in bladder cancer. METHODS: Clinical samples obtained by transurethral resection from 22 patients with bladder cancer were examined (histological grade G1, 5 cases; G2, 6 cases; G3, 11 cases). CH was evaluated by immunohistochemistry using anti-pericentrin antibody. CIN was evaluated by fluorescence in situ hybridization (FISH). FISH probes for pericentromeric regions of chromosomes 3, 7, and 17 were hybridized to touch preparations of nuclei from frozen tissues. We also analyzed the centrosome replication cycle of bladder cancer by laser scanning cytometry (LSC). RESULTS: Of the 22 cases examined, 18 (81.8%) had centrosome hyperamplification: CH 0, 4 cases (18.1%); CH I, 5 cases (22.7%); CH II, 5 cases (22.7%); CH III, 8 cases (36.4%). The grade of CH was directly proportional to the histological grade (p=0.03, chi(2) test). LSC analysis showed that the centrosome replication cycle was well regulated in pathologically low-grade bladder cancer, which did not have chromosomal instability. In contrast, we found marked variability of centrosomes in pathologically high-grade bladder cancer, which had chromosomal instability. CH and CIN were both detected in pathologically high-grade tumors. The grade of CH was directly proportional to the CIN grade (p=0.0079, chi(2) test). CONCLUSION: The results of the present study suggest that CH may be involved in CIN in bladder cancer.
Assuntos
Centrossomo/patologia , Aberrações Cromossômicas , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Antígenos/análise , Centrossomo/fisiologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Ploidias , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologiaRESUMO
BACKGROUND: Firearm ownership has often been used to measure access to weapons. However, persons who own a firearm may not have access to it and conversely, persons who do not own a firearm may be able to access one quickly. OBJECTIVES: To examine whether using firearm ownership is a reasonable proxy for access by describing the demographic characteristics associated with ownership and access. METHODS: Data are from the 1994 Injury Control and Risk Survey, a national, random digit dial survey. Information about household firearm ownership and ready access to a loaded firearm were collected and weighted to provide national estimates. Adjusted odds ratios for three separate models were calculated using logistic regression. RESULTS: A total of 1353 (27.9%) respondents reported both having a firearm in the household and ready access to one. An additional 313 respondents (8.1%) reported having a firearm, but were not able to access these weapons. Another 421 respondents (7.2%) did not have a firearm in or around their home, yet reported being able to retrieve and fire one within 10 minutes. Based on the logistic regression findings, the demographic characteristics of this latter group are quite different from those who report ownership. Those who do not have a firearm, but report ready access to one, are more likely to be ethnic minorities, single, and living in attached homes. CONCLUSIONS: Asking only about the presence of a firearm in a household may miss some respondents with ready access to a loaded firearm. More importantly, those who do not own a firearm, but report ready access to one, appear to be qualitatively different from those who report ownership. Caution should be exercised when using measures of ownership as a proxy for access.
Assuntos
Armas de Fogo/estatística & dados numéricos , Utensílios Domésticos/estatística & dados numéricos , Adulto , Distribuição por Idade , Escolaridade , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Estado Civil/estatística & dados numéricos , Pessoa de Meia-Idade , Razão de Chances , Análise de Regressão , Distribuição por Sexo , Estados UnidosRESUMO
OBJECTIVES: To estimate the national prevalence of youth access to alcohol, a gun, or both alcohol and a gun, in their home and to describe the demographic characteristics associated with access to either alcohol or a gun. METHODS: Cross sectional data from the 1995 in-home survey of the National Longitudinal Study of Adolescent Health, which used a nationally representative randomly selected school based sample (n=18 924) of adolescents in grades 7-12, were analyzed. The current analyses were restricted to those adolescents 12-18 years of age (n=18 454). Crude logistic regression analyses was used to determine the demographic characteristics associated with access to alcohol or a gun in the home. RESULTS: Overall, 28.7% of US adolescents reported having easy access to alcohol in the home. Availability of alcohol was associated with race/ethnicity, mother's education, family structure, and welfare status. Similarly, 24.3% of US adolescents reported easy access to a gun in the home. Availability of a gun in the home was associated with gender, race/ethnicity, mother's education, family structure, and welfare status. Among those that reported that a gun was available in their home, most reported availability of a shotgun (63.0%) followed by a rifle (61.3%), handgun (57.3%), and other gun (16.4%). Ten per cent of adolescents reported availability of both alcohol and a gun in their home. CONCLUSIONS: One quarter of US adolescents reported easy access to either alcohol or a gun in their home. Given the risks associated with the misuse of alcohol and guns among adolescents, efforts to increase public awareness of the availability of alcohol and guns in the home are needed.
Assuntos
Comportamento do Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Armas de Fogo/estatística & dados numéricos , Adolescente , Distribuição por Idade , Criança , Estudos Transversais , Coleta de Dados , Feminino , Humanos , Masculino , Prevalência , Distribuição Aleatória , Análise de Regressão , Fatores de Risco , Distribuição por Sexo , Fatores SocioeconômicosRESUMO
BACKGROUND: The aim of this study was to characterize the lymph vessels in different parts of the gastrointestinal tract and also to evaluate morphometric changes in these vessels during cirrhotic portal hypertension. METHODS: Sixteen patients with cirrhotic portal hypertension and 18 control subjects without portal hypertension were enrolled in the study. Tissue specimens were collected at autopsy or surgery, and were stained enzyme histochemically, using 5'-nucleotidase and alkaline phosphatase to distinguish lymph vessels and blood vessels, respectively. The numbers of vessels and their luminal areas were estimated using computer graphics software (National Institutes of Health [NIH] image program). RESULTS: The numbers and luminal areas of the lymph vessels varied considerably among the different organs of the gastrointestinal tract, both in controls and in the patients with cirrhotic portal hypertension. There was no significant difference in the numbers of lymph vessels between controls and patients with cirrhotic portal hypertension. However, the luminal area of the lymph vessels in the esophagus and stomach was significantly greater in the patients with cirrhotic portal hypertension than in the controls. These differences in lymph vessels were not seen in the small intestine and colon. CONCLUSIONS: These data indicate that dilatation of lymph vessels may be related to the absorption of excess interstitial fluid, resulting from congestion, in cirrhotic portal hypertension.