RESUMO
Astrocytes participate in information processing by releasing neuroactive substances termed gliotransmitters, including ATP. Individual astrocytes come into contact with thousands of synapses with their ramified structure, but the spatiotemporal dynamics of ATP gliotransmission remains unclear, especially in physiological brain tissue. Using a genetically encoded fluorescent sensor, GRABATP1.0 , we discovered that extracellular ATP increased locally and transiently in absence of stimuli in neuron-glia co-cultures, cortical slices, and the anesthetized mouse brain. Spontaneous ATP release events were tetrodotoxin-insensitive but suppressed by gliotoxin, fluorocitrate, and typically spread over 50-250 µm2 area at concentrations capable of activating purinergic receptors. Besides, most ATP events did not coincide with Ca2+ transients, and intracellular Ca2+ buffering with BAPTA-AM did not affect ATP event frequency. Clustering analysis revealed that these events followed multiple distinct kinetics, and blockade of exocytosis only decreased a minor group of slow events. Overall, astrocytes spontaneously release ATP through multiple mechanisms, mainly in non-vesicular and Ca2+ -independent manners, thus potentially regulating hundreds of synapses all together.
Assuntos
Astrócitos , Sinapses , Camundongos , Animais , Astrócitos/metabolismo , Sinapses/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio/fisiologiaRESUMO
The utility of endoscopic ultrasound fine-needle aspiration cytology (EUS-FNAC) or endoscopic ultrasound fine-needle aspiration biopsy (EUS-FNAB) for diagnosis of small and large pancreatic ductal adenocarcinomas (PDACs) remains in question. We addressed this by analyzing 97 definitively diagnosed cases of PDAC, for which both EUS-FNAC and EUS-FNAB had been performed. We subclassified the 97 solid masses into small (n = 35) or large (n = 62) according to the maximum tumor diameter (<24 mm or ≥24 mm) and compared the diagnostic sensitivity (truly positive rate) of EUS-FNAC and of EUS-FNAB for small and large masses. Diagnostic sensitivity of EUS-FNAC did not differ between large and small masses (79.0% vs. 60.0%; p = 0.0763). However, the diagnostic sensitivity of EUS-FNAB was significantly higher for large masses (85.5% vs. 62.9%; p = 0.0213). Accurate EUS-FNAC-based diagnosis appeared to depend on the degree of cytological atypia of cancer cells, which was not associated with quantity of cancer cells. The accuracy of EUS-FNAB-based diagnosis appeared to depend on cancer cell viability in large masses and cancer volume in small masses. Based on the advantages or disadvantages in each modality, both modalities play an important role in the qualitative diagnosis of PDAC as a complementary procedure.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Sensibilidade e Especificidade , Neoplasias PancreáticasRESUMO
OBJECTIVE: To assess the utility of a newly developed squash cytology (SC)-based scoring system for accurate intraoperative diagnosis of schwannoma. METHODS: We first compared SC-based and frozen section (FS) diagnoses with final pathological diagnoses of schwannoma (16 cases), meningioma (39 cases) and low-grade astrocytoma (16 cases). Then, by logistic regression modeling, we identified features of SC preparations that were independently predictive of schwannoma. To develop a diagnostic scoring system, we assigned one point to each feature, and performed receiver operating characteristic analysis to determine the score cut-off value that was most discriminatory for differentiating schwannoma from the other tumour types. We then compared accuracy, sensitivity, and specificity of diagnosis before and after the application of the scoring system. RESULTS: Overall diagnostic concordance rates for SC and FS were almost the same, at 73.2% (52/71) and 77.5% (55/71 cases), respectively. Of the 16 SC features entered into the analysis, the following nine were found to independently predict schwannoma, and were thus incorporated into the scoring system: smooth cluster margins, few or no isolated tumour cells, fibrillary stroma, spindle-shaped nuclei, parallel arrangement of stroma, parallel arrangement of nuclei, presence of anisonucleosis, absence of nucleoli, and hemosiderin deposition. A cut-off score of four items yielded the best sensitivity, specificity and predictive values for prediction of schwannoma. Use of the scoring system improved accuracy of intraoperative diagnosis from 80.3% to 94.4%, sensitivity from 56.2% to 93.8%, and specificity from 87.3% to 94.5%. CONCLUSION: Our proposed SC-based scoring system will increase accuracy of intraoperative diagnosis of schwannoma vs non-schwannoma tumours.
Assuntos
Astrocitoma , Neurilemoma , Astrocitoma/diagnóstico , Astrocitoma/patologia , Astrocitoma/cirurgia , Citodiagnóstico , Técnicas Citológicas , Humanos , Neurilemoma/diagnóstico , Neurilemoma/patologiaRESUMO
RNA localization in subcellular compartments is essential for spatial and temporal regulation of protein expression in neurons. Several techniques have been developed to visualize mRNAs inside cells, but the study of the behavior of endogenous and nonengineered mRNAs in living neurons has just started. In this study, we combined reduction-triggered fluorescent (RETF) probes and fluorescence correlation spectroscopy (FCS) to investigate the diffusion properties of activity-regulated cytoskeleton-associated protein (Arc) and inositol 1,4,5-trisphosphate receptor type 1 (Ip3r1) mRNAs. This approach enabled us to discriminate between RNA-bound and unbound fluorescent probes and to quantify mRNA diffusion parameters and concentrations in living rat primary hippocampal neurons. Specifically, we detected the induction of Arc mRNA production after neuronal activation in real time. Results from computer simulations with mRNA diffusion coefficients obtained in these analyses supported the idea that free diffusion is incapable of transporting mRNA of sizes close to those of Arc or Ip3r1 to distal dendrites. In conclusion, the combined RETF-FCS approach reported here enables analyses of the dynamics of endogenous, unmodified mRNAs in living neurons, affording a glimpse into the intracellular dynamics of RNA in live cells.
Assuntos
Corantes Fluorescentes/química , Neurônios/química , RNA Mensageiro/metabolismo , Animais , Células Cultivadas , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Corantes Fluorescentes/síntese química , Receptores de Inositol 1,4,5-Trifosfato/genética , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Imagem Óptica , RNA Mensageiro/genética , Ratos , Ratos Wistar , Espectrometria de FluorescênciaRESUMO
To address the diagnostic performance of scratch-imprint cytology (SIC), in this study we compared intraoperative diagnoses of pulmonary lesions between SIC and frozen section histology (FSH) for accuracy with respect to the final pathological diagnosis. We histologically divided 206 pulmonary lesions (resected surgically) into two groups (benign and malignant) and compared each intraoperative diagnosis by SIC and FSH with the final pathological diagnoses. We also examined the radiological existence of pure ground-glass opacity (GGO) nodules in each group. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 91.5%, 100%, 100%, 63.6%, and 92.6%, respectively for SIC, and 98.2%, 100%, 100%, 92.1% and 98.5%, respectively, for FSH. Thus, we concluded that diagnosis by SIC is reliable for malignancy, but not for benign lesions. All pure GGO nodules (19; 9.2%) were noninfectious and malignant with a high accuracy of FSH diagnosis (100%), in comparison with those of low accuracy with a SIC diagnosis (57.9%). SIC can be an appropriate intraoperative diagnostic tool where multiple cytotechnologists observe intraoperative SIC preparations scratched evenly across the whole lesion including the peripheral area of the mass.
Assuntos
Citodiagnóstico/métodos , Pneumopatias/diagnóstico , Secções Congeladas/métodos , Humanos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: We assessed whether intraoperative squash cytology could provide surgeons with a qualitative diagnosis of brain lesions when frozen section diagnosis is equivocal. METHODS: The study included 51 lesions that were diagnosed intraoperatively as equivocal brain tumour on the basis of frozen section. We retrospectively classified the lesions into five groups according to the final histopathological diagnoses (I: malignant lymphomas; II: diffuse astrocytic and oligodendroglia tumours; III: pituitary adenomas, IV: metastatic carcinomas; V: others). We assessed the squash cytology features of Groups I-IV and of the specific lesion types, and compared features among the groups. RESULTS: The four groups differed in a range of salient cytomorphological features: lymphoglandular bodies in Group I (eight of nine cases), cytoplasmic fibrillary processes in Group II (six of eight cases), low-grade nuclear atypia in Group III (seven of seven cases), and large nuclei (approximately 80 µm2 ) and nuclear crush artefacts in Group IV (seven of nine cases). CONCLUSION: Findings of lymphoglandular bodies on intraoperative squash cytology can be considered characteristic of malignant lymphomas, while cytoplasmic fibrillary processes indicate diffuse astrocytic and oligodendroglial tumours. We conclude that squash cytology could yield a qualitative intraoperative diagnosis in over 25% of cases for which frozen section yields a diagnosis of equivocal brain tumour.
Assuntos
Neoplasias Encefálicas/diagnóstico , Encéfalo/patologia , Citodiagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/diagnóstico , Astrocitoma/patologia , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Feminino , Secções Congeladas , Glioma/diagnóstico , Glioma/patologia , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
We aimed to propose a biosafety algorithm for the protection of pathology staff during intraoperative examinations of pulmonary lesions when working with cytological imprints and/or frozen sections for the intraoperative diagnosis of pulmonary lesions. We examined 148 pulmonary surgical tissues obtained intraoperatively for imprint cytology (IC) and for frozen sectioning and compared the diagnoses against the final pathological diagnoses. We analyzed concordance and non-concordance rates and then used the data to produce a biosafety algorithm. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scratch-IC were 91%, 100%, 100%, 50% and 92%, respectively, and those of frozen sectioning were 99%, 100%, 100%, 96% and 99%, respectively. Our data indicate that frozen sectioning is unnecessary if scratch-IC yields a 'malignant' diagnosis but recommended with a 'benign' diagnosis. When a scratch-IC preparation deemed inadequate for a diagnosis or an abscess, the pathologist must consult the surgeon concerning the possibility of granuloma with caseous necrosis and should ask the surgeon to be prepared for a frozen section. If granuloma with caseous necrosis is found in the frozen section, the pathologist must immediately communicate the information to entire staff and perform a PCR test before making a permanent section.
Assuntos
Algoritmos , Granuloma/diagnóstico , Abscesso Pulmonar/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Contenção de Riscos Biológicos , Citodiagnóstico , Feminino , Secções Congeladas , Granuloma/patologia , Granuloma/cirurgia , Humanos , Cuidados Intraoperatórios , Abscesso Pulmonar/patologia , Abscesso Pulmonar/cirurgia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Manejo de EspécimesRESUMO
OBJECTIVE: This study aimed to determine the reliability of imprint cytology (IC) for intraoperative diagnosis of pulmonary lesions. METHODS: We reviewed 113 cases of pulmonary lesion resection for which a scratch imprint was made intraoperatively. We divided the specimens into two groups (benign and malignant) and compared the scratch IC-based diagnoses against the final histopathological diagnoses in each group for concordance. We also analysed those cases in which the scratch IC preparation was classified as inadequate. RESULTS: The sensitivity, specificity, positive and negative predictive values, and accuracy of IC diagnoses among the patient cohort were 87.7% (72/82), 100% (7/7), 100% (72/72), 41.2% (7/17) and 88.8% (79/89), respectively. IC yielded some false-negative results in terms of malignancy, although most of these imprints were of early cancer or cancer with mild cytological atypia. Five (41.6%) of 12 lesions for which the imprint was deemed inadequate were diagnosed histologically as granulomas with caseous necrosis. CONCLUSION: IC-based diagnoses of pulmonary lesions as malignant corresponded well with the final histopathological diagnoses, but IC-based diagnoses of negative (ie, without malignant cells) were not as reliable. Thus, pathologists should recognise the limitations of IC, especially for identifying malignant lesions. Also, the possibility of latent bacterial infection in a granuloma with caseous necrosis indicates that an IC preparation deemed inadequate for diagnosis should not be ignored.
Assuntos
Citodiagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias/diagnóstico , Adulto , Idoso , Biópsia por Agulha , Feminino , Granuloma/diagnóstico , Granuloma/patologia , Humanos , Cuidados Intraoperatórios , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico , Necrose/patologia , Neoplasias/patologiaRESUMO
Macrophages in atherosclerotic lesions accumulate large amounts of unesterified cholesterol. Excess cholesterol load leads to cell death of macrophages, which is associated with the progression of atherosclerotic lesions. Calcium depletion in the endoplasmic reticulum (ER) and subsequent pro-apoptotic aberrant calcium signaling are key events in cholesterol-induced macrophage death. Although these concepts imply cytoplasmic calcium events in cholesterol-loaded macrophages, the mechanisms linking cholesterol accumulation to cytoplasmic calcium response have been poorly investigated. Based on our previous finding that extracellularly applied cholesterol evoked robust calcium oscillations in astrocytes, a type of glial cells in the brain, we hypothesized that cholesterol accumulation in macrophages triggers cytoplasmic calcium elevation. Here, we showed that cholesterol application induces calcium transients in THP-1-derived and peritoneal macrophages. Inhibition of inositol 1,4,5-trisphosphate receptors (IP3Rs) and l-type calcium channels (LTCCs) prevented cholesterol-induced calcium transients and ameliorated cholesterol-induced macrophage death. These results suggest that cholesterol-induced calcium transients through IP3Rs and LTCCs are crucial mechanisms underlying cholesterol-induced cell death of macrophages.
Assuntos
Aterosclerose , Cálcio , Humanos , Cálcio/metabolismo , Macrófagos/metabolismo , Sinalização do Cálcio , Aterosclerose/metabolismo , Colesterol/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismoRESUMO
Interleukin (IL)-3 is a pleiotropic cytokine that regulates the survival, proliferation, and differentiation of hematopoietic cells. The binding of IL-3 to its receptor activates intracellular signaling, inducing transcription of immediate early genes (IEGs) such as c-fos, c-jun, and c-myc; however, transcriptional regulation under IL-3 signaling is not fully understood. This study assessed the role of the inhibitor of nuclear factor-κB kinases (IKKs) in inducing IL-3-mediated expression of IEGs. We show that IKK1 and IKK2 are required for the IL-3-induced immediate expression of c-fos and c-jun in murine hematopoietic Ba/F3 cells. Although IKK2 is well-known for its pivotal role as a regulator of the canonical nuclear factor-κB (NF-κB) pathway, activation of IKKs did not induce the nuclear translocation of the NF-κB transcription factor. We further revealed the important role of IKK2 in the activation of c-Jun N-terminal kinase (JNK), which mediates the IL-3-induced expression of c-fos and c-jun. These findings indicate that the IKK2-JNK axis modulates the IL-3-induced expression of IEGs in a canonical NF-κB-independent manner.
Assuntos
Interleucina-3 , NF-kappa B , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-jun/genética , Animais , Quinase I-kappa B/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , NF-kappa B/metabolismo , Transdução de SinaisRESUMO
A multitude of molecular interactions with chromatin governs various chromosomal functions in cells. Insights into the molecular compositions at specific genomic regions are pivotal to deepen our understanding of regulatory mechanisms and the pathogenesis of disorders caused by the abnormal regulation of genes. The locus-specific purification of genomic DNA using the clustered regularly interspaced short palindromic repeats (CRISPR) system enables the isolation of target genomic regions for identification of bound interacting molecules. This CRISPR-based DNA purification method has many applications. In this study, we present an overview of the CRISPR-based DNA purification methodologies as well as recent applications.
Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , DNA/isolamento & purificação , Genômica/métodos , Cromatina , Imunoprecipitação da Cromatina , Proteínas de Ligação a DNA , Genoma , HumanosRESUMO
BACKGROUND: Appropriate surgical treatment of epithelial ovarian tumors is reliant on intraoperative diagnosis. A retrospective study to compare the diagnostic accuracies of imprint cytology (IC) with frozen section histology (FSH) in these tumors was performed. METHODS: About 78 cases of IC-based and FSH-based diagnoses against the final histopathologic diagnoses in terms of both histologic subtype (serous, mucinous, endometrioid, or clear cell tumor) and behavioral type (benign, borderline, or malignant) were compared. The cytomorphologic features of the tumor cells (nuclear atypia, papillary clusters, adenoma cells, and necrosis) in relation to behavioral types were also evaluated. RESULTS: While the diagnostic accuracy of IC and FSH were similar with respect to behavioral type (87% and 88%, respectively), the diagnostic accuracy of IC was superior to that of FSH with respect to histologic subtype (83% and 74%, respectively). Among histopathologically confirmed malignant tumors, the diagnostic accuracy of IC (62/64; 97%) was superior to that of FSH (58/64; 91%). The presence of necrosis and absence of adenoma cells were significantly more prevalent among malignant group than among borderline and benign groups (P < .01, for both). CONCLUSION: Since the presence of necrosis and absence of adenoma cells around the carcinoma cells appear useful in distinguishing malignant and borderline tumors, it was proposed to include IC for further intraoperative assessment of any tumors initially diagnosed as a borderline tumor by FSH.
Assuntos
Algoritmos , Carcinoma Epitelial do Ovário/diagnóstico , Citodiagnóstico/métodos , Secções Congeladas/métodos , Adulto , Idoso , Feminino , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: The aim of this study was to determine whether intraoperative cytological evaluation of squash preparations is of benefit for differentiating high-grade from low-grade astrocytomas. METHODS: Squash preparations of 42 astrocytomas were classified histologically according to the World Health Organization (WHO) 2007 classification system as grade II (n = 12), grade III (n = 11), and grade IV (n = 19) and were divided into 2 groups, namely a low-grade group (grade II) and a high-grade group (grades III and IV). The focus was on morphological cell and vessel characteristics, namely nuclear atypia, chromatin pattern, nuclear enlargement, variation in nuclear size, the presence of nucleoli, mitosis, tumor necrosis, cell density, multibranched vessels, and vascular dilatation, and these characteristics were compared between the low- and high-grade groups. RESULTS: Nuclear atypia, the presence of coarse chromatin, variations in nuclear size, and cell density ≥200 per high-power field were significantly more prevalent in high- than in low-grade astrocytomas (p = 0.0407, p < 0.01, p < 0.01, and p < 0.01, respectively). Vessels with > 3 branches and a mean vessel diameter ≥20 µm were more prevalent in high- than in low-grade astrocytomas (p < 0.01). CONCLUSION: Squash preparation cytology provides added benefit for the intraoperative identification of high-grade astrocytoma.
Assuntos
Astrocitoma/diagnóstico , Vasos Sanguíneos/patologia , Neoplasias Encefálicas/diagnóstico , Encéfalo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/irrigação sanguínea , Astrocitoma/cirurgia , Biópsia , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/cirurgia , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Adulto JovemRESUMO
In hypertensive patients with chronic renal disease, angiotensin receptor blockers (ARBs) are among the first-line drugs, and calcium channel blockers (CCBs) are recommended as a second line. We examined the effects of two therapeutic strategies using ARBs and benidipine, a CCB, on blood pressure (BP), urinary albumin excretion (UAE), and cost-effectiveness in hypertensive patients with albuminuria. Patients whose BP was 140/90 mmHg or higher despite treatment with low- or medium-dose ARBs were assigned randomly to two groups. In Group A (n=14), the ARB dose was maximized and then benidipine was added until BP targets were reached (<130/85 mmHg). In Group B (n=18), benidipine was administered first and then the ARB dose was increased until BP targets were reached. The BP targets were achieved by ARB alone in 36% of Group A patients and by the addition of benidipine in 83% of Group B patients. Finally, BP decreased in each group, reaching the targets in 93% of Group A patients and 94% of Group B patients after a 4-month therapeutic period. UAE was decreased in both groups after a 4-month therapeutic period compared to the allocation period (-33+/-6% in Group A, -31+/-6% in Group B; p<0.001, respectively). The monthly drug cost was higher (11,426+/-880 vs. 8,955+/-410 yen, p=0.012) and the cost-effectiveness of antihypertensive treatment was lower (p=0.003) in Group A than in Group B. We conclude that the addition of benidipine to low- or medium-dose ARB is, in light of the renal protection and the cost-effectiveness of this approach, a useful therapeutic strategy for controlling BP in hypertensive patients with albuminuria.
Assuntos
Albuminúria/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Di-Hidropiridinas/economia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Rim/efeitos dos fármacos , Idoso , Albuminúria/etiologia , Albuminúria/fisiopatologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/economia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Análise Custo-Benefício , Di-Hidropiridinas/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
We report two cases of advanced low rectal cancer, with preoperative chemo-radiation therapy leading to a complete histological response. Case 1 was a 74-year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a total of 45 Gy radiation+oral 5'-DFUR 800 mg/day for 3 weeks) was performed. Then, 30 days after chemo-radiation, we conducted a low anterior resection with lymph node dissection. Histological examination revealed no residual cancer cells in the resected specimen. Case 2 was a 35-year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a total of 45 Gy radiation+5-FU 500 mg/day+CDDP 10 mg/day for 3 weeks) was performed. 28 days after chemo-radiation, we conducted an abdominoperineal resection with lymph node dissection and a partial resection of the liver. Histological examination revealed well-differentiated adenocarcinoma in the resected liver tissue, but a rectal tumor was replaced by scar tissue with no viable cells.
Assuntos
Adenocarcinoma/terapia , Neoplasias Retais/terapia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Terapia Combinada , Fluoruracila/uso terapêutico , Humanos , Excisão de Linfonodo , Masculino , Dosagem Radioterapêutica , Neoplasias Retais/patologia , Neoplasias Retais/cirurgiaRESUMO
BACKGROUND: Dahl salt-sensitive (DS) rats given a high-salt diet develop renal lesions that are virtually identical to those in human hypertensive nephrosclerosis and are associated with increased oxidative stress. This study looks at the effects of a superoxide scavenger in preventing of hypertensive renal damage in high-salt-treated DS rats. METHODS: The DS rats (n = 5 per group) were treated with 0.3% NaCl diets (LS), 8% NaCl diets (HS), and 8% NaCl diets plus 10 mmol/L tempol in drinking water (HS+T) for 5 weeks. Systolic blood pressure (SBP) was measured by the tail-cuff method. As markers of renal damage, we measured serum creatinine, creatinine clearance, histopathologic indices, and transforming growth factor-beta1 (TGF-beta1; a mediator for renal fibrosis) expression. In addition, 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells and expression of heme oxygenase-1 (HO-1) were quantified as markers of oxidative stress. RESULTS: We found that a high-salt diet (8% NaCl) led to the development of hypertension, increased oxidative stress in the renal tissue (8-OHdG immunoreactive staining and HO-1 protein expression), increased renal histopathologic damage (arteriosclerosis index, matrix score, and interstitial volume) accompanied by accumulation of TGF-beta1, and decreased creatinine clearance in the DS rats. These adverse effects of salt were prevented by the tempol supplementation. CONCLUSIONS: Histopathologic and biochemical findings indicate that, in the DS rat, salt-induced hypertensive nephropathy is associated with increased oxidative stress. Superoxide mimetic tempol can reduce this detrimental effect of salt feeding through TGF-beta1 suppression and consequently prevent the development of hypertension and hypertensive nephropathy.
Assuntos
Hipertensão/patologia , Rim/patologia , Cloreto de Sódio/farmacologia , Animais , Proteínas de Choque Térmico/análise , Heme Oxigenase (Desciclizante) , Hipertensão/metabolismo , Imuno-Histoquímica , Rim/enzimologia , Masculino , Estresse Oxidativo , Oxigenases/análise , Ratos , Ratos Endogâmicos Dahl , Superóxidos/metabolismo , Sístole , Fator de Crescimento Transformador beta/fisiologiaRESUMO
To confirm that alpha1, beta adrenoceptor antagonists and angiotensin II type 1 receptor blockers (ARBs) have different abilities to attenuate progressive cardiac hypertrophy despite their comparable lowering of blood pressure, we compared the effect of these agents alone or in combination on hypertensive cardiac hypertrophy. Eight-week-old spontaneously hypertensive rats (SHR) were divided into 7 groups. Single administration of doxazosin, atenolol, or losartan, or half-dose combinations of these drugs were given orally for 6 weeks. The control group did not receive any drugs. The heart weight-to-body weight ratio (HW/BW), left ventricular mass index (LVMI), plasma brain natriuretic peptide (BNP) and left ventricular BNP mRNA expression were measured after 6-week administration. Blood pressure did not differ among the drug-treated groups, all of which showed lower blood pressure than the control group. The HW/BW and LVMI of the drug-treated groups, except the doxazosin group, were lower than in the control group. Moreover, the LVMI values of the groups receiving losartan were significantly lower than those in the groups without losartan (p < 0.05). Plasma BNP of the drug-treated groups was lower than that in the control group (p < 0.05). The left ventricular BNP mRNA expression of the drug-treated groups, except the doxazosin group, was lower than that in the control group. The atenolol group showed a higher level of BNP mRNA than the groups receiving losartan monotherapy or combination therapies (p < 0.05). In conclusion, the ARB had the strongest attenuating effect on the development of hypertensive cardiac hypertrophy, and the alpha1 and beta adrenergic receptor blockers were more effective in combination than as monotherapies in SHR.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Atenolol/farmacologia , Cardiomegalia/tratamento farmacológico , Doxazossina/farmacologia , Losartan/farmacologia , Angiotensina II/sangue , Animais , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/diagnóstico por imagem , Quimioterapia Combinada , Ecocardiografia , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Masculino , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/genética , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos SHRRESUMO
This paper presents an application of our newly developed adsorptive ozonation process using a high silica zeolite adsorbent (USY) for drinking water treatment. First, the adsorption of 2-methylisoborneol (2-MIB) on USY in a river water/pure water mixture was clarified by a batch-type adsorption experiment. The results showed that 2-MIB was adsorbed on USY; however, almost all of the adsorbed 2-MIB was desorbed over time. The desorption rate was increased with the ratio of river water to pure water, indicating that compounds dissolved in the river water, such as natural organic matter (NOM), prevent the adsorption of 2-MIB on USY. Second, the ability of the river water to consume ozone was confirmed in an experiment using a USY-packed column reactor. The ozone consumption was obviously increased by the presence of USY, indicating that USY-adsorbing compounds dissolved in the river water (probably small size NOM) consumed the ozone. However, the rapid ozone consumption was occurred by 6-8 s in the retention times when 3.14-4.38 mgL(-1) of water dissolved ozone was fed, this rapid ozone consumption lasted no more than these times. This result revealed that the rapid consumption of ozone by the adsorptive compounds in our process could be avoided within a certain retention time (6-8 s; especially for the river water used in this study) when enough concentration of ozone (3.14 mgL(-1) or more; same above) was supplied. We therefore performed a trial in which 2-MIB dissolved in river water was continuously decomposed using a USY-packed column with various ozone concentrations. In the process, the adsorptive compound dissolved in the river water adsorbed and reacted with ozone in the parts of the apparatus upstream of the column, while the adsorption and decomposition of 2-MIB took place in the parts of the apparatus downstream of the column. This resulted in a sufficient 2-MIB decomposition with minimizing bromate ion formation.
Assuntos
Canfanos/química , Oxidantes Fotoquímicos/química , Ozônio/química , Purificação da Água/métodos , Adsorção , Bromatos , Compostos Orgânicos , Rios , Zeolitas/químicaRESUMO
This work elucidates the applicability of our newly developed adsorptive ozonation process for the decomposition of 2-methylisoborneol (MIB), a typical taste and odor chemical, without the formation of possibly carcinogenic bromate ions. First, zeolite adsorbents were screened for their ability to adsorb MIB with a batch-type adsorption experimental apparatus and a flow-type decomposition experimental apparatus included an adsorbent-packed column. The USY zeolite with the highest silica to alumina ratio (SiO(2)/Al(2)O(3) molar ratio=70) showed the best performance as an adsorbent. Using this adsorbent, an ozonation experiment on an MIB solution including bromide ions was performed under various retention times using the flow-type apparatus. As a result, sufficient decomposition of MIB was achieved with preventing bromate formation.
Assuntos
Canfanos/isolamento & purificação , Ozônio/química , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Zeolitas/química , Adsorção , Óxido de Alumínio/química , Bromatos/química , Brometos/química , Canfanos/química , Odorantes , Oxidantes Fotoquímicos/química , Compostos de Potássio/química , Dióxido de Silício/químicaRESUMO
The adsorption properties of water-dissolved ozone on high silica zeolites were investigated. Adsorbed ozone was desorbed almost reversibly. The adsorption equilibrium relations were described by a linear expression written as q=betaC, where q is the amount adsorbed, C is the equilibrium concentration and beta is the equilibrium constant. Also, the beta values were strongly dependent on the SiO(2)/Al(2)O(3) ratio (mol/mol) and on the pore structure of the high silica zeolites. The larger the SiO(2)/Al(2)O(3) ratio, the larger the value of beta. ZSM-5 (SiO(2)/Al(2)O(3) ratio: 3000), which gave the highest adsorption capacity of water-dissolved ozone, was able to highly concentrate water-dissolved ozone on the adsorbent. The decomposition behavior of adsorbed ozone was also investigated. Ozone adsorbed on high silica zeolite was observed to be a little more stable than ozone existing in bulk water. The decomposition rate was independent of SiO(2)/Al(2)O(3) ratios in the range of 30-3000 or a solution pH in the range of 4-6.