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81.
Yan-huaLIN LuTIE Ai-huaLIU Xue-junLI 《Acta pharmacologica Sinica》2004,25(11):1555
AIM: To study the effect of oxygen/glucose-deprived (OGD)culture on the expression of a novel protein, brain-pancreas relative protein (BPRP), and the possible regulating mechanism in vitro. BPRP was a key protein found in our previous study of cerebral ischemia. METHODS: PC12 cells was selected and exposed to the Eagle‘s solution containing 1 mmol/L Na2S2O4 for 相似文献
82.
Arohan R. Subramanya David H. Ellison 《Clinical journal of the American Society of Nephrology》2014,9(12):2147-2163
The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice. 相似文献
83.
Quantitative susceptibility mapping and 23Na imaging‐based in vitro characterization of blood clotting kinetics 下载免费PDF全文
Till M. Schneider Armin M. Nagel Markus Zorn Andreas Wetscherek Martin Bendszus Mark E. Ladd Sina Straub 《NMR in biomedicine》2018,31(6)
Blood clotting is a fundamental biochemical process in post‐hemorrhagic hemostasis. Although the varying appearance of coagulating blood in T1‐ and T2‐weighted images is widely used to qualitatively determine bleeding age, the technique permits only a rough discrimination of coagulation stages, and it remains difficult to distinguish acute and chronic hemorrhagic stages because of low T1‐ and T2‐weighted signal intensities in both instances. To investigate new biomedical parameters for magnetic resonance imaging‐based characterization of blood clotting kinetics, sodium imaging and quantitative susceptibility mapping (QSM) were compared with conventional T1‐ and T2‐weighted imaging, as well as with biochemical hemolysis parameters. For this purpose, a blood‐filled spherical agar phantom was investigated daily for 14 days, as well as after 24 days at 7 T after initial preparation with fresh blood. T1‐ and T2‐weighted sequences, a three‐dimensional (3D) gradient echo sequence and a density‐adapted 3D radial projection reconstruction pulse sequence for 23Na imaging were applied. For hemolysis estimations, free hemoglobin and free potassium concentrations were measured photometrically and with the direct ion‐selective electrode method, respectively, in separate heparinized whole‐blood samples along the same timeline. Initial mean susceptibility was low (0.154 ± 0.020 ppm) and increased steadily during the course of coagulation to reach up to 0.570 ± 0.165 ppm. The highest total sodium (NaT) values (1.02 ± 0.06 arbitrary units) in the clot were observed initially, dropped to 0.69 ± 0.13 arbitrary units after one day and increased again to initial values. Compartmentalized sodium (NaS) showed a similar signal evolution, and the NaS/NaT ratio steadily increased over clot evolution. QSM depicts clot evolution in vitro as a process associated with hemoglobin accumulation and transformation, and enables the differentiation of the acute and chronic coagulation stages. Sodium imaging visualizes clotting independent of susceptibility and seems to correspond to clot integrity. A combination of QSM and sodium imaging may enhance the characterization of hemorrhage. 相似文献
84.
85.
《Expert opinion on therapeutic patents》2013,23(11):1297-1306
Critical reassessment of established inotropic drugs such as the phosphodiesterase inhibitors and the digitalis glycosides has reaffirmed the need for novel cardiotonic agents that will not only beneficially affect the haemodynamic and functional impairment of patients with overt congestive heart failure, but also prevent its clinical manifestation and reduce the high mortality. None of the drugs examined in these directions - calcium sensitisers, β-receptor blockers, sodium channel modulators, digitalis derivatives - have been shown to achieve these goals. The research on endogenous digitalis did not, as was hoped, reveal a general strategy for improving the therapeutic index of cardiac glycosides. The proof that Na+/K+-transporting ATPase of cardiac muscle is the molecular point of attack (receptor) for the inotropic and toxic effects of digitalis-like acting C/D-cis and C/D-trans steroids revealed the cyclopentano-perhydrophenanthrene nucleus as their common pharmacophoric lead structure. This has opened a wide field for lead development in the direction of derivatives that favourably discriminate between the inotropy-linked α1-isoform and the toxicity-linked α3-isoform of Na+/K+-ATPase as the basis for the design of inotropic agents with high therapeutic margin. 相似文献
86.
Emilio Domínguez‐Salazar Gabriela Hurtado‐Alvarado Fernanda Medina‐Flores Javik Dorantes Oscar Gonzlez‐Flores Arturo Contis‐Montes de Oca Javier Velzquez‐Moctezuma Beatriz Gmez‐Gonzlez 《Journal of sleep research》2020,29(3)
Sleep loss increases blood–brain barrier permeability. As the blood–brain barrier and the blood–tissue barriers in the reproductive tract (blood–testis and blood–epididymis barriers) share common characteristics, we hypothesized that sleep restriction may also modify their barrier function. Previous reports showed that sleep loss decreased sperm viability and progressive fast mobility, which may be a consequence of altered blood–testis and blood–epididymis barrier. Therefore, we quantified changes in blood–testis and blood–epididymis barrier after sleep loss and related them to male fertility. Adult male Wistar rats were sleep restricted using the multiple‐platform technique in a protocol of 20 hr daily sleep deprivation plus 4 hr of sleep recovery in the home‐cage. At the 10th day, barrier permeability assays were performed with Na‐fluorescein, 10 kDa Cascade blue‐dextrans and Evans blue, and the expression of tight junction proteins, actin and androgen receptor was quantified. At the 10th day of sleep restriction and after sleep recovery days 1–7, males were placed with sexually receptive females, sexual behaviour was tested, and the percentage of pregnancies was calculated. Sleep restriction increased the barrier permeability to low‐ and high‐molecular‐weight tracers, and decreased the expression of tight junction proteins, actin and androgen receptor. Concomitantly, sleep restriction reduced the percentage of ejaculating males and the number of pregnancies. Sleep recovery for 2–3 days progressively re‐established fertility, as indicated by a higher percentage of ejaculating males and impregnated females. In conclusion, chronic sleep loss alters fertility concomitantly with the disruption of the blood–tissue barriers at the reproductive tract, the mechanism involves androgen signalling. 相似文献
87.
Chia‐Hung Chen Chuen‐Ming Shih Jen‐Wei Chou Yi‐Heng Liu Liang‐Wen Hang Te‐Chun Hsia Wu‐Huei Hsu Chih‐Yen Tu 《Liver international》2011,31(3):417-424
Background: Spontaneous bacterial empyema (SBE) is a complication of cirrhotic patients in which a pre‐existing pleural effusion becomes infected. This retrospective study was designed to investigate the bacteriology and outcome predictors of SBE in cirrhotic patients. Methods: Medical records of cirrhotic patients treated in a tertiary care university hospital from December 2004 to December 2008 were retrospectively reviewed. Results: Of 3390 cirrhotic patients seen during the study period, 81 cases of SBE were diagnosed. The incidence of SBE was 2.4% (81/3390) in cirrhotic patients and 16% (81/508) in patients with cirrhosis with hydrothorax. There were 46 monomicrobial infections found in 46 SBE patients. Aerobic Gram‐negative organisms were the predominant pathogens (n=29, 63%), and Escherichia coli (n=9, 20%) was the most frequently isolated sole pathogen. The mortality rate of SBE was 38% (31/81). Univariate analysis showed that Child–Pugh score, model for end‐stage liver disease (MELD)–Na score, concomitant bacteraemia, concomitant spontaneous bacterial peritonitis, initial intensive care unit (ICU) admission and initial antibiotic treatment failure were predictors of poor outcomes. Multivariate regression analysis demonstrated that the independent factors related to a poor outcome were initial ICU admission [odds ratio (OR): 4.318; 95% confidence interval 1CI) 1.09–17.03; P=0.037], MELD–Na score (OR: 1.267; 95% CI 1.08–1.49; P=0.004) and initial antibiotic treatment failure (OR: 13.10; 95% CI 2.60–66.03). Conclusion: Spontaneous bacterial empyema in cirrhotic patients is a high mortality complication. The independent factors related to poor outcome are high MELD–Na score, initial ICU admission and initial antibiotic treatment failure. High MELD–Na score may be a useful mortality predictor of SBE in cirrhotic patients. 相似文献
88.
《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(3):303-307
Maintenance of a normal blood pressure requires a precise and fine-tuned regulation of salt metabolism. This is accomplished by a bidirectional regulation of renal tubular sodium transporters by natriuretic and antinatriuretic hormones. Dopamine, produced in the renal proximal tubular cells, plays an important role in this interactive system. Dopamine inhibits the activity of Na+,K+ATPase as well as of many important sodium influx pathways in the nephron. These effects of dopamine are particularly pronounced in situation of sodium loading.There is an abundance of evidence suggesting that the natriuretic effects of ANP are to a large extent mediated via renal dopamine 1 like receptors. The renal tubular dopamine 1 like receptors are, under basal conditions, mainly located intracellularly. ANP and its second messenger, cGMP, cause a rapid translocation of the dopamine 1 like receptors to the plasma membrane. This phenomenon may explain how ANP and dopamine act in concert to regulate sodium metabolism. Regulation of sodium metabolism and blood pressure is critically dependent on a normal function of the renal dopamine system. Hence, abnormalities in the interaction between dopamine and ANP may predispose to hypertension. 相似文献
89.
《Expert review of anticancer therapy》2013,13(7):1117-1132
Polo-like kinase 1 (Plk1) inhibitors belong to a new class of drugs for the treatment of malignant diseases. They selectively act against a target (Plk1) which is involved in different stages of mitosis such as centrosome maturation, spindle formation, chromosome separation and cytokinesis. Because Plk1 is mainly expressed in proliferating tissues and overexpressed in cancers, its inhibition is potentially less prone to toxicities associated with current antimitotic agents, which also act on nondividing cells. Several Plk1 inhibitors are being evaluated as cancer treatment drugs. Based on the essential role of Plk1 during mitosis, Plk1 inhibitors target all rapidly dividing cells irrespective of their tumor suppressor or oncogene mutations. In this article, their mechanisms of action, efficacy and toxicity profile are discussed. 相似文献
90.
Dioscorea bulbifera L. (DB) is a traditional Chinese herb used in thyroid disease and cancer. However, the clinical use of DB remains a challenge due to its hepatotoxicity, which is caused, in part, by the presence of Diosbulbin B (DIOB), a toxin commonly found in DB extracts. As abnormal expression of hepatobiliary transporters plays an important role in drug-induced liver injury, we assessed the hepatotoxicity induced by DB and DIOB, and explored their impacts on hepatobiliary transporter expression levels. Following liquid chromatography-tandem mass analysis of the DIOB content of DB extract, male ICR mice were randomly orally administered DB or DIOB for 14 days. Liver injury was assessed by histopathological and biochemical analysis of liver fuction. The levels of transporter protein and mRNA were determined by western blotting and real-time PCR. Liver function and histopathological analysis indicated that both DB and DIOB could induce liver injury in mice, and that DIOB might be the primary toxic compound in DB. Moreover, down-regulation of Mrp2 blocked the excretion of bilirubin, glutathione disulfide, and bile acids, leading to the accumulation of toxic substrates in the liver and a redox imbalance. We identified down-regulated expression of Mrp2 as potential factors linked to increased serum bilirubin levels and decreased levels of glutathione in the liver and increased liver injury severity. In summary, our study indicates that down-regulation of Mrp2 represents the primary mechanism of DB- and DIOB-induced hepatotoxicity, and provides insight into novel therapies that could be used to prevent DB- and DIOB-mediated liver injury. 相似文献