Abstract:
:1. RNA interference in vivo has tremendous potential, both with respect to the elucidation of protein function in animals and as a therapeutic platform in humans. In vitro, short interfering RNA (siRNA) has been shown to completely silence gene expression in mammalian cells at low picomolar concentrations. 2. Although many good publications have shown specific silencing to occur in vivo, there are few that have transferred the combination of maximal efficacy and high potency to this setting. The present review considers the biological barriers that limit the movement of siRNA from vascular lumen to target cell cytoplasm and the strategies that have been used to overcome them. 3. Intravenous administration of siRNA results in rapid, extensive removal of siRNA from the blood via renal excretion, tissue distribution and nuclease degradation. Movement across vascular capillaries appears to be a limiting factor in some cases; few examples of silencing have been reported in organs with a conventional capillary endothelium. 4. Cellular uptake and endosomal trapping are significant barriers, but can be overcome using strategies such as antibody mediated cellular uptake or polyethyleneimine-mediated endosomal escape.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
White PJdoi
10.1111/j.1440-1681.2008.04992.xsubject
Has Abstractpub_date
2008-11-01 00:00:00pages
1371-6issue
11eissn
0305-1870issn
1440-1681pii
CEP4992journal_volume
35pub_type
杂志文章,评审abstract::Cerebral blood flow (CBF) and cerebral O2 metabolism (CMRO2) changes were measured in these studies during treatment with three reputed cerebral vasodilators: bradykinin, adenosine triphosphate (ATP) and increased arterial PCO2. Intracerebrovascular bradykinin infusions increased CMRO2 and CBF to a similar degree. Int...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1983.tb00177.x
更新日期:1983-03-01 00:00:00
abstract::1. Arterial baroreceptor denervation produces acute hypertension, but chronically denervated animals have an average arterial pressure that is similar to that of baroreceptor intact animals. 2. Although cardiopulmonary baroreceptors and renal compensations have been suggested to mediate the restoration of a normal ave...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1997.tb01787.x
更新日期:1997-01-01 00:00:00
abstract::The antihypertensive agent rilmenidine has threefold higher affinity for I(1) imidazoline receptors compared with alpha(2)-adrenoceptors and acts on the central nervous system by reducing sympathetic activity and in the kidney by inhibiting Na(+)/H(+) exchange activity. In the present study, we examined: (i) the effec...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.04008.x
更新日期:2004-05-01 00:00:00
abstract::1. The endothelin (ET) system and NADPH oxidase play important roles in the regulation of cardiovascular function, as well as in the pathogenesis of hypertension and other cardiovascular diseases. 2. Endothelins activate NADPH oxidases and thereby increase superoxide production, resulting in oxidative stress and cardi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2007.04830.x
更新日期:2008-01-01 00:00:00
abstract::C1q/TNF-related protein 6 (CTRP6) is a member of the CTRP family that has been reported to exhibit a nephroprotective effect. However, the role of CTRP6 in renal ischaemia/reperfusion (I/R) injury (IRI) remains unclear. In the present study, we aimed to explore the protective effect of CTRP6 in renal IRI and the poten...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13274
更新日期:2020-06-01 00:00:00
abstract::In the present study, we investigated whether mood stabilizer lithium (Li) protects against d-amphetamine (AMP)-induced mania-like behaviours via modulating the novel proinflammatory potential. Repeated treatment with AMP resulted in significant increases in proinflammatory cyclooxygenase-2 (COX-2) and indolemaine-2,3...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13243
更新日期:2020-05-01 00:00:00
abstract::The efficacy of streptokinase as an intracoronary thrombolytic agent is well-recognized. The effect of streptokinase, distinct from its thrombolytic action, on ischaemic myocardium distal to an area of coronary artery occlusion when reperfusion occurs has not been well-defined. In order to do this, myocardial creatine...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb02392.x
更新日期:1986-09-01 00:00:00
abstract::1. Contraction assays and patch clamp methods were used to determine the role of K+ channels in the regulation of contractile tone of human mesangial cells (MC) in culture. 2. MC contraction was induced by vasoconstrictor agents, such as angiotensin II (AngII; 100 nmol/L) and glybenclamide (Glyb), but not by iberiotox...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1996.tb03066.x
更新日期:1996-01-01 00:00:00
abstract::To test a possible role of endogenous opioids in the blood pressure (BP) and heart rate (HR) responses to the converting enzyme inhibitor captopril in man, nine normal subjects were given captopril (50 mg) or placebo with and without the opioid antagonist naloxone (0.2 mg/kg i.v.). Treatments were given in random orde...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1440-1681.1983.tb00192.x
更新日期:1983-05-01 00:00:00
abstract::1. Pretreatment with intravenous WEB-2086 (0.5 mg/kg; an antagonist of the actions of platelet activating factor; PAF) with or without indomethacin (2 mg/kg) failed to prevent or modify the fall in blood pressure following unclipping of the renal artery of anaesthetized two-kidney, one-clip hypertensive rats. 2. The s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02535.x
更新日期:1994-05-01 00:00:00
abstract::1. Activation of peripheral chemoreceptors with KCN in the working heart-brainstem preparation from young male Wistar rats (70-90 g) increases phrenic (PNA; +105 +/- 18%) and thoracic (tSNA; +44 +/- 6%) sympathetic nerve activity compared with baseline and reduces heart rate (HR; from 377 +/- 27 to 83 +/- 6 b.p.m.). 2...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2005.04213.x
更新日期:2005-05-01 00:00:00
abstract::1. The effects of ouabain and acetazolamide on the secretion of pancreatic juice stimulated by secretin in anaesthetized dogs were investigated. 2. Intra-arterial injection of ouabain (1-10 micrograms) and acetazolamide (1-10 mg) caused dose-dependent decreases in the volume of pancreatic juice. When both drugs were a...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01538.x
更新日期:1989-03-01 00:00:00
abstract::1. Pre- and postjunctional effects of endothelin (1-10 nmol/L) have been studied in the rabbit isolated ear artery and in rat isolated atria. 2. Endothelin produced concentration-dependent increases in arterial perfusion pressure, and had positive chronotropic and inotropic effects in rat atria. 3. Vasoconstrictor res...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01548.x
更新日期:1989-04-01 00:00:00
abstract::1. To understand the roles of a putative hypertension gene in the chromosome 1 quantitative trait locus (QTL) region, the response to restraint stress was studied in strains congenic for this QTL. 2. To establish congenic strains, the QTL region was introgressed from stroke-prone spontaneously hypertensive rats (SHRSP...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03860.x
更新日期:2003-07-01 00:00:00
abstract::1. Tetramethylpyrazine (TMP) is one of the active principles contained in Ligusticum chuanxiong Hort. (Umbelliferae), a herb that has been used widely in China to treat vascular disorders. 2. In an attempt to elucidate the possible mechanisms of action of TMP, the effect of TMP on intracellular calcium concentrations ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03913.x
更新日期:2003-10-01 00:00:00
abstract::1. It has been suggested that Na+/K(+)-ATPase and Na(+)-dependent glutamate transport (GluT) are tightly linked in brain tissue. In the present study, we have investigated Na+/K(+)-ATPase activity using Rb+ uptake by 'minislices' (prisms) of the cerebral cortex. This preparation preserves the morphology of neurons, sy...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.04090.x
更新日期:2004-11-01 00:00:00
abstract::1. Despite the array of sophisticated imaging techniques available for biological applications, none of the standard biomedical techniques adequately provides the capability to measure motion and flow. Those techniques currently in use are particularly lacking in spatial and temporal resolution. 2. Herein, we introduc...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.05102.x
更新日期:2009-02-01 00:00:00
abstract::There is a strong genetic predisposition towards abdominal aortic aneurysm (AAA), but it is unknown whether persons without AAA but with first-degree relatives who are AAA patients have a generalized dilating diathesis, defect arterial wall mechanics, or increased cardiovascular risk. The aim of the study was to inves...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12395
更新日期:2015-06-01 00:00:00
abstract::1. Subacute administration of dyflos to guinea-pigs (1.2 mg/kg, s.c., daily for 10 days) led to the development of subsensitivity to carbachol in the ileum but not in the electrically stimulated left atrium. 2. Atria from dyflos-pretreated animals became supersensitive to acetylcholine but the ileum became subsensitiv...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1977.tb02683.x
更新日期:1977-11-01 00:00:00
abstract::Vancomycin is an antibiotic used in the treatment of infections caused by multidrug-resistant Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus. In the last decades, vancomycin has been widely used in hospital environments due to the increasing incidence of sepsis and septic shock. Sepsis ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.13066
更新日期:2019-04-01 00:00:00
abstract::1. Stroke is the second most common cause of death and a major cause of disability worldwide. Despite increasing knowledge of the cellular and molecular mechanisms that occur in stroke, there are still large gaps in our understanding that are impeding therapeutic progress. In addition, there are no drugs yet that can ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2009.05190.x
更新日期:2010-02-01 00:00:00
abstract::Malignant tumours are a major cause of mortality in humans. Currently used therapeutic regimens have not improved survival rates of patients suffering from malignant tumours much because of their limited efficacy and side-effects. A therapeutic approach that uses Newcastle disease virus (NDV) represents an attractive ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2011.05662.x
更新日期:2012-08-01 00:00:00
abstract::1. Epidemiological evidence indicates that low birthweight increases the risk of a number of adult-onset diseases. It is now apparent that many babies with a low birthweight may have been subjected to a combination of reduced growth rates in utero as well as preterm birth. However, the long-term effects of preterm bir...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03552.x
更新日期:2001-11-01 00:00:00
abstract::1. Rabbits were treated with the antiparasitic drug ivermectin at subcutaneous doses of 0.2, 1 and 2.5 mg/kg and blood collected weekly for 4 weeks thereafter for measuring some blood parameters. At a dose of 0.2 or 1 mg/kg the drug had no significant effect on any of the parameters measured. At a dose of 2.5 mg/kg, t...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1990.tb01273.x
更新日期:1990-10-01 00:00:00
abstract::1. The influence of the intact kidney on blood pressure, extracellular fluid volume (ECF, ferrocyanide space) and ECF volume distribution was studied in rats 60 days after constriction of the contralateral renal artery. 2. Renal artery constriction increased both blood pressure and ECF levels. The rise of both variabl...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1979.tb00033.x
更新日期:1979-09-01 00:00:00
abstract::1. Conscious experimental hypertensive rats injected intraventricularly with 5,6-dihydroxytryptamine (50 microgram) responded with a rapid and long-lasting (4 days) fall in blood pressure and this was accompanied by a bradycardia of similar duration. 2. The acute actions of 5,6-dihydroxytryptamine on the cardiovascula...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1975.tb01855.x
更新日期:1975-11-01 00:00:00
abstract::1. Elevated plasma lipoprotein (a) (Lp(a)) concentrations have been correlated with an increased risk of premature cardiovascular disease. The plasma Lp(a) concentration is quantitatively heritable and the apolipoprotein (Apo) A gene is known as a major locus-determining Lp(a) concentration. 2. The aim of the present ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.03033.x
更新日期:1999-04-01 00:00:00
abstract::Cyclo-oxygenase (COX) is an enzyme that participates in the wound healing process. Aspirin, a non-steroidal anti-inflammatory drug, simultaneously inhibits the aromatase activity of COX-1 and COX-2 isoforms, which is needed for prostaglandin synthesis. The aim of the present study was to determine whether aspirin, and...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12043
更新日期:2013-02-01 00:00:00
abstract::Accumulating reports have demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the occurrence and metastasis of cholangiocarcinoma (CCA). LncRNA myocardial infarction associated transcript (MIAT) has been widely reported in hepatocellular carcinoma, pancreatic cancer and colorectal cancer, but the r...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13283
更新日期:2020-06-01 00:00:00
abstract::Nucleocytoplasmic protein shuttling is integral to the transmission of signals between the nucleus and the cytoplasm. The nuclear/cytoplasmic distribution of proteins of interest can be determined via fluorescence microscopy, following labelling of the target protein with fluorophore-conjugated antibodies (immunofluor...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12969
更新日期:2018-10-01 00:00:00