Abstract：
:1. Irinotecan (also known as CPT-11) is a water soluble, semi-synthetic analogue of 20(S)camptothecin (CPT) with promising activity against a range of tumour types. 2. As with all other active analogues of CPT, irinotecan causes cell toxicity by stabilizing a ternary complex between the nuclear enzyme topoisomerase I (topo I) and double-stranded DNA. This leads to replication fork-arrest, double DNA strand breaks and, possibly, illegitimate recombination of vital genes. 3. This activity is much greater for its metabolite SN-38 and irinotecan is widely considered to be a prodrug of SN-38. 4. The anti-topo I activity of CPT is stereoselective at C-20 and irinotecan is synthesized from 20(S)CPT to ensure maximal activity. In aqueous solutions, the lactone ring of CPT undergoes reversible and spontaneous hydrolysis to a ring-opened and inactive carboxylate form. In patients, it has been shown that the lactone is the predominant form of SN-38 in plasma, whereas the opposite is true for irinotecan. 5. The transformation of irinotecan to SN-38 is catalysed by carboxylesterases. However, this conversion appears relatively inefficient in man. 6. Irinotecan and SN-38 show evidence of other metabolic reactions (type I and II), some of which could be subject to pharmacogenetic variability. 7. Therapy with irinotecan is associated with unusual toxicities, such as an acute cholinergic-like syndrome and delayed onset diarrhoea. Although the mechanism for the diarrhoea remains to be defined, the cholinergic toxicity appears to be due to an inhibition of acetylcholinesterase.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Rivory LPdoi
10.1111/j.1440-1681.1996.tb01158.xsubject
Has Abstractpub_date
1996-10-01 00:00:00pages
1000-4issue
10-11eissn
0305-1870issn
1440-1681journal_volume
23pub_type
杂志文章,评审abstract：:Acute kidney injury (AKI) occurs in 5% of hospitalized patients and in 50% of sepsis patients with acute renal dysfunction. However, there have been no safe and effective therapeutic strategies. The hypoxia condition is closely related to renal injury and function under AKI. As hypoxia-inducible factor 1α (HIF-1α) is ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12947
更新日期：2018-10-01 00:00:00
abstract：:1. The influence of the passive force on the contraction and endothelium-dependent relaxation in aortae of normotensive Wistar Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) were compared. 2. Force changes of endothelium-intact and -removed preparations were measured isometrically by a force...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1996.tb02765.x
更新日期：1996-06-01 00:00:00
abstract：:1. The effect of endothelin on phosphatidylinositol turnover in rat atria was investigated by measuring the generation of inositol phosphates following [3H]-inositol labelling. 2. In the presence of 10 mmol/L LiCl, endothelin caused dose-dependent increases in the accumulation of inositol mono, bis and trisphosphates ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1990.tb01320.x
更新日期：1990-04-01 00:00:00
abstract：:Glycerophospholipids (GPs) and sphingolipids (SPs) are important lipid components in the body and play biological functions. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are important nutrients, and their supplements are commonly used for preventing some diseases. However, the effect of n-3 PUFAs on the human glyce...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.13285
更新日期：2020-07-01 00:00:00
abstract：:Afferent splanchnic nerve stimulation with different frequencies in Wistar Kyoto rats caused depressor and pressor responses depending on the frequency employed. Similar visceral afferent activation in spontaneously hypertensive rats caused depressor responses at all frequencies of stimulation. It is suggested that th...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1985.tb00300.x
更新日期：1985-01-01 00:00:00
abstract：:The aim of the present study was to investigate the effect of prostaglandin (PG) E1 on hypoxia/re-oxygenation (H/R) apoptosis and the expression of bcl-2 and bax in cultured neonatal rat cardiomyocytes. The H/R model was made using the first generation of cultured neonatal rat cardiomyocytes. Hypoxia/re-oxygenation ap...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2005.04311.x
更新日期：2005-12-01 00:00:00
abstract：:The amino acid sequence of human renin was identified for the first time. This was determined from the nucleotide sequence of exons in the human renin gene identified in a genomic library by recombinant DNA techniques. Examination of amino acid residues involved in the enzymatic hydrolysis by human renin of the unique...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1984.tb00281.x
更新日期：1984-07-01 00:00:00
abstract：:1. Cardiovascular events and outcome in septic shock may be predicted by monitoring the fall in intramural pH (pHi), as an index of splanchnic perfusion and mucosal ischaemia. In the present study, a small animal model for monitoring the changes of gastric pHi or intramucosal [H+] following challenge with the endotoxi...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2001.03432.x
更新日期：2001-03-01 00:00:00
abstract：:This study tested the hypothesis that the initial fall in arterial pressure evoked by lipopolysaccharide (LPS) is mediated by the ventrolateral column of the midbrain periaqueductal gray region (vlPAG). To test this hypothesis, the local anaesthetic lidocaine (2%; 0.1 μL, 0.2 μL or 1.0 μL), the delta opioid receptor a...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12573
更新日期：2016-06-01 00:00:00
abstract：:Apelin receptors (APJ) cross-talk with other G-protein-coupled receptors. However, the role of APJ interaction with opioid receptors (OPR) on the cardiovascular effects of apelin in hypertension is not clear. Renovascular hypertension was induced by placing a Plexiglas clip on the left kidney of rats. After 16 weeks, ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12860
更新日期：2018-02-01 00:00:00
abstract：:1. Activation of bulbospinal neurons projecting from the C1 area of the rostral ventrolateral medulla evokes a pressor response. The nature of the neurotransmitters involved in mediating this response at spinal cord level has not been established. 2. Amino acid antagonists were introduced into the spinal subarachnoid ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1988.tb01056.x
更新日期：1988-02-01 00:00:00
abstract：:1. The present study sought to explain the mechanism leading to reduced availability of propranolol when given after a priming dose in the single-pass perfused rat liver. 2. Extracellular sucrose space (as a measure of sinusoidal relaxation) in perfused rat liver before and after propranolol or propranolol and N(G)-ni...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2010.05434.x
更新日期：2010-10-01 00:00:00
abstract：:According to Guyton's model, impaired renal sodium excretion plays a key role in the increased salt sensitivity of blood pressure (BP). Several factors contribute to impaired renal sodium excretion, including the sympathetic nervous system, the renin-angiotensin system and aldosterone. Accumulating evidence suggests t...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/1440-1681.12177
更新日期：2013-12-01 00:00:00
abstract：:Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte elevated gene-1 (AEG-1), a downstream target of Ras and c-Myc, has been implicated in the development of multiple tumours, but its role in melanoma remains unclear. In the present study, the role of AEG-1 in melanoma was explored through AEG-1 ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12767
更新日期：2017-07-01 00:00:00
abstract：:1. Following local vasoconstriction-inducing stimuli, such as the cold pressor test (CPT), significant changes occur in haemodynamics, with a rise in arterial blood pressure and heart rate (HR) due to the activation of the sympathetic nervous system. Among the compensatory mechanisms to local ischaemia, the endogenous...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.1999.03126.x
更新日期：1999-10-01 00:00:00
abstract：:1. Gastric emptying studies in small laboratory animals are hampered by the deficiency of a technique that is non-invasive and repeatable. The aim of the present study was to adapt the non-invasive [13C]-octanoic acid breath test, which has been validated in humans, to assess both liquid and solid gastric emptying in ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2000.03318.x
更新日期：2000-09-01 00:00:00
abstract：:1. The present study evaluated changes in autonomic control of the cardiovascular system in conscious rats following blockade of endothelin (ET) receptors with bosentan. 2. Rats were treated with bosentan or vehicle (5% gum arabic) for 7 days by gavage. 3. Baseline heart rate (HR) was higher in the bosentan-treated gr...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2008.04866.x
更新日期：2008-07-01 00:00:00
abstract：:1. The concentration of renin and angiotensinogen (Ao) and the activity of angiotensin I-converting enzyme (ACE) was measured in the ascites fluid of nephrotic rats obtained 8 days after puromycin aminonucleoside (PAN) injection. 2. Ascites fluid, serum and urine proteins of these rats were analysed by sodium dodecyl ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1998.tb02253.x
更新日期：1998-07-01 00:00:00
abstract：:1. Stimulation of the mesolimbic dopamine system, by micro-injection of the substance P analogue [pGlu5,MePhe8,Sar9] substance P (DiMe-C7) into the ventral tegmental area induced a prolonged increase in blood pressure and circulating levels of vasopressin. 2. In the present study, this treatment produced a significant...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1998.tb02264.x
更新日期：1998-07-01 00:00:00
abstract：:1. Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease. The aim of the present study was to identify the gene mutation in a Chinese family with LQTS and investigate the functional changes associated with the mutation. 2. Polymerase chain reaction and DNA sequencing were used to screen for the KCN...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2009.05150.x
更新日期：2009-08-01 00:00:00
abstract：:1. Measurements were made on blood pH, PCO2 and PO2 in mice after a single injection and following five weeks continuous clonidine hydrochloride treatment. 2. A single injection of clonidine hydrochloride exerts no effect on blood pH, PCO2 and PO2 but five weeks of continuous clonidine hydrochloride treatment lowers t...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1982.tb00840.x
更新日期：1982-11-01 00:00:00
abstract：:1. Insulin-like growth factor (IGF)-I has acute effects on cardiovascular function, including a well-characterized vasodilator response in isolated arteries. In addition to increasing the release of nitric oxide, IGF-I also has effects on a variety of other signalling pathways that affect vascular tone, in particular ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2006.04510.x
更新日期：2006-12-01 00:00:00
abstract：:Bone is a remarkable living tissue that provides a framework for animal body support and motion. However, under excessive loads and deformations, bone is prone is to damage through fracture. Furthermore, once the bone is weakened by osteoporosis, bone fracture can occur even after only minimal trauma. Various techniqu...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.2011.05652.x
更新日期：2012-08-01 00:00:00
abstract：:1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to...
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.1440-1681.1997.tb01204.x
更新日期：1997-05-01 00:00:00
abstract：:1. Reactive oxygen species (ROS) are a diverse family of molecules that are produced throughout the vascular wall. Many ROS, such as the superoxide anion (*O2-) and hydrogen peroxide (H2O2), are now known to act as cellular signalling molecules within blood vessels. In particular, these molecules can exert powerful ef...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1046/j.1440-1681.2003.03920.x
更新日期：2003-11-01 00:00:00
abstract：:1. There are hundreds of commercially available microcomputer statistics packages, ranging from the very cheap and elementary to the very expensive and complex, and from the very general to the very specialized. This review covers only those that appear to be popular with biomedical investigators who deal with fairly ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1995.tb02335.x
更新日期：1995-12-01 00:00:00
abstract：:Severe drug eruption (SDE), a common skin disease, becomes dangerous when it occurs in patients with human immunodeficiency virus (HIV). However, the molecular mechanisms are poorly understood. Forty patients including HIV+ SDE+ (n = 15), HIV- SDE+ (n = 15) and HIV+ SDE- (n = 10) subjects were enrolled in our study. A...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.13266
更新日期：2020-06-01 00:00:00
abstract：:1. Intravenous endothelin-1 releases endothelium-derived relaxing factor (EDRF) and prostacyclin from the lungs, and substantial pulmonary clearance is claimed. Since these vaso-active substances could alter the haemodynamic effects of endothelin-1, the effects of boluses of endothelin-1 injected intravenously and int...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1994.tb02521.x
更新日期：1994-04-01 00:00:00
abstract：:1. Effects of FR139317, an endothelin ETA receptor antagonist, on renal haemodynamic and excretory responses to acute nitric oxide (NO) blockade were examined using anaesthetized rats. 2. Intrarenal arterial infusion of NG-nitro-L-arginine (NOARG), the NO synthase inhibitor, at a rate of 40 micrograms/kg per min, prod...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1998.tb02229.x
更新日期：1998-06-01 00:00:00
abstract：:1. The diffusional permeability of collecting ducts to 22Na+ and 36Cl- was measured in rat papillae in vitro. 2. The permeability of the collecting duct to 36Cl- was 0.72 (s.e.m. = 0.01; n = 356) microns/sec which was significantly higher than the value of 0.51 (s.e.m. = 0.01; n = 356) microns/sec measured for 22Na+. ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1982.tb00837.x
更新日期：1982-11-01 00:00:00
