Abstract:
:1. Hypoxia arises in solid tumour because of inefficient blood supply. While hypoxic cells are resistant to radiotherapy and probably to many chemotherapeutic drugs they can, in principle, be turned to advantage through the development of hypoxia-activated cytotoxic drugs (bioreductive drugs). 2. Three general approaches to exploiting tumour hypoxia are discussed. The first relies on fluctuating blood flow in tumours and the consequent cycling of cells through the hypoxic compartment. The second incorporates a prodrug approach in which drug activation gives rise to cytotoxic metabolites which diffuse out of hypoxic zones. The third utilizes selective inhibitors of tumour blood flow to induce additional hypoxia and thus enhance bioreductive drug activation. 3. The latter two approaches are illustrated by recent studies with the dinitrobenzamide nitrogen mustard class of bioreductive drugs and their combination with the tumour blood flow inhibitor 5,6-dimethylxanthenone-4-acetic acid.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Wilson WR,Pruijn FBdoi
10.1111/j.1440-1681.1995.tb01956.xsubject
Has Abstractpub_date
1995-11-01 00:00:00pages
881-5issue
11eissn
0305-1870issn
1440-1681journal_volume
22pub_type
杂志文章abstract::Receptors for parathyroid hormone (PTH) in the renal tubule are coupled to adenylate cyclase stimulation. PTH causes a rise in urinary cAMP by leakage from adenylate cyclase stimulation. PTH causes a rise in urinary cAMP by leakage from cells of the proximal convoluted tubule. The effects of alpha-adrenergic agonists ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1984.tb00287.x
更新日期:1984-07-01 00:00:00
abstract::1. Ethionine administered acutely to the adult female rat markedly elevates and then lowers plasma iron concentration over several days. Liver iron undergoes a reverse cycle. 2. Ethionine does not cause changes in the blood parameters, including total plasma iron-binding capacity and plasma iron clearance. Erythrocyte...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1975.tb01851.x
更新日期:1975-11-01 00:00:00
abstract::1. In the present study, the effects of the administration of adenosine on absence seizures were investigated in the Wistar Albino Glaxo/Rijswijk (WAG/Rij) strain of rats, which are an adequate model for human absence epilepsy. 2. After baseline electroencephalogram (EEG) recording, adenosine was injected intraperiton...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03499.x
更新日期:2001-08-01 00:00:00
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. Hypertension plays a critical role in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD), but it has also been postulated that antihypertensive drugs that block the renin-angiotensin system (RAS) show class-specific renoprotective actions beyond their blood pressure (BP)-lowering effe...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2010.05453.x
更新日期:2010-12-01 00:00:00
abstract::This study describes the pharmacodynamic interaction between propofol and remifentanil. Sixty patients who were scheduled for elective surgery under general anaesthesia (30 males/30 females) were enrolled. Patients were randomly allocated to receive one of 15 combinations of drug levels. Baseline electroencephalograms...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,随机对照试验
doi:10.1111/1440-1681.12677
更新日期:2017-01-01 00:00:00
abstract::1. L-Type Ca2+ channels play important roles in cardiac excitation and conduction. The present study used the whole-cell patch-clamp technique to investigate properties of Ca2+ channels in guinea-pig isolated ventricular myocytes. The effects of internal application of the proteolytic enzymes trypsin and carboxypeptid...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.02999.x
更新日期:1999-02-01 00:00:00
abstract::1. The field of extracellular nucleotides and purinoceptors has undergone a resurgence of interest and enthusiasm in the past decade. More and more investigators are probing the physiological and pathophysiological roles of P2 receptors in virtually every organ system, including the kidney. 2. With this renewed intere...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2001.03450.x
更新日期:2001-04-01 00:00:00
abstract::Rutaecarpine is a major alkaloid isolated from Evodia rutaecarpa. Here, we investigated the effects of rutaecarpine on osteoclast differentiation induced by macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor κ-B ligand (RANKL) in bone marrow-derived macrophages (BMMs). Treatment with...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 信件
doi:10.1111/1440-1681.12941
更新日期:2018-08-01 00:00:00
abstract::Alpha-pinene (α-pinene) is an organic compound, found in the oils of many species of coniferous trees, especially pine. α-Pinene reportedly has antioxidant and anti-inflammatory activities; however, its effects on osteoblasts are unknown. This study investigated the effects of α-pinene on osteoblast differentiation an...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13245
更新日期:2020-05-01 00:00:00
abstract::1. Angiotensin (Ang) II causes growth-related effects on vascular smooth muscle cells in vitro and in vivo. 2. Chronic infusions of AngII systemically, at doses that are initially subpressor, result in slowly progressive increases in arterial pressure ('slow-pressor' hypertension). It has been suggested that the hyper...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03590.x
更新日期:2001-12-01 00:00:00
abstract::1. Interactions between autacoids may play important roles in the regulation of blood flow in the foetal placenta. In order to investigate this aspect of placental haemodynamics, human normal-term placentae were perfused in vitro and the responses of the foetal vessels to various combinations of vasoactive agents were...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1998.tb02280.x
更新日期:1998-09-01 00:00:00
abstract::1. The use of the isolated lung strip and single open tracheal ring for studying Schultz Dale anaphylactic contractions in both the peripheral and central airways is described. 2. This method is particularly relevant to studies of anaphylaxis because many preparations may be obtained from a single sensitized animal. 3...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1979.tb00046.x
更新日期:1979-11-01 00:00:00
abstract::1. The aim of the present study was to examine the role of dopaminergic and glutamatergic receptors on different stages of the amphetamine (AMPH) sensitized effect in schedule-induced polydipsia (SIP) in rats. 2. Three experiments were designed to evaluate the roles of DAD2 receptor antagonist haloperidol (HAL) and gl...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2010.05416.x
更新日期:2010-09-01 00:00:00
abstract::1. Currently, there is no satisfactory treatment for pulmonary fibrosis. Emodin, a component in Chinese herbs, has been shown to have an antifibrotic effect on pancreatic fibrosis and liver fibrosis. In the present study, we tested the hypothesis that emodin may attenuate the development of pulmonary fibrosis. 2. Mice...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.05048.x
更新日期:2009-02-01 00:00:00
abstract::1. Metformin is one of the most commonly used drugs for the treatment of Type 2 diabetes. Accumulating evidence suggests that metformin also has cardioprotective effects. In the present study, we investigated the cardioprotective effects of metformin and the mechanisms involved. 2. A rat model of chronic heart failure...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2010.05470.x
更新日期:2011-02-01 00:00:00
abstract::The P2X7 receptor is a ligand-gated purinergic receptor activated by extracellular ATP. The receptor is highly expressed in immune cells and in the brain, and, upon activation, the P2X7 receptor allows a cation flux, leading to the distinct activation of intracellular signalling pathways as the secretion of pro-inflam...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.13079
更新日期:2019-06-01 00:00:00
abstract::1. The aim of the present study was to produce a mathematical model that describes the way dynamic changes in renal sympathetic nerve activity affect renal, cortical and medullary blood flow. 2. Cortical blood flow (CBF) and medullary blood flow (MBF) were measured using laser-Doppler flowmetry and (total) renal blood...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2000.03298.x
更新日期:2000-08-01 00:00:00
abstract::1. Responses of splenic diameter measured by sonomicrometry to alpha- and beta-adrenoceptor stimulants were estimated together with simultaneously measured systemic arterial and splenic venous concentrations of red blood cells (RBC), white blood cells (WBC) and platelets (PLT) in anaesthetized dogs. 2. Intravenous and...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03598.x
更新日期:2002-01-01 00:00:00
abstract::1. The angiotensin type 1 (AT1) receptor antagonist, losartan (10 mg/kg) was infused intravenously into nine chronically catheterized fetal sheep (125-132 days gestation). Losartan reduced the fetal systolic (P <0.01) and diastolic (P <0.01) pressor response to 5 microg angiotensin II (AngII) i.v. from 27.4 +/- 1.5 to...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1996.tb02583.x
更新日期:1996-02-01 00:00:00
abstract::1. The aim of the present study was to assess the bioequivalence of two cefadroxil products, namely Ultracef (a reference product) in the form of a 500 mg capsule (produced by Bristol-Myers Squibb Laboratories, Princeton, NJ, USA) and Roxil (a test product) in the form of a 500 mg capsule (produced by Tabuk Pharmaceut...
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.1440-1681.2004.04012.x
更新日期:2004-07-01 00:00:00
abstract::1. Hepatocyte growth factor (HGF) has the therapeutic potential to improve renal fibrosis and proteinuria in rodents with chronic kidney disease. In contrast, long-term administration of human HGF to normal rats reportedly elicits proteinuria. Thus, the role of HGF during proteinuria remains contentious. The aim of th...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2011.05483.x
更新日期:2011-03-01 00:00:00
abstract::1. The effects of clomiphene (CLM) on cardiac outward K+ current components from rat isolated ventricular myocytes were investigated using the whole-cell patch-clamp technique. Clomiphene (10 micromol/L) significantly inhibited both peak (Ipeak) and end-pulse (Ilate) outward currents (elicited by a 500 msec voltage st...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.03956.x
更新日期:2004-01-01 00:00:00
abstract::1. While it is believed that the mammalian distal nephron is not involved in uric acid transport, this has not been directly evaluated. Nevertheless, some studies are consistent with significant distal nephron transport. 2. As uric acid transport in man may be similar to the rat, undirectional uric acid permeability w...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb02123.x
更新日期:1997-09-01 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. Motoneurons (MN) shape motor patterns by transforming inputs into action potential output. This transformation, excitability, is determined by an interaction between synaptic inputs and intrinsic membrane properties. Excitability is not static, but changes over multiple time scales. The purpose of the present paper...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2000.03202.x
更新日期:2000-01-01 00:00:00
abstract::Contrast media are considered to cause acute kidney injury by activating various factors that induce renal vasoconstriction. We analysed the renal microvascular haemodynamic response using the Doppler flow wire method. Then changes in urinary liver-type fatty acid-binding protein levels following contrast medium admin...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 信件
doi:10.1111/1440-1681.12653
更新日期:2016-11-01 00:00:00
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. Pressor responsiveness to angiotensin II (AII) and phenylephrine (PHE) was measured before and after 5 days of ACTH (1 mg i.m. daily) in six normal men maintained on low sodium diet (15 mmol daily). 2. ACTH caused a significant increase in systolic blood pressure of 9 mmHg. 3. There was no change in pressor respons...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1987.tb00382.x
更新日期:1987-03-01 00:00:00
abstract::1. Adrenaline can enhance the stimulation-induced release of transmitter noradrenaline in sympathetically innervated tissues by activating prejunctional beta-adrenoceptors. 2. Adrenaline incorporated into sympathetic transmitter stores by neuronal uptake can be subsequently released as a co-transmitter and can then ac...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1981.tb00750.x
更新日期:1981-09-01 00:00:00