Abstract：
:Small GTPases of the Rho family and their down-stream effectors Rho associated kinases (ROCKs) are the molecules that converge a spectrum of pathophysiological signals triggered by the diabetic milieu and represent promising molecular targets for nephroprotective treatment in diabetes. The review discusses recent studies exploring the consequences of diabetes-induced Rho-ROCK activation in the kidney and the effects of ROCK inhibition (ROCKi) in experimental diabetic kidney disease (DKD). Studies in models of type 1 and type 2 diabetes have indicated blood pressure-independent nephroprotective actions of ROCKi in DKD. The underlying mechanisms include attenuation of diabetes-induced increases in renal expression of prosclerotic cytokines and extracellular matrix, anti-oxidant effects and protection of mitochondrial function, resulting in slower development of glomerulosclerosis and interstitial fibrosis. The studies have also shown antiproteinuric effects of ROCKi that could be related to reductions in permeability of the glomerular barrier and beneficial effects on podocytes. Glomerular haemodynamic mechanisms might also be involved. Despite remaining questions in this field, such as the effects in podocytes later in the course of DKD, specificity of currently available ROCKi, or the roles of individual ROCK isoforms, recent evidence in experimental diabetes suggests that ROCKi might in future broaden the spectrum of treatments available for patients with DKD. This is supported by the evidence generated in models of non-diabetic kidney disease and in clinical studies in patients with various cardiovascular disorders.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Komers Rdoi
10.1111/bcp.12196subject
Has Abstractpub_date
2013-10-01 00:00:00pages
551-9issue
4eissn
0306-5251issn
1365-2125journal_volume
76pub_type
杂志文章,评审abstract：:1 Twenty-four healthy male subjects had two consecutive drug nights at 2-week intervals using placebo and 80, 140 and 240 mg doses of phenobarbitone in a double-blind cross-over design. 2 Phenobarbitone produced significant dose-related decreases in sleep latency and number of awakenings, along with increased total sl...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1981.tb01218.x
更新日期：1981-09-01 00:00:00
abstract：AIM:To study the possible influence of patient characteristics on abacavir pharmacokinetics. METHODS:A population pharmacokinetic model for abacavir was developed using data from 188 adult patients by the use of a nonlinear mixed effects modelling method performed with NONMEM. RESULTS:Abacavir pharmacokinetics was we...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2004.02259.x
更新日期：2005-02-01 00:00:00
abstract：:1 In an open, randomized cross-over investigation of thirteen patients (nine and four women, aged 37-67 years) with mild or moderate essential hypertension a comparison between atenolol and metoprolol was carried out in order to study the effects of 50, 100 and 200 mg given once daily on blood pressure and heart rate ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1981.tb01326.x
更新日期：1981-12-01 00:00:00
abstract：:The pharmacokinetic behaviour and the bioavailability of midazolam were investigated in six volunteers after intravenous (0.15 mg/kg) and oral administration (10, 20 and 40 mg). Following rapid intravenous injection of midazolam, the plasma concentration of the substance decreased to approximately 10% within 2 h owing...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1983.tb02270.x
更新日期：1983-01-01 00:00:00
abstract：:A single oral dose of lamotrigine was administered to seven volunteers with Gilbert's Syndrome (unconjugated hyperbilirubinaemia). Plasma samples were assayed by high performance liquid chromatography (h.p.l.c.) and pharmacokinetic parameters were compared with those of a group of nine normal volunteers. In the subjec...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb03514.x
更新日期：1989-07-01 00:00:00
abstract：:Calcium subserves a ubiquitous role in the organisation of cell function. Ca2+ channels which control influx may be modified in disease states. Animal models of cerebral ischaemia do present some problems when investigating potential therapies involving Ca2+ channels. However, it is important not to be too rigid in se...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.1992.tb04125.x
更新日期：1992-09-01 00:00:00
abstract：AIMS:Adenosine monophosphate (AMP) acts indirectly via primed airway mast cells to induce bronchial hyper-responsiveness, which in turn correlates with eosinophilic asthmatic inflammation and atopic disease expression. We evaluated single and short-term dosing effects of a modern histamine H1-receptor antagonist, levoc...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2004.02110.x
更新日期：2004-07-01 00:00:00
abstract：:1 Comparison of phenytoin clearance showed a marked increase in people over 65 years of age compared with people under 45 years of age. 2 This difference was apparent if phenytoin was given orally or intravenously. 3 Phenytoin clearance correlated inversely with phenytoin binding and plasma albumin, both of which were...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1975.tb00475.x
更新日期：1975-02-01 00:00:00
abstract：:There is increasing evidence suggesting that epoxyeicosatrienoic acids (EETs) play an important role in cardioprotective mechanisms. These include regulating vascular tone, modulating inflammatory responses, improving cardiomyocyte function and reducing ischaemic damage, resulting in attenuation of animal models of ca...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12603
更新日期：2015-07-01 00:00:00
abstract：AIMS:Antihistamines make up the first line of treatments against motion-sickness. Still, their efficacy and specific mechanism have come into question. The aim of this study was to investigate the effect of meclizine on motion-sensitivity. METHODS:This study was carried out as a triple-blinded randomized trial involvi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14257
更新日期：2020-08-01 00:00:00
abstract：:A double-blind, placebo-controlled, cross-over trial of quinine in leg cramps occurring at rest was conducted in 22 elderly cramp sufferers. Despite demonstration of impaired quinine elimination in the elderly, prescription of the traditional dose of 300 mg quinine bisulphate at night failed to produce a significant (...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1987.tb03076.x
更新日期：1987-04-01 00:00:00
abstract：AIMS:The aims of the present study were, firstly, to evaluate long-term trends in the occurrence and treatment of cardiovascular disease (CVD) risk factors and the occurrence of CVD events in children with type 1 diabetes mellitus (T1DM) and, secondly, to assess the determinants of undertreatment of CVD risk factors. ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13482
更新日期：2018-04-01 00:00:00
abstract：:The purpose of this randomized, double-blind, crossover trial was to compare the hypotensive effects of a fixed combination of captopril (C) 50 mg and hydrochlorothiazide (HCTZ) 25 mg (C 50/HCTZ 25) once daily with those of a fixed combination of C 25 mg and HCTZ 12.5 mg (C 25/HCTZ 12.5) twice daily. We studied 199 pa...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1991.tb05622.x
更新日期：1991-07-01 00:00:00
abstract：AIMS:High plasma cholesterol concentration and increased platelet activity are two major risk factors for atherosclerosis. Lovastatin, the lipophilic drug was shown to inhibit platelet aggregation whereas pravastatin, the hydrophilic drug had no such effect. Analysis of the effect of fluvastatin which is both a lipophi...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1046/j.1365-2125.1997.00625.x
更新日期：1997-07-01 00:00:00
abstract：:The deployment of artesunate for severe malaria and the artemisinin combination therapies (ACTs) for uncomplicated malaria has been a major advance in antimalarial therapeutics. These drugs have reduced treated mortality, accelerated recovery and reduced treatment failure rates and transmission from the treated infect...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14474
更新日期：2020-07-12 00:00:00
abstract：:1 A double-blind trial with parallel treatment groups was conducted to compare the safety and efficacy of mianserin with amitriptyline. 2 This was a six week trial with weekly visits. Measurements at each visit included: 21 item Hamilton Depression (HAMD) Scale. Clinical Global Impression (CGI) Scale and Treatment Eme...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1983.tb05870.x
更新日期：1983-01-01 00:00:00
abstract：AIMS:Flavonoids may affect platelet function by several mechanisms, including antagonism of TxA(2) receptors (TP). These TP are present in many tissues and modulate different signalling cascades. We explored whether flavonoids affect platelet TP signalling, and if they bind to TP expressed in other cell types. METHODS...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2007.02881.x
更新日期：2007-08-01 00:00:00
abstract：:Caffeine (5 mg kg-1) was administered orally to two healthy, non-smoking subjects on three separate occasions--before, and during therapy with the xanthine oxidase inhibitor allopurinol at doses of either 300 or 600 mg daily. Plasma and urinary levels of methylxanthines, endogenous oxypurines and allopurinol and its m...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1986.tb05222.x
更新日期：1986-04-01 00:00:00
abstract：:1. Twenty-two patients with moderately severe essential hypertension were treated for a period of 12 months with guanfacine (BS 100-141), a new centrally-acting antihypertensive agent. A twice daily schedule was followed and the dose range of guanfacine was 1-8 mg daily. 2. In twenty patients satisfactory blood pressu...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1980.tb04906.x
更新日期：1980-01-01 00:00:00
abstract：AIMS:To study the delivery of 15 mg beclomethasone 17,21-dipropionate (BDP) to the distal part of the small bowel for three oral sustained-release formulations (I-III) and a reference capsule in volunteer ileostomists, and to compare these findings with the in vitro dissolution profiles. METHODS:Two groups of nine ile...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.1998.00782.x
更新日期：1998-09-01 00:00:00
abstract：AIMS:To determine whether preclinical medical students are able to learn therapeutic problem solving simultaneously with gaining knowledge of pharmacology. METHODS:A randomized controlled pre/post-test study among 85 3rd year preclinical medical students from two medical faculties in Amsterdam. In addition to the norm...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2005.02571.x
更新日期：2006-03-01 00:00:00
abstract：:The effect of metronidazole, at a dose of 1.2 g daily, on theophylline disposition was studied in 10 healthy adult volunteers. Neither theophylline half-life, volume of distribution nor total body clearance was altered by the anti-microbial. It is concluded that metronidazole does not impair theophylline metabolism de...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1987.tb03146.x
更新日期：1987-07-01 00:00:00
abstract：:Oxycodone chloride (0.07 mg kg-1) was given by intravenous bolus to nine young adult surgical patients on the first postoperative day. Plasma was sampled for up to 12 h. Mean values of t1/2z, CL and Vss were 222 min, 0.78 l min-1 and 2.60 l kg-1, respectively. The concentrations of the metabolite noroxycodone was also...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1991.tb03942.x
更新日期：1991-10-01 00:00:00
abstract：AIM:This study aims to investigate the clinical and demographic factors influencing gentamicin pharmacokinetics in a large cohort of unselected premature and term newborns and to evaluate optimal regimens in this population. METHODS:All gentamicin concentration data, along with clinical and demographic characteristics...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12444
更新日期：2014-11-01 00:00:00
abstract：:Nine healthy male subjects received oral fluconazole 400 mg daily, ketoconazole 200 mg twice daily or no treatment for 6 days according to a randomized, cross-over design. A single 250 mg oral dose of phenytoin suspension was administered on day 5 and serum phenytoin concentrations were measured over the following 48 ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1992.tb04111.x
更新日期：1992-07-01 00:00:00
abstract：:1. Alfuzosin is a post-synaptic alpha-adrenoceptor antagonist with antihypertensive and peripheral vasodilator properties. 2. We measured the effect of alfuzosin, 5 mg, on sympathetically-mediated venoconstriction by changes in the venous reflex response (VRR) in a randomised, double-blind, placebo-controlled, crossov...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1989.tb05330.x
更新日期：1989-01-01 00:00:00
abstract：:1 The effects of oxprenolol 80 mg and propranolol 80 mg on resting forearm blood flow (RFBF) and skin temperature were compared in seven normotensive subjects, for 4 h after an oral dose. 2 There was a significant fall of RFBF after propranolol (mean +/- s.e. mean 0.74 +/- 0.24 ml 100 g-1 min-1) compared to a smaller ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1981.tb01154.x
更新日期：1981-05-01 00:00:00
abstract：AIMS:Kisangani is an area with intense malaria transmission and sulfadoxine-pyrimethamine resistance. Alternative antimalaria prophylaxis medication and protocols are needed, particularly with pregnant individuals. In this study, we compare the tolerance and effectiveness of mefloquine regimen as a split dose with a me...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14720
更新日期：2021-01-04 00:00:00
abstract：AIMS:The pharmacokinetics and dose proportionality of rizatriptan single oral doses from 2.5 to 15 mg administered as solutions to healthy volunteers were studied. METHODS:In a randomized, crossover study with four periods, twenty-four healthy volunteers (12 males and 12 females) took single oral doses of 2.5, 5, 10, ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.1999.00917.x
更新日期：1999-04-01 00:00:00
abstract：:We define a me-too drug as a pharmacologically active compound that is structurally related to a first-in-class compound, regarded as belonging to the same therapeutic class as the original compound, and used for the same therapeutic purposes, but which may differ in some respects, such as specificity of pharmacologic...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14327
更新日期：2020-11-01 00:00:00
