Abstract:
:Troglitazone has recently been introduced in the treatment of Type 2 diabetes. In addition to its anti-diabetic effects it acts as a perixosome proliferator activated receptor-gamma (PPAR-gamma) agonist and has anti-inflammatory properties by inhibiting macrophage tumour necrosis factor-alpha (TNF-alpha) secretion. It also inhibits the production of endothelial selectin (e-selectin). Troglitazone also reduces interleukin-1alpha induced nitric oxide production in pancreatic beta-cells, which may be relevant in preventing nitric oxide mediated damage to these cells in the Type 1 diabetes process. We tested troglitazone in the spontaneous model of autoimmune diabetes, the non-obese diabetic (NOD) mouse, to determine its effect on the disease process. When administered by gavage from weaning at a dose of 400 mg/kg body weight (n = 32), troglitazone reduced the incidence of diabetes by 16 weeks compared to controls (n = 32) in a pattern that was maintained up to the conclusion of the experiment at 31 weeks of age (p < 0.05). Insulitis was unaltered (index = 1.05 +/- 0.71 vs. 1.13 +/- 0.82, treated vs. controls, p = 0.78). The study was repeated using troglitazone in the diet of NOD mice (n = 24) to give a dose of approximately 200 mg/kg body weight in order to provide a more consistent level of troglitazone during the time course of the experiment. There was a reduction of diabetes incidence in this group but it did not reach significance. Insulin levels were reduced in gavage treated mice although such reduction did not reach significance (p < 0.07). We conclude that, in view of its effect on this model of autoimmune diabetes and because of its known function as an insulin sensitiser, troglitazone might be considered for potential use in those patients with Type 1 masquerading as Type 2 diabetes.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Beales PE,Liddi R,Giorgini AE,Signore A,Procaccini E,Batchelor K,Pozzilli Pdoi
10.1016/s0014-2999(98)00574-3subject
Has Abstractpub_date
1998-09-18 00:00:00pages
221-5issue
2-3eissn
0014-2999issn
1879-0712pii
S0014-2999(98)00574-3journal_volume
357pub_type
杂志文章abstract::We have investigated the effect of inhaled HOE 140, a novel bradykinin B2 receptor antagonist, against bradykinin- and vagal stimulation-induced airway microvascular leakage and bronchoconstriction in anesthetized guinea-pigs. Lung resistance was measured for 6 min after challenge, followed by measurement of extravasa...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90393-x
更新日期:1994-01-14 00:00:00
abstract::The present study was conducted to evaluate the effect of L-3, 4-dihydroxyphenylalanine (L-DOPA) on the daily rhythms of temperature, heart rate and locomotor activity in rats that received a 7-day continuous infusion. Our results indicate that L-DOPA does not induce a loss of the daily rhythmicity of temperature, hea...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00422-2
更新日期:2000-07-28 00:00:00
abstract::Emodin is a natural anthraquinone in rhubarb. It has been identified as a prokinetic drug for gastrointestinal motility in Chinese traditional medicine. Emodin contracts smooth muscle by increasing the concentration of intracellular Ca(2+). In many smooth muscles, increasing intracellular Ca(2+) activates Ca(2+)-activ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2009.04.045
更新日期:2009-08-01 00:00:00
abstract::Ro 40-5967 [(1S,2S)-2-[2[3-(2-benzamidopropyl]- methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl- methoxyacetate] is a new Ca2+ channel antagonist active at L-type channels. Radioligand binding studies in cardiac tissue show that Ro 40-5967 does not inhibit 1,4-dihydropyridine binding, but does in...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00194-p
更新日期:1995-07-04 00:00:00
abstract::A study was undertaken to ascertain why in the mouse vas deferens excitatory junction potentials facilitate whereas contractions depress during low frequency stimulation. In a set of contraction studies, where a conditioning stimulus was followed 2 s later by a test stimulus, depression in the first phase of contracti...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90295-x
更新日期:1994-08-11 00:00:00
abstract::A comparison was made of the effects of 5-MeoDMT or LSD on serotonergic unit activity in the dorsal raphe nucleus (DRN) and nucleus raphe pallidus (NRP) of freely moving cats. NRP neurons were substantially less responsive than DRN neurons to both drugs. NRP neurons were unresponsive to behaviorally effective low dose...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90360-0
更新日期:1982-07-30 00:00:00
abstract::Analogues of the C-terminal octapeptide of cholecystokinin (CCK) modified in the Met28-Gly29 region, were tested for their ability to interact with peripheral cholecystokinin receptors on rat pancreatic acini and to stimulate amylase secretion. These analogues were further evaluated for their ability to recognize cent...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90436-a
更新日期:1990-09-21 00:00:00
abstract::This study examined the role of dopamine systems in tolerance to caffeine-induced stimulation of motor activity in the rat. Selective dopamine D1 and D2 receptor agonists were tested alone and combined in rats receiving caffeine chronically by a method of scheduled access to a caffeine solution or in control rats rece...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90029-9
更新日期:1994-09-01 00:00:00
abstract::The biodistribution of S-(-)-4-(2-hydroxy-3-(1'-[18F]fluoroisopropyl)- aminopropoxy)carbazole ([18F]S-fluorocarazolol, a non-selective beta-adrenoceptor antagonist) was studied in rats (60 min after 18F injection when specific binding in peripheral organs was maximal). 18F uptake in brain, erythrocytes, heart and lung...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)00636-l
更新日期:1995-01-16 00:00:00
abstract::The purpose of this study was to examine the influence of ageing on the alterations in binding characteristics of adrenoceptors and membrane phospholipid fatty acids in rat heart following repeated administration of epinephrine. The maximal number of binding sites (Bmax) and dissociation constant (Kd) of [3H]prazosin ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(95)90150-7
更新日期:1995-05-26 00:00:00
abstract::FR 172357, a new non-peptide antagonist of the kinin B(2) receptor was tested in three isolated vessels, the human umbilical vein, the rabbit jugular vein, and the pig coronary artery, to evaluate its antagonistic activities against bradykinin. FR 172357 displaced to the right the concentration-response curves of brad...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00711-6
更新日期:1999-12-10 00:00:00
abstract::Chronic nitric oxide synthase (NOS) inhibition results in hypertension and myocardial injury. In a rapid and severe model of chronic NOS inhibition, we determined the role of angiotensin II in these effects by using angiotensin II receptor blockade and by measuring cardiac angiotensin II concentrations before and duri...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00384-8
更新日期:2000-07-21 00:00:00
abstract::Histamine induced a dose-dependent stimulation of 3H-catecholamine(CA) efflux (superfusion procedure) from hypothalamic, striatal, hippocampal and cortical slices. The extra-hypothalamic regions were the most sensitive to histamine. Efflux of 14C-GABA and 14C-(acetyl)choline was not affected. The effect of histamine o...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(77)90126-1
更新日期:1977-05-15 00:00:00
abstract::By far the most attention has been paid to the deleterious actions of nonsteroidal anti-inflammatory drugs (NSAIDs), including isoform selective agents that inhibit cyclooxygenase (COX), on the upper gastrointestinal tract, particularly the gastric and duodenal mucosa. However, recent studies confirm a relatively high...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2004.07.042
更新日期:2004-10-01 00:00:00
abstract::The hypothesis that K(+) channels and cell depolarization are involved in neuronal death and neuroprotection was tested in bovine chromaffin cells subjected to two treatment periods: the first period (preconditioning period) lasted 6 to 48 h and consisted of treatment with high K(+) solutions or with tetraethylammoniu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.08.084
更新日期:2006-12-28 00:00:00
abstract::Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes by increasing plasma active glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide levels. However, the effects of chronic DPP-4 inhibition on in vivo beta-cell function are poorly characterize...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.04.018
更新日期:2008-07-07 00:00:00
abstract::The protective potency of ischemic preconditioning decreases with increasing age. A key step in ischemic preconditioning is the opening of mitochondrial Ca(2+) sensitive K(+) (mK(Ca)) channels, which causes mild uncoupling of mitochondrial respiration. We hypothesized that aging reduces the effects of mK(Ca) channel o...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.09.008
更新日期:2008-01-14 00:00:00
abstract::Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of n...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.11.048
更新日期:2017-01-15 00:00:00
abstract::Agelanthus dodoneifolius is one of the medicinal plants used in African pharmacopeia and traditional medicine for the treatment of cardiovascular diseases. A chemical analysis has identified one of the active principles: Dodoneine (Ddn). It is a new dihydropyranone which exerts hypotensive and vasorelaxant effects on ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2014.01.059
更新日期:2014-04-05 00:00:00
abstract::The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. It is well established that excitatory amino acids, aspartate and glutamate, are involved in the spinal transmission of nociceptive information and in the development of hyperalgesia. In the present study, intrathecal (i.t.) admi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(96)00145-8
更新日期:1996-06-03 00:00:00
abstract::Administration of drugs activating cannabinoid CB(1) receptors in the brain induces memory deficit in rodents, and blockade of these receptors may restore memory capacity in these animals. Central administration of beta-amyloid or beta-amyloid fragments may also lead to memory disturbances. This study was undertaken t...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2003.08.026
更新日期:2003-09-23 00:00:00
abstract::The purpose of this study was to determine whether there are age-related changes in the extent of in vitro-induced nitrate tolerance. Nitroglycerin pre-exposure (10 microM for 30 min) provoked a significant shift to the right of the dose-response curve to nitroglycerin in aortae isolated from rats of 8 weeks, 12 and 1...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0926-6917(93)90036-p
更新日期:1993-08-02 00:00:00
abstract::In the rat pulmonary artery, phorbol 12,13-dibutyrate induces a contraction due to the activation of the protein kinase C. We investigated the sensitivity of this protein kinase C-mediated contraction to a variety of vascular smooth muscle relaxants. Pretreatment of rat pulmonary artery with relaxant compounds altered...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90432-h
更新日期:1993-11-09 00:00:00
abstract::The effects of rat calcitonin gene-related peptide (CGRP) on superfused rat aortic smooth muscle cells in cell culture were investigated. Exposure of the cells for 10 min to CGRP (10(-7) M), with or without pretreatment with pertussis toxin, stimulated the release of cyclic AMP but not of prostacyclin, as judged by ra...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90062-9
更新日期:1989-07-18 00:00:00
abstract::The effect of apomorphine (ap) was investigated in rats kept in a familiar cage; 0.25-5 mg/kg s.c. produced a short-lasting, abnormal hypermotility consisting mainly of locomotion and sniffing without grooming. Ap was administered to rate pretreated s.c. with various drugs. Ap hypermotility was antagonized by 12 neuro...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(76)90092-3
更新日期:1976-04-01 00:00:00
abstract::Calcium channel blockers appear to reduce the cardiac toxicity of cocaine and some stimulant-induced behaviors. The present experiment was designed to test whether the internal state induced by cocaine is altered by the calcium antagonist nimodipine. Substitution tests with the calcium agonist BAY K 8644 were also con...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)94072-6
更新日期:1990-09-04 00:00:00
abstract::We examined the mechanism of the inflammatory response induced by topical application of mustard oil (0.5-20.0%/20 microliters per ear) to the mouse ear compared to that of the response to capsaicin. The dose-dependent increases in plasma extravasation and ear thickness reached a maximum at approximately 30 min after ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01040-6
更新日期:1997-08-27 00:00:00
abstract::Recently, stable gastric pentadecapeptide BPC 157 reversed the high MDA- and NO-tissue values to the healthy levels. Thereby, BPC 157 therapy cured rats with bile duct ligation (BDL) (sacrifice at 2, 4, 6, 8 week). BPC 157-medication (10 μg/kg, 10 ng/kg) was continuously in drinking water (0.16 μg/ml, 0.16 ng/ml, 12 m...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.01.030
更新日期:2019-03-15 00:00:00
abstract::There is controversy concerning the inhibitory effect of arginine-vasopressin (AVP) on human platelet adenylate cyclase activity, which putatively involves Gi as the G-protein. To clarify this point, the effects of AVP on human platelet membranes were studied by measuring the activities of the high-affinity GTPase, as...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90020-9
更新日期:1988-06-10 00:00:00
abstract::The testicular capsules of different mammalian species exhibit spontaneous motor activity. In addition, contractions can be mediated by neuronal stimulation or exogenous drug administration. However, the physiological role of testicular capsule motor activity is still not well understood. Nevertheless, there is eviden...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2020.173345
更新日期:2020-09-15 00:00:00