Search results for "enzyme inhibitors"
showing 10 items of 559 documents
Miglustat in patients with Niemann-Pick disease Type C (NP-C): A multicenter observational retrospective cohort study
2009
Miglustat has been shown to stabilize disease progression in children, juveniles and adults with Niemann-Pick disease type C (NP-C), a rare genetic disorder characterized by progressive neurological deterioration. We report findings from a retrospective observational cohort study assessing the effects of miglustat on neurological disease progression in patients treated in the clinical practice setting. Data from all NP-C patients prescribed miglustat at 25 expert centers were evaluated using a disease disability scale. The scale analyzed four key parameters of neurological disease progression in NP-C (ambulation, manipulation, language, swallowing). Mean individual parameter scores and a co…
Phenytoin-induced glutathione depletion in rat peripheral nerve
1995
Abstract Administration of high doses (150–250 mg/kg body weight) of phenytoin (DPH) promote a 40% decrease in glutathione (GSH) content of rat sciatic nerve. This DPH-induced GSH depletion is accompanied with an electrophysiological impairment of peripheral neuromuscular function. H7 (20 mg/kg body weight IP, 30 min prior to DPH), a protein kinase C inhibitor, was able to prevent the DPH-induced GSH depletion only at the lower DPH dose used. This same inhibitor completely prevented the electrophysiological impairment at the lower DPH dose, and only partially at the higher DPH dose used. These results confirm the hypothesis of a DPH-dependent activation of PKC (that might be triggered by, o…
Long-term effects of the trehalase inhibitor trehazolin on trehalase activity in locust flight muscle.
2010
SUMMARY Trehalase (EC 3.2.1.28) hydrolyzes the main haemolymph sugar of insects, trehalose, into the essential cellular substrate glucose. Trehalase in locust flight muscle is bound to membranes that appear in the microsomal fraction upon tissue fractionation, but the exact location in vivo has remained elusive. Trehalase has been proposed to be regulated by a novel type of activity control that is based on the reversible transformation of a latent (inactive) form into an overt (active) form. Most trehalase activity from saline-injected controls was membrane-bound (95%) and comprised an overt form (∼25%) and a latent form (75%). Latent trehalase could be assayed only after the integrity of …
Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying
2002
A single intraperitoneal injection of endotoxin (40 μg/kg) significantly delayed gastric emptying of a solid nutrient meal. Blockade of nitric oxide synthase (NOS) with 30 mg/kg ip N G-nitro-l-arginine methyl ester or 20 mg/kg ip 7-nitroindazole [neuronal NOS (nNOS) inhibitor] significantly delayed gastric emptying in control animals but failed to modify gastric emptying in endotoxin-treated rats. Administration of 2.5, 5, and 10 mg/kg ip N 6-iminoethyl-l-lysine [inducible NOS (iNOS) inhibitor] had no effect in either experimental group. Indomethacin (5 mg/kg sc), NS-398 (cyclooxygenase-2 inhibitor; 10 mg/kg ip), and dexamethasone (10 mg/kg sc) but not quinacrine (20 mg/kg ip) significantl…
Increased Hypoxic Tolerance by Chemical Inhibition of Oxidative Phosphorylation: “Chemical Preconditioning”
1997
A short ischemic episode preceding sustained ischemia is known to increase tolerance against ischemic cell death. We report early-onset long-lasting neuroprotection against in vitro hypoxia by preceding selective chemical inhibition of oxidative phosphorylation: “chemical preconditioning.” The amplitude of CA1population spikes (psap) in hippocampal slices prepared from control animals (control slices) was 31 ± 27% (mean ± SD) upon 45-min recovery from 15-min in vitro hypoxia. In slices prepared from animals treated in vivo with 20 mg/kg 3-nitropropionate (3-np) 1–24 h prior to slice preparation (preconditioned slices), psap improved to 90 ± 15% (p < 0.01). Posthypoxic oxygen free radical…
Systolic Blood Pressure Variation and Mean Heart Rate Is Associated With Cognitive Dysfunction in Patients With High Cardiovascular Risk
2015
Abstract— Elevated systolic blood pressure (SBP) correlates to cognitive decline and incident dementia. The effects of heart rate (HR), visit to visit HR variation, and visit to visit SBP variation are less well established. Patients without preexisting cognitive dysfunction (N=24 593) were evaluated according to mean SBP, SBP visit to visit variation (coefficient of variation [standard deviation/mean×100%], CV), mean HR, and visit to visit HR variation (HR-CV) in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease. Cognitive function was assessed with min…
Activation of P2Y receptors by ATP and by its analogue, ADPbetaS, triggers two calcium signal pathways in the longitudinal muscle of mouse distal col…
2008
Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes. This study investigated the nature of the P2Y receptor subtype(s) and the mechanisms leading to the intracellular calcium concentration increase necessary to trigger muscular contraction. Motor responses of mouse colonic longitudinal muscle to P2Y receptor agonists were examined in vitro as changes in isometric tension. ATP or ADPbetaS induced muscular contraction, which was not affected by P2Y(11) or P2Y(13) selective antagonists. Calcium-free solution or th…
Elimination of Ehrlich tumours by ATP-induced growth inhibition, glutathione depletion and X-rays
1995
ATP-induced tumour growth inhibition is accompanied by a selective decrease in the content of the tripeptide glutathione (GSH) within the cancer cells in vivo. Depletion of cellular GSH sensitizes tumours to chemotherapy and radiation, but the usefulness of this depletion depends on whether the levels of GSH can be reduced in the tumour relative to normal tissues. We report here that administration of ATP in combination with diethylmaleate and X-rays leads to complete regression of 95% of Ehrlich ascites tumours in mice. This shows that an aggressive tumour can be eliminated by using a therapy based on modulation of GSH levels in cancer cells.
Transforming growth factor β1 and additional renoprotective effect of combination ACE inhibitor and angiotensin II receptor blocker in hypertensive s…
2005
Objective To verify the benefit of renin–angiotensin system blockade in hypertension, the effects of 24 weeks’ losartan and ramipril treatment, both alone and in combination, on urinary albumin excretion (UAE) and circulating transforming growth factor b1 (TGFb1) have been evaluated in hypertensive subjects with minor renal abnormalities. Design and methods Fifty-one patients with stage 1 and 2 essential hypertension and with UAE >—20 mg/24 h but with maintained renal function have been included. After a 4-week run-in with placebo administration, a randomized double-blind, three-arm double-dummy trial was used. All the hypertensives (HT) were allocated randomly to three treatment arms (1…
Angiotensin-Converting Enzyme Inhibitor Use and Incident Frailty: A Longitudinal Cohort Study
2019
Introduction: Angiotensin-converting enzyme inhibitors (ACEI) may have several pleiotropic effects, but the literature regarding a possible relationship between ACEI use and frailty is limited. We investigated whether ACEI use is associated with lower risk of frailty in a cohort of North American individuals. Methods: Data from the Osteoarthritis Initiative, a cohort study with 8 years of follow-up including community-dwelling adults with knee osteoarthritis or at high risk for this condition, were analyzed. ACEI use was defined through self-reported information and confirmed by a trained interviewer. Frailty was defined using the Study of Osteoporotic Fracture (SOF) index as the presence o…