Multiple low-dose and single high-dose treatments with streptozotocin do not generate nitric oxide

2000 ◽  
Vol 77 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Gianpaolo Papaccio ◽  
Francesco Aurelio Pisanti ◽  
Michael V.G. Latronico ◽  
Eduardo Ammendola ◽  
Michela Galdieri
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
High Dose ◽  
Single High Dose

scholarly journals Advantages of Repeated Low Dose against Single High Dose of Kainate in C57BL/6J Mouse Model of Status Epilepticus: Behavioral and Electroencephalographic Studies

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96622 ◽  
Author(s):  
Karen Tse ◽  
Sreekanth Puttachary ◽  
Edward Beamer ◽  
Graeme J. Sills ◽  
Thimmasettappa Thippeswamy
Keyword(s):  
Status Epilepticus ◽  
Mouse Model ◽  
Low Dose ◽  
High Dose ◽  
Single High Dose

Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults

2007 ◽  
Vol 292 (5) ◽  
pp. G1359-G1365 ◽  
Author(s):  
Christopher N. Andrews ◽  
Adil E. Bharucha ◽  
Michael Camilleri ◽  
Phillip A. Low ◽  
Barbara Seide ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
Photon Emission ◽  
Gastric Volume ◽  
Emission Computed Tomography ◽  
High Dose ◽  
Double Blind Study ◽  
Vagal Activity ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin glucagon-like peptide-1 (GLP-1), which is used to treat diabetes mellitus, delays gastric emptying by inhibiting vagal activity. GLP-1 also increases fasting and postprandial gastric volume in humans. On the basis of animal studies, we hypothesized that nitric oxide mediates the effects of GLP-1 on gastric volumes. To assess the effects of nitrergic blockade on GLP-1-induced gastric accommodation in humans, in this double-blind study, 31 healthy volunteers were randomized to placebo (i.e., saline), GLP-1, or the nitric oxide synthase inhibitor NG-monomethyl-l-arginine acetate (l-NMMA; 4 mg·kg−1·h−1) alone or with GLP-1. Thereafter, 16 additional subjects were randomized to GLP-1 alone or together with a higher dose of l-NMMA (10 mg/kg bolus plus 8 mg·kg−1·h−1 infusion). Gastric volumes (fasting pre- and postdrug, postprandial postdrug) were measured by 99mTc-single-photon-emission computed tomography imaging. GLP-1 increased ( P = 0.04) fasting gastric volume by 83 ± 16 ml (vs. 17 ± 11 ml for placebo) and augmented ( P ≤ 0.01) postprandial accommodation by 688 ± 165 ml (vs. 542 ± 29 ml for placebo). l-NMMA (low dose) alone did not affect fasting or postprandial gastric volume. l-NMMA (low dose) did not attenuate the effect of GLP-1 on gastric volumes. In contrast, l-NMMA (high dose) did not affect fasting volume but blunted GLP-1-mediated postprandial accommodation (postprandial change = 494 ± 37 ml, P ≤ 0.01 vs. GLP-1 alone). These data are consistent with the hypothesis that nitric oxide partly mediates the effects of GLP-1 on postprandial but not fasting gastric volumes in humans.

scholarly journals The effects of single high dose vs daily low dose oral cholecalciferol treatment on vitamin D levels and muscle strenght in posmenapousal women

2015 ◽  
Author(s):  
Mahmut Apaydin ◽  
Asli Gencay Can ◽  
Seyfullah Kan ◽  
Selvihan Beysel ◽  
Taner Demirci ◽  
...  
Keyword(s):  
Vitamin D ◽  
Low Dose ◽  
High Dose ◽  
Single High Dose ◽  
Vitamin D Levels ◽  
Dose Oral

Regulation of an inwardly rectifying K+ channel by nitric oxide in cultured human proximal tubule cells

2004 ◽  
Vol 287 (3) ◽  
pp. F411-F417 ◽  
Author(s):  
Kazuyoshi Nakamura ◽  
Junko Hirano ◽  
Manabu Kubokawa
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Low Dose ◽  
Specific Inhibitor ◽  
High Dose ◽  
Channel Activity ◽  
No Donor ◽  
Proximal Tubule Cells ◽  
Tubule Cells ◽  
Inwardly Rectifying

We investigated the effects of nitric oxide (NO) on activity of the inwardly rectifying K+ channel in cultured human proximal tubule cells, using the cell-attached mode of the patch-clamp technique. An inhibitor of NO synthases, Nω-nitro-l-arginine methyl ester (l-NAME; 100 μM), reduced channel activity, which was restored by an NO donor, sodium nitroprusside (SNP; 10 μM) or 8-bromo-cGMP (8-BrcGMP; 100 μM). However, SNP failed to activate the channel in the presence of an inhibitor of soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μM). Similarly, the SNP effect was abolished by a protein kinase G (PKG)-specific inhibitor, KT-5823 (1 μM), but not by a protein kinase A-specific inhibitor, KT-5720 (500 nM). Another NO donor, S-nitroso- N-acetyl-d,l-penicillamine (10 μM), mimicked the SNP-induced channel activation. In contrast to the stimulatory effect of SNP at a low dose (10 μM), a higher dose of SNP (1 mM) reduced channel activity, which was not restored by 8-BrcGMP. Recordings of membrane potential with the slow whole cell configuration demonstrated that l-NAME (100 μM) and the high dose of SNP (1 mM) depolarized the cell by 10.1 ± 2.6 and 9.2 ± 1.0 mV, respectively, whereas the low dose of SNP (10 μM) hyperpolarized it by 7.1 ± 0.7 mV. These results suggested that the endogenous NO would contribute to the maintenance of basal activity of this K+ channel and hence the potential formation via a cGMP/PKG-dependent mechanism, whereas a high dose of NO impaired channel activity independent of cGMP/PKG-mediated processes.

CCK-evoked hyperemia in rat gastric mucosa involves neural mechanisms and nitric oxide

1996 ◽  
Vol 270 (2) ◽  
pp. G253-G258 ◽  
Author(s):  
A. Heinemann ◽  
M. Jocic ◽  
B. M. Peskar ◽  
P. Holzer
Keyword(s):  
Nitric Oxide ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Low Dose ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Neural Mechanisms ◽  
High Dose ◽  
Related Peptide

This study was performed to identify the possible neural mechanisms and mediators that underlie the gastric mucosal hyperemia evoked by cholecystokinin octapeptide (CCK-8). Gastric mucosal blood flow in anesthetized rats was assessed by the clearance of hydrogen and gastric acid secretion determined in the luminally perfused stomach. The gastric mucosal hyperemic effect of a low dose of CCK-8 (0.04 nmol/min iv infusion for 7 min) was abolished by inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester (15 mg/kg iv) and significantly blunted by defunctionalization of afferent neurons with a neurotoxic dose of capsaicin (125 mg/kg sc). The hyperemic reaction to a high dose of CCK-8 (0.2 nmol/min) was not significantly affected by these pharmacological maneuvers. The vasodilator response to low-dose CCK-8 (0.04 nmol/min) was further analyzed and found to be inhibited by acute bilateral subdiaphragmatic vagotomy, atropine (1 mumol/kg ip), and the antagonistic calcitonin gene-related peptide (CGRP) fragment CGRP-(8-37) (6 nmol/ min ia). Cyclooxygenase inhibition with indomethacin (10 mg/kg ip) was ineffective. The CCK-8-induced increment of gastric acid secretion was not significantly altered by any of these procedures. These results indicate that the gastric vasodilator effect of submaximal doses of CCK-8 is brought about by a vagovagal reflex that involves acetylcholine, CGRP or a related peptide, and nitric oxide as vasodilator messengers.

scholarly journals The Optimal Condition of Poly(I: C)-Induced Knockout of Cre Recombinase for Mx1-Cre/ Cre-loxP Mice

2021 ◽  
Author(s):  
Bijie Yang ◽  
Haobiao Wang ◽  
Yuanyuan Liu ◽  
Feifei Xiao ◽  
Mei Kuang ◽  
...  
Keyword(s):  
Survival Rate ◽  
Knockout Mice ◽  
Low Dose ◽  
Gene Knockout ◽  
Conditional Knockout ◽  
Poly I:C ◽  
High Dose ◽  
P System ◽  
Single High Dose ◽  
Pure Poly

Abstract BackgroundThe Cre-loxP system is widely applied for conditional knockout mice, commonly used to study the function of specific genes. Although some different promoters drive Cre expression, the poly(I: C)-inducible Mx1-Cre is the most commonly used to delete the target gene in experimental hematology. However, the optimal induction knockout condition for Mx1-Cre/ Cre-loxP mice using the Poly(I:C)-inducible Cre-loxP conditional system remains unclear. Here, we present two different components and three injection protocols of poly(I: C) to find the optimized condition. ResultsThe results showed that the better knockout efficiency of Cre-loxP in mice injected with pure poly(I: C) has than those injected with poly(I: C) with some components. From the perspective of lethal genes (Brg1), data showed that mice injected with a single high dose (500 µg) of pure Poly (I:C) had a lower knockout rate. For mice injected media-dose (10µg/g) poly(I: C) triple, which induced a high knockout rate, but the mortality rate was still high. Importantly, the mice injected low-dose (6µg/g) poly(I: C) triple, both the knockout rate and survival rate of mice was high. Similarly, the knockout rate of non-lethal mice injected with media-dose (10µg/g) or low-dose (6μg/g) poly(I: C) triple was very high, but injected with a single high dose (500 µg) of pure poly(I: C) had a low knockout rate. ConclusionOur studies provided the optimized condition for using poly(I: C)-inducible effective knockout and maintaining the survival rate for the Cre-loxP mice, which might be applied in other knockout mice for this system to ensure both the gene knockout and the mice survival.

Sign in / Sign up

Export Citation Format

Share Document