Search results for "Dose dependence"

A mechanistic underpinning for sigmoid dose-dependent infection

2016

Bioequivalence decision for nanoparticular iron complex drugs for parenteral administration based on their disposition

2017

Although parenteral iron products have been established to medicinal use decades before, their structure and pharmacokinetic properties are not fully characterized yet. With its' second reflection paper on intravenous iron-based nano-colloidal products (EMA/CHMP/SWP/620008/2012) the European Medicine Agency provided an extensive catalogue of methods for quality, non-clinical and pharmacokinetic studies for the comparison of nano-sized iron products to an originator (EMA, 2015). For iron distribution studies, the reflection paper assumed the use of rodents. In our tests, we used a turkey fetus model to investigate time dependent tissue concentrations in pharmacological and toxicological rele…

HDAC5 Inhibitors as a Potential Treatment in Breast Cancer Affecting Very Young Women

2020

Background: Breast cancer in very young women (BCVY) defined as &lt

Levels of GHB in hair after regular application.

2021

Gamma hydroxybutyrate (GHB) is a central nervous system depressant that is an approved drug for the treatment of narcolepsy with cataplexy and other syndromes. Due to its dose dependent stimulating, relaxing or sedative effects, illicit abuses include recreational use by young people and cases of drug-facilitated crime (DFC). Since GHB is also produced endogenously, for forensic questions, it is important to be able to differentiate between endogenous GHB and elevated levels due to additional intake. In this study, we measured GHB concentrations in hair of patients with narcolepsy receiving daily GHB treatment. The results were compared to endogenous concentrations and concentrations after …

Pathophysiology of anthracycline cardiotoxicity.

2016

Anthracyclines (ANTs) are powerful drugs that have reduced the mortality of cancer patients. However, their use is limited by the development of cardiotoxicity (CTX), which is dose dependent and may lead to left ventricular dysfunction and heart failure. Although various strategies have been suggested to reduce the negative effects of ANTs, CTX is still an important unresolved clinical issue. This may be due at least partly to the incomplete characterization of the molecular and cellular mechanisms of ANT-induced CTX. In addition, although various forms of cardiac damage have been demonstrated with the use of these drugs in experimental studies, it is not yet clear how these translate to th…

The rat liver foci bioassay: II. Investigations on the dose-dependent induction of ATPase-deficient foci by vinyl chloride at very low doses

1985

In order to study the dose-dependence of the genotoxic effect of vinyl chloride (VC) hepatocellular ATPase-deficient foci were evaluated after subchronic exposure of newborn rats. Wistar rats were exposed from day 1 after birth over 10 weeks to 10, 40, 70, 150, 500 and 2000 p.p.m. VC (8 h/day; 5 days/week). One week after cessation of exposure hepatic ATPase-deficient foci were quantitated. For a subsequent investigation lower dose range groups of female and male Wistar and Sprague-Dawley rats were exposed (8 h/day; 5 days/week) to 2.5, 5, 10, 20, 40 and 80 p.p.m. VC. Exposure started at day 3 of life and lasted for 3 weeks. After cessation of exposure the animals were maintained for 10 wee…

The Higher the Dose, the Greater the Sex Differences in Escape–Avoidance Response in Mice After Acute Administration of Haloperidol

1998

Abstract MONLEON, S. AND A. PARRA. The higher the dose, the greater the sex differences in escape–avoidance response in mice after acute administration of haloperidol . PHARMACOL BIOCHEM BEHAV 60 (1) 279–284, 1998.—Sex differences in the effects of haloperidol in the escape–avoidance response have previously been found in various studies carried out in our laboratory in which mice were used as experimental subjects. Males were more affected than females by the disruptive effects of this neuroleptic of frequent clinical use. In the present work these sex differences were evaluated in a unique training session using several doses of the drug (0.075, 0.25, and 0.75 mg/kg IP). The number of avo…

Dose-dependent impairing effects of morphine on avoidance acquisition and performance in male mice.

1998

The effects of morphine (6.3, 12.6, and 25.2 mg/kg) on active avoidance behavior of BALB/C mice are explored in three acquisition sessions and in two subsequent performance sessions. Morphine-treated animals showed an increase in avoidance acquisition with respect to control group without differences in performance. However, a dramatical, concomitant rise in the locomotor activity of the animals (increase in the number of crossings during the intertrial intervals) prompted us to transform the data employing a formula with which a measure of actual learning was obtained. Applying this formula, we have observed that morphine administration impairs, dose-dependently, acquisition and performanc…

Interleukin-1 inhibits drinking behaviour through prostaglandins, but not by nitric oxide formation

1997

Interleukin-1 beta (IL-1 beta) causes inhibition of drinking behaviour. Moreover it induces formation of prostaglandins (PGs) and nitric oxide (NO). Both PGs and NO are able to inhibit drinking stimulated by water deprivation or by intracerebroventricular (i.c.v.) administration of angiotensin II. In this study, we studied in the preoptic area (POA) the possible role of PGs and NO in the antidipsogenic action induced by IL-1 beta. IL-1 beta was injected in the lateral cerebral ventricle (i.c.v.) (2.5, 10, 20, and 40 ng/rat) or into POA (0.625, 1.25, 2.5, and 10 ng/rat). L-arginine (12.5, 25, 50, and 100 ng/rat), the precursor of NO, or NG-nitro-L-arginine methyl ester (L-NAME) (25, 50, and …

Dose Dependency of Sex Differences in the Effects of Repeated Haloperidol Administration in Avoidance Conditioning in Mice

1999

Sex differences in the effects of haloperidol in active avoidance conditioning in mice have previously been found in various studies carried out in our laboratory. Males were more affected than females by the disruptive effects of this neuroleptic. The work described here broadens the study of these sex differences to higher doses of haloperidol (0.1 and 0.2 mg/kg) using a repeated administration schedule (5 days). The results did not show sex differences in the deteriorating effects of this dopamine antagonist in the escape-avoidance response, but a tendency in the number of nonresponses was observed in the same direction as former results: male animals were more sensitive than females to …