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Results for “actionable alterations”

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At least 73 records · Page 4Linked to original sources
PubMed1986

Altered estrogen action in the senescent rat uterus: a model for steroid resistance during aging.

The estrogen stimulated rat uterus serves as a useful model to examine steroid resistance during aging. This system exhibits receptor loss, impaired stimulation of RNA polymerase II and defects in nuclear translocation (or enhanced association) of receptor-estradiol complexes. All of these defects appear to contribute in part to decreased estrogen responsiveness of the senescent rodent uterus.

Aging↗
PubMed2006

Activation of liver X receptors promotes lipid accumulation but does not alter insulin action in human skeletal muscle cells.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of liver X receptor (LXR) activation on lipid metabolism and insulin action in human skeletal muscle cells prepared from control subjects and from patients with type 2 diabetes. SUBJECTS AND METHODS: Cultured myotubes were obtained from muscle biopsies of 11 lean, healthy control subjects and ten patients with type 2 diabetes. The mRNA levels of LXR isoforms and lipogenic genes were estimated by RT-quantitative PCR, and the effects of LXR agonists on insulin action were evaluated by assays of protein kinase B serine 473 phosphorylation and glycogen synthesis. RESULTS: Both LXRalpha and LXRbeta were expressed in human skeletal muscle and adipose tissue and there was no difference in their mRNA abundance in tissues from patients with type 2 diabetes compared with control subjects. In cultured muscle cells, LXR activation by T0901317 strongly increased expression of the genes encoding lipogenic enzymes, including sterol regulatory element binding protein 1c, fatty acid synthase and stearoyl-CoA desaturase 1, and also promoted triglyceride accumulation in the presence of a high glucose concentration. Importantly, these effects on lipid metabolism did not affect protein kinase B activation by insulin. Furthermore, LXR agonists did not modify insulin action in muscle cells from patients with type 2 diabetes. CONCLUSIONS/INTERPRETATION: These data suggest that LXR agonists may lead to increased utilisation of lipids and glucose in muscle cells without affecting the mechanism of action of insulin. However, the long-term consequences of triglyceride accumulation in muscle should be evaluated before the development of effective LXR-based therapeutic agents.

Adult↗
PubMed1999

The actions of altered osmolarity on guinea-pig detrusor smooth muscle contractility and intracellular calcium.

The study measured the effects in vitro of changing extracellular osmolarity on the contractility of detrusor smooth muscle strips. The data were interpreted in the context of separate measurements from isolated cells of alterations to the intracellular [Ca2+], [Ca2+]i. Increased osmolarity (300-700 mosmol l-1) reduced phasic contractions but increased resting tension regardless of whether sucrose, LiCl or NaCl were used as osmolytes. [Ca2+]i was decreased slightly only when NaCl increased osmolarity, otherwise it was unchanged. The contractile effects may be explained by tissue shrinkage and reduction of detrusor excitability. Lowered osmolarity (300-64 mosmol l-1) decreased phasic contractions but increased resting tension and [Ca2+]i. The raised resting tension was due solely to low osmolarity and was independent of changes to [Na], [Cl] or ionic strength. The rise of [Ca2+]i was due partly to Ca2+ influx through Na(+)-Ca2+ exchange but a fraction was independent of extracellular Ca, unaffected by Gd3+, and persisted in the presence of caffeine. By contrast, reduction of phasic tension was due mainly to the reduced ionic strength, not osmolarity. The results do not support the presence of functional stretch-activated channels and suggest only a minor role for Na(+)-Ca2+ exchange under these conditions. However, they do suggest an intracellular source of Ca2+, which is independent of the sarcoplasmic reticulum.

Animals↗
PubMed1987

Altered modulatory actions of serotonin on dentate granule cells of aged rats.

The effects of serotonin (5-HT) on dentate granule (DG) neurons in hippocampal slices taken from young mature (6-8 months) and old (25-29 months) rats were compared. Intracellular measurements of membrane potential, cell input resistance and slow postspike afterhyperpolarization did not differ significantly between young and old neurons. Neurons recorded in slices taken from old animals responded with less hyperpolarization to increasing doses of the drug, and their responses were significantly reduced after repeated applications of 5-HT. Serotonin-mediated reduction of the slow afterhyperpolarization in young DG neurons was less prominent or totally absent in the old cells. It is concluded that serotonergic postsynaptic actions are impaired in old age.

Aging↗
PubMed2005

Repeated stress alters caffeine action on motor coordination in C57Bl6/J male mice.

This study was aimed to evaluate the effects of stress on caffeine action on motor coordination in mice. For 6 consecutive days, the mice were subjected to three different stressors. Saline or caffeine (30, 60 or 120 mg kg(-1)) was i.p. administered after the last stressful experience, then the animals were behaviorally tested in the holeboard. Their stumbling frequency was compared to that of unstressed mice injected with either saline or caffeine. (1) There was a strong trend for stress to impair motor coordination. (2) In unstressed mice, caffeine induced a linear dose-dependent increase of stumbling frequency. (3) Stress decreased the stumbling frequency induced by the highest dose of caffeine. The results are discussed in terms of interaction of stress and caffeine on dopaminergic and GABAergic systems.

Animals↗
PubMed2004

Stress alters caffeine action on investigatory behaviour and behavioural inhibition in the mouse.

A lot of studies have demonstrated that the physiological action of drugs can be modified by stressors. The present study investigates the effects of stressors on caffeine action on investigatory behaviour and behavioural inhibition in C57Bl6/J mice. For 6 consecutive days, the mice were subjected to one stressful procedure each day consisting on days 1 and 3 of immersion in cold water for 10 periods of 10s each, on days 2 and 5 of a restraint stress for 2 periods of 5 min each, and on days 3 and 6 of placing the animals in a lit openfield for a 10-min period. Saline or caffeine (30, 60 or 120 mgkg-1) were i.p. administered immediately after the last stressful experience, and the animals were tested behaviourally 10 min later. Their behaviour was compared to that of unstressed mice injected with either saline or caffeine. The results show that: (1) in saline-treated mice, stress decreased the investigatory behaviour and increased the behavioural inhibition; (2) in unstressed mice, caffeine decreased the investigatory behaviour in a dose-dependent manner; moreover, behavioural disinhibition, which appeared at low doses of the drug, did not at higher doses; (3) in stressed mice, the dose-dependent action of caffeine was almost abolished and the drug elicited, whatever the dose, a slight increase of the investigatory behaviour and a strong behavioural disinhibition. It is concluded that stress antagonizes the inhibitory action of caffeine on the investigatory behaviour and potentiates its action on behavioural disinhibition. The results are discussed in terms of interaction of stress and caffeine on the dopaminergic system.

Animals↗
PubMed1990

Pentobarbital anesthesia alters renal actions of alpha-hANP in dogs.

The magnitude of the natriuretic response to an infusion of alpha-human atrial natriuretic peptide (alpha-hANP) has varied considerably in different studies. The greatest renal responses to alpha-hANP infusion have been observed in barbiturate-anesthetized dogs. We therefore examined the renal, hormonal, and cardiovascular responses to alpha-hANP infusion in eight female dogs, once awake and again anesthetized with pentobarbital sodium (25 mg/kg body wt). After a 20-min control period, alpha-hANP was infused at a rate of 25 ng.kg-1.min-1 for 60 min. In dogs when awake, infusion of alpha-hANP produced a significant increase in sodium excretion from a control value of 39 +/- 7 to 73 +/- 13 and 89 +/- 15 mu eq/min after 40 and 60 min. In dogs when anesthetized, infusion of alpha-hANP produced an increase in sodium excretion from 21 +/- 3 to 105 +/- 12 and 143 +/- 21 mu eq/min after 40 and 60 min. The increase in sodium excretion was significantly greater in dogs when anesthetized than when awake. We also investigated the role of the renal sympathetic nerves on these responses in six dogs after chronic bilateral renal denervation. In dogs with denervated kidneys when awake, infusion of alpha-hANP did not change sodium excretion significantly. In dogs with denervated kidneys when anesthetized, infusion of alpha-hANP significantly increased sodium excretion; however, the increase was significantly attenuated when compared with anesthetized dogs with intact kidneys. We conclude that the natriuretic response to an infusion of alpha-hANP is enhanced in dogs when anesthetized. Also, the natriuretic response was attenuated by renal denervation in dogs when anesthetized.

Anesthesia↗
PubMed1995

Underfeeding of rat mothers during the first two trimesters of gestation does not alter insulin action and insulin secretion in the progeny.

It has been suggested that impaired insulin action and/or insulin secretion in adult mammals could be a consequence of severe food restriction during fetal life. We have determined to what extent glucose homeostasis and insulin action are modified in male offspring of rats undernourished only during the first two trimesters of pregnancy. Pregnant females then were assigned to one of the following three experimental conditions. Rats in the first group had their food restricted to 50% of their pregnancy intake during the first 2 weeks of pregnancy, after which they were allowed to eat ad libitum. Rats in the second group were similarly restricted during the first 2 weeks, but beginning on day 14 of gestation were pair-fed to control rats until weaning on day 21 after birth: Such an experimental group was introduced because we observed that food-restricted mothers increased their food intake significantly above control levels in the last week of gestation and maintained this increase into the first postnatal week, when they were returned to ad libitum feeding on day 14 of gestation. Control rats (third group) were given access to food ad libitum throughout pregnancy and lactation. Offspring of mothers in the three groups are referred to as food-restricted/ad libitum refed (RA), food-restricted/pair-refed (RP) and control (C) groups, respectively. From 6 weeks of age, RA males ate significantly more food and gained significantly more weight on a standard laboratory diet than control offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Glycosidation of chlormadinol acetate alters its actions on Na+/K+-transporting ATPase and cardiac contractility: a contribution to the endogenous digitalis problem.

Compared to the progesterone derivative chlormadinol acetate 1, the arabinofuranoside 2, rhamnoside 3 and glucoside 4 of 1 are less potent in the Na/K-ATPase assay, but evoke, contrary to 1, positive inotropy in vivo. In anaesthetized cats the circulation effects of 2 and 3 appear to be more favourable than those of the digitalis glycoside digitoxin. Hence, the progestin 1 is transformed through glycosidation into an interesting cardioactive steroid.

Animals↗
PubMed1985

Direct opioid application to peripheral nerves does not alter compound action potentials.

The identification of opiate receptors on primary afferent fibers near the dorsal root ganglia suggests that opiates may be able to affect conduction in primary afferent nerve fibers. We examined the effect of directly applied, preservative-free morphine sulfate (0.1 mg/kg) and fentanyl citrate (25 micrograms/kg) on the A beta, A delta, and C components of the compound action potential of the superficial radial nerve in decerebrate cats (n = 18). Neither drug caused any significant change in the area under the curve of any of the compound action potentials studied. These data indicate that systemically administered opiates are unlikely to cause changes in primary afferent nerve conduction.

Action Potentials↗