Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Oct 2006
ReviewHypoxia-induced erythropoietin production: a paradigm for oxygen-regulated gene expression.
The mechanisms controlling the expression of the gene encoding for the hormone erythropoietin (EPO) are exemplary for oxygen-regulated gene expression. In humans and other mammals, hypoxia modulates EPO levels by increasing expression of the EPO gene. An association between polycythaemia and people living at high altitudes was first reported more than 100 years ago. ⋯ In addition to erythropoiesis, HIF-1 regulates a broad range of physiologically relevant genes involved in angiogenesis, apoptosis, vasomotor control and energy metabolism. Therefore, the HIF system is implicated in the pathophysiology of many human diseases. In addition to the tight regulation by oxygen tension, temporal and tissue-specific signals limit expression of the EPO gene primarily to the fetal liver and the adult kidney.
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Clin. Exp. Pharmacol. Physiol. · Sep 2006
ReviewPre-eclampsia: contribution of maternal constitutional factors and the consequences for cardiovascular health.
1. Pre-eclampsia is a serious complication of pregnancy that is potentially life threatening for both the mother and baby. It encompasses a number of abnormalities that may be present in other clinical conditions. 2. ⋯ Underlying hypertension, diabetes and obesity strongly predispose to pre-eclampsia. However, a continuum of risk may exist for blood pressure, bodyweight, glucose and lipids, which, in combination with each other and some degree of placental abnormalities, may lead to the development of pre-eclampsia. 4. The present review will focus on the maternal constitutional factors that define the metabolic syndrome and examine their contribution to pre-eclampsia and the long-term consequences for cardiovascular health.
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Clin. Exp. Pharmacol. Physiol. · Aug 2006
Comparative StudyReduced sinoatrial cAMP content plays a role in postnatal heart rate slowing in the rabbit.
1. Decreasing heart rate during development is known to be the result of parasympathetic nervous system maturation that depresses the pacemaker current (If) by acetylcholine (ACh). However, a direct effect of ACh on If has been ruled out and the involvement of other secondary messengers, such as cAMP, was verified in previous studies. ⋯ Significantly reduced heart rate, but unchanged HRV, was observed in perfused hearts in the older age groups, accompanied with a slowed phase 4 spontaneous depolarization rate (90.5 +/- 4.7 vs 49.6 +/- 2.6 mV/s for 2 week vs 4 week hearts, respectively; n = 5; P < 0.05), a negative shift of the If threshold potential (-45.5 +/- 3.0 vs -51.1 +/- 6.0 mV for 2 week vs 4 week hearts, respectively; n = 9; P < 0.05) and decreasing basal levels of SA nodal cAMP (0.31 +/- 0.05 vs 0.025 +/- 0.002 micromol/L for 2 week vs 4 week hearts, respectively; n = 6; P < 0.05). Gene expression levels of PDE1A, 4A and 8A were increased in the 12 week group compared with the 2 week group 1.5-, 2- and 1.8-fold, respectively (P < 0.05), with little change in ADCY1 and 5. 4. These data suggest that, in addition to autonomic innervation, slowing of heart rate during postnatal maturation can be attributed to a negative shift of the If activation caused by diminished baseline cAMP content in SA nodal cells.
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Clin. Exp. Pharmacol. Physiol. · Aug 2006
Comparative StudyCarnitine esters prevent oxidative stress damage and energy depletion following transient forebrain ischaemia in the rat hippocampus.
1. The present study investigated whether propionyl-L-carnitine (PLC) has neuroprotective effects, similar to those reported for acetyl-L-carnitine (AC), against transient forebrain ischaemia-induced neuronal damage and biochemical derangement in the rat hippocampal CA1 region. 2. In total, 105 adult male Wistar albino rats were divided into seven groups of 15 animals each. ⋯ Results from the present study suggest, for the first time, that PLC attenuates forebrain ischaemia-induced neuronal injury, oxidative stress and energy depletion in the hippocampal CA1 region. Propionyl-L-carnitine has neuroprotective effects similar to AC and could have a potential use in the treatment of neurodegenerative diseases. 7. The results of the present study will open up new perspectives for the use of PLC in the treatment of neurodegenerative diseases associated with, or secondary to, myocardial ischaemia-reperfusion injury and chronic circulatory failure.
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Clin. Exp. Pharmacol. Physiol. · Jan 2006
Comparative StudyMelatonin reduces urinary excretion of N-acetyl-beta-D-glucosaminidase, albumin and renal oxidative markers in diabetic rats.
1. Increased oxidative stress has an important role in the pathogenesis of diabetic nephropathy. The aim of the present study was to evaluate diabetic nephropathy by determining markers of oxidative stress and the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), albumin and to investigate the possible protective effects of in vivo melatonin on renal tubular oxidative damage in diabetic rats. 2. ⋯ Therefore, on the basis of these data, we suggest that urinary NAG, albumin excretion, XO activity and MDA levels are more valuable parameters showing the degree of renal tubular injury than classical markers of oxidative stress, including SOD and GSH-Px, in diabetic rat kidneys. Melatonin has an ameliorating effect on oxidative stress-induced renal tubular damage via its anti-oxidant properties. Thus, it may be suggested that urinary NAG excretion and microalbuminuria may be important markers showing the degree of renal changes and the success of long-term treatment of renal impairment with melatonin.