Optimization of magnesium therapy after severe diffuse axonal brain injury in rats.
A number of studies have demonstrated that magnesium salts given after traumatic brain injury improve subsequent neurologic outcome. However, given that these earlier studies have used a number of different salts, dosages, and routes of administration, follow-up studies of the neuroprotective properties of magnesium are complicated, with comparisons to the earlier literature virtually impossible. The present study has therefore characterized the dose-response characteristics of the most commonly used sulfate and chloride salts of magnesium in a severe model of diffuse traumatic axonal injury in rats. Both magnesium salts improved neurologic outcome in rats when administered as a bolus at 30 min after injury. The i.v. and i.m. optima of each salt was 250 micromol/kg and 750 micromol/kg, respectively. The identical concentrations required for improved neurologic outcome suggest that improvement in outcome was dependent on the magnesium cation and not the associated anion. Subsequent magnetic resonance studies demonstrated that the administered magnesium penetrated the blood-brain barrier after injury and resulted in an increased brain intracellular free magnesium concentration and associated bioenergetic state as reflected in the cytosolic phosphorylation potential. Both of these metabolic parameters positively correlated with resultant neurologic outcome measured daily in the same animals immediately before the magnetic resonance determinations. (+info)
Decreases by magnesium of QT dispersion and ventricular arrhythmias in patients with acute myocardial infarction.
AIMS: Magnesium treatment suppresses ventricular arrhythmias in acute myocardial infarction and possibly mortality after infarction, but the underlying mechanisms are inadequately understood. We tested whether the effect of magnesium could be attributed to an influence on the autonomic control of the heart, changes in disturbed repolarization, relief of ischaemia or limitation of myocardial injury. METHODS AND RESULTS: Fifty-nine consecutive patients with acute myocardial infarction were randomized to receive 70 mmol of magnesium (n = 31) infused over 24 h or placebo (n = 26). Occurrence of ventricular arrhythmias and heart rate variability (SD of 5-min mean sinus beat intervals over a 24 h period, SDANN; low frequency/high frequency amplitude ratio, LF/HF ratio), and the number of ischaemic episodes on vectorcardiography were measured from the first day of treatment. QT dispersion corrected for heart rate was measured from the 12-lead ECG. Magnesium decreased the number of hourly ventricular premature beats (P < 0.001) and the number of ventricular tachycardias (P < 0.05). QT dispersion corrected for heart rate was decreased in both measurements at 24 h and 1 week (P < 0.001). SDANN and LF/HF ratio were unchanged. The number of ischaemic episodes on vectorcardiography were equal, and peak creatine kinase MB release did not differ between the groups. In testing the pathophysiological mechanisms, serum magnesium levels after infusion correlated with hourly ventricular premature beats (rs = -0.47; P < 0.01), ventricular tachycardias (rs = -0.26; P < 0.05), and QT dispersion corrected for heart rate (rs = -0.75; P < 0.001), but not with SDANN, LF/HF ratio or peak creatine kinase MB. QT dispersion corrected for heart rate correlated with hourly ventricular premature beats (rs = 0.48; P < 0.001) and ventricular tachycardias (rs = 0.27; P < 0.05). CONCLUSIONS: Magnesium suppresses early ventricular arrhythmias in acute myocardial infarction. The decreased arrhythmicity is related to enhancement of homogeneity in repolarization, but not to attenuation of prevailing ischaemia, improvement of autonomic nervous derangements or myocardial salvage. (+info)
Assessment of the effects of endothelin-1 and magnesium sulphate on regional blood flows in conscious rats, by the coloured microsphere reference technique.
There is evidence to suggest that magnesium (Mg2+) is beneficial in the treatment of a number of conditions, including pre-eclampsia and acute myocardial infarction. The mode of action of Mg2+ in these conditions is not clear, although the vasodilator properties of Mg2+ are well documented both in vitro and in vivo. Previously, we demonstrated that i.v. infusion of magnesium sulphate (MgSO4) alone, or in the presence of vasoconstrictors, caused increases in flow and conductance in the common carotid, internal carotid and hindquarters vascular beds, in conscious rats. Therefore, the objective of the present study was to investigate the regional and subregional changes in haemodynamics in response to the vasoconstrictor peptide endothelin-1 (ET-1) and MgSO4 in more detail, using the coloured microsphere reference technique. Infusion of ET-1 and MgSO4 had similar effects on heart rate and mean arterial pressure as in our previous study. Infusion of ET-1 caused a rise in mean arterial pressure and a fall in heart rate, and infusion of MgSO4 returned mean arterial pressure to control levels with no effect on heart rate. The responses to MgSO4 in the presence of ET-1 showed considerable regional heterogeneity with blood flow increasing (e.g. skeletal muscle), decreasing (e.g. stomach) or not changing (e.g. kidney). Of particular interest was the finding that MgSO4 caused increases in flow in the cerebral and coronary vascular beds. This, and our previous studies, have shown that MgSO4 can reverse vasoconstriction in a number of vascular beds, and indicate that this compound may have therapeutic benefit in conditions associated with vasospasm. (+info)
Effects of temperature, Mg2+ concentration and mismatches on triplet-repeat expansion during DNA replication in vitro.
The human genome contains many simple tandem repeats that are widely dispersed and highly polymorphic. At least one group of simple tandem repeats, the DNA trinucleotide repeats, can dramaticallyexpand in size during transmission from one generation to the next to cause disease by a process known as dynamic mutation. We investigated the ability of trinucleotide repeats AAT and CAG to expand in size during DNA replication using a minimal in vitro system composed of the repeat tract, with and without unique flanking sequences, and DNA polymerase. Varying Mg2+concentration and temperature gave dramatic expansions of repeat size during DNA replication in vitro. Expansions of up to 1000-fold were observed. Mismatches partially stabilized the repeat tracts against expansion. Expansions were only detected when the primer was complementary to the repeat tract rather than the flanking sequence. The results imply that cellular environment and whether the growing strand contains a nick or gap are important factors for the expansion process in vivo. (+info)
Antagonism of vecuronium-induced neuromuscular block in patients pretreated with magnesium sulphate: dose-effect relationship of neostigmine.
We have investigated the dose-effect relationship of neostigmine in antagonizing vecuronium-induced neuromuscular block with and without magnesium sulphate (MgSO4) pretreatment. Neuromuscular block was assessed by electromyography with train-of-four (TOF) stimulation. First, we determined neostigmine-induced recovery in patients pretreated with MgSO4 (group A) or saline (group B) (n = 12 each). The height of T1, 5 min after neostigmine, was 43 (7)% in group A and 65 (6)% in group B (P < 0.01). Respective values after 10 min were 59 (7)% and 83 (5)% (P < 0.01). TOF ratio, 5 min after neostigmine, was 29 (6)% in group A and 29 (5)% in group B. Respective values after 10 min were 38 (11)% and 51 (7)% (P < 0.01). To gain insight into the mechanisms leading to delayed recovery after MgSO4, we calculated assisted recovery, defined as neostigmine-induced recovery minus mean spontaneous recovery. Spontaneous recovery was assessed in another 24 patients. Patients in group C received MgSO4/vecuronium and patients in group D vecuronium only (n = 12 each). Five minutes after neostigmine, assisted recovery was 22 (7)% in the MgSO4 pretreated patients and 28 (6)% in controls (P < 0.05). Ten minutes after neostigmine, values were 24 (7)% and 22 (6)%. Maximum assisted recovery was not influenced by MgSO4 pretreatment (27 (6)% in group A and 32 (6)% in group B) and time to maximum effect was comparable between groups: 6 (4-10) min and 7 (5-8) min, respectively. We conclude that neostigmine-induced recovery was attenuated in patients treated with MgSO4. This was mainly a result of slower spontaneous recovery and not decreased response to neostigmine. (+info)
Spontaneous labour at term is associated with fetal monocyte activation.
The aetiology of both term and preterm labour remains incompletely understood. Maternal infectious diseases as well as intra-uterine infections were shown to be a well established cause of uncontrollable preterm delivery, indicating that inflammatory reactions, regulated by maternal immunecompetent cells, are implicated in labour-promoting mechanisms. To investigate the possibility that the activation of the fetal immune system may be involved in labour induction, we examined cytokine production patterns of different cord blood cell populations obtained from neonates after spontaneous onset of normal term labour and vaginal delivery (n = 25), vaginal delivery but induced term labour (n = 17), and preterm delivery because of uncontrollable labour (n = 27, 20 patients received corticoid treatment for fetal lung maturation), in comparison with cells obtained from neonates after elective term caesarean delivery in the absence of labour (n = 15). Our results demonstrate that spontaneous term labour, but not induced term labour, was associated with significantly increased IL-6 production by myelomonocytic cell populations. Preterm delivery due to uncontrollable labour with resistance to tocolysis was not associated with increased IL-6 production by fetal myelomonocytic cells. Two-colour flow cytometry combined with intracellular cytokine staining was used to identify fetal monocytes as sources of labour-associated IL-6 release at term. We did not find any activation of cord blood T cells in association with spontaneous term or uncontrollable preterm labour. Therefore, fetal T cell responses may not cause monocyte activation. Our results suggest that increased release of IL-6 from fetal monocytes is involved in mechanisms promoting normal term, but not preterm labour, and that mechanisms inducing term and preterm labour are completely different. (+info)
Developmental change in magnesium sulfate-induced relaxation of rabbit pulmonary arteries.
Magnesium causes a variety of vascular smooth muscle to relax. The present study was designed to determine whether there is a developmental change in the magnesium-induced response of pulmonary vasculature. Isolated pulmonary arteries (PA) of newborn (1- to 3-day-old) and juvenile (4- to 6-wk-old) rabbits were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O(2)-5% CO(2), 37.0 degrees C), and their isometric tension was recorded. In arteries preconstricted with endothelin-1 to a similar tension level, MgSO(4) caused greater relaxation of juvenile rabbit PA than that of the newborn rabbit PA. Verapamil, a voltage-dependent Ca(2+) channel blocker, attenuated magnesium-induced relaxation in juvenile rabbit PA but not in newborn PA. The uptake of Ca(2+) of juvenile rabbit PA was inhibited by MgSO(4), and the inhibition was attenuated by verapamil. The uptake of Ca(2+) of newborn rabbit PA was smaller than that of the juvenile PA and was not significantly affected by MgSO(4) and verapamil. These results demonstrate that there is a developmental increase in the dilator effect of MgSO(4) in rabbit PA. In newborn rabbit PA, an incomplete maturation of the voltage-dependent Ca(2+) channels may contribute to the smaller vasodilation induced by MgSO(4). (+info)
Efficacy of various chemotherapeutic agents on the growth of Spironucleus vortens, an intestinal parasite of the freshwater angelfish.
Seven chemotherapeutic agents (dimetridazole, metronidazole, pyrimethamine, albendazole, fenbendazole, mebendazole and magnesium sulfate) were examined for growth inhibition on the cultivation of Spironucleus vortens. Dimetridazole and metronidazole were effective in inhibiting the parasite's growth. At concentrations of 1 microgram ml-1 or higher, both dramatically decreased numbers of parasites. At 24 h exposure, 33% of parasites were inhibited when exposed to dimetridazole or metronidazole at concentrations of 2 and 4 micrograms ml-1, respectively. Dimetridazole at 4 micrograms ml-1 or higher concentrations decreased the number of organisms to 50% or less after 48 h exposure. During the same period of time, the numbers of parasites decreased to 50% or less when exposed to metronidazole at 6 micrograms ml-1 or higher. Pyrimethamine at concentrations of 1 to 10 micrograms ml-1 was not effective in inhibiting the parasite's growth. Albendazole and fenbendazole at concentrations of 0.1 and 0.5 microgram ml-1 were similar in inhibiting the growth of the organism. Both compounds suppressed parasite growth at concentrations of 1.0 microgram ml-1 or higher after 24 h exposure. Mebendazole inhibited the parasite's growth at concentrations of 0.5 microgram ml-1 or higher. At 72 h exposure, 45 to 50% of the parasites were inhibited when exposed to mebendazole at concentrations higher than 0.5 microgram ml-1. Magnesium sulfate at concentrations of 70 mg ml-1 or higher also suppressed the growth of parasites after 24 h exposure. These results indicate that dimetridazole, metronidazole and mebendazole are the most effective chemotherapeutic agents in vitro at inhibiting the growth of S. vortens. (+info)