Anticonvulsant effects of magnesium sulfate in hippocampal-kindled rats

The objective of the present study was to determine whether magnesium sulfate has anticonvulsant actions in the hippocampal-kindled rat model of epilepsy. Fully kindled rats received acute intraperitoneal injections of magnesium sulfate (270 mg/kg), phenytoin (20 mg/kg) or saline in random order. Electrical seizure duration, behavioral seizure stage and duration of postictal EEG depression were examined 15, 30 and 60 min after injection. In an additional group of rats, kindled seizures were measured before and after chronic (2 h) intraperitoneal injections of magnesium sulfate versus saline. There was a significant decrease in electrical seizure duration (p<0.01) and behavioral seizure stage (p<0.01) with acute magnesium sulfate injections compared to saline injections. Phenytoin had no statistically significant effects on hippocampal-kindled seizures. Chronic magnesium sulfate treatment significantly reduced behavioral seizure stage at 2, 24, and 48 h postinjection (p<0.05), but did not affect seizure duration. There was a significant time by treatment effect for magnesium sulfate on postictal EEG depression (p<0.01). We conclude that in this model of hippocampal epilepsy-induced (kindled) rats, magnesium sulfate has significant anticonvulsant effects.     

Antiarrhythmic effect of magnesium sulfate against occlusion-induced arrhythmias

The antiarrhythmic effect of magnesium sulfate (Mg) as well as the hemodynamics were studied using the coronary ligation and reperfusion models in rats.In the study on coronary ligation arrhythmia, i.v. administration of Mg (0.6, 2, 6, 20 and 60 \sgmaelig;mol) was conducted at 5 min after coronary ligation. Mg had an action to decrease the total number of premature ventricular contraction (PVC), the duration of ventricular tachycardia (VT), the frequency of VT and ventricular fibrillation (Vf) and the mortality ratio for 30 min after coronary ligation. In the 6-60 \sgmaelig;mol groups, significant antiarrhythmic action (p < 0.01 vs. control) was attained.In the study on reperfusion arrhythmia, i.v. administration of Mg (20, 60 and 200 \sgmaelig;mol) was conducted at 4 min after coronary ligation, and at 1 min after ligation, the coronary artery was reperfused. Mg had an action to decrease the frequency of Vf, the mortality ratio and the duration of VT and Vf and to extend the interval between the initiation of reperfusion and the occurrence of VT and Vf for 10 min after reperfusion. In the 200 \sgmaelig;mol group, significant antiarrhythmic action (p < 0.05 vs. control) was attained. Administration of Mg decreased the heart rate and blood pressure.We concluded that Mg can control myocardial ischemia-induced and reperfusion-induced arrhythmia and that sudden cardiac death which occurs as a result of arrhythmia can be prevented.     

Effect of magnesium sulfate on bronchoconstriction in the lung periphery

Magnesium sulfate has been shown to be effective clinically as a bronchodilator, but its mechanism of action is unknown. We used a wedged bronchoscope technique to study the ability of MgSO4 at clinically relevant concentrations to attenuate hypocapnia-, acetylcholine- (ACh), and dry air-induced bronchoconstriction in the canine lung periphery. Control experiments demonstrated that consecutive challenges of either hypocapnia or ACh resulted in greater collateral system resistance (Rcs) after the second challenge compared with the first. Intravenous infusion of MgSO4 diminished the maximum response to a second hypocapnic challenge (Rcs = 1.59 +/- 0.29 cmH2O.ml-1.s prechallenge vs. 1.12 +/- 0.20 postchallenge) but had no effect on either ACh- or dry air-induced bronchoconstriction. Serum magnesium levels before MgSO4 administration were 1.59 +/- 0.04 meq/l and rose to 6.20 +/- 0.13 during the infusion. Previous studies demonstrated that nifedipine, like MgSO4 in this study, attenuates hypocapnia-induced bronchoconstriction in the canine lung periphery but has no effect on ACh- or dry air-induced bronchoconstriction. We conclude that these results are consistent with the idea that, like nifedipine, magnesium acts in the airway as a voltage-sensitive calcium channel blocker.     

Effect of magnesium sulfate administration on subendocardial and subepicardial perfusion

The objective of this study was to determine the effect of systemic MgSO₄ infusion on subendocardial and subepicardial perfusion. Seventeen spontaneously breathing piglets were examined. Myocardial perfusion was measured using radiolabeled microspheres at baseline, 30 and 60 min after either MgSO₄ (80 mg/kg) or saline infusion. Blood pressure, heart rate, and cardiac output were also measured at these time intervals. Comparison of the magnesiuminduced changes in systemic blood pressure and on subendocardial and subepicardial perfusion at 30 and 60 min with values obtained with saline solution at 30 and 60 min, yielded no statistically significant difference (Tables 1–3). The ratio of subendocardial/subepicardial blood flow and subendocardial and subepicardial coronary vascular resistance at 30 and 60 min revealed no statistically significant differences between the magnesium and the control group (Table 3). There were no statistically significant difference in cardiac output and heart rate during any of the measured periods (Table 2). Our results suggest that the administration of MgSO₄ does not alter the ratio of subendocardial/subepicardial blood flow and the ratio of subendocardial/subepicardial coronary vascular resistance.     

Hypophosphatemia: A Practical Guide to Evaluation and Management

Phosphate plays a critical and diverse role in human physiology. In addition to its importance in skeletal mineralization, it is essential for energy homeostasis, enzyme function, and cell membrane integrity. These diverse functions of phosphate provide an explanation for the range of symptoms and clinical manifestations observed in patients with both acute and chronic causes of hypophosphatemia. Normal phosphate homeostasis involves several major systems, including the gastrointestinal tract, bones, and kidneys. Phosphate balance is maintained directly and indirectly by 1α,25-dihydroxyvitamin D₃, parathyroid hormone, and the osteocyte-derived phosphatonin fibroblast growth factor 23. This review discusses normal phosphate homeostasis, the clinical manifestations and causes of hypophosphatemia, and an approach to establish a diagnosis and appropriate management.     

Acute cord occlusion increases blood ionized magnesium concentration in preterm fetal sheep during maternal magnesium sulfate exposure

This study tested the hypothesis that a pathophysiologic insult to the fetus that decreases pH (umbilical cord occlusion) produces an increase in physiologically active (i.e., ionized) magnesium concentration. Preterm pregnant sheep (n = 7) were instrumented with maternal and fetal catheters and an inflatable vascular occluder was placed around the umbilical cord. After a 2-day recovery period, each ewe received a 4-g loading dose, followed by continuous intravenous infusion of 1 g magnesium sulfate/h. After 48 h, an episode of acute fetal distress was produced by inflation of the umbilical occluder for 10 min. Maternal and fetal arterial blood samples were collected at regular intervals to quantitate ionized magnesium concentration and monitor physiologic status. Magnesium sulfate infusion increased maternal and fetal blood ionized magnesium concentration. In vitro blood analysis demonstrated that there was a linear inverse correlation (r2 = 0.99) between fetal sheep blood pH and ionized magnesium concentration. In vivo, 10 min of umbilical cord occlusion produced an increase in fetal blood ionized magnesium concentration in all animals (P = 0.02) that was temporally related to the decrease in fetal blood pH. Whether this increase in physiologically active magnesium concentration is beneficial (via neuroprotection) or deleterious (via suppression of stress response) to the distressed fetus remains to be determined.     

The effect of magnesium sulfate infusion on systemic and renal prostacyclin production

Recent in vitro studies have suggested that magnesium sulfate (MgSO4) infusions may increase prostacyclin production. We studied the effect of MgSO4 infusion on prostacyclin (PGI2) metabolite excretion in women with either pregnancy induced hypertension or preterm labor. Excretion of renal and systemic metabolites of PGI2 was measured prior to and following the start of MgSO4 infusion in the two groups. An increased in renal PGI2 metabolite preterm labor excretion was noted in the hypertension group but no change was noted in systemic PGI2 excretion in either group. These data fail to support a generalized, short term increase in endothelial cell PGI2 production as the basis for the beneficial effect of MgSO4.     

Effects of sodium and magnesium sulfate in drinking water on mallard ducklings

One-day-old mallard (Anas platyrhynchos) ducklings were given drinking water for up to 28 days that contained concentrations of sodium and/or magnesium similar to those found in saline wetlands. Growth, tissue development, and biochemical characteristics of these ducklings were compared to those reared on fresh water. Much of the ingested salt was excreted by passage of voluminous fluid excreta. This effect occurred in birds given water with as little as 500 ppm Mg or 1,000 ppm Na. The supraorbital salt gland was active within 4 days in ducklings drinking water containing greater than or equal to 1,500 ppm of Na. Feather growth was decreased in ducklings drinking water with greater than or equal to 1,500 ppm of either Na or Mg. Ducklings drinking water with 3,000 ppm of either ion, or 1,500 ppm of each, grew more slowly than control birds. Ducklings drinking water with 3,000 ppm of either Na or Mg had reduced thymus size and bone breaking strength. Those drinking water with 3,000 ppm of Mg, or 3,100 ppm Na and 1,300 ppm Mg also had less trabecular bone and enlarged adrenals. Birds drinking the latter water had an elevated concentration of Na and calcium, and a decreased concentration of phosphorus and chloride in their serum, and elevated plasma protein levels. Ducklings reared on fresh or slightly saline water adapted very poorly to an abrupt change to more saline water (specific conductivity = 15,250 microns hos/cm) at 14 days of age. These birds stopped eating, became inactive and some died within 3 days; survivors had many tissue and biochemical abnormalities at 20 days of age. The level of salinity in these trials was similar to that in "brackish" or "moderately saline" wetlands and lower than that previously found to have effects on growth and feathering of ducklings. Many of the sublethal effects were subtle and non-specific manifestations of stress, and would be difficult to detect in wild ducklings on saline wetlands.     

RbgA ensures the correct timing in the maturation of the 50S subunits functional sites

RbgA is an essential protein for the assembly of the 50S subunit in Bacillus subtilis. Depletion of RbgA leads to the accumulation of the 45S intermediate. A strain expressing a RbgA variant with reduced GTPase activity generates spontaneous suppressor mutations in uL6. Each suppressor strain accumulates a unique 44S intermediate. We reasoned that characterizing the structure of these mutant 44S intermediates may explain why RbgA is required to catalyze the folding of the 50S functional sites. We found that in the 44S particles, rRNA helices H42 and H97, near the binding site of uL6, adopt a flexible conformation and allow the central protuberance and functional sites in the mutant 44S particles to mature in any order. Instead, the wild-type 45S particles exhibit a stable H42-H97 interaction and their functional sites always mature last. The dependence on RbgA was also less pronounced in the 44S particles. We concluded that the binding of uL6 pauses the maturation of the functional sites, but the central protuberance continues to fold. RbgA exclusively binds intermediates with a formed central protuberance and licenses the folding of the functional sites. Through this mechanism, RbgA ensures that the functional sites of the 50S mature last.     

Effects of magnesium sulfate on the luminescence of Vibrio fischeri under nutrient-starved conditions

In this study, we investigated the relationship between MgSO(4) and luminescence in Vibrio fischeri under nutrient-starved conditions. When V. fischeri was cultured in an artificial seawater medium, the luminescence intensity was low relative to that observed under normal growth conditions. It decreased during the initial 14 h, and then increased slightly at 24 h. This regulation of luminescence was not dependent on the quorum-sensing mechanism, because the cell densities had not reached a critical threshold concentration. Under MgSO(4)-starved conditions, luminescence was not fully induced at 14 h, and decreased at 24 h. In contrast, induction of luminescence occurred under MgSO(4)-supplemented conditions, but MgSO(4) alone was insufficient to induce luminescence, and required NaHCO(3) or KCl. These results suggest that the luminescence of V. fischeri is controlled by an exogenous sulfur source under nutrient-starved conditions. In addition, they indicate that the induction of sulfur-dependent luminescence is regulated by the NaHCO(3) or KCl concentration.     

Effects of magnesium sulfate on an unfolding step of human cyanomet myoglobin.

The effects of magnesium sulfate (MgSO4) on an unfolding step of human cyanomet myoglobin (Mb) were examined for wild-type and three L-->A mutant Mbs. The unfolding was induced at acidic pH (3.6-4.5) with various concentrations of MgSO4 (0-2 M). The monophasic process was monitored by visible absorption spectroscopy. We observed quite nonlinear delta G not equal to-[MgSO4] relations for all the Mbs. delta G not equal to-[MgCl2] relations were also determined for a comparative study. Thermodynamic evaluation of the results indicated that an upward reflection of delta G not equal to-[MgSO4] relations in high [MgSO4] is caused by the strong Hofmeister effect of the salt. Results obtained for three mutants (L29A, L72A, and L104A) at pH 4.0 and 4.5 were consistent with our previous observation that the structure of the transition state is determined by the stability of Mb cores in the balance with the pH conditions of unfolding (T. Konno and I. Morishima. 1993. Biochim. Biophys. Acta. 1162:93-98).     

Resistance artery vasodilation to magnesium sulfate during pregnancy and the postpartum state

This study compared the vasodilatory responses to magnesium sulfate (MgSO(4)) of cerebral and mesenteric resistance arteries and determined whether the responses varied between different gestational groups. Third-order branches (<200 microm) of the posterior cerebral (PCA) and mesenteric arteries (MA) were dissected from nonpregnant (NP; n = 6), late pregnant (LP; day 19, n = 6), and postpartum (PP; day 3, n = 6) Sprague-Dawley rats. A concentration-response curve was performed by replacing the low-MgSO(4) (1.2 mM) HEPES buffer solution with increasing concentrations of MgSO(4) (4, 6, 8, 16, and 32 mM) and measuring lumen diameter at each concentration. All groups exhibited concentration-dependent dilation to MgSO(4), decreasing the amount of tone in the vessels. However, MA were significantly more sensitive to MgSO(4) than PCA. Whereas there was no difference in the response between different gestational groups in MA, the PCA from the LP and PP groups showed a significantly diminished response to MgSO(4). The percent dilation at 32 mM MgSO(4) for PCA versus MA in NP, LP, and PP animals was 36 +/- 2 vs. 51 +/- 7% (P < 0.05), 19 +/- 9 vs. 54 +/- 6% (P < 0.01 vs. PCA and NP), and 12 +/- 5 vs. 52 +/- 11% (P < 0.01 vs. PCA and NP). These results demonstrate that MgSO(4) is a vasodilator of small resistance arteries in the cerebral and mesenteric vascular beds. The refractory responses of the PCA in LP and PP groups demonstrate changes in the cerebrovascular vasodilatory mechanisms with gestation. The greater sensitivity of the MA to MgSO(4)-induced vasodilation suggests that the prophylactic effect of MgSO(4) on eclamptic seizures may be more closely related to the lowering of systemic blood pressure than to an effect on cerebral blood flow.     

50 years after--examination of some circumstances around the establishment of the correct chromosome number of man

Three authors, Levan (1975, 1978), Tjio (1978) and Hultén (2002) have independently described the establishment of the correct chromosome number of man (Tjio and Levan 1956) and the background to that study. However, the three authors provide strikingly different accounts of this historical discovery. In this study I have examined the consistency between these accounts and details provided by the logbook kept at Cancer Chromosome Laboratory, University of Lund. For complementary details I have also consulted several persons that were active at the Institute of Genetics, Univ. of Lund, at the time of the discovery. Levan's (1975)Levan's (1978) accounts are both written in a modest way compared to the more self-centered narratives of Tjio and Hultén. His accounts are also consistent with all details that can be collected from the logbook. However, and most unfortunately, Levan is not explicit with respect to the dates of what might be different cytogenetic observations related to the determination of the correct chromosome number of man. The logbook leaves no room for various temporal details given by Tjio, which, if correct, might substantiate his account. Also Tjio's introduction of an alter ego into the narrative is apt to lessen the general credibility of his account. Tjio's (1978) contention of having made his human chromosome preparations at 2 a.m. on December 22nd or 23rd would be consistent with his claim that he arrived from Spain in early December 1955. His account of this crucial issue is incorrect, however, as he did not arrive at the Cancer Chromosome Laboratory until December 19. Hultén's claim of involvement becomes highly questionable in the light of her fading recollections of both the localities at the Institute of Genetics and the persons working there. Her temporal account, like that of Tjio, remains unsupported by the logbook. Examination of the logbook for temporal details relating to the establishment of the correct chromosome number of man suggests that Levan made his first preliminary 2n=46 human chromosome counts around December 20th-23rd, 1955, and that Tjio made his first conclusive preparations two-three weeks after his arrival from Spain, that is in early January 1956.