Effect of 0.9% NaCl compared to plasma-lyte on biomarkers of kidney injury, sodium excretion and tubular transport proteins in patients undergoing primary uncemented hip replacement - a randomized trial.

BACKGROUND: Isotonic saline (IS) is widely used to secure perioperative cardiovascular stability. However, the high amount of chloride in IS can induce hyperchloremic acidosis. Therefore, IS is suspected to increase the risk of acute kidney injury (AKI). Biomarkers may have potential as indicators. METHODS: In a double-blinded, placebo-controlled study, 38 patients undergoing primary uncemented hip replacement were randomized to IS or PlasmaLyte (PL). Infusion was given during surgery as 15 ml/kg the first hour and 5 ml/kg the following two hours. Urinary samples were collected upon admission and the day after surgery. As surgery was initiated, urine was collected over the course of 4 h. Hereafter, another urine collection proceeded until the morning. Urine was analyzed for markers of AKI neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Arterious and venous blood samples for measurements of pH and plasma electrolytes including chloride (p-Cl) were collected as surgery was initiated, at the end of surgery and the following morning. RESULTS: IS induced an increase in p-Cl (111 ± 2 mmol/L after IS and 108 ± 3 after PL, p = 0.004) and a decrease in pH (7.39 ± 0.02 after IS and 7.43 ± 0.03 after PL, p = 0.001). Urinary NGAL excretion increased in both groups (ΔNGAL: 5.5 [4.1; 11.7] µg/mmol creatinine p = 0.004 after IS vs. 5.5 [2.1;9.4] µg/mmol creatinine after PL, p < 0.001). No difference was found between the groups (p = 0.839). Similarly, urinary KIM-1 excretion increased in both groups (ΔKIM-1: IS 115.8 [74.1; 156.2] ng/mmol creatinine, p < 0.001 vs. PL 152.4 [120.1; 307.9] ng/mmol creatinine, p < 0.001). No difference between the groups (p = 0.064). FENa increased (1.08 ± 0.52% after IS and 1.66 ± 1.15% after PL, p = 0.032). ENaC excretion was different within groups (p = 0.019). CONCLUSION: A significantly higher plasma chloride and a lower pH was present in the group receiving isotonic saline. However, u-NGAL and u-KIM-1 increased significantly in both groups after surgery despite absence of changes in creatinine. These results indicate that surgery induced subclinical kidney injury. Also, the IS group had a delayed sodium excretion as compared to the PL group which may indicate that IS affects renal sodium excretion differently from PL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:  NCT02528448 , 19/08/2015.

When All Else Fails: Alternative Methods of Euthanasia.

Barbiturate overdose as a method of euthanasia is becoming unacceptable. This has made alternative methods of euthanasia very important. Gunshot or captive bolt euthanasia is among methods that are acceptable, but they may not be esthetically acceptable. This has led to the use of other methods of euthanasia. Inducing anesthesia prior to euthanasia offers an easier method of control. Adjunctive techniques using intravenous potassium or magnesium salts administered intravenously and intracardiac administration of potassium chloride or intrathecal lidocaine offer alternatives that work well and are more environmentally safer than barbiturates. Pithing and exsanguination are also environmentally safer but may not be as esthetically acceptable as the other methods.

Physico-chemical stability of Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose with eight common intravenous medications.

BACKGROUND: Plasma-Lyte 148® is a balanced, crystalloid intravenous (IV) fluid which is both calcium-free and isotonic. It prevents the hyperchloremic metabolic acidosis and iatrogenic hyponatremia seen with use of 0.9% sodium chloride and hypotonic solutions, respectively. However, data on compatibility with commonly used drugs are lacking. AIMS: To investigate the stability of Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose with eight commonly used therapeutic agents when compared with 5% glucose and 0.9% sodium chloride as diluents. We aimed to provide vital data which may facilitate the introduction of what appears to be a safer and more economic fluid. METHODS: Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose were mixed with morphine, midazolam, fentanyl, ketamine, clonidine, aminophylline, salbutamol, and furosemide at set concentrations. Comparisons were made to 0.9% sodium chloride and 5% glucose fluid controls. Six repeats of each IV fluid and drug admixture were analyzed through high-performance liquid chromatography at three time points: 0, 2, and 24 hours. A concentration change of <5% was defined as chemically stable. Physical stability was assessed by observation of precipitate formation or color change. pH changes were measured using a Fisherbrand Hydrus 300 pH meter. RESULTS: Relative to starting concentration, all drugs except midazolam were stable to ±3%. All examined therapeutic agents were chemically stable at 2 and 24 hours relative to control solutions. No precipitate formed in any of the samples. All Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose drug admixtures remained in a safe, peripheral administration pH range of 5-9 and were closer to the pH of blood than standard fluid-drug admixtures. CONCLUSION: Morphine, fentanyl, ketamine, salbutamol, aminophylline, and clonidine are stable for 24 hours when mixed with Plasma-Lyte 148® and Plasma-Lyte 148®+5% Glucose for administration at concentrations equivalent to those found at a typical Y-site with maintenance fluid. Furosemide is stable at lower concentrations than those seen at a Y-site, but midazolam displayed instability.

EVALUATION OF EUTHANASIA OF MOON JELLYFISH (AURELIA AURITA) USING SIMPLE SALT SOLUTIONS.

Immersion euthanasia methods reported over the most recent decades for aquatic invertebrates use organic alcohols or halogenated hydrocarbons that can interfere with nuclear magnetic resonance (NMR) analysis. A rolling study design evaluated potassium chloride (KCl), magnesium chloride (MgCl2), and magnesium sulfate (MgSO4) as potential ion-based euthanasia methods for moon jellyfish (Aurelia aurita) destined for metabolomic analysis by NMR spectroscopy. Death was defined as the cessation of autonomous bell pulsing and response to external stimulus. MgCl2 applied at a dose of 142 g/L provided euthanasia within 32 sec of applications without the untoward effects observed with the other two salts. Euthanasia with KCl at the doses tested was associated with abnormal behavior and tissue degradation during dissection. MgSO4 at the doses tested resulted in abnormal behavior and failed to provide rapid euthanasia.

Neurobehavioral and biochemical effects of magnesium chloride (MgCl2), magnesium sulphate (MgSO4) and magnesium-L-threonate (MgT) supplementation in rats: A dose dependent comparative study.

Magnesium (Mg) is an essential biomineral that acts as an intracellular cofactor for more than 300 enzymes. It is an important modulator of the N-methyl-D-aspartate (NMDA) receptor which is involved in memory function and depression. The purpose of this study was to compare the dose dependent effect of oral supplementation of Magnesium chloride (MgCl2), Magnesium sulphate (MgSO4) and Magnesium-L-threonate (MgT) on memory and depression-related behaviors in rats. Rats were orally administered with different doses (50 mg/kg, 100 mg/kg and 150 mg/kg) of each Mg salt. Following 28 days of oral supplementation, animals were subjected to behavioral tests. After completion of behavioral test, rats were decapitated. Brain and plasma samples were used for neurochemical and biochemical analysis. Assessment of behaviors in elevated plus maze (EPM) test and forced swim test (FST) showed that MgT more significantly improved memory of rats and decreased depression-like symptoms in healthy rats as compared to controls. Biochemical analysis indicated significant increase in plasma Mg levels dose dependently following MgT administration. This increase might be related to observe enhanced cholinergic functions and decline in oxidative stress in rats in the present study. This comparative study highlights that MgT (100mg/kg) is the most appropriate Mg salt and dose for oral treatment that strengthens cholinergic system and improves brain related functions through attenuation of oxidative burden in adult healthy rats.

Effect of 0.9% Saline or Plasma-Lyte 148 as Crystalloid Fluid Therapy in the Intensive Care Unit on Blood Product Use and Postoperative Bleeding After Cardiac Surgery.

OBJECTIVE: To evaluate the effect of Plasma-Lyte 148 (PL-148) compared with 0.9% saline (saline) on blood product use and postoperative bleeding in patients admitted to the intensive care unit (ICU) following cardiac surgery. DESIGN: A post hoc subgroup analysis conducted within a multicenter, double-blind, cluster-randomized, double-crossover study (study 1) and a prospective, single-center nested-cohort study (study 2). SETTING: Tertiary-care hospitals. PARTICIPANTS: Adults admitted to the ICU after cardiac surgery requiring crystalloid fluid therapy as part of the 0.9% saline vs. PL-148 for ICU fluid therapy (SPLIT) trial. INTERVENTIONS: Blinded saline or PL-148 for 4 alternating 7-week blocks. MEASUREMENTS AND MAIN RESULTS: 954 patients were included in study 1; 475 patients received PL-148, and 479 received saline. 128 of 475 patients (26.9%) in the PL-148 group received blood or a blood product compared with 94 of 479 patients (19.6%) in the saline group (OR [95% confidence interval], 1.51 [1.11-2.05]; p = 0.008). In study 2, 131 patients were allocated to PL-148 and 120 patients were allocated to saline. There were no differences between groups in chest drain output from the time of arrival in the ICU until 12 hours postoperatively (geometric mean, 566 mL for the PL-148 group v 547 mL in the saline group; p = 0.60). CONCLUSIONS: The findings did not support the hypothesis that using PL-148 for fluid therapy in ICU following cardiac surgery reduces transfusion requirements compared to saline. The significantly increased proportion of patients receiving blood or blood product with allocation to PL-148 compared to saline was unexpected and requires verification through further research.

A randomized-controlled trial of high- or low-volume intravenous Plasma-Lyte(®) to prevent hypotension during sedation for colonoscopy.

PURPOSE: The purpose of this study was to compare the incidence of hypotension during sedation in adults presenting for elective colonoscopy and randomized to intravenous Plasma-Lyte 148(®) at either 2 mL·kg(-1) (low volume) or 20 mL·kg(-1) (high volume). METHODS: Patients aged ≥ 18 yr presenting for elective colonoscopy, with or without gastroscopy, after oral bowel preparation were randomized to receive the intervention immediately before the start of the procedure. Hypotension was defined as a ≥ 25% decrease in systolic blood pressure (SBP) from baseline during the procedure. Secondary outcomes included SBP < 90 mmHg, lowest SBP during sedation, duration of hypotension, use of vasopressors, postoperative outcomes, and cost. RESULTS: Seventy-five patients were randomly allocated to either the low-volume or high-volume group, respectively (total n = 150). The incidence of hypotension was similar in the two groups (59% vs 56%, respectively; odds ratio, 0.90; 95% confidence interval, 0.47 to 1.71; P = 0.74). The incidence of SBP < 90 mmHg, the lowest SBP during sedation, the duration of hypotension, the use of vasopressors, and postoperative outcomes were also similar in the two groups. CONCLUSIONS: This study does not support the routine use of 20 mL·kg(-1) of intravenous Plasma-Lyte 148 to prevent hypotension and other complications during sedation for elective colonoscopy in adult patients. Clinical Trials Registry (ANZCTR 12615001288516).

Late gadolinium enhancement in the assessment of the infarcted mouse heart: a longitudinal comparison with manganese-enhanced MRI.

PURPOSE: To evaluate late gadolinium-enhanced (LGE) assessment of infarct size, a comparison with manganese-enhanced magnetic resonance imaging (MEMRI), and histology was performed in a permanent infarction model in the mouse at the acute and chronic stage. MATERIALS AND METHODS: In a paired fashion at the acute and chronic stage after infarction (3-4 days and 21 days, respectively), LGE and MEMRI was performed using a self-gated fast low flip angle shot (FLASH). Infarct size was evaluated as the enhanced area relative to the complete myocardial wall area in a mid-ventricular slice. Paired comparisons were made between contrast agents and between timepoints, as well as to histology. RESULTS: At the acute stage, LGE delineated a larger infarct size as compared to both MEMRI and histology. Infarct size from LGE decreased from the acute to chronic stage, a temporal development not seen with MEMRI. At the chronic stage, no significant differences in infarct size were found between the methods. CONCLUSION: This study indicates an overenhancement of infarct size when using LGE, supported by an initial overestimation at the acute stage and a temporal decrease in infarct size from the acute to chronic stage, as compared to infarct size from MEMRI.

[Correction of isoproterenol-induced myocardial injury with magnesium salts in magnesium-deficient rats].

The effect of Mg L-asparaginate (Mg-L-Asp), Mg chloride (MgCl2) and Mg sulfate (MgSO4) on the severity of isoproterenol-induced myocardial injury in Mg-deficient rats has been evaluated. To induce Mg deficiency, twenty-eight rats were placed on a low Mg diet (Mg content < 15 mg/kg) and demineralized water for 10 weeks. Twelve control rats were fed a basal control diet (Mg content = 500 mg/kg) and water (with Mg content 20 mg/l) for equal duration. On day 49 of low Mg diet, Mg-deficient rats were randomly divided into four groups: 1) group that continued to receive low Mg diet; 2) low Mg diet plus oral MgSO4; 3) low Mg diet plus oral Mg-L-Asp and 4) low Mg diet plus oral MgCl2 (50 mg of Mg per kg of body weight). Isoproterenol was injected subcutaneously (30 mg/kg BW, twice, at an interval of 24 hours) on the day 70 of the study, when plasma and erythrocyte Mg level in rats fed a low Mg diet were significantly decreased by 47% and 45% compared to intact animals. Twenty-four hours after second injection of isoproterenol, tests for activities of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were run and histopathological study was carried out. Administration of isoproterenol to rats resulted in significantly elevated plasma CK, LDH and AST, however analyses in Mg deficient group demonstrated more dramatically increased activity of CK and AST compared to control rats (3,06 and 4,67 fold in Mg-deficient group vs. 1,91 and 3,92 fold in intact group). Increased leakage of cardiac injury markers was concomitant to increased volume of fuchsinophilic cardiomyocytes (54.2 +/- 1.7% in Mg-deficient group and 38.9 +/- 1.9% in intact group, p < 0.05). However, pretreatment with of MgCl2, MgSO4 and Mg-L-Asp during 21 days favorably decreased sensitivity of myocardium to isoproterenol-induced ischemic injury. All evaluated salts significantly decreased myocyte marker enzymes as well as protected myocardium against isoproterenol-induced histopathological perturbations.

Galactomannan antigenemia after infusion of gluconate-containing Plasma-Lyte.

We demonstrated that sodium gluconate was the factor causing false-positive galactomannan (GM) antigenemia of Plasma-Lyte hydration solution. Infusion of sodium gluconate-containing solution but not gluconate-free Plasma-Lyte resulted in positive serum GM antigenemia. Serum GM concentrations also correlated with the volume and in vitro concentrations of GM within gluconate-containing solutions of infused Plasma-Lyte.

Magnesium improves the beta-cell function to compensate variation of insulin sensitivity: double-blind, randomized clinical trial.

BACKGROUND: Given that role of magnesium in insulin secretion is uncertain, our objective was to determine whether oral supplementation with magnesium chloride (MgCl(2)) improves the ability of beta-cells to compensate for variations in insulin sensitivity in non-diabetic individuals with significant hypomagnesaemia. MATERIALS AND METHODS: Eligible individuals were non-diabetic, normo-tensive men and non-diabetic, normo-tensive, non-pregnant women with serum magnesium levels ≤0·70 mM/L; they were enrolled in a randomized double-blind clinical trial to receive either 50 mL of 5% MgCl(2) solution or 50 mL of inactive solution daily for 3 months. The primary trial end point was a change in the AUC of the hyperbolic model of beta-cell function (HMbCF) derived from the fasting state. Individuals, caregivers and personnel who assessed the outcomes were all blinded to the group assignments. RESULTS: A total of 54 and 52 individuals were assigned to the MgCl(2) and placebo groups, respectively; five individuals in the MgCl(2) group and four in the placebo group dropped out. There were no serious adverse events or side effects because of MgCl(2) or placebo. At the beginning of the study, the AUC of the HMbCF was similar in both groups (AUC = 7·591 and 7·895 cm(2)); at the end of follow-up, the curve of the MgCl(2) group showed a hyperbolic distribution (AUC = 18·855 cm(2)), whereas in the placebo group, there were no changes (AUC = 7·631 cm(2)). CONCLUSIONS: MgCl(2) 2·5 g daily improves the ability of beta-cells to compensate for variations in insulin sensitivity in non-diabetic individuals with significant hypomagnesaemia.

Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects - a double-blind, placebo-controlled, randomized trial.

The incidence of insulin resistance and metabolic syndrome correlates with the availability of magnesium (Mg). We studied the effect of oral Mg supplementation on insulin sensitivity and other characteristics of the metabolic syndrome in normomagnesemic, overweight, insulin resistant, non-diabetic subjects. Subjects were tested for eligibility using oral glucose tolerance test (OGTT) and subsequently randomized to receive either Mg-aspartate-hydrochloride (n = 27) or placebo (n = 25) for 6 months. As trial endpoints, several indices of insulin sensitivity, plasma glucose, serum insulin, blood pressure and lipid profile were determined. Mg supplementation resulted in a significant improvement of fasting plasma glucose and some insulin sensitivity indices (ISIs) compared to placebo. Blood pressure and lipid profile did not show significant changes. The results provide significant evidence that oral Mg supplementation improves insulin sensitivity even in normomagnesemic, overweight, non-diabetic subjects emphasizing the need for an early optimization of Mg status to prevent insulin resistance and subsequently type 2 diabetes.

The effects of 0.9% saline versus Plasma-Lyte 148 on renal function as assessed by creatinine concentration in patients undergoing major surgery: A single-centre double-blinded cluster crossover trial.

OBJECTIVES: Saline and Plasma-Lyte have different physiochemical contents; consequently, they may differently affect patients' renal function. We compared the effects of fluid therapy with 0.9% saline and with Plasma-Lyte 148 on renal function as assessed by creatinine concentration among patients undergoing major surgery. METHODS: We conducted a prospective, double-blinded cluster crossover trial comparing the effects of the two fluids on major surgery patients. The primary aim was to establish the pilot feasibility, safety and preliminary efficacy evidence base for a large interventional trial to establish whether saline or Plasma-Lyte is the preferred crystalloid fluid for managing major surgery patients. The primary efficacy outcome was the proportion of patients with changes in renal function as assessed by creatinine concentration during their index hospital admission. We used changes in creatinine to define acute kidney injury (AKI) according to the RIFLE criteria. RESULTS: The study was feasible with 100% patient and clinician acceptance. There were no deviations from the trial protocol. After screening, we allocated 602 patients to saline and 458 to Plasma-Lyte. The median (IQR) volume of intraoperative fluid received was 2000 mL (1000:2000) in both groups. Forty-nine saline patients (8.1%) and 49 Plasma-Lyte patients (10.7%) developed a postoperative AKI (adjusted incidence rate ratio [aIRR]: 1.34; 95% CI: 0.93-1.95; p = 0.120). No differences were observed in the development of postoperative complications (aIRR: 0.98; 95% CI: 0.89-1.08) or the severity of the worst complication (aIRR: 1.00; 95% CI: 0.78-1.30). The median (IQR) length of hospital stay was six days (3:11) for the saline group and five days (3:10) for the Plasma-Lyte group (aIRR: 0.85; 95% CI: 0.73-0.98). There were no serious adverse events relating to the trial fluids, nor were there fluid crossover or contamination events. CONCLUSIONS: The study design was feasible to support a future follow-up larger clinical trial. Patients treated with saline did not demonstrate an increased incidence of postoperative AKI (defined as changes in creatinine) compared to those treated with Plasma-Lyte. Our findings imply that clinicians can reasonably use either solution intraoperatively for adult patients undergoing major surgery. TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; ACTRN12613001042730; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364988.

Anxiolytic effect of chronic intake of supplemental magnesium chloride in rat.

Evidence suggest that magnesium dietary supplementation has several health benefits including lowering blood pressure, reducing insulin resistance, and improving symptoms of depression, anxiety, and migraine. Here, we aimed to study the effect of chronic magnesium supplementation on anxiety-like behavior in rats by supplementing with magnesium their drinking water for 30 days. Anxiety-like behavior was induced by subcutaneous injection of veratrin 30 min before performing elevated plus maze and open field tests to measure anxiety levels and locomotion, respectively. We quantify the concentration of magnesium in plasma and cerebrospinal fluid. We used diazepam to compare the efficacy of magnesium supplementation as an anxiolytic agent. Our results show that rats supplemented with magnesium had a statistically significant decrease in anxiety levels with not effects on locomotion and a statistically significant increase in concentration of magnesium in plasma and cerebrospinal fluid. However, the anxiolytic effect of magnesium supplementation washes-out in 12 days. We discuss the advantages of using supplemental magnesium as anxiolytic.

Effect of combination therapy of hydroxyurea with l-carnitine and magnesium chloride on hematologic parameters and cardiac function of patients with beta-thalassemia intermedia.

BACKGROUND: l-Carnitine and magnesium have antioxidant properties. They have the potential to stimulate production of fetal hemoglobin and stabilize the RBC membrane, respectively. Several studies have also shown the beneficial effects of hydroxyurea in thalassemic patients. We assessed the effect of combination therapy of hydroxyurea with l-carnitine and magnesium chloride on hematologic parameters and cardiac function of patients with beta-thalassemia intermedia. METHODS: One-hundred-and-twenty patients with thalassemia intermedia (range, 4-35 yr; mean, 19 +/- 6.4 yr) who had no need for blood transfusion or requirement for blood transfusion with an interval of >6 months were randomly selected. All patients had been on hydroxyurea for >6 months. They were randomly divided into four groups: group A (hydroxyurea alone); group B (hydroxyurea and l-carnitine); group C (hydroxyurea and magnesium chloride); and group D (hydroxyurea, l-carnitine and magnesium chloride). RESULTS: In groups B, C, and D, mean Hb and hematocrit increased during 6-month treatment (P < 0.001). Echocardiographic studies revealed a significant decrease in left ventricular end-diastolic diameter in group B (P = 0.032), increase in pulmonary acceleration time in group C (P = 0.012), and increase in left ventricular ejection fraction in groups C and D (P < 0.000 and 0.006, respectively). CONCLUSION: Combination of hydroxyurea with l-carnitine or magnesium could be more effective in improving hematologic parameters and cardiac status in patients with beta-thalassemia intermedia than hydroxyurea alone.

Effects of magnesium on postprandial serum lipid responses in healthy human subjects.

Postprandial hyperlipidaemia has been recognised to be a risk factor for atherosclerosis development. Epidemiological and animal studies have shown that Mg intake is inversely associated with some risk factors of atherosclerosis, including lipid metabolism. The present study was performed to determine the effects of Mg supplementation on postprandial responses in serum lipid levels. We used bittern (Nigari, in Japanese), a natural MgCl(2) solution from sea or salt lake water, for Mg supplementation. In a two-way, randomised, crossover study, sixteen healthy male volunteers consumed 30 g butter with or without 5 ml bittern containing 500 mg of Mg. Fasting and postprandial blood samples were taken 2, 3, 4 and 6 h after ingestion. Postprandial lipid responses were evaluated by serum TAG, chylomicron TAG, apo-B48, remnant-like particle cholesterol (RLP-C) and NEFA concentrations. We found that the serum and the chylomicron TAG responses after the fat load were reduced and delayed by Mg supplementation. The concentrations of apo-B48 (P < 0.05), RLP-C (P < 0.05) and NEFA (P < 0.05) were significantly lower at 2 h after the fat-with-Mg meal compared with the fat-only meal. The present study indicated that Mg supplementation could inhibit fat absorption and improve postprandial hyperlipidaemia in healthy subjects.

Administration of lithium and magnesium chloride inhibited tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice.

Although morphine has an anticonvulsant effect in several animal models of seizures, its potential clinical application in epilepsy may be hindered by its adverse effects like opioid tolerance. The present study evaluated the development of tolerance to the anticonvulsant effect of morphine in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male Swiss mice. We also examined whether administration of either lithium chloride (LiCl) or magnesium chloride (MgCl(2)) was able to prevent the probable tolerance. Our data demonstrated that the anticonvulsant effect of a potent dose of morphine (1mg/kg) was abolished in chronic morphine-treated mice (mice administered the same dose of morphine intraperitoneally twice daily for 4 days). Four days of pretreatment with low and noneffective doses of MgCl(2) (2 and 5mg/kg) and LiCl (5mg/kg) inhibited the development of tolerance to the anticonvulsant effect of morphine (1mg/kg, ip). Moreover, a single acute injection of the aforementioned agents at the same doses reversed the expression of tolerance to the anticonvulsant effects of morphine (1mg/kg, ip). Chronic 17-day treatment with LiCl (600 mg/L in drinking water) also inhibited the development of tolerance to the anticonvulsant effects of 1mg/kg morphine. These results demonstrate that the anticonvulsant effect of morphine is subject to tolerance after repeated administration. Both development and expression of tolerance are inhibited by either LiCl or MgCl(2). As both LiCl and MgCl(2) can modulate the function of N-methyl-d-aspartate (NMDA) receptors, we discuss how NMDA receptor functioning might be involved in the effects of LiCl and MgCl(2) on the development of tolerance to the anticonvulsant effect of morphine.

Pretreatment effect of magnesium on alloxan induced hyperglycemia in rats.

The role of vitamins and mineral supplementation in the management of Diabetes mellitus is not well elucidated. We therefore carried out a preliminary study to assess the effect of prior administration of Magnesium on induction of alloxan diabetes, a model of type 1 diabetes mellitus. Twenty Male albino rats were used for this study. The animals were divided into 4 groups of 5 animals each. Animals in group 1 were normal rats and were not given any treatment, these served as healthy control. Animals in group 2 were diabetic rats that were not given any treatment, they served as diabetic control. Animals in group 3 were treated with magnesium (100mg/kg) intraperitoneally one hour prior to alloxan (150mg/kg) administration. Animals in group 4 were given intraperitoneal injection of magnesium (100mg/kg) once, and blood samples were obtained one hour after administration. Blood samples were obtained from all animals after 48 hours and plasma glucose levels determined using the glucose oxidase method. There was significant increase (p<0.001) in plasma glucose level in the alloxan treated group when compared with the control. There was also a significant increase (p<0.01) in magnesium-pretreated diabetic group. However, there was a significant reduction (p<0.01) in blood glucose level 48 hours after alloxan administration in the magnesium pre-treated diabetic group when compared with the diabetic controls. Magnesium pretreatment may delay the onset of alloxan induced hyperglycemia and this may be due to the scavenging effect of magnesium on the highly reactive hydroxyl radicals (OH) which was generated through alloxan reaction.

[Comparative study of magnesium salts bioavailability in rats fed a magnesium-deficient diet].

The purpose of this study was to compare efficiency of compensation of alimentary Mg deficiency after administration of 12 organic and 8 inorganic magnesium salts and to evaluate the ability of vitamin B6 to accelerate their effect. Two hundred eighty rats were placed on a Mg-deficient diet (Mg content (15 mg/kg) and demineralized water for 7 weeks. Twelve control rats were fed a basal diet (Mg content 500 mg/kg). Starting from day 49 of the Mg-deficient diet, the rats were given magnesium salts (50 mg magnesium and 5 mg pyridoxine per kg): Mg chloride, Mg sulphate, Mg oxide, M nitrate, Mg thiosulphate, Mg hydrophosphate, Mg carbonate, Mg trisilicate, Mg (L-, D- and DL-) aspartate, Mg (L- and DL-) pyroglutamate, Mg succinate, Mg glycinate, Mg orotate, Mg taurate, Mg lactate or their combination with vitamin B6 (5 mg/kg b.w.). Erythrocyte and plasma Mg levels were measured by spectrophotometry following the colour reaction between Mg and titanium yellow. Mg L-aspartate compensated for magnesium deficit more effectively and faster than all other salts. Mg chloride showed the highest efficiency among inorganic magnesium salts. Both Mg chloride and Mg L-aspartate in combination with vitamin B6 caused statistically significant compensation of magnesium deficit.