Antioxidant and Neuroprotector Influence of Endo-Polyphenol Extract from Magnesium Acetate Multi-Stage Addition in the Oak Bracket Medicinal Mushroom, Phellinus baumii (Agaricomycetes).

The objective of this study was to explore the effect of magnesium acetate (MA) addition on the endo-polyphenol yield by Phellinus baumii and establish a feasible additive strategy. The optimal three-point MA addition strategy (0.05 g/L concentration of MA added at 0 h and 6 h, 0.9 g/L concentration of MA added at 12 h) was employed to obtain maximum endo-polyphenol yield. The maximum endo-polyphenol production was reached at 1.22 g/L, which was 1.39-fold higher than that of the control. Additionally, the endo-polyphenol showed stronger antioxidant activity in vitro compared with the control, including DPPH· scavenging capacity (78.76%) and Trolox equivalent antioxidant capacity (TEAC) (32.28 µmol Trolox/g sample). HPLC analysis showed that the endo-polyphenol production of the crude ethanol extracts was significantly higher than that of the control. Hispidin was isolated and identified from the ethanol extract of the culture mycelia from Ph. baumii with the three-point MA addition strategy. Hispidin showed a strong ability to scavenge DPPH free radicals and TEAC, equivalent to positive (vitamin C) value of 89.41% and 75.98%, respectively. Furthermore, hispidin protected H2O2-induced PC12 cells injured by decreased oxidative stress level. These results indicated that the MA multi-stage addition strategy was dependable, and could be used to develop new natural antioxidants for foods or medicines.

Biodegradable magnesium alloy (WE43) in bone-fixation plate and screw.

The purpose of the present study was to evaluate the mechanical strength and the absorption rate of WE43 material and to develop an absorbable metallic plate and screw for craniofacial application. The extruded WE43 plate and screw were evaluated using a LeFort I osteotomy canine model of 10 beagle dogs. Animals were divided into two groups: five dogs in the experimental group and five dogs in the control group. µCT was acquired at 4, 12, and 24 weeks. At 24 weeks after the operation, all animals were sacrificed, and histologic evaluation was performed. Swelling and gas formation were observed in three dogs in the experimental groups at 8 weeks. From 12 weeks, infraorbital fistula and inflammation were observed in three dogs in the experimental group, which gradually decreased and disappeared at 24 weeks. Other two dogs showed less gas formation at 12 weeks. The plates were completely absorbed, and gas formation was not observed at 24 weeks in these two dogs. New bone was well formed around the plates and screws in both groups. Histologic examination showed no specific differences between two groups. The mechanical strength of extruded WE43 was sufficient for mid-facial application. Plates and screws made with appropriately treated WE43 have the potential to be useful clinically.

Efficacy and Safety of Magnesium for the Management of Chronic Pain in Adults: A Systematic Review.

Chronic pain is a highly prevalent and complex health problem that is associated with a heavy symptom burden, substantial economic and social impact, and also, very few highly effective treatments. This review examines evidence for the efficacy and safety of magnesium in chronic pain. The previously published protocol for this review was registered in International Prospective Register of Systematic Reviews (PROSPERO), MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched until September 2018. We included randomized controlled trials (RCTs) comparing magnesium (at any dose, frequency, or route of administration) with placebo using participant-reported pain measures. A total of 9 RCTs containing 418 participants were included. Three studies examined neuropathic pain (62 participants), 3 examined migraines (190 participants), 2 examined complex regional pain syndrome (86 participants), and 1 examined low back pain with a neuropathic component (80 participants). Heterogeneity of included studies precluded any meta-analyses. No judgment could be made about safety because adverse events were inconsistently reported in the included studies. Evidence of analgesic efficacy from included studies was equivocal. However, reported efficacy signals in some of the included trials provide a rationale for more definitive studies. Future, larger-sized trials with good assay sensitivity and better safety assessment and reporting, as well as careful attention to formulations with optimal bioavailability, will serve to better define the role of magnesium in the management of chronic pain.

Experiences of an outpatient infusion center with intravenous magnesium therapy for status migrainosus.

OBJECTIVES: Exploratory study to investigate the effectiveness of intravenous magnesium as an abortive for status migrainosus in an outpatient infusion center, and characterize the patients who benefit from the therapy. PATIENTS & METHODS: Retrospective analysis of 234 migraine patients who received IV magnesium as a headache abortive, at the headache clinic of University of Southern California. Additional intramuscular (IM) injections for nausea (prochlorperazine, odansetron, metoclopramide) or for refractory pain (ketorolac, dexamethasone, sumatriptan, dihydroergotamine), were administered as necessary. Immediately before and after treatment, self-reported pain levels were recorded using an 11-point numeric pain rating scale (0-10). RESULTS: Our patient sample has a mean age of 44 years and was predominantly female (79%). 36 (19%) had migraine with aura. Overall, pain score decreased from 5.46±2.39 to 3.56 ± 2.75 (P < 0.001) after magnesium infusion. One hundred twenty-seven (54%) patients had clinically significant pain reduction, as defined by pain decrease ≥ 30%. One hundred and four patients (44%) received IV magnesium and did not require additional intramuscular (IM) medications for pain. In patients who did not receive additional IM medications for pain, pain score decreased from 4.76 ± 2.41 to 2.95 ± 2.70 (p < 0.001), and 61 out of 104 (59%) experienced ≥ 30% pain reduction. Patients with less severe pain tended to have a better response than patients with more severe pain, as patients with ≥30% pain reduction had a significantly lower pre-treatment pain score (p = 0.018). CONCLUSION: For a subset of patients with status migrainosus, IV magnesium therapy results in clinically significant pain relief without the need for intramuscular pain medications. Therefore, IV magnesium may be useful as a cost-effective first-line parental therapy for status migrainosus, especially for patients who initially present with lower pain intensity.

A survey of facilitators and barriers to recruitment to the MAGNETIC trial.

BACKGROUND: Recruitment to randomised controlled trials with children is challenging. It is imperative to understand the factors that boost or hinder recruitment of children to clinical trials. We conducted a survey of facilitators and barriers to recruitment to the MAGNETIC trial, using a previously developed web-based tool. METHODS: MAGNETIC is a multicentre randomised trial of nebulised magnesium in acute severe asthma, recruiting 508 children from 30 UK sites. Recruiters were asked to grade a list of factors from -3 to +3 depending on whether the factor was perceived as a strong, intermediate or weak barrier (-3 to -1) or facilitator (+1 to + 3), and using (0) if it was thought to be not applicable. Free text responses were invited on strategies applied to counter the identified barriers. RESULTS: The commonly identified facilitators were motivation and experience of study teams, effective communication and coordination between teams at site and between sites and the Clinical Trials Unit, the presence of designated research nurses, good trial management, clinical trial publicity, simple inclusion criteria, effective communication with parents and presentation of trial information in a simple and clear manner. The commonly identified barriers were heavy clinical workload, shift patterns of work, Good Clinical Practice (GCP) training, inadequate number of trained staff, time and setting of consent seeking, non-availability of research staff out of hours and parents' concerns about their child taking an experimental medicine. Having a designated research nurse, arranging GCP training and trial-related training sessions for staff were the most commonly reported interventions. CONCLUSIONS: This study highlights important generic and trial-specific facilitators and barriers to recruitment to a paediatric trial in the acute setting and provides information on the recruitment strategies or interventions that were applied to overcome these barriers. This information can be very useful in informing the design and conduct of future clinical trials with children, particularly in the acute or emergency setting. TRIAL REGISTRATION: ISRCTN, ISRCTN81456894 . Registered on 15 November 2007.

Iron Supplements and Magnesium Peroxide: An Example of a Hazardous Combination in Self-Medication.

The use of self-medication, which includes dietary supplements and over-the-counter drugs, is still on the rise, while safety issues are not well addressed yet. This especially holds for combinations. For example, iron supplements and magnesium peroxide both produce adverse effects via the formation of reactive oxygen species (ROS). This prompted us to investigate the effect of the combination of three different iron supplements with magnesium peroxide on ROS formation. Hydroxyl radical formation by the three iron supplements either combined with magnesium peroxide or alone was determined by performing a deoxyribose assay. Free iron content of iron supplements was determined using ferrozine assay. To determine hydrogen peroxide formation by magnesium peroxide, a ferrous thiocyanate assay was performed. Finally, electron spin resonance spectroscopy (ESR) was performed to confirm the formation of hydroxyl radicals. Our results show that magnesium peroxide induces the formation of hydrogen peroxide. All three iron supplements induced the formation of the extremely reactive hydroxyl radical, although the amount of radicals formed by the different supplements differed. It was shown that combining iron supplements with magnesium peroxide increases radical formation. The formation of hydroxyl radicals after the combination was confirmed with ESR. All three iron supplements contained labile iron and induced the formation of hydroxyl radicals. Additionally, magnesium peroxide in water yields hydrogen peroxide, which is converted into hydroxyl radicals by iron. Hence, iron supplements and magnesium peroxide is a hazardous combination and exemplifies that more attention should be given to combinations of products used in self-medication.

Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials.

BACKGROUND: Systemic magnesium has been used to minimize postoperative pain with conflicting results by clinical studies. It remains unknown whether the administration of perioperative systemic magnesium can minimize postoperative pain. The objective of the current investigation was to evaluate the effect of systemic magnesium on postoperative pain outcomes. METHODS: A wide search was performed to identify randomized controlled trials that evaluated the effects of systemic magnesium on postoperative pain outcomes in surgical procedures performed under general anesthesia. Meta-analysis was performed using a random-effect model. Publication bias was evaluated by examining the presence of asymmetric funnel plots using Egger regression. RESULTS: Twenty randomized clinical trials with 1,257 subjects were included. The weighted mean difference (99% CI) of the combined effects favored magnesium over control for pain at rest (≤4 h, -0.74 [-1.08 to -0.48]; 24 h, -0.36 [-0.63 to -0.09]) and with movement at 24 h, -0.73 (-1.37 to -0.1). Opioid consumption was largely decreased in the systemic magnesium group compared with control, weighted mean difference (99% CI) of -10.52 (-13.50 to -7.54) mg morphine IV equivalents. Publication bias was not present in any of the analysis. Significant heterogeneity was present in some analysis, but it could be partially explained by the sole intraoperative administration of magnesium compared with the intraoperative and postoperative administration. None of the studies reported clinical toxicity related to toxic serum levels of magnesium. CONCLUSION: Systemic administration of perioperative magnesium reduces postoperative pain and opioid consumption. Magnesium administration should be considered as a strategy to mitigate postoperative pain in surgical patients.

The effect of routine magnesium supplementation on fetal cardiac time intervals: a fetal magnetocardiographic study.

OBJECTIVES: Magnesium deficiency in pregnancy is frequent, and in consequence magnesium supplementation is widely used. As magnesium crosses the placental barrier and since the fetal kidney does not excrete magnesium as efficiently as the mature kidney, effects on fetal cardiac time intervals are probable, but still unknown. STUDY DESIGN: Sixty pregnant women were included in an observational study: 31 patients received oral routine magnesium supplementation. In addition to routine fetal echocardiography, fetal magnetocardiography (fMCG) was used to investigate electrophysiological rhythm patterns with high temporal resolution. fMCG tracings were analyzed according to a predefined procedure for fetal cardiac time interval (CTI)-detection. fCTI findings (P-wave, PQ-segment, PR-interval, QRS complex, ST segment, T-wave and QTc interval) were registered. RESULTS: Significant widening of the QRS-complex (p=0.004) was demonstrated in fetuses whose mothers received magnesium supplementation (240 mg/day) relative to the control group. CONCLUSION: Magnesium exposed fetuses demonstrated a prolonged ventricular arousal, but healthy neonatal outcome was found in all exposed fetuses. Although fMCG is a preclinical method and limited in its availability, the procedure could help to monitor fetuses.

Reactive skin decontamination lotion (RSDL) for the decontamination of chemical warfare agent (CWA) dermal exposure.

Rapid decontamination of the skin is the single most important action to prevent dermal absorption of chemical contaminants in persons exposed to chemical warfare agents (CWA) and toxic industrial chemicals (TICs) as a result of accidental or intentional release. Chemicals on the skin may be removed by mechanical means through the use of dry sorbents or water. Recent interest in decontamination systems which both partition contaminants away from the skin and actively neutralize the chemical has led to the development of several reactive decontamination solutions. This article will review the recently FDA-approved Reactive Skin Decontamination Lotion (RSDL) and will summarize the toxicity and efficacy studies conducted to date. Evidence of RSDL's superior performance against vesicant and organophosphorus chemical warfare agents compared to water, bleach, and dry sorbents, suggests that RSDL may have a role in mass human exposure chemical decontamination in both the military and civilian arenas.

Long-term safety of naproxen and esomeprazole magnesium fixed-dose combination: phase III study in patients at risk for NSAID-associated gastric ulcers.

OBJECTIVE: To evaluate long-term safety of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg fixed-dose combination (FDC) in patients at risk of NSAID-associated upper gastrointestinal (UGI) ulcers. RESEARCH DESIGN AND METHODS: In this open-label, multicenter, phase III study, Helicobacter pylori-negative patients aged ≥50 years or 18-49 years with history of uncomplicated ulcer within the past 5 years, who had osteoarthritis, rheumatoid arthritis, or other condition requiring daily NSAIDs for ≥12 months received naproxen/esomeprazole twice daily for 12 months. CLINICAL TRIAL REGISTRATION: NCT00527904. MAIN OUTCOME MEASURES: Adverse events (AEs), vital signs, physical examination, and laboratory tests. Subgroup analyses included age and low-dose aspirin (LDA) use. Predefined NSAID-associated UGI and cardiovascular AEs were analyzed. RESULTS: Of 239 patients treated (safety population), 135 completed ≥348 treatment days (12-month completers). AE incidence was approximately 70%; dyspepsia, constipation, upper respiratory tract infection, nausea, back pain, and contusion were most frequent (≥5% patients, either population). Treatment-related AEs occurred in 28.0% and 23.7% of patients in the safety and 12-month completer populations, respectively; 18.8% of patients withdrew due to AEs (safety population). Few serious AEs and no deaths occurred. In the safety population, AE incidence was 71.4% and 76.9% in patients aged <65 years (n = 161) and ≥65 years (n = 78), respectively, and 67.6% and 75.8% in LDA users (n = 74) and non-users (n = 165), respectively. Predefined UGI and cardiovascular AEs were observed in 18.8% and 6.3% of patients, respectively, in the safety population, and 16.3% and 5.2%, respectively, in 12-month completers. Dyspepsia and hypertension were most common. Additional assessments showed no unexpected findings. CONCLUSIONS: Based on these outcome measures, long-term treatment with FDC naproxen/esomeprazole is not associated with any new safety issues, including predefined UGI and cardiovascular AEs, in patients requiring NSAID therapy who are at risk of UGI complications.

[Biodegradable synthetic implant materials : clinical applications and immunological aspects]. / Degradable synthetische Implantatmaterialien : Klinische Applikationen und immunologische Aspekte.

In the last decade biodegradable synthetic implant materials have been established for various clinical applications. Ceramic materials such as calcium phosphate, bioglass and polymers are now routinely used as degradable implants in the clinical practice. Additionally these materials are now also used as coating materials or as microspheres for controlled drug release and belong to a series of examples for applications as scaffolds for tissue engineering. Because immense local concentrations of degradation products are produced during biodegradation, this review deals with the question whether allergic immune reactions, which have been reported for classical metallic and organic implant materials, also play a role in the clinical routine for synthetic biodegradable materials. Furthermore, possible explanatory theories will be developed to clarify the lack of clinical reports on allergy or sensitization to biodegradable synthetic materials.

Tocolytic treatment for the management of preterm labor: a review of the evidence.

OBJECTIVE: Preterm labor is often a prelude to early births and the significant attendant burden of infant morbidity and mortality. Treatment consists of bedrest, hydration, pharmacologic interventions, and combinations of these. We systematically reviewed the effectiveness of tocolytics to stop uterine contractions (first-line therapy) or maintain quiescence (maintenance therapy). Our objective was to evaluate the evidence on the benefits and harms of five classes of tocolytic therapy for treating uterine contractions related to preterm labor--beta-mimetics, calcium channel blockers, magnesium, nonsteroidal anti-inflammatory agents, and ethanol. STUDY DESIGN: Reports of randomized controlled trials and other study designs in English, French, and German identified from searches of MEDLINE, EMBASE, specialized databases, bibliographies of review articles, unpublished literature, and discussions with investigators in the field were identified. Studies on women with preterm labor between 1966 and February 1999 that met our inclusion criteria were included. Through dual review, we abstracted the following information: study design and masking; definitions of preterm labor and successful tocolysis; patient inclusion/exclusion characteristics; patient demographic characteristics; drug and cointerventions; and numerous birth, maternal, and neonatal outcome measures. RESULTS: Of the 256 articles evaluated, we abstracted data from 60 first-line and 15 maintenance studies. Of these, 16 first-line and 8 maintenance studies met more stringent requirements for meta-analyses. Studies of first-line tocolysis (grade Fair) reveal a mixed outcome pattern with small improvement in pregnancy prolongation and birth at term relative to placebo. Data were insufficient to show directly a beneficial effect on neonatal morbidity or mortality. Ethanol was less beneficial than, and beta-mimetics were not superior to, other tocolytic options. Maintenance tocolytics (grade Poor) showed no improvements in birth or infant outcomes relative to placebo; these results were confirmed through meta-analysis. In contrast to other tocolytic treatments, maternal harms from beta-mimetics were rated High; all tocolytics were rated as Low risk for short-term neonatal harms. CONCLUSIONS: Management of uterine contractions with first-line tocolytic therapy can prolong gestation. Among the tocolytics, however, beta-mimetics appear not to be better than other drugs and pose significant potential harms for mothers; ethanol remains an inappropriate therapy. Continued maintenance tocolytic therapy has little or no value.

Laxatives for bowel clearing before investigations.

It is important to clear the bowel of its contents thoroughly before colonoscopy or radiological procedures such as barium enema. This article reviews laxatives for bowel clearing that can be taken by patients at home prior to the procedure. We concentrate on drug efficacy and patient acceptability.

[Study on lipid peroxidation of electrolyzing-aluminum workers].

In order to study the changes in lipid peroxidation level and anti-oxidase activity in electrolyzing-aluminum workers exposed to both aluminum and fluoride and to find out the sensitive biological monitoring indicators, 65 electrolyzing-aluminum workers are recruited as exposed group and 52 healthy workers as control group. Serum and urine aluminum and fluoride concentration, serum glutathione peroxidase(GSH-Px) activity, serum malonyl dialdehyde (MDA) concentration, whole blood superoxide dismutase(SOD) activity, serum cuprum and zinc concentration, and X-ray of skeleton are detected and taken. The results showed that aluminum and fluoride concentration in serum and urine increase, GSH-Px activity reduces, MDA concentration increases and SOD activity increases, cuprum concentration increases and zinc concentration reduces significantly (P < 0.001) in exposed group compared with those of control group. Both serum aluminum and fluoride concentration are correlated inversely with GSH-Px activity, and correlated with MDA concentration and SOD activity. It is suggested that serum aluminum and fluoride concentration can clearly reflect the loading capacity of body aluminum and fluoride. Occupational exposure to both aluminum and fluoride lead to rising of lipid peroxidation and abnormal metabolism of cuprum and zinc before changes in skeleton occurred. Serum MDA concentration and GSH-Px activity might be the potential early-stage indicators of biological surveillance for electrolyzing-aluminum workers' health. The increase of SOD activity may be a kind of body compensations.

Surreptitious abuse of magnesium laxatives as a cause of chronic diarrhoea.

Surreptitious laxative abuse is increasingly considered as a possible cause of unexplained chronic diarrhoea. Laboratory services for detection of colonic stimulant laxatives are widely available; however, laboratory facilities for identifying patients with magnesium-induced diarrhoea are not commonly provided, making diagnosis difficult. We describe three patients who surreptitiously abused magnesium laxatives, and whose diagnoses were delayed, leading in each case to extensive investigations and lengthy in-patient stays. In all three cases, the diagnosis was eventually made by the simple measurement of magnesium in a random faecal sample. We would like to increase the awareness of surreptitious magnesium laxative abuse as a cause of chronic diarrhoea so that costly and unnecessary investigations may be minimized.

Familial hypomagnesemia--hypercalciuria and pseudotumor cerebri.

Approximately 30 patients with familial hypomagnesemia-hypercalciuria have been reported. We describe an 8-year-old girl with cardinal findings of familial hypomagnesemia-hypercalciuria (hypomagnesemia, hypermagnesiuria, hypercalciuria, renal insufficiency, hyperuricemia, elevated serum parathormone, hyposthenuria and nephrocalcinosis), who received combination therapy consisting of magnesium salts, thiazide diuretic and potassium supplementation. At the 4-year follow-up investigation under this treatment, the patient was found to have cerebral pseudotumor (increased intracranial pressure with normal or small ventricles on neuroimaging, no evidence of an intracranial mass and normal cerebrospinal fluid composition) with papilledema and visual field defects. Thiazide therapy was terminated and the cerebral pseudotumor disappeared. The authors hypothesize that cerebral pseudotumor in this patient was related to severe hypocalcemia, as a consequence of profound hypomagnesemia induced by protracted thiazide treatment. To our knowledge, this is the first report of a child with familial hypomagnesemia-hypercalciuria who developed pseudotumor cerebri after thiazide therapy.