A Patented Dietary Supplement (Hydroxy-Methyl-Butyrate, Carnosine, Magnesium, Butyrate, Lactoferrin) Is a Promising Therapeutic Target for Age-Related Sarcopenia through the Regulation of Gut Permeability: A Randomized Controlled Trial.

Adequate diet, physical activity, and dietary supplementation with muscle-targeted food for special medical purposes (FSMP) or dietary supplement (DS) are currently considered fundamental pillars in sarcopenia treatment. The aim of this study is to evaluate the effectiveness of a DS (containing hydroxy-methyl-butyrate, carnosine, and magnesium, for its action on muscle function and protein synthesis and butyrate and lactoferrin for their contribution to the regulation of gut permeability and antioxidant/anti-inflammation activity) on muscle mass (assessed by dual X-ray absorptiometry (DXA)), muscle function (by handgrip test, chair test, short physical performance battery (SPPB) test, and walking speed test), inflammation (tumor necrosis factor-alpha (TNF-a), C-reactive protein (CRP), and visceral adipose tissue (VAT)) and gut axis (by zonulin). A total of 59 participants (age 79.7 ± 4.8 years, body mass index 20.99 ± 2.12 kg/m2) were enrolled and randomly assigned to intervention (n = 30) or placebo (n = 28). The skeletal muscle index (SMI) significantly improved in the supplemented group compared to the placebo one, +1.02 (CI 95%: -0.77; 1.26), p = 0.001; a significant reduction in VAT was observed in the intervention group, -70.91 g (-13.13; -4.70), p = 0.036. Regarding muscle function, all the tests significantly improved (p = 0.001) in the supplemented group compared to the placebo one. CRP, zonulin, and TNF-alpha significantly decreased (p = 0.001) in intervention, compared to placebo, -0.74 mg/dL (CI 95%: -1.30; -0.18), -0.30 ng/mL (CI 95%: -0.37; -0.23), -6.45 pg/mL (CI 95%: -8.71; -4.18), respectively. This DS improves muscle mass and function, and the gut muscle has emerged as a new intervention target for sarcopenia.

Role of preoperative zinc, magnesium and budesonide gargles in Postoperative Sore Throat (POST) - a randomised control trial.

BACKGROUND: Post-operative sore throat (POST) has an incidence ranging from 21 to 80%. To prevent the development of POST, several pharmacological measures have been tried. Aim of this study was to compare the efficacy of preoperative zinc, magnesium and budesonide gargles in reducing the incidence and severity of POST in patients who underwent endotracheal intubation for elective surgeries. METHODS: We conducted a prospective, randomized, double-blind, controlled equivalence trial in 180 patients admitted for elective surgical procedures under general anaesthesia. Patients were randomised into three groups; group Z received 40 mg Zinc, group M received 250 mg Magnesium Sulphate and group B received 200 µg Budesonide in the form of 30 ml tasteless and colourless gargle solutions. Sore throat assessment and haemodynamic recording was done postoperatively at immediate recovery (0 h) and 2, 4, 6, 8, 12 and 24 h post-operatively. POST was graded on a four-point scale (0-3). RESULTS: POST score was comparable at all recorded time points i.e. 0,2,4,6,8,12 and 24 h. Maximum incidence was seen at 8 h in group B (33.3%) and the minimum incidence was at 24 h in group Z (10%) (p > 0.05). It was found that the incidence of POST was more in the surgeries lasting longer than 2 h in all groups. This difference was found to be statistically significant in Groups M and B. The incidence of POST was found to be comparable between laparoscopic and open procedures. CONCLUSION: Magnesium, zinc and budesonide have an equivocal effect in the prevention of POST at different time points. The incidence of sore throat increases significantly in surgeries lasting more than two hours if magnesium or budesonide have been used as premedicant. Duration of surgery is an independent predictor for POST. TRIAL REGISTRATION: CTRI/2021/05/033741 Date-24/05/2021(Clinical Trial Registry of India).

The Use of a Checklist to Optimize Electrolyte Replacement in the ICU.

Electrolyte replacement protocols are routinely used in intensive care units (ICU) to guide magnesium replacement. Guided by serum levels, these protocols include no patient-specific factors despite a literature showing ICU patients routinely have significant deficits despite normal serum levels. The authors developed a checklist to help identify patients requiring more aggressive magnesium replacement than the electrolyte replacement protocol would provide. The checklist included risk factors for having significant magnesium deficits and for developing arrhythmias. The checklist was retrospectively applied to 364 medical ICU patients. Diabetic patients prescribed outpatient diuretics were defined as the highest-risk population. A total of 88% of patients in this subgroup had normal magnesium levels. Despite averaging 3.4 risk factors per patient, only 3 of 32 patients received magnesium. Applying the checklist would have suggested additional repletion for at least 85% of patients. A checklist can help identify ICU patients who may require more aggressive magnesium supplementation than protocols will provide.

Are the elements zinc, copper, magnesium, and rubidium related to nutrition and iodine deficiency in pregnant Bulgarian women from iodine deficient region?

OBJECTIVE: Trace elements are essential for the biochemistry of the cell. Their reference values have been found to differ considerably in pregnant women stratified by age, place of residence, anthropometric status, and length of pregnancy. In optimal amounts, these elements reduce the risk of pregnancy complications. Subclinical hypothyroidism in pregnancy is associated with adverse maternal and neonatal outcomes. The aim of the study was to determine the effects of zinc (Zn), copper (Cu), magnesium (Mg), and rubidium (Rb) on pregnant women in an iodine deficiency region and find the relationship with the thyroid status and nutrition. METHODS: We evaluated the iodine status of 61 healthy pregnant women from an iodine deficient region in Bulgaria. Thyroid stimulating hormone (TSH) and thyroxin free (FT4) levels were measured using ELISA. RESULTS: We found elevated levels of copper that differed the most between the first and second trimesters; Cu and TSH were found to be positively correlated (р < 0.05). Lower Cu levels were found in pregnant women consuming pulses more than 2-3 times a week (р = 0.033). The women consuming fish more than 2-3 times a week had higher levels of Rb. We found a pronounced iodine deficiency in more than half of the examined women in the first to third trimesters, without any effect of pregnancy on the ioduria (р=0.834). All second and third trimester cases were associated with severe ioduria (< 150 µg/L). CONCLUSION: The high Cu levels were associated with subclinical hypothyroidism (SCH) and less pulse consumption during pregnancy in an iodine deficiency endemic area. SCH was found in 24% of the pregnant women in such an area while in 13% of them SCH had progressed to overt hypothyroidism.

Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial.

BACKGROUND: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. METHODS: The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. RESULTS: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed. CONCLUSIONS: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. TRIAL REGISTRATION: JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

A randomized clinical trial investigating the impact of magnesium supplementation on clinical and biochemical measures in COVID-19 patients.

BACKGROUND: This study sought to examine the impact of magnesium supplementation on clinical outcomes and biochemical factors among hospitalized patients with COVID-19. METHODS: This double-blind, randomized clinical trial was conducted at Razi Hospital, Ahvaz, Iran, between September 2021 and March 2022. Participants aged 18-70 years with moderate disease severity were enrolled. Magnesium supplementation (300 mg daily) was administered to the intervention group, while the control group received a placebo. Clinical outcomes, including the need for oxygen therapy, oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health, were assessed. Blood samples were collected to measure biochemical variables. RESULTS: The main result was the count of individuals requiring oxygen therapy. Additional outcomes comprised of oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health. Out of 64 participants, 60 completed the study. The results showed that magnesium supplementation significantly reduced the number of patients requiring oxygen therapy (9 vs. 14; P < 0.001). Moreover, the magnesium group demonstrated improved oxygen saturation compared to the control group (4.55 ± 2.35 vs. 1.8 ± 1.67; P < 0.001). Furthermore, we observed a noteworthy enhancement in the quality of life and depression score in the magnesium group. No significant differences were observed in respiratory rate, fever, hs-CRP, and TNF-α levels (P > 0.05). CONCLUSION: The findings suggest that magnesium supplementation may have beneficial effects on clinical outcomes and arterial oxygen saturation in COVID-19 patients. More investigation is necessary to delve into its potential mechanisms and long-term effects on patient outcomes. TRIAL REGISTRATION: This study is registered on Iranian Registry of Clinical Trials (IRCT) under identifier IRCT20210413050957N1. (The registration date: May 1, 2021).

Associations of the magnesium depletion score and magnesium intake with diabetes among US adults: an analysis of the National Health and Nutrition Examination Survey 2011-2018.

OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS: MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.

The Association Between Dietary Magnesium Intake with Chronic Obstructive Pulmonary Disease and Lung Function in US Population: a Cross-sectional Study.

Chronic obstructive pulmonary disease (COPD) is now considered among the top three contributors to mortality globally. There is limited understanding surrounding the contribution of magnesium to the progression of COPD. This survey aims to evaluate the connection between dietary magnesium intake and both lung function and COPD prevalence among the US population. The research comprised 4865 participants in the National Health and Nutrition Examination Survey (NHANES) program conducted from 2007 to 2012. To evaluate the association between dietary magnesium intake and lung function as well as COPD, the study conducted multiple regression analyses, stratified analyses, and smoothed curves. In this study, we explored the relationship between higher magnesium intake and higher FEV1 [ß = 0.21 (95% CI 0.12, 0.30)] and FVC [ß = 0.25 (95% CI 0.14, 0.36)] after accounting for all potential confounding factors. We demonstrated a relationship between increased magnesium intake and reduced odds of developing COPD [OR = 0.9993 (95% CI 0.9987, 1.0000)]. The results of stratified analyses further indicated that the relationship between magnesium intake and the risk of COPD is more pronounced in the 40-60 age group and males. The study demonstrated positive associations between the intake of dietary magnesium and both FEV1 and FVC. Additionally, an adverse relationship between magnesium intake and the prevalence of COPD was also observed, suggesting that supplementation with magnesium may be a practical approach to preventing and managing COPD.

Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial.

AIMS/HYPOTHESIS: Hypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown. METHODS: Using a randomised, double-blind (both participants and investigators were blinded to the participants' treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age ≥18 years, BMI 18-40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium ≤0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic-euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up. RESULTS: We recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg-1 min-1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms. CONCLUSIONS/INTERPRETATION: Despite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels. TRIAL REGISTRATION: EudraCT number 2021-001243-27. FUNDING: This study was supported by a grant from the Dutch Diabetes Research Foundation (2017-81-014).

Association between a Calcium-to-Magnesium Ratio and Osteoporosis among Puerto Rican Adults.

BACKGROUND: The ratio of calcium-to-magnesium intake (Ca:Mg) may be important for bone due to their competitive absorption. The Ca:Mg ratio has been related to health outcomes, but few studies have related it to bone. OBJECTIVES: The purpose of this analysis was to examine associations between the Ca:Mg intake with bone mineral density (BMD) and osteoporosis among Puerto Rican adults. METHODS: Adults, aged 47-79 y, from the Boston Puerto Rican Osteoporosis Study, with complete BMD and dietary data (n = 955) were included. BMD was assessed with dual-energy X-ray absorptiometry and diet by a food frequency questionnaire. Calcium and magnesium intakes from food were energy adjusted, and the Ca:Mg was calculated. Adjusted linear and logistic regression models were utilized for testing associations between Ca:Mg and bone outcomes. RESULTS: Calcium intake was greater in the highest compared with lowest tertile, whereas magnesium intake was similar across tertiles. Mean BMD at hip sites was higher in the middle, compared with the lowest, tertile. Higher odds of osteoporosis were observed for the highest and lowest tertiles, compared with the middle tertile, after adjustment (T3 compared with T2 OR: 2.79; 95% CI: 1.47, 5.3; T1 compared with T2 OR: 2.01; 95% CI: 1.03, 3.92). Repeated analyses without supplement users (n = 432) led to stronger differences and ORs, but lost significance for some comparisons. CONCLUSIONS: Dietary calcium and magnesium are important for bone, perhaps not independently. The Ca:Mg intake ratio appeared most protective within a range of 2.2-3.2, suggesting that a balance of these nutrients may be considered in recommendations for osteoporosis..

Magnesium in the treatment of alcohol withdrawal syndrome: a multicenter randomized controlled trial.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a frequent and potentially life-threatening condition experienced in alcohol use disorder. Since hypomagnesemia is involved in AWS's severity, we conducted a multicenter double-blind randomized placebo-controlled trial to examine the efficacy of oral magnesium supplementation as an adjuvant therapy of AWS. MATERIAL AND METHODS: Inpatients were recruited in six different centers if they had a baseline score higher than eight on the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The experimental treatment was magnesium lactate dehydrate, administrated three times per day providing a total of 426.6 mg per day and up to 15 days. The primary endpoint was the significant between-group difference of the CIWA-Ar total score change from baseline to 3 days later. The treatment group and baseline score were introduced as covariables in an analysis of covariance. RESULTS: A total of 98 inpatients were included {71.4% of men; mean age of 49.1 years [standard deviation (SD): 10.3]}. In the intention-to-treat population, the mean reduction of the CIWA-Ar score in the experimental group between baseline and 3 days later was 10.1 (SD: 5.2), whereas it was 9.2 (SD: 3.9) in the control group. The absolute difference of the adjusted mean in the experimental group compared with the control group was -0.69 (SD: 0.72), which did not correspond to a significant between-group difference (P = 0.34). Per-protocol analysis and sensitivity analyses also supported this result. Supplementary analyses found no significant difference regarding benzodiazepine consumption, magnesium blood concentration, and satisfaction to care. CONCLUSIONS: The present study does not support the rationale of systematic oral magnesium supplementation in patients with AWS.

Magnesium Intake, C-Reactive Protein, and Muscle Mass in Adolescents.

Background: Adult studies have suggested that magnesium intake may regulate C-reactive protein (CRP) and muscle mass, known risk factors for cardiometabolic diseases. Given the large deficiencies in magnesium intake in adolescents, we aimed to investigate sex and race differences in dietary magnesium intake and test the hypothesis that lower magnesium intake is associated with higher CRP and lower muscle mass. Methods: A total of 766 black and white adolescents, 14 to 18 years old (51% black; 50% female) were previously recruited. Diet was assessed with four to seven independent 24-h recalls. Body composition was measured by dual-energy X-ray absorptiometry. High-sensitivity CRP (hs-CRP), leptin, resistin, and adiponectin were measured using fasting blood samples by ELISA. Results: There were sex and race differences in the daily consumption of magnesium. The average daily magnesium intakes were 200.66 ± 7.09 mg and 205.03 ± 7.05 mg for males and females, respectively, far below the recommended amounts of 410 mg for males and 360 mg for females. White subjects (217.95 ± 6.81 mg/day) consumed more than black subjects (187.75 ± 6.92 mg/day). Almost none of the adolescents met the recommendations. Adjusted multiple linear regressions revealed that lower magnesium intake was associated with higher hs-CRP and lower fat-free mass (FFM) (p-values < 0.05). Higher hs-CRP was associated with lower FFM. Moreover, an interaction between magnesium intake and hs-CRP on FFM was identified (p-value < 0.05). Lower magnesium intake amplified the inverse relationships between hs-CRP and FFM (p-values < 0.05). Conclusion: Magnesium consumption in our adolescents was far below daily recommended levels with male and black subjects consuming less than female and white subjects. Lower magnesium intake was associated with higher CRP and lower muscle mass. Low magnesium intake may also augment the inverse relationship between CRP and FFM.

Magnesium and Zinc Intake Ratio Mediates the Increase of Coronary Artery Calcification through Upregulating Interleukin 6.

The relation between dietary minerals and coronary artery calcification (CAC) has been emphasized. However, the effects of multiple dietary minerals on CAC progression remain unclear. This study Investiagetes the effect of combined dietary mineral intake on the progression of CAC. We analyzed a population-based cohort with 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores were measured at baseline and subsequent follow-up examinations by Multi-detector computed tomography (MDCT) scans with Agatston scores. Then, the progression of CAC was defined through increased CAC scores in the follow-up from the baseline exam. The results revealed that the dietary intake of individual minerals did not show significant differences across CAC progression vs non progression groups. However, participants with CAC progression had an increased Magnesium (Mg):Zinc (Zn) ratio (P < 0.05). This effect was significant in logistic regression after adjusting for multiple established risk factors of CAC progression (OR 1.050; 95% CI 1.003, 1.099; P = 0.038). The increased risk of CAC associated with Mg/Zn was mediated through an increase level of IL-6, which increased with association to the Mg: Zn ratio. In conclusion, the dietary of Mg: Zn ratio, rather than individual mineral intake is associated with increased risk of CAC progression, which is mediated by pro-calcific IL-6. Therefore, the consideration of dietary intake of Zn and Mg together would play a cardio protective role among CAC patients.

Magnesium sensing via LFA-1 regulates CD8+ T cell effector function.

The relevance of extracellular magnesium in cellular immunity remains largely unknown. Here, we show that the co-stimulatory cell-surface molecule LFA-1 requires magnesium to adopt its active conformation on CD8+ T cells, thereby augmenting calcium flux, signal transduction, metabolic reprogramming, immune synapse formation, and, as a consequence, specific cytotoxicity. Accordingly, magnesium-sufficiency sensed via LFA-1 translated to the superior performance of pathogen- and tumor-specific T cells, enhanced effectiveness of bi-specific T cell engaging antibodies, and improved CAR T cell function. Clinically, low serum magnesium levels were associated with more rapid disease progression and shorter overall survival in CAR T cell and immune checkpoint antibody-treated patients. LFA-1 thus directly incorporates information on the composition of the microenvironment as a determinant of outside-in signaling activity. These findings conceptually link co-stimulation and nutrient sensing and point to the magnesium-LFA-1 axis as a therapeutically amenable biologic system.

Chronic magnesium deficiency causes reversible mitochondrial permeability transition pore opening and impairs hypoxia tolerance in the rat heart.

Chronic magnesium (Mg) deficiency induces and exacerbates various cardiovascular diseases. We previously investigated the mechanisms underlying decline in cardiac function caused by chronic Mg deficiency and the effectiveness of Mg supplementation on this decline using the Langendorff-perfused isolated mouse heart model. Herein, we used the Langendorff-perfused isolated rat heart model to demonstrate the chronic Mg-deficient rats (Mg-deficient group) had lower the heart rate (HR) and left ventricular pressure (LVDP) than rats with normal Mg levels (normal group). Furthermore, decline in cardiac function due to hypoxia/reoxygenation injury was significantly greater in the Mg-deficient group than in the normal group. Experiments on mitochondrial permeability transition pore (mPTP) using isolated mitochondria revealed that mitochondrial membrane was fragile in the Mg-deficient group, implying that cardiac function decline through hypoxia/reoxygenation injury is associated with mitochondrial function. Mg supplementation for chronic Mg-deficient rats not only improved hypomagnesemia but also almost completely restored cardiac and mitochondrial functions. Therefore, proactive Mg supplementation in pathological conditions induced by Mg deficiency or for those at risk of developing hypomagnesemia may suppress the development and exacerbation of certain disease states.

Effect of calcium and magnesium on inflammatory cytokines in accidentally multiple fracture adults: A short-term follow-up.

ABSTRACT: Calcium (Ca) and magnesium (Mg), which play an important role in several cellular processes, is essential for normal development of the skeleton and maintenance of tissue homeostasis. Deficiency of these elements might delay bone fracture recovery or accelerates bone loss. We aimed to examine whether supplementation of trace element (TE) promotes fracture healing in accidentally fracturing adults by involvement of inflammatory mechanism.A short-term follow-up in clinic was performed. Totally, 117 subjects diagnosed with multiple fractures by traffic accidents were recruited in this study. Serum Ca and Mg levels were measured by inductively coupled plasma atomic emission spectrophotometry. Short-term changes such as serum C-reactive protein, interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha in normal treatment and TE supplement groups were detected by enzyme-linked immunosorbent assay. Student t test and the Spearman correlation were performed to analyze the data.Significantly negative correlations between Ca (r = 0.7032; P < .001) and Mg (r = 0.2719; P < .05) and injury severity score were observed. Serum Ca and Mg were significantly increased at Day 5, 7, and 9 following TE supplements. After treatment, serum C-reactive protein, IL-1ß, IL-6, and tumor necrosis factor alpha were significantly reduced whereas cytokine levels of the TE supplement group were found to be lower than that of the normal treatment group after Day 3.These findings suggest that Ca and Mg levels are associated with the injury severity of multiple fractures, and the supplement could reduce the inflammation, which may be beneficial for the bone recovery and disease process.

Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review.

Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.

ALM Fluid Therapy Shifts Sympathetic Hyperactivity to Parasympathetic Dominance in the Rat Model of Non-Compressible Hemorrhagic Shock.

ABSTRACT: Excessive sympathetic outflow following trauma can lead to cardiac dysfunction, inflammation, coagulopathy, and poor outcomes. We previously reported that buprenorphine analgesia decreased survival after hemorrhagic trauma. Our aim is to examine the underlying mechanisms of mortality in a non-compressible hemorrhage rat model resuscitated with saline or adenosine, lidocaine, magnesium (ALM). Anesthetized adult male Sprague-Dawley rats were randomly assigned to Saline control group or ALM therapy group (both n = 10). Hemorrhage was induced by 50% liver resection. After 15 min, 0.7 mL/kg 3% NaCl ±â€ŠALM intravenous bolus was administered, and after 60 min, 0.9% NaCl ±â€ŠALM was infused for 4 h (0.5 mL/kg/h) with 72 h monitoring. Animals received 6-12-hourly buprenorphine for analgesia. Hemodynamics, heart rate variability, echocardiography, and adiponectin were measured. Cardiac tissue was analyzed for adrenergic/cholinergic receptor expression, inflammation, and histopathology. Four ALM animals and one Saline control survived to 72 h. Mortality was associated with up to 97% decreases in adrenergic (ß-1, α-1A) and cholinergic (M2) receptor expression, cardiac inflammation, myocyte Ca2+ loading, and histopathology, indicating heart ischemia/failure. ALM survivors had higher cardiac output and stroke volume, a 30-fold increase in parasympathetic/sympathetic receptor expression ratio, and higher circulating adiponectin compared to Saline controls. Paradoxically, Saline cardiac adiponectin hormone levels were higher than ALM, with no change in receptor expression, indicating intra-cardiac synthesis. Mortality appears to be a "systems failure" associated with CNS dysregulation of cardiac function. Survival involves an increased parasympathetic dominance to support cardiac pump function with reduced myocardial inflammation. Increased cardiac α-1A adrenergic receptor in ALM survivors may be significant, as this receptor is highly protective during heart dysfunction/failure.