Dietary supplementation with a silicate clay mineral (palygorskite) alleviates inflammatory responses and intestinal barrier damage in broiler chickens challenged with Escherichia coli.

This experiment aimed to explore the protective effects of dietary palygorskite (Pal) supplementation on inflammatory responses and intestinal barrier function of broiler chickens challenged with Escherichia coli (E. coli). A 2 × 2 factorial arrangement was designed to assess the effects of Pal administration (0 or 5 g/kg of feed) and E. coli challenge (E. coli or bacterial culture medium) on broilers in a 21-d feeding trial. Birds were randomly assigned into one of the 4 groups, and each group had 8 replicates with ten birds each. The challenged chickens were orally gavaged with E. coli suspended in Luria-Bertani broth on 14 d of age, while unchallenged birds were administrated with an equivalent amount of culture medium. The sampling was performed at 21 d of age. Compared with the normal birds, an oral E. coli challenge reduced final body weight, and decreased feed intake, weight gain, and feed efficiency during the challenge period (P < 0.05). E. coli challenge promoted colonization of E. coli in cecal content and their translocation to internal organs (heart, liver, and spleen) (P < 0.05). E. coli infection also increased levels of pro-inflammatory cytokines in jejunum and ileum possibly through activating the toll-like receptor-4-mediated signaling pathway (P < 0.05). Moreover, E. coli administration increased intestinal mucosal permeability (higher serum D-lactate level and diamine oxidase activity, and lower intestinal mucosal disaccharidase activities), altered intestinal morphology, and downregulated the gene expression of intestinal tight junction proteins (P < 0.05). In contrast, Pal supplementation enhanced growth performance, inhibited colonization of E. coli, reduced intestinal inflammation, decreased intestinal permeability, restored intestinal morphology, and normalized the expression of genes responsible for inflammatory processes and maintenance of intestinal mucosal barrier (P < 0.05), and most of these beneficial effects resulting from Pal administration were independent of bacterial challenge. The results indicated dietary Pal incorporation was effective in improving growth performance and alleviating inflammation and intestinal mucosal barrier damage in broilers challenged with E. coli.

Effect of magnesium oxide or citrate supplements on metabolic risk factors in kidney stone formers with idiopathic hyperoxaluria: a randomized clinical trial.

Magnesium is one of the recommended treatments for calcium stone formers (CSFs) with hyperoxaluria. In this study, we compared the effect of magnesium oxide (MgO) or magnesium citrate (MgCit) with placebo on 24-hour urine (24-U) metabolites and the calcium oxalate supersaturation index (CaOx SS). In a randomized, double-blind, placebo-controlled clinical trial, 90 CSFs with idiopathic hyperoxaluria were recruited from a tertiary stone prevention clinic. Patients were randomly assigned into three groups: 120 mg MgO, 120 mg MgCit or placebo (supplements were taken three times per day, with meals). Finally, 76 patients were included in the final analysis. Analyses of 24-U were performed at baseline and after eight weeks. Study outcomes included changes in 24-U oxalate, magnesium, citrate, and CaOx SS. Dietary factors were controlled by 24-hour food recalls. Repeated measure ANOVA was used to compare the results. After the intervention, both MgO and MgCit supplements decreased 24-U oxalate excretion (-8.13±16.45 in the MgO group and -16.99±18.02 in the MgCit group) and CaOx SS compared to the placebo, with the effects of MgCit reaching statistical significance (p=0.011 and p=0.010, respectively). An increasing trend was observed for 24-U magnesium and citrate excretion without significant differences among groups. Interestingly, MgCit exhibited a significantly greater inhibitory effect on 24-U oxalate in patients with normal urine magnesium levels (p=0.021). Clinically, both MgO and MgCit reduced 24-U oxalate and CaOx SS compared to placebo. However, MgCit demonstrated a greater effect, especially in patients with normal urine magnesium levels.

Magnesium dietary intake and physical activity in Type 2 diabetes by gender in White, African-American and Mexican American: NHANES 2011-2014.

Aims: To analyse the causal relationships of nutrition intake and physical activity on haemoglobin A1c (HbA1C) in patients diagnosed with type 2 diabetes mellitus (T2DM) stratified by gender and ethnicity. Materials and Methods: An historical cohort of patients with diagnosed T2DM (n = 2831) was extracted from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 public database, including but not limited to, measurements of physical activity, nutrition, body mass index (BMI) and HbA1c. Multivariate analyses and path analyses were employed to estimate the regression coefficients and path coefficients (ρ) of causal path models of physical activity and nutrition intake on HbA1c stratified by gender and three ethnicity groups (ie non-Hispanic white, non-Hispanic black and Mexican American). Results: A significant causal path from increased physical activity to increased magnesium (Mg) intake to decreased HbA1c was found. In addition, increased physical activity significantly decreased BMI, which further decreased HbA1c. These results varied by gender and ethnicity but were directionally consistent. Physical activity decreased HbA1c through BMI for males and through Mg intake for females. Mexican American decreased HbA1c through Mg intake, while non-Hispanic black had an increased HbA1c due to its ethnicity and through increased BMI. Conclusions: The beneficial effects of physical activity on decreased HbA1c were mediated through the increased Mg intake and decreased BMI. This aligned with recent investigations of the inverse causal association of Mg intake with insulin resistance and with decreased inflammation.

A pH/redox-dual responsive, nanoemulsion-embedded hydrogel for efficient oral delivery and controlled intestinal release of magnesium ions.

It remains a major challenge to achieve efficient oral delivery and controlled intestinal release of ions using hydrogels. Herein, we report a novel, pH/redox-dual responsive, nanoemulsion-embedded composite hydrogel to address this issue. The hydrogel was first synthesized by crosslinking a biocompatible, pH-responsive pseudopeptide, poly(l-lysine isophthalamide) (PLP), and redox-sensitive l-cystine dimethyl ester dihydrochloride (CDE). A suitable amount of magnesium acetate was encapsulated into oil-in-water nanoemulsions, which were then embedded into the lysine-based hydrogel. The resulting composite hydrogel collapsed into a compact structure at acidic gastric pH, but became highly swollen or degraded in the neutral and reducing intestinal environment. The ion release profiles indicated that the nanoemulsion-embedded composite hydrogel could well retain and protect magnesium ions in the simulated gastric fluid (SGF) buffer at pH 1.2, but efficiently release them in the simulated intestinal fluid (SIF) buffer at pH 6.8 in the presence of 1,4-dithiothreitol (DTT) as a reducing agent. Moreover, this composite hydrogel system displayed good biocompatibility. These results suggested that the pH/redox-dual responsive, nanoemulsion-embedded composite hydrogel could be a promising candidate for efficient oral delivery and controlled intestinal release of magnesium and other ions.

Development and statistical optimization of alginate-Neusilin US2 micro-composite beads to elicit gastric stability and sustained action of hesperidin.

The Alginate-Neusilin US2 micro-composite (MC) beads were fabricated and optimized for oral delivery of hesperidin (HES). A 32 full factorial design encompassing independent variables (factors) such as the concentration of sodium alginate (X1), and Neusilin US2 (X2) and dependant variables (response) such as particle size (Y1), entrapment efficiency (Y2), and swelling degree (Y3). Nine batches were prepared by formulation design employing statistical software JMP 13.2.1. The multiple regression analysis (MLRA) was carried to explore the influence of factor over responses. Further, a prediction profiler was used to trace the optimum concentration of factors based on desirable responses. The optimized beads (OF) were characterized for their morphology and size by motic microscopy and scanning electron microscopy. In vitro release, kinetic studies were performed in simulated gastric and intestinal fluids. In vivo pharmacokinetic studies revealed better absorption of HES from optimized beads (OF) compared to HES suspension which could be due to the prevention of acidic degradation of HES in the stomach. The estimated shelf life of OF formulation was found to be 3.86 years suggested better stability after fabrication. In a nutshell, the developed micro-composite beads of HES could be a better alternative for promising oral sustained delivery of HES.

An in vitro and in vivo comparison of Mg(OH)2-, MgF2- and HA-coated Mg in degradation and osteointegration.

Magnesium hydroxide (Mg(OH)2), magnesium fluoride (MgF2), and hydroxyapatite (HA) films on Mg are widely studied owing to their easy preparation and favorable corrosion protection. Nevertheless, the most suitable film with the best performance for biomedical applications between the three films remains unknown. Therefore, the performance of the three coatings from in vitro to in vivo must be systematically investigated. In this study, Mg(OH)2, MgF2, and HA films were fabricated on pure Mg. Electrochemical analysis and the hydrogen evolution test suggested that the HA film showed the best in vitro corrosion resistance, followed by MgF2 and Mg(OH)2 films. In vitro cell culture indicated that the extract of the MgF2-coated sample was most beneficial for the osteogenic differentiation of MC3T3-E1 cells and the vascularization of human umbilical vein endothelial cells (HUVECs), which might be ascribed to the existence of the F element in the film. The result of this subcutaneous implantation showed that the HA film exhibited the best in vivo corrosion resistance and induced the lightest inflammatory response. Femoral implantation data revealed that the HA film exhibited the best osseointegration. Furthermore, the major organs and blood indicators of all of the tested rats were normal in 8 weeks. In summary, though the in vitro biological performance of the MgF2 film was the best among the three films, the HA film showed the best in vivo performance, suggesting that it is a more promising modification method for orthopedic applications.

Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm.

AIM: Canagliflozin (CFZ), a novel SGLT II antagonist, exhibits erratic absorption after oral administration. The current study entails development and evaluation of spray dried lipid based formulation (solid SMEDDS) for enhancing oral bioavailability and anti-diabetic activity of CFZ. METHODS: Solid SMEDDS developed through spray drying containing Neusilin US2 as an adsorbent. The formed solid SMEDDS were characterized for physicochemical and solid state attributes. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were used to confirm the spherical morphology. In vitro dissolution, ex vivo permeability and in vivo pharmacokinetic studies were conducted to determine the release rate, permeation rate and absorption profile of CFZ, respectively. Pharmacodynamic studies were done as per standard protocols. RESULTS: The optimized solid SMEDDS exhibited acceptable practical yield and flow properties and is vouched with enhanced amorphization, nanoparticulate distribution and acceptable drug content. The spherical morphology of solid SMEDDS and reconstituted SMEDDS were confirmed in SEM and TEM, respectively. In vitro dissolution studies revealed multi-fold release behavior in CFZ in various dissolution media, whereas, remarkable permeability was observed in jejunum segment of rat intestine. Pharmacokinetic studies of CFZ in solid SMEDDS demonstrated 2.53 and 1.43 fold enhancement in Cmax and 2.73 and 1.98 fold in AUC 0-24h, as compared to pure API and marketed formulation, respectively. Pharmacological evaluation of solid SMEDDS revealed enhanced anti-diabetic activity of CFZ through predominant SGLT II inhibition in rats, as evident from evaluation of biochemical levels, urinary glucose excretion studies and SGLT II expression analysis. CONCLUSION: The current work describes significant improvement biopharmaceutical properties of CFZ in solid SMEDD formulation. Graphical abstract Graphical Abstract: Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm.

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.

Effects of magnesium citrate, magnesium oxide and magnesium sulfate supplementation on arterial stiffness in healthy overweight individuals: a study protocol for a randomized controlled trial.

BACKGROUND: Arterial stiffness is closely related to the process of atherosclerosis, an independent cardiovascular risk factor, and predictive of future cardiovascular events and mortality. Recently, we showed that magnesium citrate supplementation results in a clinically relevant improvement of arterial stiffness. It remained unclear whether the observed effect was due to magnesium or citrate, and whether other magnesium compounds may have similar effects. Therefore, we aim to study the long-term effects of magnesium citrate, magnesium oxide and magnesium sulfate on arterial stiffness. In addition, we aim to investigate possible underlying mechanisms, including changes in blood pressure and changes in gut microbiota diversity. METHODS: In this randomized, double-blind, placebo-controlled trial, a total of 162 healthy overweight and slightly obese men and women will be recruited. During a 24-week intervention, individuals will be randomized to receive: magnesium citrate; magnesium oxide; magnesium sulfate (total daily dose of magnesium for each active treatment 450 mg); or placebo. The primary outcome of the study is arterial stiffness measured by the carotid-femoral pulse wave velocity (PWVc-f), which is the gold standard for quantifying arterial stiffness. Secondary outcomes are office blood pressure, measured by a continuous blood pressure monitoring device, and gut microbiota, measured in fecal samples. Measurements will be performed at baseline and at weeks 2, 12 and 24. DISCUSSION: The present study is expected to provide evidence for the effects of different available magnesium formulations (organic and inorganic) on well-established cardiovascular risk markers, including arterial stiffness and blood pressure, as well as on the human gut microbiota. As such, the study may contribute to the primary prevention of cardiovascular disease in slightly obese, but otherwise healthy, individuals. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03632590 . Retrospectively registered on 15 August 2018.

Electroacupuncture plus on-demand gastrocaine for refractory functional dyspepsia: Pragmatic randomized trial.

BACKGROUND AND AIM: Treatment options for functional dyspepsia (FD) refractory to pharmacological treatments are limited but the effectiveness of electroacupuncture (EA) is uncertain. We assessed the effectiveness of EA combined with on-demand gastrocaine. METHODS: We conducted a single-center, assessor-blind, randomized parallel-group 2-arm trial on Helicobacter pylori negative FD patients of the postprandial distress syndrome subtype refractory to proton pump inhibitor, prokinetics, or H2 antagonists. Enrolled participants were block randomized in a 1:1 ratio, with concealed random sequence. The treatment and control groups both received on-demand gastrocaine for 12 weeks, but only those in treatment group were offered 20 sessions of EA over 10 weeks. The primary endpoint was the between-group difference in proportion of patients achieving adequate relief of symptoms at week 12. RESULTS: Of 132 participants randomly assigned to EA plus on-demand gastrocaine (n = 66) or on-demand gastrocaine alone (n = 66), 125 (94.7%) completed all follow-up at 12 weeks. The EA group had a compliance rate 97.7%. They had a significantly higher likelihood in achieving adequate symptom relief at 12 weeks, with a clinically relevant number needed to treat (NNT) value of 2.36 (95% CI: 1.74, 3.64). Among secondary outcomes, statistically and clinically significant improvements were observed among global symptom (NNT = 3.85 [95% CI: 2.63, 7.69]); postprandial fullness and early satiation (NNT = 5.00 [95% CI: 2.86, 25.00]); as well as epigastric pain, epigastric burning, and postprandial nausea (NNT = 4.17 [95% CI: 2.56, 11.11]). Adverse events were minimal and nonsignificant. CONCLUSION: For refractory FD, EA provides significant, clinically relevant symptom relief when added to on-demand gastrocaine (ChiCTR-IPC-15007109).

The protective effects of modified palygorskite on the broilers fed a purified zearalenone-contaminated diet.

This study was conducted to evaluate the protective effects of dietary modified palygorskite (Pal) supplementation on broiler chickens fed a purified zearalenone (ZEN)-contaminated diet. A total of 144 1-day-old male chicks were allocated to one of the 3 treatments, with each treatment being composed of 6 replicates of 8 birds each. The birds were fed with a control diet (Control group), the ZEN-contaminated diet (2.0 mg ZEN/kg diet), and the ZEN-contaminated diet supplemented with 1.0 g/kg diet of modified Pal for 42 d, respectively. Compared with control group, feeding ZEN-contaminated diet reduced weight gain and feed conversion efficiency of broilers during the finisher and overall experimental period (P < 0.05), while the values of these parameters in broilers fed the diet contaminated with ZEN increased after modified Pal administration (P < 0.05). ZEN challenge increased the 21-d serum aspartate aminotransferase and 42-d serum alanine aminotransferase activities, 42-d relative liver weight, and ZEN residues in the liver at both 21 and 42 d and kidney at 42 d (P < 0.05). In contrast, birds fed the ZEN-contaminated diet that was supplemented with modified Pal exhibited lower serum alanine aminotransferase activity at 42 d, relative liver weight at 42 d, and hepatic and renal ZEN accumulation at both 21 and 42 d (P < 0.05), when compared with their counterparts fed the contaminated diet. ZEN contamination decreased superoxide dismutase activity in the serum at 21 d, kidney at 42 d, and liver at both 21 and 42 d, respectively (P < 0.05). The hepatic and renal malondialdehyde accumulation at 42 d increased, while renal glutathione level at 42 d decreased, when feeding broilers with the ZEN-contaminated diet (P < 0.05). Dietary modified Pal supplementation reduced hepatic malondialdehyde accumulation, whereas increased renal superoxide dismutase activity in broilers fed a ZEN-contaminated diet at 42 d (P < 0.05). This finding suggested that dietary modified Pal administration could promote growth performance, reduce hepatonephric ZEN residues, and improve liver function and antioxidant status of broiler chickens receiving a ZEN-contaminated diet.

Effects of palygorskite composites on growth performance and antioxidant status in broiler chickens.

This work aimed to investigate the effects of the palygorskite (PAL) composites on the growth performance and antioxidant status in broiler chickens. A total of 192 one-day-old Ross 308 broilers were randomly divided into 3 treatment groups. Broilers were fed basal diets supplemented with either 50 mg/kg chlortetracycline (CTC group), 1 g/kg ZnO/PAL (ZnO/PAL group), or 1 g/kg chitooligosaccharides/ZnO/PAL (COS/ZnO/PAL group), respectively. The results showed that PAL composites were found to exhibit similar effects on growth performance as CTC (P > 0.05). ZnO/PAL and COS/ZnO/PAL enhanced the activity of serum glutathione peroxidase (GSH-Px) compared with CTC both at 21 and 42 d (P < 0.05). Compared with the CTC group, COS/ZnO/PAL enhanced serum catalase (CAT) activity at 21 d (P < 0.05), and decreased serum malondialdehyde (MDA) content at 42 d (P < 0.05). Compared with the CTC group, ZnO/PAL decreased duodenal mucous MDA content at 21 d, while ZnO/PAL did not affect activities of superoxide dismutase (SOD) and GSH-Px in the duodenum (P > 0.05). The duodenal mucous activities of SOD and GSH-Px were the highest in the COS/ZnO/PAL group at 42 d (P < 0.05). At 21 d, broilers in the COS/ZnO/PAL group had the lowest MDA content and the highest total antioxidant capacity (T-AOC) in the jejunum (P < 0.05). Palygorskite composites decreased ileum mucous MDA content compared with CTC treated broilers at 21 d (P < 0.05). At 42 d, ileum mucous T-AOC was increased both in the ZnO/PAL and COS/ZnO/PAL groups compared with the CTC group (P < 0.05). The ileum mucous GSH-Px activities both in the ZnO/PAL and COS/ZnO/PAL groups were increased compared with the CTC group (P < 0.05). In conclusion, the broilers given the basal diet supplemented with the PAL composites exhibited similar growth performance to their counterparts in the AGP group. Additionally, the PAL composites improved the antioxidant status of broilers and the beneficial effects of COS/ZnO/PAL on the antioxidant status are more pronounced.

Dose-Dependent Absorption Profile of Different Magnesium Compounds.

Magnesium, one of the basic elements for the human body, is necessary for many physiological functions. Magnesium deficiency is widely observed as a result of the reduced nutrient content of foods, over-cooking, diseases, drugs, alcohol, and caffeine consumption. Taking a dietary supplement is necessary magnesium deficiency. It has been demonstrated that absorption of organic magnesium compounds is better than absorption of inorganic compounds. The aim of this study is to investigate transitions to tissues of different organic magnesium compounds in different doses and whether there is a difference in the organic acid-bounded compounds (magnesium citrate and magnesium malate) and the amino acid-bounded compounds (magnesium acetyl taurate and magnesium glycinate), associated with transition and bioavailability. In addition, the effects of split dosages of high doses in a high volume of solvent on tissue magnesium levels are being investigated, because galenic formulation problems are regarded to prepare convenient dosage that can be taken once a day. All magnesium compounds were administered as three different doses, 45, 135, and 405 mg/70 kg elemental magnesium, were given per orally to Balbc mice. In a second set of experiments, 405 mg/70 kg high dose was divided into two doses of 202.5 mg/70 kg each and administered every 12 h. Brain, muscle tissues, and serum magnesium levels measured in all experimental groups and control 24 h later. Brain magnesium levels were found increased in all magnesium acetyl taurate administered subjects. Magnesium citrate increased muscle and brain magnesium levels in a dose-independent manner. We showed that dividing high doses of daily administered magnesium compounds did not sufficiently increase tissue magnesium levels. Although passive paracellular mechanism by solvent drag is the main mechanism of Mg absorption, other factors (electrochemical gradient effects, transcellular transporter mechanisms, magnesium status) should be effective on our results. It is necessary for further research on long-term administration of different magnesium compounds and their effect on other tissues.

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.

Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?

Magnesium is an element of great importance functioning because of its association with many cellular physiological functions. The magnesium content of foods is gradually decreasing due to food processing, and magnesium supplementation for healthy living has become increasingly popular. However, data is very limited on the bioavailability of various magnesium preparations. The aim of this study is to investigate the bioavailability of five different magnesium compounds (magnesium sulfate, magnesium oxide, magnesium acetyl taurate, magnesium citrate, and magnesium malate) in different tissues. Following a single dose 400 mg/70 kg magnesium administration to Sprague Dawley rats, bioavailability was evaluated by examining time-dependent absorption, tissue penetration, and the effects on the behavior of the animals. Pharmacokinetically, the area under the curve calculation is highest in the magnesium malate. The magnesium acetyl taurate was found to have the second highest area under the curve calculation. Magnesium acetyl taurate was rapidly absorbed, able to pass through to the brain easily, had the highest tissue concentration level in the brain, and was found to be associated with decreased anxiety indicators. Magnesium malate levels remained high for an extended period of time in the serum. The commonly prescribed dietary supplements magnesium oxide and magnesium citrate had the lowest bioavailability when compared to our control group. More research is needed to investigate the bioavailability of magnesium malate and acetyl taurate compounds and their effects in specific tissues and on behavior.

Effects of different levels of modified palygorskite supplementation on the growth performance, immunity, oxidative status and intestinal integrity and barrier function of broilers.

This experiment was designed to investigate effects of different levels of modified palygorskite (MPal) supplementation on growth performance, immunity, oxidative status and intestinal integrity and barrier function of broilers. A total of 320 1-day-old Arbor Acres broilers were randomly assigned into 5 dietary treatments and fed a basal diet supplemented with 0, 0.25, 0.5, 1 and 2 g/kg MPal, respectively, for a 42-day feeding trial. Treatments quadratically reduced feed/gain ratio (F:G) during 1-21 days and linearly decreased average daily feed intake and F:G during 22-42 days, and linearly and quadratically decreased average daily feed intake and F:G during overall period (p < 0.05, 0.50 g/kg treatment showed the lowest F:G). MPal supplementation increased the contents of 21-day jejunal secretory immunoglobulin A (SIgA) quadratically, and 21-day jejunal immunoglobulin G (IgG), immunoglobulin M (IgM) and 42-day jejunal total superoxide dismutase (T-SOD) activity linearly and quadratically (0.50 g/kg treatment showed the highest immunoglobulin concentration), whereas linearly reduced 21-day ileal SIgA level and 42-day jejunal malondialdehyde (MDA) accumulation and serum diamine oxidase activity, and quadratically decreased 21-day ileal MDA level (p < 0.05). The 42-day jejunal SIgA, IgG and IgM concentrations, and T-SOD activity in jejunum at 21 days and ileum at both 21 days and 42 days were quadratically increased with MPal administration (p < 0.05, 0.50 g/kg treatment showed the highest T-SOD activity). The mucin 2 mRNA abundances in 42-day jejunum and 21-day ileum were quadratically increased with MPal supplementation (p < 0.05). Treatments linearly increased 42-day ileal zonula occludens-1, claudin-3 and jejunal claudin-3 mRNA level, whereas linearly and quadratically increased ileal claudin-2 mRNA level (p < 0.05). In conclusion, MPal supplementation exhibited beneficial effects on growth performance, intestinal immunity, antioxidant capacity and intestinal integrity and barrier function of broiler with its optimum dosage being 0.5 g/kg.

Effects of Modified Palygorskite Supplementation on Egg Quality and Mineral Element Content, and Intestinal Integrity and Barrier Function of Laying Hens.

This study was conducted to investigate effects of modified palygorskite (MPal) supplementation on the laying performance, egg quality and mineral element content, immunity, oxidative status, and intestinal integrity and barrier function of laying hens. A total of 360 52-week-old Hyline Brown hens were randomly assigned into four dietary treatments for a 7-week feeding trial. The birds were fed a basal diet supplemented with 0 (control group), 0.25, 0.5, and 1 g/kg MPal, respectively. The supplementation of MPal did not alter laying performance and egg quality among groups. Compared with the control group, MPal inclusion decreased lead (Pb) content in yolks at 49 days, and either 0.5- or 1-g/kg MPal supplementation decreased Pb accumulation in yolks at 25 days and manganese (Mn) accumulation in yolks at 25 and 49 days. The contents of jejunal secretory immunoglobulin A (SIgA), ileal SIgA, and immunoglobulin G were decreased by the dietary 0.5-g/kg MPal supplementation. The supplementation of MPal also decreased malondialdehyde content in jejunum and ileum, and decreased serum diamine oxidase activity of the laying hens at 25 and 49 days. The inclusion of 0.5 and 1 g/kg MPal enhanced villus height in jejunum and ileum, and also increased the ratio of villus height to crypt depth in ileum. In conclusion, MPal supplementation decreased Pb and Mn contents in yolks, and exhibited beneficial effects on the intestinal immunity, oxidative status, and intestinal integrity and barrier function of laying hens and its optimal dosage was 0.5 g/kg.

Suitability of oral administration of monosodium phosphate, disodium phosphate, and magnesium phosphate for the rapid correction of hypophosphatemia in cattle.

BACKGROUND: Hypophosphatemia is commonly associated with disease and decreased productivity in dairy cows particularly in early lactation. Oral supplementation with phosphate salts is recognized as suitable for the rapid correction of hypophosphatemia. Little information is available about the differences in efficacy between salts used for oral phosphorus supplementation. OBJECTIVES: Comparison of efficacy of oral administration of NaH2 PO4 , Na2 HPO4 , and MgHPO4 in treating hypophosphatemia in cattle. ANIMALS: 12 healthy dairy cows in the fourth week of lactation in their second to fifth lactation. METHODS: Randomized clinical study. Phosphorus deficient, hypophosphatemic cows underwent a sham treatment and were afterwards assigned to 1 of 3 treatments-NaH2 PO4 , Na2 HPO4 , or MgHPO4 (each provided the equivalent of 60 g of phosphorus). Blood samples were obtained immediately before and repeatedly after treatment. RESULTS: Treatment with NaH2 PO4 and Na2 HPO4 resulted in rapid and sustained increases of plasma phosphate concentrations ([Pi]). Significant effects were apparent within 1 hour (NaH2 PO4 : P = .0044; Na2 HPO4 : P = .0077). Peak increments of plasma [Pi] of 5.33 mg/dL [5.26-5.36] and 4.30 mg/dL [3.59-4.68] (median and interquartile range) were reached after 7 and 6 hours in animals treated with NaPH2 PO4 and Na2 HPO4 , respectively, whereas treatment with MgHPO4 led to peak increments 14 hours after treatment (3.19 mg/dL [2.11-4.04]). CONCLUSIONS AND CLINICAL IMPORTANCE: NaH2 PO4 and Na2 HPO4 are suitable to rapidly correct hypophosphatemia in cattle. Because of the protracted and weaker effect, MgHPO4 cannot be recommended for this purpose. Despite important differences in solubility of NaH2 PO4 and Na2 HPO4 only small plasma [Pi] differences were observed after treatment.

Investigation of Dissolution Behavior HPMC/Eudragit®/Magnesium Aluminometasilicate Oral Matrices Based on NMR Solid-State Spectroscopy and Dynamic Characteristics of Gel Layer.

Burst drug release is often considered a negative phenomenon resulting in unexpected toxicity or tissue irritation. Optimal release of a highly soluble active pharmaceutical ingredient (API) from hypromellose (HPMC) matrices is technologically impossible; therefore, a combination of polymers is required for burst effect reduction. Promising variant could be seen in combination of HPMC and insoluble Eudragits® as water dispersions. These can be applied only on API/insoluble filler mixture as over-wetting prevention. The main hurdle is a limited water absorption capacity (WAC) of filler. Therefore, the object of this study was to investigate the dissolution behavior of levetiracetam from HPMC/Eudragit®NE matrices using magnesium aluminometasilicate (Neusilin® US2) as filler with excellent WAC. Part of this study was also to assess influence of thermal treatment on quality parameters of matrices. The use of Neusilin® allowed the application of Eudragit® dispersion to API/Neusilin® mixture in one step during high-shear wet granulation. HPMC was added extragranularly. Obtained matrices were investigated for qualitative characteristics, NMR solid-state spectroscopy (ssNMR), gel layer dynamic parameters, SEM, and principal component analysis (PCA). Decrease in burst effect (max. of 33.6%) and dissolution rate, increase in fitting to zero-order kinetics, and paradoxical reduction in gel layer thickness were observed with rising Eudragit® NE concentration. The explanation was done by ssNMR, which clearly showed a significant reduction of the API particle size (150-500 nm) in granules as effect of surfactant present in dispersion in dependence on Eudragit®NE amount. This change in API particle size resulted in a significantly larger interface between these two entities. Based on ANOVA and PCA, thermal treatment was not revealed as a useful procedure for this system.

Magnesium in Migraine Prophylaxis-Is There an Evidence-Based Rationale? A Systematic Review.

OBJECTIVE: The primary objective was to systematically evaluate the existing evidence base on magnesium in migraine prophylaxis. METHODS: The search for clinical trials published from 1990 to 2016 was separately conducted by AvL and FR using standard search terms as well as MeSh terms on PubMed and EMBASE. Randomized, double-blind, placebo-controlled trials investigating prophylactic magnesium administration in migraineurs aged 18-65 were considered eligible. In a mutual effort, the studies found were sorted and analyzed under consideration of the guidelines for controlled trials for drugs in migraine by the International Headache Society and using predefined eligibility criteria. The resulting clinical trials were jointly analyzed by FR and AvL applying the evidence classification scheme by the American Academy of Neurology and the Cochrane bias tool to assess the evidence-base. In accordance with the guidelines for controlled trials, the number of migraine days and number of migraine attacks were chosen as primary efficacy parameters. The present review was not registered. RESULTS: Out of 204 search results, five clinical trials fulfilling the selection procedure were found. One out of two Class I evidence trials showed a significant reduction of the number of migraine attacks compared with placebo, while two out of three Class III trials evinced a statistically significant reduction of the primary efficacy parameters compared with placebo. CONCLUSION: This systematic review provides Grade C (possibly effective) evidence for prevention of migraine with magnesium. Prophylactic treatment of migraine by means of high levels of magnesium dicitrate (600 mg) seems to be a safe and cost efficient strategy in clinical use.