Effect of an Antacid (Aluminum Hydroxide/Magnesium Hydroxide/Simethicone) or a Proton Pump Inhibitor (Omeprazole) on the Pharmacokinetics of Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) in Healthy Adult Subjects.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug being developed for the treatment of serious bacterial infections. This open-label, 3-period, fixed sequence study evaluated the effect of gastric acid-reducing agents, aluminum hydroxide/magnesium hydroxide/simethicone, and omeprazole on the pharmacokinetics (PK) of tebipenem (TBP), the active moiety, following coadministration with immediate release TBP-PI-HBr during fasting. In Period 1, subjects received a single oral dose of TBP-PI-HBr 600 mg (2 × 300 mg tablets). In Period 2, subjects received a single oral dose of aluminum hydroxide 800 mg/magnesium hydroxide 800 mg/simethicone 80 mg suspension co-administered with a single dose of TBP-PI-HBr 600 mg. In Period 3, subjects received a single oral dose of omeprazole 40 mg once daily over 5 days, followed by single dose administration of TBP-PI-HBr 600 mg on day 5. In each period, whole blood samples were obtained prior to, and up to 24 h, following TBP-PI-HBr dose administration in order to characterize TBP PK. A 7-day washout was required between periods. Twenty subjects were enrolled and completed the study. Following co-administration of TBP-PI-HBr with either aluminum hydroxide/magnesium hydroxide/simethicone or omeprazole, total TBP exposure (area under the curve [AUC]) was approximately 11% (geometric mean ratio 89.2, 90% confidence interval: 83,2, 95.7) lower, and Cmax was 22% (geometric mean ratio 78.4, 90% confidence interval: 67.9, 90.6) and 43% (geometric mean ratio 56.9, 90% confidence interval: 49.2, 65.8) lower, respectively, compared to administration of TBP-PI-HBr alone. Mean TBP elimination half-life (t1/2) was generally comparable across treatments (range: 1.0 to 1.5 h). Concomitant administration of TBP-PI-HBr with omeprazole or aluminum hydroxide/magnesium hydroxide/simethicone is not expected to impact the efficacy of TBP-PI-HBr, as there is minimal impact on TBP plasma AUC, which is the pharmacodynamic driver of efficacy. Co-administration was generally safe and well tolerated.

Formation and loss of metastable brucite: does Fe(II)-bearing brucite support microbial activity in serpentinizing ecosystems?

Ultramafic rocks undergo successive stages of hydration and oxidation during water/rock interaction, giving rise to secondary minerals such as brucite, serpentine, magnetite and the production of H2(g). Ferroan brucite (MgxFe(1-x)2+(OH)2) often forms under low water/rock ratios early during the 'serpentinization' process. The formation of ferroan brucite sequesters Fe(II) and suppresses the production of H2, thereby limiting the flux of reductants suitable for sustaining microbial metabolism. Yet ferroan brucite is a relatively soluble mineral 'reservoir' for reactive Fe(II). Brucite is often metastable and can be lost at later stages of peridotite hydration when there is a significant increase in the water/rock ratio or the activity of SiO2 or CO2. The Fe(OH)2 component of brucite has the thermodynamic potential to reduce most aqueous oxidants. Therefore, ferroan brucite may reduce water and/or dissolved carbon, nitrogen and sulfur species, while the Fe(II) is converted into more stable secondary minerals such as Fe(II/III)-oxides and hydroxides (e.g. green-rust, magnetite, iowaite and pyroaurite) and ferric serpentine. The reactivity of ferroan brucite, and the associated rate of Fe solubilization and oxidation in subsurface fluids, could be a key regulator on the rate of electron transfer from serpentinites to the rock-hosted biosphere. Aqueous alteration of ferroan brucite may significantly modulate the H2 activity in fluids circulating within partially serpentinized rocks, and buffer H2 as it is lost by advection or in situ consumption by a hydrogenotrophic microbial community. Moreover, there may be microbial organisms that specifically colonize and use ferroan brucite as an electron donor for their metabolism. The energy fluxes sustained by localized brucite oxidation may often be sufficiently large to sustain abundant microbial communities; water/rock reaction zones where brucite is consumed could serve as environments to search for extant or fossil serpentinite-hosted life. This article is part of a discussion meeting issue 'Serpentinite in the Earth System'.

Antimicrobial Activity of Nano-Magnesium Hydroxide Against Oral Bacteria and Application in Root Canal Sealer.

BACKGROUND The goal of the present work was to assess the antibacterial activity of nano-magnesium hydroxide (NMH) against Streptococcus mutans (S. mutans) and to explore the antimicrobial function of AH Plus™ sealer incorporating NMH. MATERIAL AND METHODS The antimicrobial behavior of NMH against S. mutans was evaluated with bactericidal tests. A modified direct contact test was used to assess the antimicrobial activity of unset AH Plus containing NMH after 5 minutes, 20 minutes, and 60 minutes of contact with bacteria. The antimicrobial effects and the amount of surface-adhering bacteria of the solidified materials were explored by SEM and confocal laser scanning microscopy, respectively. RESULTS NMH powder presented excellent antimicrobial activity against S. mutans. Mg²âº and OH⁻ were not the main factors resulting in bacterial death. Approximately 93.1% and 98% of the S. mutans were killed in the AH Plus+7% NMH group after incubation for 5 minutes and 20 minutes, respectively. AH Plus with 5% or 7% NMH were more potent against S. mutans compared with AH Plus alone (P<0.05). Moreover, the antibacterial function of AH Plus was lost after setting. NMH enabled the solidified AH Plus to still have antibacterial properties on the seventh day. CONCLUSIONS NMH can be used to modify AH Plus sealer to eradicate residual bacteria and prevent reinfection.

Hydrotalcite Can Prevent the Damaging Effects of Helicobacter Pylori on Gastric Epithelial Cells.

BACKGROUND: Helicobacter pylori is a major cause of gastric diseases including gastric cancer. This study was aimed to explore whether hydrotalcite can inhibit H. pylori infection of gastric epithelial cells. METHODS: the gastric epithelial cell line GES-1 and the gastric cancer cell line BGC823 were infected with H. pylori at multiplicities of infections (MOIs) of 50:1 and 100:1. Hydrotalcite was added to cell cultures. Cell apoptosis and cell cycle analysis were performed to measure the situation of cell growth. The main changes of cell ultrastructure were observed by transmission electron microscopy. H. pylori cell adhesion was observed by scanning electron microscopy. RESULTS: hydrotalcite could significantly inhibit cell apoptosis of GES-1 and cell proliferation of BGC823 induced by H. pylori infection at an MOI of 50:1. Hydrotalcite treatment protected gastric cells from H. pylori infection, and H. pylori adhesion to gastric cells was reduced. However, hydrotalcite could not reverse damage induced by H. pylori infection at an MOI of 100:1. CONCLUSION: hydrotalcite can protect gastric cells from H. pylori infection when cell damage is not serious. It can weaken the damage of cells induced by H. pylori and decrease H. pylori adhesion to gastric cells.

Co-instillation of nano-solid magnesium hydroxide enhances corneal permeability of dissolved timolol.

We prepared magnesium hydroxide (MH) nanoparticles by a bead mill method, and investigated whether the co-instillation of MH nanoparticles improves the low transcorneal penetration of water-soluble drugs, such as the anti-glaucoma eye drug timolol maleate (TM). MH particle size was decreased by the bead mill treatment to a mean particle size of 71 nm. In addition, the MH nanoparticles were highly stable. Next, we demonstrated the effect of MH nanoparticles on the corneal surface. MH shows only slight solubility in lacrimal fluid, and the instillation of MH nanoparticles for 14 days did not affect the behavior (balance of secretion and excretion) of the lacrimal fluid in rabbit corneas. Moreover, there was no observable corneal toxicity of MH nanoparticles, and treatment with MH nanoparticles enhanced the intercellular space ratio in the eyes of rats. MH alone did not permeate into the cornea; however, the co-instillation of MH nanoparticles and dissolved TM (nMTFC) enhanced the corneal penetration of TM. In addition, the intraocular pressure (IOP)-reducing effect of nMTFC was significantly higher than those of the TM solution or the co-instillation of MH microparticles and TM. In conclusion, we found that MH nanoparticles enhance the corneal penetration of dissolved TM with no observable corneal stimulation or obstruction of the nasolacrimal duct by the MH nanoparticles. It is possible that the co-instillation of MH nanoparticles may provide a useful way to improve the bioavailability of water-soluble drugs in the ophthalmic field. These findings provide significant information that can be used to design further studies aimed at developing anti-glaucoma eye drugs.

Magnesium hydroxide-based dentifrice as an anti-erosive agent in an in situ intrinsic erosion model.

PURPOSE: To evaluate in situ a magnesium hydroxide-[Mg(OH)2] based dentifrice on enamel erosion. METHODS: Human dental enamel slabs were selected by surface microhardness and randomly assigned to one out of the following three groups (n=18): non-fluoride (control), NaF (1,450 ppm F), and Mg(OH)2 dentifrices. 18 volunteers were enrolled in a randomized, crossover and double-blind study, with three phases in 5 days. They wore acrylic palatal appliances containing two human enamel slabs, which were treated with one of the three dentifrices. During each experimental phase, the specimens were subjected to erosion by immersion in 0.01 M HCl for 60 seconds, 4x/day, followed by a 1-minute treatment with the correspondent slurry (saliva/dentifrice). Enamel changes were determined by the percentage of surface hardness loss (%SHL) and mechanical profilometry analysis. Data were analyzed by ANOVA, followed by Tukey's test (P< 0.05). RESULTS: The means (SD) for %SHL and surface wear (µm) were, respectively, as follows: control [50.67(17.48), 2.70(1.24) ], NaF [45.45(15.44), 1.95(0.70) ] and Mg(OH)2 [53.94(19.48), 1.95(0.67) ]. There was no statistically significant difference among the treated and control groups for %SHL (P= 0.349); however, for wear rates, a statistically significant difference was found between the groups treated with NaF and Mg(OH)2 and the control group (P= 0.04). CLINICAL SIGNIFICANCE: Dentifrices containing magnesium hydroxide or sodium fluoride might be an important strategy to minimize the effects of erosive challenges.

Anti-Helicobacter pylori and antiulcerogenic activity of Aframomum pruinosum seeds on indomethacin-induced gastric ulcer in rats.

CONTEXT: Peptic ulcer is one of the most common diseases affecting mankind. Although there are many products used for its treatment, most of these products produce severe adverse reactions requiring the search for novel compounds. Some Afromomum species are used traditionally to cure acute gastritis. OBJECTIVE: To evaluate the antiulcer activity of the methanol extract of Aframomum pruinosum Gagnepain (Zingiberaceae) seeds against two major etiologic agents of peptic ulcer disease; Helicobacter pylori and non-steroidal anti-inflammatory drugs. MATERIALS AND METHODS: The anti-Helicobacter activity of A. pruinosum was evaluated using the broth microdilution method. After oral administration of indomethacin (5 mg/kg) for 5 consecutive days, gastric ulcerated animals were divided into control group and five other groups: three groups that recieved respectively 125, 250 and 500 mg/kg of plant extract, the fourth group received Maalox (50 mg/kg) and the fifth group, Misoprostol (100 µg/kg), respectively, for 5 days. Ulcer areas, gastric mucus content and nitric oxide gastric levels of animals were assessed 24 h after this treatment. RESULTS: A. pruinosum extract shows a moderate anti-Helicobacter activity with an MIC value of 128 µg/mL. A. pruinosum extract, like Misoprostol and Maalox, markedly reduces the % of ulcerated area from 8.15 ± 0.33 to 1.71 ± 0.44% (500 mg/kg). It also increased significantly mucus and NO gastric production with respective values of 4.44 ± 1.35 and 965.81 ± 106.74 µmol/g (500 mg/kg). DISCUSSION AND CONCLUSION: These findings suggest that A. pruinosum methanol extract possesses antiulcer properties as ascertained by the comparative decreases in ulcer areas, increase of mucus and NO gastric production.

[Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats].

OBJECTIVE: To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. METHODS: Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. RESULTS: Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all P<0.01), and content of NO in the compound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29±0.51) vs(10.80±0.36)nmol/ml, P<0.05). The gastric mucosal lesion index, contents of TNF, and IL-1, 2, 8 were significantly lower in all the protection groups than in the injury group (all P<0.01), and contents of IL-2 and IL-8 in the compound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17±6.56) vs(340.23±8.05)pg/ml, P<0.01; (170.82±7.31) vs(179.31±7.80)pg/ml, P<0.05). Tissue injury and inflammatory reaction in all the protection groups were obviously mitigated compared with the injury group. CONCLUSION: Compound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury.

Size-Optimized Layered Double Hydroxide Nanoparticles Promote Neural Progenitor Cells Differentiation of Embryonic Stem Cells Through the Regulation of M6A Methylation.

Purpose: The committed differentiation fate regulation has been a difficult problem in the fields of stem cell research, evidence showed that nanomaterials could promote the differentiation of stem cells into specific cell types. Layered double hydroxide (LDH) nanoparticles possess the regulation function of stem cell fate, while the underlying mechanism needs to be investigated. In this study, the process of embryonic stem cells (ESCs) differentiate to neural progenitor cells (NPCs) by magnesium aluminum LDH (MgAl-LDH) was investigated. Methods: MgAl-LDH with diameters of 30, 50, and 100 nm were synthesized and characterized, and their effects on the cytotoxicity and differentiation of NPCs were detected in vitro. Dot blot and MeRIP-qPCR were performed to detect the level of m6A RNA methylation in nanoparticles-treated cells. Results: Our work displayed that LDH nanoparticles of three different sizes were biocompatible with NPCs, and the addition of MgAl-LDH could significantly promote the process of ESCs differentiate to NPCs. 100 nm LDH has a stronger effect on promoting NPCs differentiation compared to 30 nm and 50 nm LDH. In addition, dot blot results indicated that the enhanced NPCs differentiation by MgAl-LDH was closely related to m6A RNA methylation process, and the major modification enzyme in LDH controlled NPCs differentiation may be the m6A RNA methyltransferase METTL3. The upregulated METTL3 by LDH increased the m6A level of Sox1 mRNA, enhancing its stability. Conclusion: This work reveals that MgAl-LDH nanoparticles can regulate the differentiation of ESCs into NPCs by increasing m6A RNA methylation modification of Sox1.

Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water.

Various carcinomas including skin cancer are explosively increasing in arsenicosis patients who drink arsenic-polluted well water, especially in Bangladesh. Although well drinking water in the cancer-prone areas contains various elements, very little is known about the effects of elements except arsenic on carcinogenicity. In order to clarify the carcinogenic effects of coexposure to arsenic and iron, anchorage-independent growth and invasion in human untransformed HaCaT and transformed A431 keratinocytes were examined. Since the mean ratio of arsenic and iron in well water was 1:10 in cancer-prone areas of Bangladesh, effects of 1 µM arsenic and 10 µM iron were investigated. Iron synergistically promoted arsenic-mediated anchorage-independent growth in untransformed and transformed keratinocytes. Iron additionally increased invasion in both types of keratinocytes. Activities of c-SRC and ERK that regulate anchorage-independent growth and invasion were synergistically enhanced in both types of keratinocytes. Our results suggest that iron promotes arsenic-mediated transformation of untransformed keratinocytes and progression of transformed keratinocytes. We then developed a low-cost and high-performance adsorbent composed of a hydrotalcite-like compound for arsenic and iron. The adsorbent rapidly reduced concentrations of both elements from well drinking water in cancer-prone areas of Bangladesh to levels less than those in WHO health-based guidelines for drinking water. Thus, we not only demonstrated for the first time increased carcinogenicity by coexposure to arsenic and iron but also proposed a novel remediation system for well drinking water.

Gelatin/polyethylene glycol-loaded magnesium hydroxide nanocomposite to attenuate acetylcholinesterase, neurotoxicity, and activation of GPR55 protein in rat models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease marked by mitochondrial dysfunction, amyloid-ß (Aß) aggregation, and neuronal cell loss. G-protein-coupled receptor 55 (GPR55) has been used as a promising target for insulin receptors in diabetes therapy, but GPR55's role in AD is still unidentified. Gelatin (GE) and polyethylene glycol (PEG) polymeric hydrogels are commonly used in the drug delivery system. Therefore, the aim of the present study was the preparation of magnesium hydroxide nanocomposite using Clitoria ternatea (CT) flower extract, GE, and PEG (GE/PEG/Mg(OH)2NCs) by the green precipitation method. The synthesized GE/PEG/Mg(OH)2NCs were used to determine the effect of GPR55 activation of intracerebroventricular administration on streptozotocin (ICV-STC)-induced cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive deficits. The GE/PEG/Mg(OH)2NCs were administered following bilateral ICV-STC administration (3 mg/kg) in experimental rats. Neurobehavioral assessments were performed using a Morris water maze (MWM) and a passive avoidance test (PA). Cholinergic and antioxidant activity, oxidative stress, and mitochondrial complex activity were estimated in the cortex and hippocampus through biochemical analysis. Inflammatory markers (TNF-α, IL-6, and IL-1ß) were determined using the ELISA method. Our study results demonstrated that the GE/PEG/Mg(OH)2NCs treatment significantly improved spatial and non-spatial memory functions in behavioral studies. Moreover, the treatment with GE/PEG/Mg(OH)2NCs group significantly attenuated cholinergic dysfunction, oxidative stress, and inflammatory markers, and also highly improved anti-oxidant activity (GSH, SOD, CAT, and GPx) in the cortex and hippocampus regions. The western blot results suggest the activation of the GPR55 protein expression through GE/PEG/Mg(OH)2NCs. The histopathological studies showed clear cytoplasm and healthy neurons, effectively promoting neuronal activity. Furthermore, the molecular docking results demonstrated the binding affinity and potential interactions of the compounds with the AChE enzyme. In conclusion, the GE/PEG/Mg(OH)2NCs treated groups showed reduced neurotoxicity and have the potential as a therapeutic agent to effectively target AD.

Hepatoprotective effect of combination of L-carnitine and magnesium-hydroxide in nonalcoholic fatty liver disease patients: a double-blinded randomized controlled pilot study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) still has no accepted pharmacological therapy. Even though monotherapy of L-carnitine or magnesium supplementation exhibits an essential beneficial role in NAFLD treatment, and despite that new NAFLD treatment strategies focus on combination therapies, the combination of L-carnitine with magnesium has not yet been examined in NAFLD patients. We aimed to assess the efficacy of L-carnitine in combination with magnesium in NAFLD patients. PATIENTS AND METHODS: Double-blinded, randomized controlled trial with 22 NAFLD participants who were randomized to either control group receiving placebo for the first 8 weeks and an additional 8 weeks with CIRRHOS product (2 gr L-carnitine and 150 mg magnesium) or treatment group receiving CIRRHOS product for 16 weeks. Weight, serum aspartate aminotransferase (AST), alanine transaminase (ALT) and C-reactive protein (CRP) levels were measured monthly. Lipid profile and serum insulin levels were monitored at baseline and at week 16 of treatment. Shear-wave elastography was used to evaluate liver stiffness (LS). RESULTS: While AST and ALT levels decreased progressively over 16 weeks of treatment in the treatment group, AST and ALT levels of the control group were increased modestly or unaffected. AST and ALT levels of the treatment group decreased by 25% (p=0.9) and 20% (p=0.1) respectively, compared to AST and ALT levels at baseline. However, serum CRP levels, insulin levels, lipid profile and LS were not affected by treatment. CONCLUSIONS: Our findings suggest that L-carnitine with magnesium supplementation could be a potential therapy for NAFLD. However, further studies with a larger population and high-sensitivity diagnostic parameters for early stages of NAFLD are needed to elucidate L-carnitine and magnesium efficacy in NAFLD.

Gelatin/polyvinyl alcohol loaded magnesium hydroxide nanocomposite attenuates neurotoxicity and oxidative stress in Alzheimer's disease induced rats.

Amyloid-ß (Aß) plaque formation, neuronal cell death, mitochondrial and cholinergic dysfunction are key indicators of Alzheimer's disease (AD). In this study, gelatin and polyvinyl alcohol (PVA) were tethered with magnesium hydroxide (Mg(OH)2) to synthesize nanocomposite (Ge/PVA/Mg(OH)2) through alkali co-precipitation. The characterization studies using FT-IR, XRD, DLS, and SEM-EDX confirmed the successful formation of Ge/PVA/Mg(OH)2 nanocomposite. Further, in vitro study it clearly demonstrated the impact of Ge/PVA/Mg(OH)2 nanocomposite on biocompatibility, cellular uptake, reduced Aß protein expression and protection of neuronal cell death. The confocal study further confirmed the down-regulation of Aß expression. The subsequent in vivo analysis witnessed the protective effect of Ge/PVA/Mg(OH)2 nanocomposites on the cognitive and synaptic impairments of AD in intraceribroventricular streptozotocin (ICV-STZ) treated rats. Oxidative stress, antioxidant enzymes, cholinergic and mitochondrial complex activity were conducted and revealed that the Acetylcholineesterase (AChE) and Malondialdehyde (MDA) activities were significantly decreased by contrast the antioxidant enzyme activities were found to be increased in the cortex and hippocampus regions of the brain. Thus, the present investigation recommends Ge/PVA/Mg(OH)2 nanocomposite to target AD and clinical translation.

Contribution of pH to systemic exposure of niflumic acid following oral administration of talniflumate.

PURPOSE: Systemic exposure to niflumic acid was significantly increased when talniflumate was given orally together with a meal. To clarify the underlying mechanism, an in vitro dissolution study of talniflumateonducted at different pH values, and magnesium hydroxide was co-administered in healthy volunteers. METHODS: In vitro dissolution tests of talniflumate tablets were performed in a USP Paddle apparatus at pH 1.2, 4.0, and 6.8, respectively, in the presence and absence of Tween 80 (2%). Serial samples of the talniflumate solution were taken and analyzed on a high-performance liquid chromatography (HPLC)/ultraviolet system. Healthy volunteers were divided randomly into two groups, and each volunteer received a single 740-mg dose of talniflumate, with or without 1 g of magnesium hydroxide, following an overnight fast. The plasma concentrations of niflumic acid were measured using HPLC coupled with tandem mass spectrometry. RESULTS: Talniflumate was completely insoluble at each of the tested pHs in the absence of Tween 80. The drug was slowly and steadily dissolved (54%) at pH 4 in the presence of the surfactant, but the extent of dissolution was only 15 and 0.5% at pH 1.2 and 6.0, respectively. Magnesium hydroxide co-administered with talniflumate significantly increased systemic exposure to niflumic acid: the mean maximum plasma concentration (C (max)) and area under the concentration-time curve (AUC (inf)) were augmented by 2.0- and 1.9-fold, respectively, compared with those in the absence of the antacid. Magnesium hydroxide significantly accelerated the appearance of niflumic acid in plasma by 2.8-fold. CONCLUSIONS: Magnesium hydroxide increases the rate and extent of systemic exposure to niflumic acid owing to the enhanced solubility of talniflumate and absorption of niflumic acid. The possible combination of talniflumate and an antacid should be considered in the development of pharmaceutical formulations.

Comparative study of sodium bicarbonate- and magnesium hydroxide-based gastric antacids for the effectiveness of Salmonella delivered Brucella antigens against wild type challenge in BALB/c mice.

We compared the effects of two antacid formulations based on sodium bicarbonate and magnesium hydroxide on a Salmonella-delivered oral Brucella live attenuated vaccine. We conducted a series of in vitro and in vivo experiments to investigate the pH buffering capacity, buffering longevity and the effects of these formulations on the survival of Salmonella under neutralized pH conditions and its impact on immune responses. Magnesium hydroxide had a greater, stable and prolonged buffering capacity than sodium bicarbonate and was safer when administered orally. Oral administration of sodium bicarbonate resulted in discomfort as reflected by mouse behavior and mild muscle tremors, whereas mice treated with magnesium hydroxide and PBS were completely normal. Gastric survival studies using BALB/c mice revealed that a higher number of Salmonella reached the intestine when the magnesium hydroxide-based antacid buffer was administrated. Co-administration with attenuated Salmonella secreting Brucella antigens, SodC and Omp19 along with individual antacid formulations, significantly enhanced the antigen-specific protective immune responses against virulent Brucella challenge. Together, our results indicated that the pre vaccinated oral administration of bicarbonate-citric acid or magnesium hydroxide-based neutralizing buffers significantly counteract stomach acidity by maintaining the viability of an oral enteric vaccine formulation.

Fluorescent Magnesium Hydroxide Nanosheet Bandages with Tailored Properties for Biocompatible Antimicrobial Wound Dressings and pH Monitoring.

Magnesium hydroxide (Mg(OH)2) is hailed as a cheap and biocompatible material with antimicrobial potential; however, research aimed at instilling additional properties and functionality to this material is scarce. In this work, we synthesized novel, fluorescent magnesium hydroxide nanosheets (Mg(OH)2-NS) with a morphology that closely resembles that of graphene oxide. These multifunctional nanosheets were employed as a potent antimicrobial agent against several medically relevant bacterial and fungal species, particularly on solid surfaces. Their strong fluorescence signature correlates to their hydroxide makeup and can therefore be used to assess their degradation and functional antimicrobial capacity. Furthermore, their pH-responsive change in fluorescence can potentially act as a pH probe for wound acidification, which is characteristic of healthy wound healing. These fluorescent antimicrobial nanosheets were stably integrated into biocompatible electrospun fibers and agarose gels to add functionality to the material. This reinforces the suitability of the material to be used as antimicrobial bandages and gels. The biocompatibility of the Mg(OH)2-NS for topical medical applications was supported by its noncytotoxic action on human keratinocyte (HaCaT) cells.

Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome.

Adjuvants are vaccine additives that stimulate the immune system without having any specific antigenic effect of itself. In this study we show that alum adjuvant induces the release of IL-1beta from macrophages and dendritic cells and that this is abrogated in cells lacking various NALP3 inflammasome components. The NALP3 inflammasome is also required in vivo for the innate immune response to OVA in alum. The early production of IL-1beta and the influx of inflammatory cells into the peritoneal cavity is strongly reduced in NALP3-deficient mice. The activation of adaptive cellular immunity to OVA-alum is initiated by monocytic dendritic cell precursors that induce the expansion of Ag-specific T cells in a NALP3-dependent way. We propose that, in addition to TLR stimulators, agonists of the NALP3 inflammasome should also be considered as vaccine adjuvants.

Encapsulation of curcumin into layered double hydroxides improve their anticancer and antiparasitic activity.

OBJECTIVES: Curcumin (CUR) has well-known activity against cancer cells and parasites; however, its applications are limited since this is an unstable molecule, which may suffer degradation by light and temperature, also, the low water solubility reduce its bioavailability. Layered double hydroxides (LDH) are well-known materials owing to the excellent anion exchange capacity, good biocompatibility and low toxicity. METHODS: Layered double hydroxides nanoparticles prepared with zinc and magnesium cations were used as a vehicle for CUR in Caco-2, Giardia lamblia and Entamoeba histolytica cultures. The physicochemical properties of Mg-LDH-CUR and Zn-LDH-CUR were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectrometry (FTIR) and X-ray powder diffraction (XRD). Additionally, the load efficiency, release profiles and photostability of CUR were quantified by high-performance liquid chromatography (HPLC) and UV-Vis spectrometry. Then, Mg-LDH-CUR and Zn-LDH-CUR were tested on Caco-2, G. lamblia and E. histolytica cultures. KEY FINDINGS: The experiments demonstrated that Zn-LDH-CUR protects better against photodegradation by UV light, while Mg-LDH-CUR showed increased toxicity against Caco-2 cell, G. lamblia and E. histolytica, in comparison with free CUR. CONCLUSIONS: Layered double hydroxides are good vehicles to improve stability, resistance to degradation of CUR, also they are useful to improve solubility, provide a controlled release and improve the cytotoxic activity. Additionally, it was shown that the composition of the M+2 cation of LDH affects its properties and structure and that this directly influences its biological activity. The findings are important to select the composition of the encapsulation vehicle for a specific activity.

Enhanced mechanical and biological characteristics of PLLA composites through surface grafting of oligolactide on magnesium hydroxide nanoparticles.

Poly(l-lactic acid) (PLLA) is a biocompatible and biodegradable polymer that has received much attention as a biomedical material. However, PLLA also produces by-products that acidify the surrounding tissues during in vivo degradation, which induces inflammatory responses. To overcome these problems, magnesium hydroxide nanoparticles (nano-magnesium hydroxide; nMH) were added to the PLLA matrix as a bioactive filler that can suppress inflammatory responses by neutralizing the acidified environment caused by the degradation of PLLA. Despite the advantages of nMH, the strong cohesion of these nanoparticles toward each other makes it difficult to manufacture a polymer matrix containing homogeneous nanoparticles through thermal processing. Here, we prepared two types of surface-modified nMH with oligolactide (ODLLA) utilizing grafting to (GT) and grafting from (GF) strategies to improve the mechanical and biological characteristics of the organic-inorganic hybrid composite. The incorporation of surface-modified nMH not only enhanced mechanical properties, such as Young's modulus, but also improved homogeneity of magnesium hydroxide particles in the PLLA matrix due to the increase in interfacial interaction. Additionally, the PLLA composites with surface-modified nMH exhibited reduced bulk erosion during hydrolytic degradation with lower cytotoxicity and immunogenicity. Hemocompatibility tests on the PLLA composites with nMH showed a higher albumin to fibrinogen ratio (AFR) and a lower influence of platelet activation, when compared with unmodified control samples. Taken all together, the surface-modified nMH could be seen to successfully improve the physical and biological characteristics of polymer composites. We believe this technology has great potential for the development of hybrid nanocomposites for biomedical devices, including cardiovascular implants.

Enhanced bactericidal activity of brucite through partial copper substitution.

Brucite Mg(OH)2 belongs to a family of two-dimensional compounds with a CdI2-type structure built up from layers of edge-sharing octahedra delineating 2D galleries. In the current study, nanometer-sized platelets of copper substituted Mg(OH)2 were prepared by co-precipitation at room temperature in mixed alkaline (NaOH/Na2CO3) medium. Very weak substitution of a few hydroxyl ions by carbonate groups was highlighted at first by infrared spectroscopy and then quantified by thermogravimetric (TG) and mass spectrometric (MS) evolved gas analyses. The presence in a very low amount of water molecules in the galleries induces disorder in the stacking of layers of edge-sharing octahedra along the c-axis. The dehydration of the hydroxides taking place below 225 °C preserves the brucite-type structure of the samples while suppressing the stacking disorder. Copper substitution greatly enhances the bactericidal activity of nanometer-sized platelets of brucite against two bacteria frequently involved in healthcare-associated-infections. 10 mol% of cupric ions in Mg(OH)2 (a copper loading of 0.102 mg mL-1 in the suspension) were sufficient to induce, after 3 h in contact, 100% and 99.3% reductions in viability of Gram-negative E. coli and Gram-positive S. aureus, respectively (reductions as low as 23% and 48% are reported for the parent compound Mg(OH)2 in the same conditions). A good compromise between fast bactericidal kinetics and a high reduction in viability is reached by the 15 mol% copper-substituted Mg(OH)2 hydroxide. Its use gives the opportunity to five-fold reduce the copper loading of the bactericidal agent while being at least equally or even more efficient compared to the conventional CuO (a Cu loading of 0.799 mg mL-1 and 0.154 mg mL-1 in the suspension of CuO and 15 mol% copper substituted Mg(OH)2 particles, respectively).