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The rapid evolution of antimicrobial resistant genes (AMRs) in water resources is well correlated to the persistent occurrence of ciprofloxacin in water. For the first time, encapsulated nanoscale zerovalent iron (nZVI) with a shell of magnesium hydroxide (Mg/Fe0) was used to adsorb ciprofloxacin from water. Optimization of the removal conditions exhibited that 5% was the optimum mass ratio between magnesium hydroxide and nZVI [Mg(OH)2/nZVI)] as more than 96% of 100 mg L−1 of ciprofloxacin was removed. In addition, 0.5 g L−1 of Mg/Fe0 showed an extraordinary performance in removing ciprofloxacin over a wide range of pH (3–11) with removal efficiencies exceeded 90%. Kinetic analysis displayed that the kinetic data was well described by both Pseudo first-order and second-order models. Also, the equilibrium data was well fitted by Freundlich isotherm model. In addition, thermodynamic analysis evidenced that the removal of ciprofloxacin by Mg/Fe0 was exothermic, and spontaneous. The experiments also revealed that physisorption and chemisorption were the responsible mechanisms for ciprofloxacin removal. The proposed treatment system remediated 10 litters of 100 mg L−1 of ciprofloxacin solution with 100% overall removal efficiency. This treatment system could be a promising and practical solution to decrease ciprofloxacin concentration in different water bodies.

Based on the promising biomedical developments in wound healing strategies, herein, a new nanobiocomposite scaffold was designed and presented by incorporation of carboxymethyl cellulose hydrogels prepared using epichlorohydrin as a cross-linking agent (CMC hydrogel), a natural silk fibroin (SF) protein, and magnesium hydroxide nanoparticles (Mg(OH)2 NPs). Biological evaluation of the CMC hydrogel/SF/Mg(OH)2 nanobiocomposite scaffold was conducted via in vitro cell viability assays and in vivo assays, red blood cell hemolysis, and antibiofilm assays. Considering the cell viability percentage of Hu02 cells (84.5%) in the presence of the prepared nanobiocomposite after 7 days, it was indicated that this new nanoscaffold was biocompatible. The signs of excellent hemocompatibility and the high antibacterial activity were observed due to the low-point hemolytic effect (8.3%) and high-level potential in constraining the P. aeruginosa biofilm formation with a low OD value (0.13). Moreover, in vivo wound healing assay results indicated that the wound healing method was faster in mice treated with the prepared nanobiocomposite scaffold (82.29%) than the control group (75.63%) in 12 days. Apart from the structural characterization of the CMC hydrogel/SF/Mg(OH)2 nanobiocomposite through FTIR, EDX, FESEM, and TG analyses, compressive mechanical tests, contact angle, porosity, and swelling ratio studies indicated that the combination of the CMC hydrogel structure with SF protein and Mg(OH)2 NPs could significantly impact Young's modulus (from 11.34 to 10.14 MPa), tensile strength (from 299.35 to 250.78 MPa), elongation at break (12.52 to 12.84%), hydrophilicity, and water uptake capacity (92.5%).

Introduction Increasing dialysate magnesium (D-Mg2+) appears to be an intriguing strategy to obtain cardiovascular benefits in subjects with end-stage kidney disease (ESKD) on hemodialysis. To date, however, hemodialysis guidelines do not suggest to increase D-Mg2+ routinely set at 0.50 mmol/L. Methods A randomized 4-week crossover study aimed at investigating the consequences of increasing D-Mg2+ from 0.50 to 0.75 mmol/L on arterial stiffness, hemodynamic profile, and endothelial function in subjects undergoing hemodialysis. The long-term effect of higher D-Mg2+ on mineral metabolism markers was investigated in a 6-month follow-up. Data were analyzed by linear mixed models for repeated measures. Results Data of 39 patients were analyzed. Pulse wave velocity and pulse pressure significantly decreased on the higher D-Mg2+ compared with the standard one by − 0.91 m/s (95% confidence interval − 1.52 to − 0.29; p = 0.01) and − 9.61 mmHg (− 18.89 to − 0.33, p = 0.04), respectively. A significant reduction in systolic blood pressure of − 12.96 mmHg (− 24.71 to − 1.22, p = 0.03) was also observed. No period or carryover effects were observed. During the long-term follow-up phase the higher D-Mg2+ significantly increased ionized and total serum Mg (respectively from 0.54 to 0.64 and from 0.84 to 1.07 mmol/L; mean percentage change from baseline to follow-up + 21% and + 27%; p ≤ 0.001), while parathormone (PTH) decreased significantly (from 36.6 to 34.4 pmol/L; % change − 11%, p = 0.03). Conclusions Increasing dialysate magnesium improves vascular stiffness in subjects undergoing maintenance hemodialysis. The present findings merit a larger trial to evaluate the effects of 0.75 mmol/L D-Mg2+ on major clinical outcomes. Trial Registration The study was retrospectively registered on the ISRCTN registry (ISRCTN 74139255) on 18 June 2020.

The silver, magnesium oxide and gyrotactic microorganism-based hybrid nanofluid flow inside the conical space between disc and cone is addressed in the perspective of thermal energy stabilization. Different cases have been discussed between the spinning of cone and disc in the same or counter wise directions. The hybrid nanofluid has been synthesized in the presence of silver Ag and magnesium oxide MgO nanoparticulate. The viscous dissipation and the magnetic field factors are introduced to the modeled equations. The parametric continuation method (PCM) is utilized to numerically handle the modeled problem. Magnesium oxide is chemically made up of Mg2+ and O2- ions that are bound by a strong ionic connection and can be made by pyrolyzing Mg(OH)2 (magnesium hydroxide) and MgCO3 (magnesium carbonate) at high temperature (700–1500 °C). For metallurgical, biomedical and electrical implementations, it is more efficient. Similarly, silver nanoparticle's antibacterial properties could be employed to control bacterial growth. It has been observed that a circulating disc with a stationary cone can achieve the optimum cooling of the cone-disk apparatus while the outer edge temperature remains fixed. The thermal energy profile remarkably upgraded with the magnetic effect, the addition of nanoparticulate in base fluid and Eckert number.

Background and Aims. Hydrotalcite plays an important role in the therapy of gastric ulcer induced by nonsteroidal anti-inflammatory drugs (NSAIDs), but little is known about the mechanism. We designed two experiments to study the preventive and curative effects of hydrotalcite on NSAIDs-related gastric injury in rats and to investigate the relationship between the protective and curative mechanism of hydrotalcite and the secretion of epidermal growth factor (EGF)/prostaglandin E2 (PGE2).Methods. Two experiments were separately designed to evaluate the preventive and curative effects of hydrotalcite. A total of 25 male rats and 25 female rats were randomly divided into five groups (vehicle group, model group, omeprazole group, hydrotalcite group, and ranitidine group) in each experiment. Rats were treated with indomethacin by gavage to build the model of acute gastric mucosal injury. The concentrations of EGF and PGE2 in blood specimens and mucosal injury indexes by gross inspection were measured and an immunohistochemical technique was also employed to test the levels of EGF, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) in gastric mucosa.Results. Comparing with model group in both preventive and curative experiments, hydrotalcite decreased the gastric injury in the mucosa of stomach significantly (7±4.5 vs. 16±11.25, 1.5±2 vs. 2.5±6;P, PPPP, PConclusions. Hydrotalcite promotes gastric protection and healing via several mechanisms, including increased levels of PGE2 in blood serum, activation of EGF, and antagonising the inhibition of cyclooxygenase (COX) caused by NSAIDs.

Doxycycline (DOX) and amoxicillin (AMOX) are important Broad-spectrum antibiotics used in treating multiple human and animal diseases. For the sake of exploring novel medical applications, both antibiotics were loaded into magnesium aluminium layer double hydroxide (Mg-Al)/LDH nanocomposite through the co-precipitation method. The synthesized materials were characterized by XRD, FT-IR, particle size analysis, FESEM and HRTEM. Acute toxicological studies were conducted using median lethal dose LD50, where a total number of 98 rats (200–150 gm) of both sexes were used. An experimental wound was aseptically incised on the anterior-dorsal side of each rat, while 98% of pure medical ethanol was used for ulcer induction. Acute toxicity, wound closure rate, healing percentages, ulcer index, protective rate and histopathological studies were investigated. Antibiotic Nanocomposites has significantly prevented ulcer formation and improved wound healing process to take shorter time than that of the typical processes, when compared with that of same drugs in microscale systems or commercial standard drugs. These results were confirmed by the histopathological findings. By converting it into the Nanoform, which is extremely important, especially with commonly used antibiotics, novel pharmacological properties were acquired from the antibiotics. The safe uses of DOX/LDH and AMOX/LDH Nanocomposites in this study were approved for biomedical applications.

Two clinical studies were performed in healthy volunteers to investigate food and antacid effects on lesinurad, a novel selective uric acid reabsorption inhibitor approved for treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors. Study 1 evaluated a high-fat, high-calorie meal or high doses of antacids (3000 mg calcium carbonate or 1600 mg magnesium hydroxide/1600 mg aluminum hydroxide) on the pharmacokinetics (PK) and pharmacodynamics (PD) of 400 mg oral lesinurad. Study 2 evaluated low doses of antacids (1250 mg calcium carbonate or 800 mg magnesium hydroxide/800 mg aluminum hydroxide) on the PK and PD of 400 mg lesinurad. Food did not alter the plasma AUC of lesinurad and only reduced its Cmax by 18%. In the fasted conditions, high-dose calcium carbonate reduced the Cmax and AUC of lesinurad by 54% and 38%, respectively, whereas high-dose magnesium hydroxide/aluminum hydroxide reduced Cmax and AUC by 36% and 31%, respectively. Food enhanced the maximum serum urate (sUA)-lowering effect of lesinurad by approximately 20% despite reducing the Cmax of lesinurad. High-dose calcium carbonate decreased the urate-lowering effect approximately 20% in the first 6 hours, whereas high-dose magnesium hydroxide/aluminum hydroxide reduced the effect by 26%. Low-dose calcium carbonate or magnesium hydroxide/aluminum hydroxide in the presence of food did not significantly affect plasma lesinurad Cmax and AUC or the sUA lowering and renal handling of uric acid. In summary, study results suggest food did not meaningfully alter lesinurad PK and PD. High doses of antacids reduced lesinurad AUC up to 40% and reduced the lesinurad uric acid-lowering effect.

Current approaches of biomaterials for the repair of critical-sized bone defects still require immense effort to overcome numerous obstacles. The biodegradable polymer-based scaffolds have been required to expand further function for bone tissue engineering. Poly(lactic-co-glycolic) acid (PLGA) is one of the most common biopolymers owing to its biodegradability for tissue regenerations. However, there are major clinical challenges that the byproducts of the PLGA cause an acidic environment of implanting site. The critical processes in bone repair are osteogenesis, angiogenesis, and inhibition of excessive osteoclastogenesis. In this study, the porous PLGA (P) scaffold was combined with magnesium hydroxide (MH, M) and bone-extracellular matrix (bECM, E) to improve anti-inflammatory ability and osteoconductivity. Additionally, the bioactive polydeoxyribonucleotide (PDRN, P) was additionally incorporated in the existing PME scaffold. The prepared PMEP scaffold has pro-osteogenic and pro-angiogenic effects and inhibition of osteoclast due to the PDRN, which interacts with the adenosine A2A receptor agonist that up-regulates expression of vascular endothelial growth factor (VEGF) and down-regulates inflammatory cytokines. The PMEP scaffold has superior biological properties for human bone-marrow mesenchymal stem cells (hBMSCs) adhesion, proliferation, and osteogenic differentiation in vitro. Moreover, the gene expressions related to osteogenesis and angiogenesis of hBMSCs increased and the inflammatory factors decreased on the PMEP scaffold. In conclusion, it provides a promising strategy and clinical potential candidate for bone tissue regeneration and repairing bone defects.

Poly(L-lactic acid) (PLLA) has been used as a biodegradable vascular scaffold (BVS) material due to high mechanical property, biodegradability, and biocompatibility. However, acidic byproducts from hydrolysis of PLLA reduce the pH after the surrounding implanted area and cause inflammatory responses. As a result, severe inflammation, thrombosis, and in-stent restenosis can occur after implantation by using BVS. Additionally, polymers such as PLLA could not find on X-ray computed tomography (CT) because of low radiopacity. To this end, here, we fabricated PLLA films as the surface of BVS and divided PLLA films into two coating layers. At the first layer, PLLA film was coated by 2,3,5-triiodobenzoic acid (TIBA) and magnesium hydroxide (MH) with poly(D,L-lactic acid) (PDLLA) for radiopaque and neutralization of acidic environment, respectively. The second layer of coated PLLA films is composed of polydopamine (PDA) and then cystamine (Cys) for the generation of nitric oxide (NO) release, which is needed for suppression of smooth muscle cells (SMCs) and proliferation of endothelial cells (ECs). The characterization of the film surface was conducted via various analyses. Through the surface modification of PLLA films, they have multifunctional abilities to overcome problems of BVS effectively such as X-ray penetrability, inflammation, thrombosis, and neointimal hyperplasia. These results suggest that the modification of biodegradable PLLA using TIBA, MH, PDA, and Cys will have important potential in implant applications.

GLP-1 receptor agonists are a class of diabetes medicines offering self-regulating glycemic efficacy and may best be administrated in long-acting forms. Among GLP-1 receptor agonists, exenatide is the one requiring the least dose so that controlled-release poly(d, l-lactic-co-glycolic acid) (PLGA) microspheres may best achieve this purpose. Based on this consideration, the present study extended the injection interval of exenatide microspheres from one week of the current dosage form to four weeks by simply blending Mg(OH)2 powder within the matrix of PLGA microspheres. Mg(OH)2 served as the diffusion channel creator in the earlier stage of the controlled-release period and the decelerator of the self-catalyzed degradation of PLGA (by the formed lactic and glycolic acids) in the later stage due to its pH-responsive solubility. As a result, exenatide gradually diffused from the microspheres through Mg(OH)2-created diffusion channels before degradation of the PLGA matrix, followed by a mild release due to Mg(OH)2-buffered degradation of the polymer skeleton. In addition, an extruding–settling process comprising squeezing the PLGA solution through a porous glass membrane and sedimentation-aided solidification of the PLGA droplets was used to prepare the microspheres to ensure narrow size distribution and 95% encapsulation efficiency in an aqueous continuous phase. A pharmacokinetic study using rhesus monkey model confirmed the above formulation design by showing a steady blood concentration profile of exenatide with reduced CMAX and dosage form index. Mg·(OH)2

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.

Bullo Saifullah,1,2 Palanisamy Arulselvan,3,4 Mohamed E El Zowalaty,3,5 Woan Sean Tan,3 Sharida Fakurazi,6 Thomas J Webster,7 Rabia Baby,1 Mohd Zobir Hussein1 1Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Department of Management Sciences and Technology, The Begum Nusrat Bhutto Women University Sukkur, Sukkur, Sindh, 65170, Pakistan; 3Laboratory for Vaccine and Immunotherapeutics, Institute of Biosciences, University Putra Malaysia, Serdang, Selangor, 43400, Malaysia; 4Muthayammal Centre for Advanced Research, Muthayammal College of Arts and Science, Namakkal, Tamil Nadu, 637408, India; 5Zoonosis Science Center, Department of Microbiology and Immunology, Uppsala University, Uppsala, Sweden; 6Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 7Department of Chemical Engineering, Northeastern University, Boston, MA, USACorrespondence: Mohd Zobir HusseinMaterials Synthesis and Characterization Laboratory, Institute of Advanced Technology, (ITMA), Universiti Putra Malaysia, Serdang, Selangor, MalaysiaTel +60 397698092Email mzobir@upm.edu.myIntroduction: Mycobacterium tuberculosis infections are associated with severe local inflammatory reactions, which may be life-threatening and lead to tuberculosis pathogenesis and associated complications. Inorganic nanolayers have been vastly exploited for biomedical applications (especially in drug delivery) because of their biocompatible and biodegradable nature with the ability to release a drug in a sustained manner. Herein, we report a new nanodelivery system of inorganic nanolayers based on magnesium layered hydroxides (MgLH) and a successfully intercalated anti-tuberculosis drug para-aminosalicylic acid (PAS).Methods: The designed anti-tuberculosis nanodelivery composite, MgLH-PAS, was prepared by a novel co-precipitation method using MgNO3 as well MgO as starting materials.Results: The designed nano-formulation, PAS-MgLH, showed good antimycobacterial and antimicrobial activities with significant synergistic anti-inflammatory effects on the suppression of lipopolysaccharide (LPS) stimulated inflammatory mediators in RAW 264.7 macrophages. The designed nano-formulation was also found to be biocompatible with human normal lung cells (MRC-5) and 3T3 fibroblast cells. Furthermore, the in vitro release of PAS from PAS-MgLH was found to be sustained in human body simulated phosphate buffer saline (PBS) solutions of pH 7.4 and pH 4.8.Discussion: The results of the present study are highly encouraging for further in vivo studies. This new nanodelivery system, MgLH, can be exploited in the delivery of other drugs and in numerous other biomedical applications as well.Keywords: Mycobacterium tuberculosis, magnesium layered hydroxides, biomaterial, sustained release, anti-tuberculosis, anti-inflammatory

Objective: To study the profile and the therapeutic response of patients with laryngopharyngeal reflux (LPR) at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) according to the initial pepsin saliva concentration. Methods: From January 2018 to January 2020, patients with positive LPR diagnosis at the HEMII-pH were consecutively recruited from 3 European Hospitals. Saliva pepsin concentration (Peptest™) was measured during the HEMII-pH testing period and patients were classified into 2 groups: negative versus positive Peptest. The clinical outcomes, that is, gastrointestinal and HEMII-pH findings, reflux symptom score-12 (RSS-12), and 3-month therapeutic response, were compared between groups. Results: A total of 124 patients completed the study. Among them, 30 patients had negative Peptest. Pharyngeal reflux events occurred outside 1-hour post-meal time in 74.0%, after the meals in 20.5% and nighttime in 5.5%. The pepsin saliva level was not significantly associated with the reflux events preceding the sample collection. Patients with positive Peptest had better improvement of RSS-12 digestive and respiratory subscores and oral, pharyngeal, and laryngeal findings compared with patients with negative Peptest. Conclusion: Patients with high saliva pepsin concentration had no stronger gastrointestinal, HEMII-pH, or clinical outcomes compared with those with low or undetectable saliva pepsin concentration.

Almagate (aluminium-magnesium hydroxycarbonate hydrate) is a widely used antacid in Spain as an over-the-counter formulation. However, data on the control of acidity in patients with gastroesophageal reflux disease (GERD) are scarce. Herein we report a post-hoc analysis of a randomized crossover double-blind trial (ALR-006; data on file), in which equivalent single oral doses (1.5 g) of two formulations of almagate (AlmaxRetard® and Almax®, Laboratorios Almirall, Barcelona, Spain) were both effective for reflux esophagitis.

Although drug-eluting stents (DESs) are mainly coated with biodegradable polymers such as PLGA and PLLA, their acidic degradation products can alter the local microenvironment and affect the homeostasis of adjacent tissue. Previously, we developed anti-inflammatory PLGA-based materials including magnesium hydroxide (MH) to relieve the side effects caused by PLGA degradation. However, the underlying molecular mechanism of its protective effects has not yet been clarified. Here, we demonstrated the pathological mechanism of vascular endothelial activation caused by PLGA by-products. The PLGA by-products accumulated in HCAECs through MCT1, followed by oxidative stress and the activation of the MAPK/NF-κB signaling pathway. Finally, the PLGA by-products increased the expression of VCAM-1 as well as the secretion of proinflammatory cytokines. However, the addition of MH particles significantly diminished the activation of this molecular pathway and the expression of inflammation-related factors induced by acidic PLGA degradation products. Furthermore, Mg2+ released from MH particles restored endothelial function in both intracellular and extracellular spaces. Taken together, MH particles prevent the accumulation of PLGA degradation products in HCAECs, thereby repressing the associated vascular endothelial activation. These findings on the biochemical mechanisms are expected to provide important clues for addressing the safety issues in nearly all biodegradable polymer-based implants.

Fibroblast-derived extracellular matrix (fECM)-supported scaffolds made up of poly(lactic-co-glycolic acid) were prepared with the enhanced preservation of ECM components by composites with magnesium hydroxide nanoparticles (MH NPs), and were applied for the renal tissue regeneration. MH NP utilization resulted in an increased ECM protein amount, decreased scaffold degradation, and surface hydrophilic modification. These effects were correlated with the improved adhesion and viability of renal proximal tubule epithelial cells on the scaffold. In vivo experiments demonstrated effects of fECM and MH NPs on renal regeneration. The number of glomeruli was the largest in the ECM scaffold with MH NPs as compared to the pristine scaffold and ECM scaffold without MH NPs. Quantitative PCR analysis exhibited less inflammation (IL-1β, TNF-α, and IL-6) and fibrosis-related (vimentin, collagen I, and α-SMA) markers, whereas opposite results were found in regeneration-related markers (Pax2, vWf, Wt1, and Emx2). The concentration of renal function-related molecules, creatinine and blood urea nitrogen diminished in the ECM scaffold with MH NPs. All results indicate that MH NPs utilization for the renal regenerative scaffold is effective for in vitro and in vivo environments and is, therefore, a good model for regeneration of kidneys and other tissues, and organs.

Objective The 13C-urea breath test (UBT) is the most widely used non-invasive diagnostic test for Helicobacter pylori. Debate continues to surround the possible interference of antacid intake on its result. This study aims to confirm the non-interference of almagate in the determination of H. pylori by UBT. Patients and methods Observational, multicentre study in adult patients treated with almagate in whom a UBT (TAUKIT®) was indicated. When the UBT result was negative, use of almagate was stopped for 30 days and the UBT was repeated. When the result was positive, no further determinations were made. The primary endpoint was the percentage of patients who, having had a negative result in the first breath test, were positive in the second after having stopped taking almagate (UBT false negatives, possibly attributable to almagate). Results Of the 167 evaluable patients, 59% were female, average age was 49 and 97% had gastrointestinal symptoms. The result of the first UBT was negative in 71% of cases. Of these, in the second UBT test after stopping the almagate, the negative result was confirmed in 97.5%. Out of the total number of cases evaluated, the rate of false negatives was 1.8%. Conclusions Taking almagate has minimal or no interference in the result of UBT for the diagnosis of H. pylori infection. It can therefore be used in the weeks prior to a UBT.

To investigate the effect of simulated weightlessness on the pharmacokinetics of orally administered moxifloxacin and the antacid Maalox or the antidiarrheal Pepto-Bismol using a tail-suspended (TS) rat model of microgravity. Fasted control and TS, jugular-vein-cannulated, male Sprague-Dawley rats received either a single 5 mg/kg intravenous dose or a single 10 mg/kg oral dose of moxifloxacin alone or with a 0.625 mL/kg oral dose of Maalox or a 1.43 mL/kg oral dose of Pepto-Bismol. Plasma concentrations of moxifloxacin were measured by HPLC. Pharmacokinetic data were analyzed using WinNonlin. Simulated weightlessness had no effect on moxifloxacin disposition after intravenous administration but significantly decreased the extent of moxifloxacin oral absorption. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. In contrast, the coadministration of moxifloxacin with Pepto-Bismol to TS rats had no significant effect on either the rate or the extent of moxifloxacin absorption. These interactions showed dose staggering when oral administrations of Pepto-Bismol and moxifloxacin were separated by 60 min in control rats but not in TS rats. Dose staggering was more apparent after the coadministration of Maalox and moxifloxacin in TS rats.

Osteonecrosis of femoral head (ONFH) has been one of the most common diseases, and thus the development of novel biomaterials with superior osteogenic ability is the key issue. In this work, Yb-containing MgAl-layered double hydroxide (LDH) monolayer nanosheets (MgAlYb-LDHs) were designed and synthesized and were used as a new biomaterial with outstanding osteogenic differentiation ability. The LDH monolayer nanosheets gave a high loading content (LC) of 197% for alendronate (AL) with an encapsulation efficiency (EE) of 98.6%. Notably, outstanding in vitro osteogenic differentiation performance of MgAlYb-LDHs was demonstrated in the transcriptional level of Collagen I, with a 3000-fold enhancement compared with the blank control. For in vivo tests with rabbits, the total volume of bone regeneration after treatment with the LDH group was 2.77 and 1.41 times larger than that with the negative control group and positive control group (autologous bone graft, clinical gold standard) at 8 weeks postoperatively. In addition, with the degradation of AL/LDHs, the bone mass density (BMD) of the femoral head increased by 1.52 times compared with that for the positive control group at 8 weeks postoperatively. Therefore, this work provides a new perspective for the design and preparation of 2D monolayer MgAlYb-LDHs and their drug formulation (AL/LDHs), which show great promise in ONFH accompanied by osteoporosis.

Drug-eluting stents (DESs) have been widely used as a treatment approach for coronary artery diseases. Generally, conventional DESs were fully covered with drugs and biodegradable polymers on both abluminal and luminal layers (i.e., conformal coating). However, uncontrolled drug release from the luminal drug-coating layer of the stent is known to inhibit re-endothelialization. Furthermore, the acidification of the surrounding tissue by the decomposed coating polymer causes inflammation, resulting in restenosis and late thrombosis. To overcome these limitations, here we demonstrated a functional DES coated with poly(lactic-co-glycolic acid) (PLGA), sirolimus (SRL), and magnesium hydroxide (Mg(OH)2, MH) precisely only on the abluminal layer. The acidic neutralization effect of MH was elucidated by measuring the pH change of the fabricated film in PBS solution. In an in vitro cell study, the stent coated with MH exhibited higher compatibility with human coronary artery endothelial cells (ECs) and a lower inflammation score as compared to the control stent. Finally, in an in vivo large porcine model, the abluminal coated DES with SRL and MH showed excellent re-endothelialization and anti-inflammatory and anti-thrombotic effects. In conclusion, it is believed that this approach has great potential for the development of functional DES for the treatment of cardiovascular diseases.

Artificial scaffolds made up of various synthetic biodegradable polymers have been reported to have many advantages including cheap manufacturing, easy scale up, high mechanical strength, convenient manipulation, and molding into an unlimited variety of shapes. However, the synthetic biodegradable polymers still have the insufficiency for cartilage regeneration owing to their acidic degradation products. To reduce acidification by degradation of synthetic polymers, we incorporated magnesium hydroxide (MH) nanoparticles into porous polymer scaffold not only to effectively neutralize the acidic hydrolysate but also to minimize the structural disturbance of scaffolds. The neutralization effect of poly(D,L-lactic-co-glycolic acid; PLGA)/MH scaffold was confirmed with the maintenance of neutral pH, contrary to a PLGA scaffold with low pH. Further, the scaffolds were applied to evaluate the chondrogenic differentiation of the human bone marrow mesenchymal stem cells. In in vitro study, the PLGA/MH scaffold enhanced the chondrogenesis markers and reduced the calcification, compared to the PLGA scaffold. Additionally, the PLGA/MH scaffold reduced the release of inflammatory cytokines, compared to the PLGA scaffold, as the cell death decreased. Moreover, the addition of MH reduced necrotic cell death at the early stage of chondrogenic differentiation. Further, the necrotic cell death by the PLGA scaffold was mediated by cleavage of caspase-1, the so-called interleukin 1-converting enzyme, and MH alleviated it as well as nuclear factor kappa B expression. Furthermore, the PLGA/MH scaffold highly supported chondrogenic healing of rat osteochondral defect sites in in vivo study. Therefore, it was suggested that a synthetic polymer scaffold containing MH could be a novel healing tool to support cartilage regeneration and further treatment of orthopedic patients. Statement of Significance Synthetic polymer scaffolds have been widely utilized for tissue regeneration. However, they have a disadvantage of releasing acidic products through degradation. This paper demonstrated a novel type of synthetic polymer scaffold with pH-neutralizing ceramic nanoparticles composed of magnesium hydroxide for cartilage regeneration. This polymer showed pH-neutralization property during polymer degradation and significant enhancement of chondrogenic differentiation of mesenchymal stem cells. It reduced not only chondrogenic calcification but also release of proinflammatory cytokines. Moreover, it has an inhibitory effect on necrotic cell death, particularly caspase-1-mediated necrotic cell death (pyroptosis). In in vivo study, it showed higher healing rate of the damaged cartilage in a rat osteochondral defect model. We expected that this novel type of scaffold can be effectively applied to support cartilage regeneration and further treatment of orthopedic patients.

Biodegradable polymers have been extensively used in biomedical applications, ranging from regenerative medicine to medical devices. However, the acidic byproducts resulting from degradation can generate vigorous inflammatory reactions, often leading to clinical failure. We present an approach to prevent acid-induced inflammatory responses associated with biodegradable polymers, here poly(lactide- co-glycolide), by using oligo(lactide)-grafted magnesium hydroxide (Mg(OH)2) nanoparticles, which neutralize the acidic environment. In particular, we demonstrated that incorporating the modified Mg(OH)2 nanoparticles within degradable coatings on drug-eluting arterial stents efficiently attenuates the inflammatory response and in-stent intimal thickening by more than 97 and 60%, respectively, in the porcine coronary artery, compared with that of drug-eluting stent control. We also observed that decreased inflammation allows better reconstruction of mouse renal glomeruli in a kidney tissue regeneration model. Such modified Mg(OH)2 nanoparticles may be useful to extend the applicability and improve clinical success of biodegradable devices used in various biomedical fields.

The highly acidic nature of the gastric fluids inside the human stomach can cause have health problems in certain individuals e.g., acid reflux and ulcers. Antacid-loaded biopolymer microgels can be used to control the acidity of the gastric fluids, which may be useful for developing functional foods to treat these problems. In this study, the impact of biopolymer microgel dimensions and composition on the dissolution rate of encapsulated antacid was determined under simulated gastric conditions. The microgels were formed by injecting antacid (magnesium hydroxide) and biopolymers (alginate or alginate/pectin) into a calcium chloride solution to promote cross-linking. Microgels of varying dimensions were formed using either a hand-held syringe or a vibrating nozzle encapsulation device with different nozzle sizes. The rate of antacid dissolution was measured using an automatic titration device (pH stat) that added HCl solution into the simulated gastric fluids to maintain a constant pH of 2.5. The antacid dissolution rate decreased with increasing microgel diameter (300 to 1660 μm) and decreasing pore size (0.8 to 2.0% alginate). The slowest dissolution rate was observed in microgels containing 80% alginate and 20% pectin, which may have been due to the impact of biopolymer composition on bead dimensions and pore size. The results of this study may be useful for the design of biopolymer microgels that can control the release of antacids in the stomach, thereby leading to better control over the pH of the gastric fluids.

This study proposed and validated a method integrating in situ hydrotalcite precipitation (Virtual Curtain™ (VC) technology) with bioprocess for treating a cyanide (CN)-augmented (ca. 5 mg-CN L−1) sulfate-laden neutral mine drainage, from a waste rock dump (WD2) of an Australian gold mine. Efficacies of various carbon (C) sources (ethanol, lactate, and two natural substrates; Eucalyptus wood sawdust (EW) and Typha biomass (TB)) for promoting microbial reduction in both: CN-augmented WD2 water and VC-treated CN-augmented WD2 water were assessed in a 60-days microcosms study at 30 °C. The microcosms were monitored over time for pH, redox potential, dissolved hydrogen sulfide, chloride, nitrite, nitrate, sulfate, phosphate, biogas production, dissolved organic carbon, total dissolved nitrogen, and dissolved CN. The VC treatment removed a range of metals (Mg, Ni and Zn) and metalloid Se from the CN-augmented WD2 water to below detection. Other elements substantially reduced in concentration included Ba, F, Si and U. However, the VC treatment did not remove substantial nitrate, sulfate or CN. Microcosm trials revealed that the indigenous microbial community in WD2 could effectively denitrify and reduce sulfate, with TB was the most efficient C source for promoting sulfate and CN removal; whereas, EW facilitated only marginally higher sulfate reduction compared with controls. The highest sulfate reduction rate (76 g-SO42− m−3 d−1) was achieved with VC-treated water amended with TB, indicating that VC pre-treatment was beneficial. Further, all treatments amended with external C, facilitated 100% removal of dissolved CN after 60 days, whereas only partial (65%) CN removal was recorded in the control. Overall, the proposed integrated method appears a viable option for treating neutral gold mine drainage.

Objective: Cardiac arrhythmias are a common challenge following open-heart surgeries. Hypomagnesemia is believed to be correlated with this condition. Prophylactic intravenous magnesium supplementation has been practiced for a long time in patients undergoing CABG. This study was designed in an attempt to compare the efficacy of oral versus intravenous routes in the prevention of hypomagnesemia and arrhythmia. Methods: In this interventional clinical study, 82 patients were randomly assigned to 2 groups. All patients were evaluated for baseline serum magnesium level and arrhythmias. One group received 1,600 mg of oral magnesium hydroxide through nasogastric (NG) tube prior to surgery, while the other group received 2 g of magnesium sulfate during the induction of anesthesia. The serum magnesium level was monitored for 48 hours after the operation. The difference in preoperative hypomagnesemia was non-significant (Sig: 0.576). Results: During the operation, the serum magnesium level peaked around 4 mg/dL, and no hypomagnesemia was detected in any patient. Although the curve of oral group declined parallel and below that of intravenous (IV) group, no significant differences were detected during postoperative monitoring. In addition, a prevalence of arrhythmia of 13.9% and 6.5% was noticed in IV and oral groups, respectively (OR: 0.428). Conclusion: Providing 1,600 mg of oral magnesium supplement to patients is as effective as 2,000 mg of magnesium sulfate IV in preventing hypomagnesemia and arrhythmia after CABG. Thus, the authors introduce this treatment regimen as a promising and cost-effective method.

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.

International audience; 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 betweenfast 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).

We previously found the instillation of sericin to be useful as therapy for keratopathy with or without diabetes mellitus. In this study, we investigated whether a combination of solid magnesium hydroxide nanoparticles (MHN) enhances epithelial corneal wound healing by sericin using rabbits, normal rats and type 2 diabetes mellitus rats with debrided corneal epithelium (ex vivo and in vivo studies). Ophthalmic formulations containing sericin and MHN (N-Ser) were prepared using a bead mill method. The mean particle size of the N-Ser was 110.3 nm at the time of preparation, and 148.1 nm one month later. The instillation of N-Ser had no effect on the amount of lacrimal fluid in normal rabbits (in vivo), but the MHN in N-Ser was found to expand the intercellular space in ex vivo rat corneas. In addition, the instillation of N-Ser increased the phosphorylation of Extracellular Signal-regulated Kinase (ERK)1/2, a factor involved in cell adhesion and cell proliferation in the corneal epithelium, in comparison with the instillation of sericin alone. The combination with MHN enhanced epithelial corneal wound healing by sericin in rat debrided corneal epithelium (in vivo). This study provides significant information to prepare potent drugs to cure severe keratopathy, such as diabetic keratopathy.

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.

Data about pathogenetically justification of use, efficiency and safety of acetylsalicylic acid as antiplatelet agents in cardiology practice are analysed in the article. The article contains short analysis of the domestic market of acetylsalicylic acid preparations, that are used in cardiology practice. The article also contains recommendation of practical character for optimization of choice of acetylsalicylic acid preparations. The authors of the article pay great attention to the analysis of data about influence of medicinal form of acetylsalicylic acid preparations and composition of the combined preparations that contain it on pharmacokinetic parameters and profile of their safety. Based on these data the authors of the article come to the conclusion that one of the most safe and effective preparations of acetylsalicylic acid that is presented today at the market of Ukraine there is Magnicor.

Objectives Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice daily (BID). Raltegravir for once-daily regimen (QD) at a dose of 1200 mg is under development. The effect of calcium carbonate and magnesium/aluminium hydroxide antacids on the pharmacokinetics of a 1200 mg dose of raltegravir was assessed in this study. Methods An open-label, four-period, four-treatment, fixed-sequence study in 20 HIV-infected patients was performed. Patients needed to be on raltegravir as part of a stable treatment regimen for HIV, and upon entry into the trial received 5 days of 1200 mg raltegravir as pretreatment, before they entered the four-period study: 1200 mg of raltegravir alone (period 1), calcium carbonate antacid as TUMS® Ultra Strength (US) 1000 and 1200 mg raltegravir given concomitantly (Period 2), magnesium/aluminium hydroxide antacid as 20 ml MAALOX® Maximum Strength substitute MS given 12 h after administration of 1200 mg raltegravir (period 3), and calcium carbonate antacid as TUMS® US 1000 given 12 h after administration of 1200 mg raltegravir (period 4). Patients received their dose of 1200 mg QD raltegravir during the intervals between periods to re-establish steady state. AUC0–24, C24, Cmax and Tmax were calculated from the individual plasma concentrations of 1200 mg QD raltegravir after administration alone or with a calcium carbonate antacid or with a staggered dose of a calcium carbonate antacid or magnesium/aluminium hydroxide antacid. Adverse events, in addition to laboratory safety tests (haematology, serum chemistry and urinalysis), 12-lead electrocardiograms and vital signs were assessed. Key findings All treatments were well tolerated in the study. Metal-cation antacids variably affected the pharmacokinetics of 1200 mg QD raltegravir. When calcium carbonate antacid was given with 1200 mg raltegravir concomitantly, the geometric mean ratio (GMR) and its associated 90% confidence interval (90% CI) for AUC0–24, Cmax and C24 h were 0.28 (0.24, 0.32), 0.26 (0.21, 0.32) and 0.52 (0.45, 0.61), respectively. When calcium carbonate antacid and magnesium/aluminium hydroxide were given 12 h after raltegravir 1200 mg QD dosing, the GMR (90% CI) values for AUC0–24 and Cmax were 0.90 (0.80, 1.03), 0.98 (0.81, 1.17), and 0.86 (0.73, 1.03), 0.86 (0.65, 1.15), respectively. However, significant reduction in the trough concentrations of raltegravir was observed: C24 h 0.43 (0.36, 0.51) in the presence of calcium carbonate antacids and 0.42 (0.34, 0.52) in presence of magnesium/aluminium hydroxide, respectively. Conclusions Overall, the use of metal-cation antacids with 1200 mg QD raltegravir is not recommended.

Radiation proctitis is a common complication after radiotherapy for pelvic malignant tumors. This study was conducted to assess the efficacy of novel almagate enemas in hemorrhagic chronic radiation proctitis (CRP) and evaluate risk factors related to rectal deep ulcer or fistula secondary to CRP. All patients underwent a colonoscopy to confirm the diagnosis of CRP and symptoms were graded. Typical endoscopic and pathological images, risk factors, and quality of life were also recorded. A total of 59 patients were enrolled. Gynecological cancers composed 93.1% of the primary malignancies. Complete or obvious reduction of bleeding was observed in 90% (53/59) patients after almagate enema. The mean score of bleeding improved from 2.17 to 0.83 (P

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. Mg²⁺ 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

In designing drug delivery systems with improved release properties and bioavailability, the dynamic features of the active pharmaceutical ingredient can be crucial for the final product properties. In this work, we aimed at obtaining the first characterization of the molecular dynamic properties of one of the most common nonsteroidal anti-inflammatory drug, ibuprofen, intercalated in hydrotalcite, an interesting inorganic carrier. By exploiting a variety of solid state NMR techniques, including H-1 and C-13 MAS spectra and T-1 relaxation measurements, performed at variable temperature and carrying out a synergic analysis of all results, it has been possible to ascertain that the mobility of ibuprofen within the carrier is remarkably increased. In particular, strong indications have been obtained that ibuprofen molecules, in addition to internal interconformational dynamics, experience an overall molecular motion. Also considering that ibuprofen is "anchored" to the charged surface of the hydrotalcite layers through its carboxylate moiety, such motion could be a wobbling-in-a-cone. Activation energies and correlation times of all the motions of intercalated ibuprofen have been determined.

Anti-caries activity of fluoride ions is due to the protection against demineralization and the enhancement of remineralization of tooth enamel. Dentifrices available on the market contain sodium fluoride, sodium monofluorophosphate, stannous fluoride, and amine fluoride as source of these ions. A new compound working both as fluoride ion source and as abrasive was projected. Hybrids based on F- ions intercalated between the lamellae of hydrotalcite-like compounds (HTlc-F), namely MgAl-HTlc-F and ZnAl-HTlc-F, were prepared and characterized. Then, three different percentages (2, 3, and 4%) of both HTlc-F compounds were assayed. After the rheological characterization, the dentifrices containing 3 and 4% of MgAl-HTlc-F and ZnAl-HTlc-F, respectively, resulted to be the most suitable ones. Two novel in vitro methods, "rotary toothbrush method" and "manual brushing method," were developed and used in order to study the F- ions release from the prepared dentifrices. The obtained results showed that the dentifrice containing ZnAl-HTlc-F (4%) was the most effective in releasing fluoride ions. The "rotary toothbrush method" resulted to be the most suitable as the simulation of the brushing movements is standardizable and reproducible.

In this work, nano-hybrid electrospun non-woven mats made of wool keratin combined with diclofenac loaded hydrotalcites (HTD) were prepared and characterized as potential drug delivery systems and scaffolds for fibroblast cell growth. Nano-hybrid electrospun non-woven mats showed a good adaptability to wet skin, effortlessly conforming to the three-dimensional topography of the tissue. Nanosized HTD exercised an overall reinforcing action on the electrospun non-woven mats since the nanohybrid samples displayed a reduced swelling ratio and a slower degradation profile compared to keratin-based nanofiber non-woven mats containing free diclofenac, without negative effects on drug release. The cell viability test indicated a decreased toxicity of the drug when loaded into nanofibers and confirmed the biocompatibility of keratin/HTD electrospun non-woven mats; moreover, a controlled diclofenac release within the first 24 hours does not compromise the fibroblast cell growth in a significant manner.

Doravirine is a novel non-nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus type 1 infection. Because of potential concomitant administration with acid-reducing agents, a drug-interaction trial was conducted to evaluate the potential impact of these types of medications on doravirine pharmacokinetics. In an open-label, 3-period, fixed-sequence trial, healthy adult participants received the following: period 1, a single dose of doravirine 100 mg; period 2, coadministration of a single dose of doravirine 100 mg and an antacid (1600 mg aluminum hydroxide, 1600 mg magnesium hydroxide, and 160 mg simethicone); period 3, 40 mg pantoprazole once daily on days 1-5 coadministered with a single dose of doravirine 100 mg on day 5. There was a minimum 10-day washout between periods. Plasma samples for pharmacokinetic evaluation were collected, and safety was assessed. Fourteen participants (8 male, 6 female) were enrolled, and 13 completed the trial. Geometric mean ratios (90% confidence intervals) for doravirine AUC0-inf , Cmax , and C24 for doravirine + antacid/doravirine were 1.01 (0.92-1.11), 0.86 (0.74-1.01), and 1.03 (0.94-1.12), respectively, and for doravirine + pantoprazole/doravirine were 0.83 (0.76-0.91), 0.88 (0.76-1.01), and 0.84 (0.77-0.92), respectively. Doravirine was generally well tolerated administered alone or with either of the acid-reducing agents. Coadministration of an aluminum/magnesium-containing antacid or pantoprazole did not have a clinically meaningful effect on doravirine pharmacokinetics, supporting the use of acid-reducing agents with doravirine.

Objective: The current research was carried out to evaluate the use of magnesium hydroxide as buffer to control acidosis in rumen culture fermenting carbohydrates in vitro. Materials and Methods: The experiments were carried out in the chemostat system in which the reactor used was a 200 ml of working volume. A series of fed-batch trials were carried out in fed-batch system with hydraulic retention time of 4 days. All digesters were completely mixed with the rotation of 55 rpm, and the temperature was controlled at 39°C ± 0.5°C. Results: Results showed that the supplementation of magnesium hydroxide (50 mM/day) to the corn starch feed (12.5 gm/l per day) for the rumen culture could prevent acidosis while at the same concentration of sodium bicarbonate addition to rumen culture, acidosis cannot be prevented in which lactic acid accumulated up to 200 mM. Supplementing magnesium hydroxide to the mixture of starch and sugar feeds prevented acidosis in which the major fermentation end product formed was acetate. A daily feeding with the ratio of 4.5:1 [starch: Mg(OH)2 ] was feasible to prevent rumen acidosis. Conclusion: Magnesium hydroxide added to the rumen culture could prevent lactic acid accumulation while sodium bicarbonate supplementation did not prevent acidosis and had lactic acid accumulation. [J Adv Vet Anim Res 2019; 6(1.000): 100-107]

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.

Background/Aims: Bile is the main cause of poor bowel preparation for capsule endoscopy (CE). We aimed to determine whether cholestyramine and hydrotalcite can eliminate bile in the bowel. Patients and Methods: Patients undergoing CE were randomized into two groups. Group A patients (n = 75) recieved 250 mL 20% mannitol and 1 L 0.9% saline orally at 20:00 hours on the day before and at 05:00 hours on the day of CE and 20 mL simethicone 30 min before CE. Group B patients (n = 73) were treated identically, except for taking oral cholestyramine and hydrotalcite, starting 3 days before CE. Greenish luminal contents were assessed by four tissue color bar segments using Color Area Statistics software. Bowel cleanliness was evaluated by visualized area percentage assessment of cleansing (AAC) score. Result: Bowel cleanliness (82.7% [62/75] vs 46.6% [34/73]; χ2 = 14.596, P = 0.000). and detected greenish luminal contents (20.0% [15/75] vs 8.2% [6/73]; χ2 = 4.217, P = 0.040) were significantly greater in Group A than in Group B. Greenish luminal contents in the two groups differed significantly in the captured small-bowel (t = −13.74, P = 0.000) segments and proximal small-bowel (t = −0.7365, P = 0.000) segments, but not for the distal small-bowel (t = −0.552, P = 0.581) segments. Conclusions: Cholestyramine and hydrotalcite were ineffective in eliminating bile and improving small-bowel preparation.

Background Deflation cough (DC), i.e. the cough-like expiratory expulsive efforts evoked by maximal lung emptying, is partially inhibited by prior intake of an antacid. We wished to compare the effects of an anti-reflux medical device ( Gastrotuss ® ) and of a widely used antacid drug ( Maalox ® ) on the number of expiratory thrusts evoked by maximal lung emptying in chronic cough patients. Methods Twenty consecutive chronic cough outpatients also presenting DC attended the clinic on three separate occasions and were requested to inhale to near total lung capacity and then exhale maximally for at least 6 s. Trained investigators detected aurally the number of cough efforts evoked by maximal lung emptying prior to and 1, 5, 10, 30 e 60 min after administration of either Maalox ® , or Gastrotuss ® or placebo. The liking of the administered agents was also rated. Results In control conditions, maximal lung emptying was consistently accompanied by the appearance of DC. The number of efforts was unchanged after placebo whereas it was markedly (P Maalox ® and Gastrotuss ® administration. The value of liking for Gastrotuss ® was greater (P Maalox ® and placebo. Conclusions Pre-treatment with anti-reflux agents with a substantially different composition are equally effective in inhibiting DC. The liking of the two compounds used in the present experiments differed considerably and may be important to improve adherence to treatment in patients undergoing long-term therapy for reflux-related symptoms.

Background/aims Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms. Methods A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter ≤15 mm, GB ejection fraction ≥50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated. Results A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients. Conclusions Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.

Fluoride-releasing restorative dental materials can be beneficial to remineralize dentin and help prevent secondary caries. However, the effects of fluoride release from dental materials on the activity of dental pulp stem cells are not known. Here we investigate whether different fluoride release kinetics from dental resins supplemented with modified hydrotalcite (RK-F10) or fluoride-glass filler (RK-FG10) could influence the behavior of a human dental pulp stem cell subpopulation (STRO-1+ cells) known for its ability to differentiate toward an odontoblast-like phenotype. The 2 resins, characterized by similar physicochemical properties and fluoride content, exhibited different long-term fluoride release kinetics. Our data demonstrate that long-term exposure of STRO-1+ cells to a continuous release of a low amount of fluoride by RK-F10 increases their migratory response to transforming growth factor β1 (TGF-β1) and stromal cell–derived factor 1 (SDF-1), both important promoters of pulp stem cell recruitment. Moreover, the expression patterns of dentin sialoprotein ( dspp), dentin matrix protein 1 ( dmp1), osteocalcin ( ocn), and matrix extracellular phosphoglycoprotein ( mepe) indicate a complete odontoblast-like cell differentiation only when STRO-1+ cells were cultured on RK-F10. On the contrary, RK-FG10, characterized by an initial fluoride release burst and reduced lifetime of the delivery, did not elicit any significant effect on both STRO-1+ cell migration and differentiation. Taken together, our results highlight the importance of taking into account fluoride release kinetics in addition to fluoride concentration when designing new fluoride-restorative materials.

During pregnancy, both the mother and fetus are vulnerable to environmental pollution by particulate matters and chemicals. Although the toxicity of free pollutants has been frequently reported, the impact of nanoparticle/pollutant adducts on the vulnerable pregnant population remains unclear. In this study, pregnant mice were orally exposed to Mg(OH)2 nanoflakes and nanoflakes adsorbed with Cr(VI) anions during the peri-implantation and organogenesis stages of pregnancy at doses that did not induce systemic toxicity or pregnancy complications. The nano-Mg(OH)2/Cr(VI) adducts formation reduced fetal developmental toxicity compared with the toxicity induced by the same concentration of free Cr(VI) anions.

Nano-Mg(OH)2 is efficiently used in pollutant adsorption and removal due to its high adsorption capability, low-cost, and recyclability. A recent research from our group showed that Mg(OH)2 nanoflakes are not evidently internalized by cancer cells and are not cytotoxic. But the biocompatibility and potential toxicity of nano-Mg(OH)2 in a normal biological system are largely unclear. Nanoparticles could affect the function of endothelial cells, and endothelial dysfunction represents an early sign of lesion within the vasculature. Here, we applied the human umbilical vein vascular endothelial cells (HUVECs) as an in vitro model of the endothelium to study the cytotoxicity of nano-Mg(OH)2. Our results showed that nano-Mg(OH)2 at 200 μg/ml impaired proliferation and induced dysfunction of HUVECs, but did not result in cell necrosis and apoptosis. Transmission electron microscopy images and immunofluorescence results showed that the nano-Mg(OH)2 could enter HUVECs through caveolin-1-mediated endocytosis. Nano-Mg(OH)2 at high concentrations decreased the level of caveolin-1 and increased the activity of endothelial nitric oxide synthase (eNOS), thus leading to the production of excess nitric oxide (NO). In this work, we provide the cell damage concentrations of nano-Mg(OH)2 nanoparticles, and we propose a mechanism of injury induced by nano-Mg(OH)2 in HUVECs.

In recent years, magnesium (Mg) alloys show a promising application in clinic as degradable biomaterials. Nevertheless, the poor corrosion resistance of Mg alloys is the main obstacle to their clinical application. Here we successfully seal the pores of plasma electrolytic oxidation (PEO) coating on AZ31 with Mg-Al layered double hydroxide (LDH) via hydrothermal treatment. PEO/LDH composite coating possess a two layer structure, an inner layer made up of PEO coating (~5 μm) and an outer layer of Mg-Al LDH (~2 μm). Electrochemical and hydrogen evolution tests suggest preferable corrosion resistance of the PEO/LDH coating. Cytotoxicity, cell adhesion, live/dead staining and proliferation data of rat bone marrow stem cells (rBMSCs) demonstrate that PEO/LDH coating remarkably enhance the cytocompatibility of the substrate, indicating a potential application in orthopedic surgeries. In addition, hemolysis rate (HR) test shows that the HR value of PEO/LDH coating is 1.10 ± 0.47%, fulfilling the request of clinical application. More importantly, the structure of Mg-Al LDH on the top of PEO coating shows excellent drug delivery ability.

Mastitis es un proceso infeccioso e inflamatorio de la glándula mamaria, que altera el tejido glandular, y los aspectos físicos, químicos y bacteriológicos de la leche. La mastitis en caninos se presenta con mayor frecuencia durante el periodo postparto o después de repetidos episodios de gestación sicológica e está relacionada con la excesiva producción y acumulación de leche. El presente reporte tiene como objetivo relatar, describir y discutir la ocurrencia, diagnóstico, tratamiento y evolución de un caso de mastitis gangrenosa aguda en una hembra canina adulta durante el periodo postparto, la importancia de un diagnóstico certero, la selección de la terapia antimicrobiana basada en los test de antibiograma y el tratamiento tópico alterativo, asociando azúcar e hidróxido de magnesio al mismo. Como conclusión la mastitis gangrenosa es una enfermedad grave en la clínica de pequeños animales, el éxito de su tratamiento depende de la selección adecuada del tratamiento antimicrobiano basado en el cultivo y antibiograma, así como de un tratamiento de soporte adecuado de las lesiones y complicaciones clínicas secundarias.

Objective To evaluate, in vitro, the effect of Mg(OH)2 dentifrice, and the influence of the number of experimental days, on the extrinsic (citric acid –CA) and intrinsic (hydrochloric acid –HCl) enamel erosion models. Design Human enamel slabs were selected according to surface hardness and randomly assigned to 3 groups (n = 9) as follows: non-fluoridated (negative control), NaF (1450 ppm F- positive control) and Mg(OH)2 (2%) dentifrices. The slabs were daily submitted to a 2-h period of pellicle formation and, over a period of 5 days, submitted to cycles (3×/day) of erosive challenge (CA 0.05 M, pH = 3.75 or HCl 0.01 M, pH = 2 for 30 s), treatment (1 min −1:3 w/w of dentifrice/distilled water) and remineralization (artificial saliva/120 min). Enamel changes were determined by surface hardness loss (SHL) for each day and mechanical profilometry analysis. Data were analyzed by two-way ANOVA followed by Tukey’s test to % SHL and one-way ANOVA to profilometry (p Results The number of experimental days influenced the erosion process for the two types of erosion models (p Conclusion The findings suggest that Mg(OH)2 dentifrices might protect enamel against slight erosion, but protection was not effective for stronger acid erosion.