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International Journal of Molecular... Mar 2023This work represents research into materials designed to improve the environment. The study was carried out on aluminum hydroxide xerogels and alumina catalysts obtained...
This work represents research into materials designed to improve the environment. The study was carried out on aluminum hydroxide xerogels and alumina catalysts obtained by the Controlled Double Jet Precipitation (CDJP) process at different pH values. It has been shown that the pH of the CDJP process determines the content of aluminum-bound nitrate ions in the aluminum hydroxide. These ions are removed at a higher temperature than the decomposition of ammonium nitrate. The high content of aluminum-bound nitrate ions determines the structural disorder of the alumina and the high content of the penta-coordinated alumina catalyst.
Topics: Aluminum Oxide; Nitrates; Aluminum Hydroxide; Aluminum; Spectroscopy, Fourier Transform Infrared
PubMed: 36982226
DOI: 10.3390/ijms24065151 -
Genetics and Molecular Research : GMR Jul 2014This study evaluated different dosage forms of aluminum adjuvant in generating allergic rhinitis animal models. Forty female BALB/c mice were assigned to four groups,...
This study evaluated different dosage forms of aluminum adjuvant in generating allergic rhinitis animal models. Forty female BALB/c mice were assigned to four groups, including three dosage forms of aluminum adjuvant [powder, gel, and hydrosolvent of aluminum hydroxide, Al(OH)3] mixed with ovalbumin to simulate the symptoms of allergic rhinitis and one control group. Although the aluminum adjuvants were in different dosage forms, the content was 5 mg after conversion in all groups. The fourth group was given normal saline instead as a control. Mice of the powder group displayed typical symptoms of allergic rhinitis. We also found discrete eosinophils in the nasal mucosa of mice from the hydrosolvent group; however, no eosinophils were found in the gel group. These two groups both displayed cytotoxic symptoms and foreign body granuloma. Aluminum adjuvant used in producing animal models can induce foreign body granuloma and other untoward reactions, which are associated with the dosage level and form.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Animals; Disease Models, Animal; Eosinophils; Female; Gels; Granuloma, Foreign-Body; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Powders; Rhinitis, Allergic
PubMed: 25061742
DOI: 10.4238/2014.July.7.10 -
Toxins Nov 2020The combination of a low-dose coagulant (polyaluminium chloride-'Floc') and a ballast able to bind phosphate (lanthanum modified bentonite, LMB-'Sink/Lock') have been...
The combination of a low-dose coagulant (polyaluminium chloride-'Floc') and a ballast able to bind phosphate (lanthanum modified bentonite, LMB-'Sink/Lock') have been used successfully to manage cyanobacterial blooms and eutrophication. In a recent 'Floc and Lock' intervention in Lake de Kuil (the Netherlands), cyanobacterial chlorophyll- was reduced by 90% but, surprisingly, after one week elevated cyanobacterial concentrations were observed again that faded away during following weeks. Hence, to better understand why and how to avoid an increase in cyanobacterial concentration, experiments with collected cyanobacteria from Lakes De Kuil and Rauwbraken were performed. We showed that the from Lake de Kuil could initially be precipitated using a coagulant and ballast but, after one day, most of the filaments resurfaced again, even using a higher ballast dose. By contrast, the from Lake Rauwbraken remained precipitated after the Floc and Sink/Lock treatment. We highlight the need to test selected measures for each lake as the same technique with similar species () yielded different results. Moreover, we show that damaging the cells first with hydrogen peroxide before adding the coagulant and ballast (a 'Kill, Floc and Lock/Sink' approach) could be promising to keep precipitated.
Topics: Aluminum Hydroxide; Bentonite; Chemical Precipitation; Chlorophyll A; Harmful Algal Bloom; Hydrogen Peroxide; Lakes; Lanthanum; Planktothrix; Time Factors; Water Microbiology; Water Purification
PubMed: 33167347
DOI: 10.3390/toxins12110700 -
Journal of the American Veterinary... Jan 2002To determine the effects of a commercially available orally administered antacid agent containing aluminum hydroxide and magnesium hydroxide on abomasal luminal pH in...
OBJECTIVE
To determine the effects of a commercially available orally administered antacid agent containing aluminum hydroxide and magnesium hydroxide on abomasal luminal pH in clinically normal milk-fed calves.
DESIGN
Randomized trial.
ANIMALS
5 male dairy calves.
PROCEDURE
Throughout the study, calves were fed milk replacer at 7:30 AM and 7:30 PM. Cannulae for pH electrodes were placed in the abomasal body and pyloric antrum. Treatments consisted of oral administration of a high (50 ml) or low (25 ml) dose of the antacid agent and oral administration of milk replacer alone (control). Antacid was given at 7:30 AM, 3:30 PM, and 11:30 PM, and luminal pH was monitored continuously for 24 hours, beginning 15 minutes before administration of the first dose of antacid.
RESULTS
Administration of the first dose of antacid at the time of the morning feeding resulted in an increase in mean abomasal body luminal pH of < 1 pH unit, whereas administration of the second and third doses of the antacid caused transient (< 3 hours) increases in mean luminal pH of approximately 1.5 (low dose) and 2.5 (high dose) pH units.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggest that clinically normal milk-fed calves given a commercially available antacid agent, PO, will have a transient increase in abomasal luminal pH. Such agents may, therefore, have a role in the treatment of abomasal ulceration in calves; however, the long-term effects of orally administered antacid agents in milk-fed calves and the clinical efficacy of such agents in treating abomasal ulceration remain to be determined.
Topics: Abomasum; Administration, Oral; Aluminum Hydroxide; Animals; Animals, Newborn; Antacids; Cattle; Cattle Diseases; Hydrogen-Ion Concentration; Magnesium Hydroxide; Male; Random Allocation; Time Factors; Ulcer
PubMed: 12680452
DOI: 10.2460/javma.2002.220.74 -
Cleveland Clinic Journal of Medicine 1987
Topics: Adult; Aluminum Hydroxide; Antacids; Drug Combinations; Female; Humans; Magnesium; Magnesium Hydroxide; Osteomalacia; Peptic Ulcer
PubMed: 3608134
DOI: 10.3949/ccjm.54.3.214 -
Journal of Controlled Release :... Apr 2018Aluminum salts have been used as vaccine adjuvants for >50 years, and they are currently present in at least 146 licensed vaccines worldwide. In this study we examined...
Aluminum salts have been used as vaccine adjuvants for >50 years, and they are currently present in at least 146 licensed vaccines worldwide. In this study we examined whether adsorption of Army Liposome Formulation (ALF) to an aluminum salt that already has an antigen adsorbed to it might result in improved immune potency of the aluminum-adsorbed antigen. ALF is composed of a family of anionic liposome-based adjuvants, in which the liposomes contain synthetic phospholipids having dimyristoyl fatty acyl groups, cholesterol and monophosphoryl lipid A (MPLA). For certain candidate vaccines, ALF has been added to aluminum hydroxide (AH) gel as a second adjuvant to form ALFA. Here we show that different methods of preparation of ALF changed the physical structures of both ALF and ALFA. Liposomes containing the saponin QS21 (ALFQ) have also been mixed with AH to form ALFQA as an effective combination. In this study, we first adsorbed one of two different antigens to AH, either tetanus toxoid conjugated to 34 copies of a hapten (MorHap), which has been used in a candidate heroin vaccine, or gp140 protein derived from the envelope protein of HIV-1. We then co-adsorbed ALF or ALFQ to the AH to form ALFA or ALFQA. In each case, the immune potency of the antigen adsorbed to AH was greatly increased by co-adsorbing either ALF or ALFQ to the AH. Based on IgG subtype and cytokine analysis by ELISPOT, ALFA induced predominately a Th2-type response and ALFQ and ALFQA each induced more balanced Th1/Th2 responses.
Topics: Adjuvants, Immunologic; Adsorption; Aluminum Hydroxide; Animals; Antigens; Female; Haptens; Immunoglobulin G; Liposomes; Mice, Inbred BALB C; Saponins; Tetanus Toxoid; Vaccines; env Gene Products, Human Immunodeficiency Virus
PubMed: 29432824
DOI: 10.1016/j.jconrel.2018.02.006 -
BMC Medicine Apr 2024The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines. Transmission-blocking vaccines aim to induce human antibodies that block parasite development in the mosquito and mosquitoes becoming infectious. The Pfs48/45 protein is a leading Plasmodium falciparum transmission-blocking vaccine candidate. The R0.6C fusion protein, consisting of Pfs48/45 domain 3 (6C) and the N-terminal region of P. falciparum glutamate-rich protein (R0), has previously been produced in Lactococcus lactis and elicited functional antibodies in rodents. Here, we assess the safety and transmission-reducing efficacy of R0.6C adsorbed to aluminium hydroxide with and without Matrix-M™ adjuvant in humans.
METHODS
In this first-in-human, open-label clinical trial, malaria-naïve adults, aged 18-55 years, were recruited at the Radboudumc in Nijmegen, the Netherlands. Participants received four intramuscular vaccinations on days 0, 28, 56 and 168 with either 30 µg or 100 µg of R0.6C and were randomised for the allocation of one of the two different adjuvant combinations: aluminium hydroxide alone, or aluminium hydroxide combined with Matrix-M1™ adjuvant. Adverse events were recorded from inclusion until 84 days after the fourth vaccination. Anti-R0.6C and anti-6C IgG titres were measured by enzyme-linked immunosorbent assay. Transmission-reducing activity of participants' serum and purified vaccine-specific immunoglobulin G was assessed by standard membrane feeding assays using laboratory-reared Anopheles stephensi mosquitoes and cultured P. falciparum gametocytes.
RESULTS
Thirty-one participants completed four vaccinations and were included in the analysis. Administration of all doses was safe and well-tolerated, with one related grade 3 adverse event (transient fever) and no serious adverse events occurring. Anti-R0.6C and anti-6C IgG titres were similar between the 30 and 100 µg R0.6C arms, but higher in Matrix-M1™ arms. Neat participant sera did not induce significant transmission-reducing activity in mosquito feeding experiments, but concentrated vaccine-specific IgGs purified from sera collected two weeks after the fourth vaccination achieved up to 99% transmission-reducing activity.
CONCLUSIONS
R0.6C/aluminium hydroxide with or without Matrix-M1™ is safe, immunogenic and induces functional Pfs48/45-specific transmission-blocking antibodies, albeit at insufficient serum concentrations to result in transmission reduction by neat serum. Future work should focus on identifying alternative vaccine formulations or regimens that enhance functional antibody responses.
TRIAL REGISTRATION
The trial is registered with ClinicalTrials.gov under identifier NCT04862416.
Topics: Adolescent; Adult; Animals; Female; Humans; Male; Middle Aged; Young Adult; Adjuvants, Immunologic; Aluminum Hydroxide; Antibodies, Protozoan; Malaria Vaccines; Malaria, Falciparum; Membrane Glycoproteins; Netherlands; Plasmodium falciparum; Protozoan Proteins
PubMed: 38649867
DOI: 10.1186/s12916-024-03379-y -
International Journal of Molecular... Feb 2023Aluminum-based adjuvants have been extensively used in vaccines. Despite their widespread use, the mechanism behind the immune stimulation properties of these adjuvants...
Aluminum-based adjuvants have been extensively used in vaccines. Despite their widespread use, the mechanism behind the immune stimulation properties of these adjuvants is not fully understood. Needless to say, extending the knowledge of the immune-stimulating properties of aluminum-based adjuvants is of utmost importance in the development of new, safer, and efficient vaccines. To further our knowledge of the mode of action of aluminum-based adjuvants, the prospect of metabolic reprogramming of macrophages upon phagocytosis of aluminum-based adjuvants was investigated. Macrophages were differentiated and polarized in vitro from human peripheral monocytes and incubated with the aluminum-based adjuvant Alhydrogel. Polarization was verified by the expression of CD markers and cytokine production. In order to recognize adjuvant-derived reprogramming, macrophages were incubated with Alhydrogel or particles of polystyrene as control, and the cellular lactate content was analyzed using a bioluminescent assay. Quiescent M0 macrophages, as well as alternatively activated M2 macrophages, exhibited increased glycolytic metabolism upon exposure to aluminum-based adjuvants, indicating a metabolic reprogramming of the cells. Phagocytosis of aluminous adjuvants could result in an intracellular depot of aluminum ions, which may induce or support a metabolic reprogramming of the macrophages. The resulting increase in inflammatory macrophages could thus prove to be an important factor in the immune-stimulating properties of aluminum-based adjuvants.
Topics: Humans; Aluminum; Aluminum Hydroxide; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Macrophages; Vaccines
PubMed: 36901849
DOI: 10.3390/ijms24054409 -
Journal of Pharmaceutical Sciences Jan 2020A nonreplicating rotavirus vaccine (NRRV) containing 3 recombinant fusion proteins adsorbed to aluminum adjuvant (Alhydrogel [AH]) is currently in clinical trials. The... (Comparative Study)
Comparative Study
A nonreplicating rotavirus vaccine (NRRV) containing 3 recombinant fusion proteins adsorbed to aluminum adjuvant (Alhydrogel [AH]) is currently in clinical trials. The compatibility and stability of monovalent NRRV antigen with key components of a multidose vaccine formulation were examined using physicochemical and immunochemical methods. The extent and strength of antigen-adjuvant binding were diminished by increasing phosphate concentration, and acceptable levels were identified along with alternate buffering agents. Addition of the preservative thimerosal destabilized AH-adsorbed P2-VP8-P[8] as measured by differential scanning calorimetry. Over 3 months at 4°C, AH-adsorbed P2-VP8-P[8] was stable, whereas at 25°C and 37°C, instability was observed which was greatly accelerated by thimerosal addition. Loss of antibody binding (enzyme-linked immunosorbent assay) correlated with loss of structural integrity (differential scanning calorimetry, fluorescence spectroscopy) with concomitant nonnative disulfide bond formation (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and Asn deamidation (liquid chromatography -mass spectrometry peptide mapping). An alternative preservative (2-phenoxyethanol) showed similar antigen destabilization. Due to limited availability, only key assays were performed with monovalent P2-VP8-P[4] and P2-VP8-P[6] AH-adsorbed antigens, and varying levels of preservative incompatibility were observed. In summary, monovalent AH-adsorbed NRRV antigens stored at 4°C showed good stability without preservatives; however, future formulation development efforts are required to prepare a stable, preservative-containing, multidose NRRV formulation.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Antigens, Viral; Buffers; Drug Compounding; Drug Stability; Hydrogen-Ion Concentration; Preservatives, Pharmaceutical; Protein Conformation; Protein Stability; Rotavirus Vaccines; Temperature; Thimerosal; Vaccines, Subunit; Vaccines, Synthetic; Viral Proteins
PubMed: 31589875
DOI: 10.1016/j.xphs.2019.10.004 -
British Journal of Clinical Pharmacology Feb 19781 The effect of aluminium hydroxide and/or of glycopyrrhonium on the absorption of a single oral 50 mg/kg dose of ethambutol (EMB) was investigated on thirteen... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
1 The effect of aluminium hydroxide and/or of glycopyrrhonium on the absorption of a single oral 50 mg/kg dose of ethambutol (EMB) was investigated on thirteen tuberculous in-patients and on two groups of healthy volunteers with six subjects each. The EMB concentrations in serum and 10+h urine were measured by colorimetry. 2 In order to assess gastric emptying the healthy volunteers ingested ethanol, either 0.5 g/kg in 10% solution or 0.8 g/kg in 20% solution, simultaneously with the drug, and breath alcohol levels were measured repetitively. 3 Aluminium hydroxide significantly lowered the serum EMB levels of the patients during the first 4 h after the EMB intake. No consistent effect was found in the first student experiment, whereas in the second experiment aluminium hydroxide and glycopyrrhonium, alone or in combination, clearly retarded the EMB absorption. 4 Repeated breath alcohol analysis proved unsuitable to indicate the time course of gastric emptying in these circumstances.
Topics: Adult; Aluminum Hydroxide; Breath Tests; Ethambutol; Ethanol; Gastric Emptying; Glycopyrrolate; Humans; Intestinal Absorption; Middle Aged; Pyrrolidines
PubMed: 619949
DOI: 10.1111/j.1365-2125.1978.tb01618.x