Aluminum Hydroxide Research Papers - Academia.edu (original) (raw)

2025, Human vaccines & immunotherapeutics

Herpes simplex virus (HSV) type 2 (HSV-2) is the main cause of genital and neonatal herpes and is highly prevalent worldwide. Previous phase I and II studies showed the immunogenicity and safety of the candidate prophylactic HSV-2 glycoprotein D-based subunit vaccine (gD2-AS04), containing aluminum hydroxide and 3-O-deacylated monophosphoryl lipid A (MPL) as adjuvant (AS04), in healthy adults. The primary objective of the study presented here was to compare the immunogenicity and safety of five different vaccine formulations: 3 different antigen doses [20, 40 or 80 μg of truncated glycoprotein D from HSV-2 strain (gD-2t)], different aluminum salts [AlPO₄ or Al(OH)₃], different preservatives or different volumes of vaccine (0.5 or 1 ml). One hundred and fifty healthy men and women aged 18-45 years, with negative serological markers for HSV-1 and HSV-2 infection, were vaccinated with one of 5 formulations of the gD2-AS04 candidate vaccine according to a 0-, 1-, 6-month schedule. No st...

2025, American Journal of Kidney Diseases

Hyperphosphatemia, a common complication in patients with end-stage renal disease, is treated with oral phosphate-binding medications that restrict phosphorus absorption from the gastrointestinal (GI) tract. Impaired product performance, such as failure to disintegrate and/or dissolve in the GI tract, could limit the efficacy of the phosphate binder. Disintegration may be as important as dissolution for predicting in vitro product performance for medications that act locally on the GI tract, such as phosphate binders. Furthermore, patients with end-stage renal disease have a wide range in GI pH, and pH can influence a product's performance. The purpose of this study was to determine the effect of pH on in vitro disintegration of phosphate binders. Fifteen different commercially available phosphate binders (seven calcium carbonate tablet formulations, two calcium acetate tablet formulations, three aluminum hydroxide capsule formulations, and three aluminum hydroxide tablet formulations) were studied using the United States Pharmacopeia (USP) standard disintegration apparatus. Phosphate binders were tested in simulated gastric fluid (pH 1.5), distilled water (pH 5.1), and simulated intestinal fluid (pH 7.5). Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within 30 minutes. Results indicate that 9 of the 15 phosphate binders tested showed statistically significant differences in disintegration time (DT) based on pH. The percentage of binders that passed the disintegration study test in distilled water, gastric fluid, and intestinal fluid were 80%, 80%, and 73%, respectively. The findings of this study show that the disintegration of commercially available phosphate binders is highly variable. The pH significantly affected in vitro disintegration in the majority of phosphate binders tested; how significantly this affects in vivo performance has yet to be studied.

2025, American Journal of Kidney Diseases

2025, Journal of Immunological Methods

CpG oligodeoxynucleotides are potent immunostimulants. For parenterally delivered alum based vaccines, the immunostimulatory effect of CpG depends on the association of the CpG and antigen to the alum. We describe effects of buffer components on the binding of CPG 7909 to aluminum hydroxide (Alhydrogel), assays for measuring binding of CPG 7909 to alum and CPG 7909 induced dissociation of antigen from the alum. Free CPG 7909 is a potent inducer of IP-10 in mice. However the lack of IP-10 production from formulations containing bound CPG 7909 suggested that CPG 7909 does not rapidly dissociate from the alum after injection. It also suggests that IP-10 assays are not a good basis for potency assays for alum based vaccines containing CPG 7909.

2025, Vaccine

Aluminum based adjuvants (alum), including aluminum hydroxide (Alhydrogel ® ) and aluminum phosphate are the most commonly used adjuvant in the US. In order to ensure quality of vaccines, regulatory authorities require evaluation of antigen content in final vaccine products. Currently, there are no generic methods available for the determination of protein content in alum based vaccines. Aluminum hydroxide gels exist as particles in solution, which interfere with direct quantitation of protein content in formulations using assays such as Lowry, BCA or Bradford protein assay. The present study adapts a simple fluorescent assay to directly (without the need for antigen extraction) determine antigen content on Alhydrogel ® with accuracy and sensitivity using the o-phthalaldehyde (OPA) reagent. Malaria vaccine candidates AMA1-C1/Alhydrogel, AMA1-C2/Alhydrogel, MSP1 42 -3D7/Alhydrogel, MSP1 42 -C1/Alhydrogel or BSAM-2/Alhydrogel were used as model formulations. The results of the present study show that the OPA assay is highly accurate (87-100%), reproducible, and simple with a linear detection range of 25-400 μg/mL for Alhydrogel ® vaccines (except for MSP1 42 -C1, which has a linear detection range of 31.25-500 μg/mL). This assay has proven to be highly useful in our laboratory and been used in routine vaccine quality control processes.

2025, Journal of Immunological Methods

2025, Vaccine

Efficient antigen extraction from vaccines formulated on aluminum hydroxide gels is a critical step for the evaluation of the quality of vaccines following formulation. It has been shown in our laboratory that the efficiency of antigen extraction from vaccines formulated on Alhydrogel decreased significantly with increased storage time. To increase antigen extraction efficiency, the present study determined the effect of surfactants on antigen recovery from vaccine formulations. The Plasmodium falciparum apical membrane antigen 1 (AMA1) formulated on Alhydrogel and stored at 2-8°C for 3 years was used as a model in this study. The AMA1 on Alhydrogel was extracted in the presence or absence of 30 mM sodium dodecyl sulfate (SDS) or 20mM cetylpyridinium chloride in the extraction buffer (0.60 M citrate, 0.55 M phosphate, pH 8.5) using our standard antigen extraction protocols. Extracted AMA1 antigen was analyzed by 4-20% Tris-glycine SDS-PAGE followed by silver staining or western blot...

2025, Environmental Science & Technology

Release of reactive (phosphate-like) phosphorus (P) from freshwater sediments represents a significant internal P source for many lakes. Hypolimnetic P release occurs under reducing conditions that cause reductive dissolution of ferric hydroxide [Fe(OH) 3 ]. This hypolimnetic P release may be naturally low or artificially reduced by sediment with naturally high or artificially elevated concentrations of aluminum hydroxide [Al(OH) 3 ]. We present field and laboratory data for a common extraction analysis of sediments from 43 lakes differing in trophic status, pH regime, climate, and P loading. The results indicate that a simple sequential extraction of sediment may be a useful predictor of sediment's ability to release P. Sequential extractions of sediment P, Al, and Fe by water (H 2 O), bicarbonate-dithionite (BD), and NaOH (at 25 °C) showed that negligible amounts of P would be released from lake sediments during hypolimnetic anoxia if either (1) the molar Al NaOH∼25 :Fe BD ratio is >3 or (2) the molar Al NaOH∼25 :P (H2O+BD) ratio is >25. These ratios can be used as operational targets for estimation of sediment P release potential and Al dosing of P-rich sediment to prevent hypolimnetic P release under anoxic conditions.

2025, Molecules

A comparison was made of the effectiveness of the functionalization reactions of pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8,11-dione (PCU) using sulphated zirconia in protection-deprotection reactions and Mg/Al hydrotalcite in a cyanosilylation reaction, under classical thermal conditions and imposing microwave radiation; improved yields and reaction times were considered.

2025, Vaccine

GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in ol...

2025, The Journal of Infectious Diseases

To determine whether systemic immunization against Helicobacter pylori could be achieved with an adjuvant approved for human use, the efficacy of vaccination with Helicobacter antigen in combination with aluminum hydroxide (AlOH) was evaluated in a murine model of Helicobacter infection. Immunization with antigen and AlOH induced interleukin-5secreting, antigen-specific T cells, and immunization with antigen and complete Freund's adjuvant induced interferon-g-secreting, antigen-specific T cells, as determined by ELISPOT assay. Both immune responses conferred protection after challenge with either H. pylori or H. felis, as confirmed by the complete absence of any bacteria, as assessed by both histology and culture of gastric biopsy samples. Protection was antibody independent, as demonstrated with antibody-deficient mMT mice (immunoglobulin-gene knockout mice), and CD4 + spleen T cells from immunized mice were sufficient to transfer protective immunity to otherwise immunodeficient rag1 Ϫ/Ϫ recipients. These results suggest an alternative and potentially more expeditious strategy for development of a human-use H. pylori vaccine. Helicobacter pylori, one of the world's most prevalent pathogens, is an extracellular bacterium that infects the gastric mucosa and plays an etiologic role in gastritis and peptic ulcer disease . It is generally believed that infection occurs primarily in young children. Therefore, a prophylactic vaccine administered to infants might prevent H. pylori infection and the long-term consequences that occur in adults. Vaccination strategies have focused primarily on orally and intranasally administered immunizations to induce mucosal immunity . These immunizations require bacterial exotoxin adjuvants that are unsafe for use in humans. Systemic immunization has recently been reported as a possible means of inducing protective

2025, Peritoneal Dialysis International

with SH in phase B (p = NS). Moreover, SH administration was associated with a 10.5% ± 9.4% and a 20.1% ± 6.8% fall in total cholesterol (p < 0.05) and low-density lipoprotein cholesterol (p < 0.001) in phase A, and 11.9% ± 7.2% (p < 0.05) and 21.5% ± 2.4% (p < 0.001), respectively, in phase B. In both phases of the study, AH administration was not followed by a significant change in serum lipid parameters. ♦ ♦ ♦ ♦ ♦ Conclusion: Sevelamer hydrochloride is a well-tolerated alternative to calcium-or aluminum-containing phosphorus binder in the control of serum phosphorus in CAPD patients. Furthermore, SH improves the lipid profile in these patients.

2025, Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis

Background Dietary phosphorus restriction, oral administration of phosphorus binders, and dialysis are the main strategies to control hyperphosphatemia in patients with stage 5 chronic kidney disease. Aluminum hydroxide (AH) and calcium carbonate, the most commonly used phosphorus binders, have serious disadvantages, such as aluminum toxicity and hypercalcemia. Sevelamer hydrochloride (SH) is a relatively new nonabsorbed calcium- and aluminum-free phosphorus binder. The present study was designed to evaluate the efficacy of SH in the control of hyperphosphatemia and its effect, compared to AH, on serum lipid parameters in patients on continuous ambulatory peritoneal dialysis (CAPD). Methods 30 stable patients on CAPD were included in an open-label, randomized crossover study. After a 2-week phosphorus binder washout period, 15 patients (group I) were administered SH for 8 weeks and in the remaining patients (group II), AH was introduced (phase A). After a new 2-week washout period, ...

2025

Treatment of Acid Mine Drainage (AMD) using fly ash (FA) has been investigated extensively and it has been demonstrated that significant levels of toxic elements can be removed by precipitation, co-precipitation and adsorption. Treatment of AMD using alkalis and FA has been investigated and the chemistry of toxic metal removal is well understood. This treatment method was studied extensively from the laboratory to jet loop reactor pilot plant 80 L capacity and the results were successful, reducing sulphate by 7090%, while removing most toxic metals. Based on preliminary results, a large-scale jet loop reactor pilot plant of 1000 L capacity was designed and constructed for the treatment of AMD using South African coal fly ash. AMD from a selected coalmine was treated with different amount of fly ash from a Free State power station. After characterisation by XRF, it was observed that the ash was ASTM C618 Class F fly ash with CaO by mass at 4.61 %. Treatment of AMD using different AMD...

2025

Microcystis aeruginosa is a widespread, toxin producing cyanobacterium that causes negative ecological, economical, and human health impacts. The use of polyacrylamides (PAM) as an algal control is gaining notice and attention. Previous work with PAM has shown anionic PAMs to be ineffective or less effective than cationic PAMs at flocculating algal cell due to the opposing negative charges of the PAM and the cell. In this study the 703d#3 Floc Log, an anionic PAM blend with a cationic bridging agent, was used to treat Microcystis aeruginosa and the green algae Pseudokirchneriella subcapitata. The treatment reduced cell number and chlorophyll a concentrations significantly in M. aeruginosa and the non-target comparison species P. subcapitata. The extent of the reductions varied depending on the initial cell density of the samples as well as the day after sampling the measurements was taken. The treatment was more effective at lower cell concentrations and the majority of reductions occurred immediately after treatment. Anionic PAMs can be effective at flocculating cyanobacteria when a cationic bridging material is present. It is a viable option for treatment and provides a safer alternative to cationic PAMs which have a higher toxicity to fish. ii Copyright by Kyla Jayne Iwinski 2013 iii DEDICATION My Thesis study is dedicated to my family. A special thanks to my parents, Joyce and Steve Iwinski for their endless support and guidance. Also to my sisters Virginia and Seva Iwinski, they are not only my sisters, but my colleagues and friends. I also want to dedicate this to my Marquette family for keeping me grounded, happy and making the many hours working at the kitchen table much more enjoyable. First of all I would like to thank my adviser Dr. Mac Strand for his help, guidance, and for support through the years. Without him I would not have had the opportunity to begin this journey let alone finish it. I would also like to thank my committee members Dr. Donna Becker and Dr. Erich Ottem for reviewing my thesis as well as their expertise. Dr. Becker was integral in learning culturing techniques and provided valuable knowledge on microorganisms. Without Dr. Ottem I would not have been able to obtain the confocal images that added a new and exciting dimension to my project. I would like to thank Dr. John Rebers for teaching me direct cell counts and for taking the time to review my thesis. I would also like to thank Dr. Jill Leonard for her guidance and support throughout my entire graduate school experience. I want to acknowledge the time that Jing F. Niu spent helping me with equipment and instruments, working through laboratory procedures, and for always showing an interest in me and my project. I would also like to thank Applied Polymer Systems, Inc. for supplying me with materials as well as their time and information. Finally I would like to thank my family. Without their love and emotional as well as financial support this would not have been possible.

2025

In this study, a series of rhodanine derivatives containing various substituents was synthesized and tested for in vitro algicidal activity. Among the tested substituent groups, phenyl substituents with halogen groups showed good inhibitory potency. Furthermore, the compound with chlorine at the C2 position of the phenyl ring exhibited a higher algicidal effect than the compound with chlorine at the C3 position of the phenyl ring. Among the various rhodanine derivatives tested, 5-(2,4-dichlorobenzylidene)rhodanine (compound 20) was the most potent inhibitor against M. aeruginosa with a lethal concentration 50 (LC 50) value of 0.65 μM and Selenastrum capricornutum with an LC 50 value of 0.82 μM. To verify the feasibility of their use in ecosystems, 25 h of acute ecotoxicity tests were carried out for three derivatives against Danio rerio and Daphnia magna. No mortality was observed in groups exposed to 2.0 μM of compound 20 after 100 h of exposure. Moreover, a survival rate of 100% was observed in D. magna exposed to 2 μM of compound 20 for 100 h. Overall, the results show that rhodanine derivatives are a possible method for controlling and inhibiting harmful algal blooms.

2025, Molecular Therapy

The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines-chimpanzee adenovirus ChAd63 and the orthopoxvirus MVA. A variety of promising "mixed-modality" regimens were tested. All volunteers were primed with ChAd63, and then subsequently boosted with MVA and/or protein-in-adjuvant using either an 8-or 16-week prime-boost interval. We report on the safety of these regimens, as well as the T cell, B cell, and serum antibody responses. Notably, IgG antibody responses primed by ChAd63 were comparably boosted by AMA1 protein vaccine, irrespective of whether CPG 7909 was included in the Alhydrogel adjuvant. The ability to improve the potency of a relatively weak aluminium-based adjuvant in humans, by previously priming with an adenoviral vaccine vector encoding the same antigen, thus offers a novel vaccination strategy for difficult or neglected disease targets when access to more potent adjuvants is not possible.

2025

Available vaccines against Brucella spp. are live attenuated Brucella strains. In order to engineer a better vaccine to be used in animals and humans, in our laboratory we aim to develop an innocuous subunit vaccine. Particularly, we are interested in the outer membrane proteins (Omps) of B. abortus: Omp16 and Omp19. In this study, we assessed the use of these proteins as vaccines against Brucella in BALB/c mice. Immunization with lipidated (L)-Omp16 or L-Omp19 in incomplete Freund's adjuvant (IFA) conferred significant protection against B. abortus infection. Vaccination with unlipidated (U)-Omp16 or U-Omp19 in IFA induced a higher degree of protection than the respective lipidated versions. Moreover, the level of protection induced after U-Omp16 or U-Omp19 immunization in IFA was similar to the elicited by live B. abortus strain 19 (S19) immunization. Flow cytometric analysis showed that immunization with U-Omp16 or U-Omp19 induced antigen-specific CD4 + as well as CD8 + T cells producing interferon-γ. In vivo depletion of CD4 + or CD8 + T cells in U-Omp16or U-Omp19-plus IFA-immunized mice resulted in a loss of the elicited protection, indicating that both cell types are mediating immune protection. U-Omp16 or U-Omp19 vaccination induced a T helper 1 response, systemic protection in Alum formulation and oral protection with cholera toxin adjuvant against B. abortus infection. Both immunization routes exhibited a similar degree of protection to attenuated Brucella vaccines (S19 and RB51 respectively). Overall these results indicate that U-Omp16 or U-Omp19 would be useful candidates for a subunit vaccine against human and animal brucellosis.

2025, Infection and Immunity

Brucella spp. are live attenuated Brucella strains. In order to engineer a better vaccine to be used in animals and humans, our laboratory aims to develop an innocuous subunit vaccine. Particularly, we are interested in the outer membrane proteins (OMPs) of B. abortus: Omp16 and Omp19. In this study, we assessed the use of these proteins as vaccines against Brucella in BALB/c mice. Immunization with lipidated Omp16 (L-Omp16) or L-Omp19 in incomplete Freund's adjuvant (IFA) conferred significant protection against B. abortus infection. Vaccination with unlipidated Omp16 (U-Omp16) or U-Omp19 in IFA induced a higher degree of protection than the respective lipidated versions. Moreover, the level of protection induced after U-Omp16 or U-Omp19 immunization in IFA was similar to that elicited by live B. abortus S19 immunization. Flow cytometric analysis showed that immunization with U-Omp16 or U-Omp19 induced antigen-specific CD4 ؉ as well as CD8 ؉ T cells producing gamma interferon. In vivo depletion of CD4 ؉ or CD8 ؉ T cells in mice immunized with U-Omp16 or U-Omp19 plus IFA resulted in a loss of the elicited protection, indicating that both cell types are mediating immune protection. U-Omp16 or U-Omp19 vaccination induced a T helper 1 response, systemic protection in aluminum hydroxide formulation, and oral protection with cholera toxin adjuvant against B. abortus infection. Both immunization routes exhibited a similar degree of protection to attenuated Brucella vaccines (S19 and RB51, respectively). Overall these results indicate that U-Omp16 or U-Omp19 would be a useful candidate for a subunit vaccine against human and animal brucellosis.

2025, Hemodialysis International

A grid was developed to evaluate control of serum calcium, phosphate, and parathyroid hormone levels in hemodialysis patients, based on guideline recommendations (National Kidney Foundation Kidney Disease Outcomes Quality Initiative and Canadian Society of Nephrology), and its face validity was examined in a representative sample of Canadian patients. A retrospective chart review was undertaken in hemodialysis patients from 7 Canadian units. Patients 418 years, on hemodialysis for ! 12 months, and ! 3 parathyroid hormone levels measured ! 1 month apart were included. The grid classified mineral metabolism control as optimal, suboptimal, or poor (mean of 3 measurements). Medication use, hospitalization, and Emergency Department visits were evaluated in relation to grid occupancy. A second comparative analysis of grid occupancy was undertaken on prevalent hemodialysis cases in British Columbia in 2008. Data from 268 patients (mean age 62.3 years) were analyzed. Using National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines, 17.5%, 28.8%, and 53.7% of patients had optimal, suboptimal, and poor control, respectively, of all 3 parameters (calcium, phosphate, and parathyroid hormone). Using Canadian Society of Nephrology criteria, optimal, suboptimal, and poor control rates were 6.3%, 4.2%, and 89.5%, respectively. Poor control was a possible or a probable cause of hospitalization or Emergency Department attendance in 8 patients. Data from British Columbia in 2008 (n= 1858) show optimal, suboptimal, and poor control rates of 15.8%, 24.5%, and 59.7%, respectively. Poor mineral metabolism control among Canadian hemodialysis patients is not showing improvement. The therapeutic grid is a valid tool and may help guide therapeutic decisions, quality control initiatives, and patient counseling. .

2025, Dalton Transactions

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

2025, Chemical Communications

We report on the one-pot synthetic procedure of cyclen derivatives bearing three acetate groups attached on boehmite nanoparticles, the complexing capabilities of these inorganicorganic hybrid materials with rare earth cations, and the... more

2025, Scientific Reports

Potassium channels and aquaporins expressed by astrocytes are key players in the maintenance of cerebral homeostasis and in brain pathophysiologies. One major challenge in the study of astrocyte membrane channels in vitro, is that their expression pattern does not resemble the one observed in vivo. Nanostructured interfaces represent a significant resource to control the cellular behaviour and functionalities at micro and nanoscale as well as to generate novel and more reliable models to study astrocytes in vitro. However, the potential of nanotechnologies in the manipulation of astrocytes ion channels and aquaporins has never been previously reported. Hydrotalcite-like compounds (HTlc) are layered materials with increasing potential as biocompatible nanoscale interface. Here, we evaluate the effect of the interaction of HTlc nanoparticles films with primary rat neocortical astrocytes. We show that HTlc films are biocompatible and do not promote gliotic reaction, while favouring ast...

2025

ll.A ~L...:.I •1 J.::o. ~u....--.<'tl I~L ~~ ~-•~ ~~WI <Li:il..uJI ~~ ~WLA • I.) .\ll bJJ ~I J.lall_, t ~~~~ ~p uA .u.:.~ d~ .tu~ uA l.o~ ~ ~I ~ -. ~~-I •~1 I~ .wllll.A t~ t.s--• ~~ ~~ bJi:!.J.:a ~~ b~ tl~~~ J.k. dlA_, ~6..bJJ ~~ J.lall... more

2025, Gut

The effectiveness of antacid maintenance therapy in preventing duodenal ulcer (DU) relapse was investigated. Two hundred and fifty one asymptomatic patients with healed DU were stratified into smokers and non-smokers and randomised to receive for one year either placebo, or Maalox TC three tablets (81 mmol) at bedtime (hs), or Maalox TC three tablets in the morning plus three tablets at bedtime (bd) (162 mmol), or cimetidine 400 mg at bedtime. A double dummy technique was used to render the study double blind. In 176 patients evaluable for efficacy, the cumulative relapse at one year was: placebo 57%; Maalox TC hs 39%; Maalox TC bd 23%; cimetidine 25%. Maalox TC bd and cimetidine were equally effective and superior to placebo (p<O.Ol) and bedtime Maalox TC (p<004). The benefit of treatment was significant for the overall sample and for the subgroup of smokers. The results for the non-smokers also supported efficacy for these two treatments but, perhaps because of small sample sizes, these comparisons were not significant. All 251 patients were assessed for safety. Approximately half the patients in each treatment group had adverse events, leading to withdrawal in three, seven, 12, and four patients on placebo, Maalox hs, Maalox bd, and cimetidine respectively. Diarrhoea occurred in 12 patients in Maalox TC bd and eight in each other group. Serum magnesium concentrations were unchanged; aluminium concentrations were higher than baseline at six and 12 months in both antacid groups and at 12 months in the cimetidine group but the differences were not significant. Maalox TC three tablets bd are as effective as cimetidine 400 mg at bedtime in reducing DU relapse and both are superior to placebo. The efficacy of antacids in healing duodenal ulcer (DU) is well known.`' Their value in preventing DU recurrence when given as maintenance therapy is not established, although Bianchi Porro et all have reported that in 69 evaluable healed DU patients treated for one year, the effects of low dose antacids were indistinguishable from those of cimetidine 400 mg hs or the combination. We therefore conducted a multicentre study to investigate the

2025, Protein & Peptide Letters

Botulism is a neuroparalytic disease caused by Clostridium botulinum, which produces seven (A-G) neurotoxins (BoNTs). The mouse bioassay is the gold standard for the detection of botulinum neurotoxins, however it requires at least 3-4 days for completion. Most of the studies were carried out in botulinum toxin A and less on type B. Attempts have been made to develop an ELISA based detection system, which is potentially an easier and more rapid method of botulinum neurotoxin detection. In the present study, the synthetic BoNT/B LC gene was constructed using PCR overlapping primers, cloned in a pET28a+ vector and expressed in E. coli BL21DE3. The maximum yield of recombinant proteins was optimized after 16 hrs of post induction at 21°C and purified the recombinant protein in soluble form. Antibodies were raised in Mice and Rabbit. The IgG antibody titer in the case of Mice was 1: 1,024,000 and Rabbit was 1: 512,000 with alum as adjuvant via intramascular route. The biological activity of the recombinant protein was confirmed by in-vitro studies using PC12 cells by the synaptobrevin cleavage, the rBoNT/B LC protein showed the maximum blockage of acetylcholine release at a concentration of 150nM rBoNT/B LC in comparison to the control cells. When the cells were incubated with rBoNT/B LC neutralized by the antisera raised against it, the acetylcholine release was equivalent to the control. IgG specific to rBoNT/B LC was purified from raised antibodies. The results showed that the developed antibody against rBoNT/B LC protein were able to detect botulinum toxin type B approximately up to 1 ng/ml. These developed high titer antibodies may prove useful for the detection of botulinum neurotoxins in food and clinical samples.

2025, Innate Immunity

It has already been shown that tetanus toxoid (TTd) hyper-immunization is a suitable experimental method for creating the animal model of antiphospholipid syndrome (APS) in BALB/c mice. The severity of APS pathology in BALB/c mice mainly correlates to the affinity of anti-β2glycoprotein I (β2GPI) antibodies. In this study we have investigated reproductive pathology induced in C57BL/6 mice by TTd hyper-immunization using a combination of different pretreatments (complete Freund's adjuvant or glycerol) and adjuvants (alhydrogel or glycerol). A decrease in fecundity was recorded in only C57BL/6 mice immunized with alhydrogel adjuvant, irrespective of the kind of applied pretreatment; it was associated with an increase in abundance of low affinity anti-β2GPI IgG antibodies and Th1 prevalence.

2025, Microbiology and Immunology

ABSTRACTResults are presented concerning our attempts to create a suitable model system for studying the connection between microbial antigen (micAg), autoimmunity and autoimmune disease on the basis of hyper‐immunization and application of micAg in different contexts. Our research was focused on tetanus toxoid (TTd) as a model micAg. Non‐pretreated and complete Freund's adjuvant pretreated BALB/c mice were immunized with high doses of TTd mixed with glycerol or aluminum hydroxide as adjuvants. The main aims of the experiments were to evaluate the properties of induced humoral immune responses, evaluate the pathological potential of induced immune responses and determine possible correlations between the properties of a humoral immune response and its pathological potential. The production of TTd‐specific and self‐reactive β2‐glycoprotein I (β2‐GP I)‐specific antibodies (Abs) was detected in all groups but with specific, context‐related properties. Analysis of pregnancy‐related ...

2025, International Journal of Gynecology & Obstetrics

2025, Environmental Science & Technology

This supporting information contains a total of nine pages, including the materials preparation procedure, description of characterization techniques, Two tables: • Chemical Formulae for different HT compounds. • Chemical composition... more

2025, European Journal of Pharmacology

This study was undertaken to investigate the role of the aldose reductase in the refractoriness of diabetic rats to allergic inflammation. Wistar rats were actively sensitized with a mixture of Al(OH) 3 plus ovalbumin and intrapleurally challenged with ovalbumin, 14 days later. Diabetes was induced by intravenous injection of alloxan into fasted rats, 7 days before sensitization, and the aldose reductase inhibitor zopolrestat was administered after 3 days of diabetes induction, once a day during 18 consecutive days. The treatment with zopolrestat restored antigen-induced protein extravazation and mast cell degranulation in the pleural cavity of diabetic sensitized rats. Zopolrestat also significantly reversed the suppression in the increase of total and specific levels of serum immunoglobulin E (IgE) noted in sensitized animals under conditions of diabetes. In addition, we noted that the drop in the pleural mast cell numbers as well as the increase in serum corticosterone levels in diabetic rats were inhibited by the drug. Our findings show that zopolrestat restored the hyporesponsiveness of diabetic rats to antigen provocation, in parallel with impairment of alloxan-induced mast cell depletion and hypercorticolism, indicating that polyol pathway activity seems to play an important role in these phenomena.

2025, Aluminum in food and potential role on Alzheimer’s disease of aluminum

Several studies have shown the relationship between the aluminum exposure and the Alzheimer's disease. The gastrointestinal absorption of Aluminum (Al) is low. Also, If the renal filtering system works as needed, generally urine can be enough to eliminate overdose (rational over concentrations) of Al. But Al can be found in kinds of foods and drinks such as processed foods (because of additives, packaging materials, utensils…), fresh vegetables and fruits (because of soil) and even in drinking water therefore, in some cases, the Al level may pose a health risk. Chronic high concentration to Al exposure preferably intakes by oral, intravascular ways with also not having a good condition of Glomerular Filtering System of Kidneys (GFR). Nowadays, although mankind is having more Al by oral ways than past and many studies have been conducted to determine whether there is a relationship between aluminum and Alzheimer's disease(AD) or not. Therefore, this review is intended to provide a short summary of the works done in the past and it may warn people about Al intake in the next decade, therefore human can change their life to be more natural less industrial.

2025, Giornale di Tecniche Nefrologiche e Dialitiche

2025, Magnetic Resonance in Chemistry

First-principles quantum mechanical calculations of NMR chemical shifts and quadrupolar parameters have been carried out to assign the 27 Al MAS NMR resonances in gibbsite. The 27 Al NMR spectrum shows two signals for octahedral aluminum revealing two aluminum sites coordinated by six hydroxyl groups each, although the crystallographic positions of the two Al sites show little difference. The presence of two distinguished 27 Al NMR resonances characterized by rather similar chemical shifts but quadrupolar coupling constants differing by roughly a factor of two is explained by different character of the hydrogen bonds, in which the hydroxyls forming the corresponding octahedron around each aluminum site, are involved. The Al-I site characterized by a C Q = 4.6 MHz is surrounded by OH-groups participating in four intralayer and two interlayer hydrogen bonds, while the Al-II site with the smaller quadrupolar constant (2.2 MHz) is coordinated by hydroxides, of which two point toward the intralayer cavities and four OH-bonds are aligned toward the interlayer gallery. In high-resolution solid-state 1 H CRAMPS (combination of rotation and multiple-pulse spectroscopy) four signals with an intensity ratio of 1 : 2 : 2 : 1 are resolved which allow to distinguish six nonequivalent hydrogen sites reported in the gibbsite crystal structure and to ascribe them to two types of structural OH groups associated with intralayer and interlayer hydrogen bonds. This study can be applied to characterize the gibbsite-like layer -intergallery interactions associated with hydrogen bonding in the more complex systems, such as synthetic aluminum layered double hydroxides.

2025, Vaccine

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

2025, Proteomics

Stimulation of protective immune responses against intracellular pathogens is difficult to achieve using non-replicating vaccines. BALB/c mice immunized by intramuscular injection with killed Francisella tularensis (live vaccine strain) adjuvanted with preformed immune stimulating complexes admixed with CpG, were protected when systemically challenged with a highly virulent strain of F. tularensis (Schu S4). Serum from immunized mice was used to probe a whole proteome microarray in order to identify immunodominant antigens. Eleven out of the top 12 immunodominant antigens have been previously described as immunoreactive in F. tularensis. However, 31 previously unreported immunoreactive antigens were revealed using this approach. Twenty four (50%) of the ORFs on the immunodominant hit list belonged to the category of surface or membrane associated proteins compared to only 22% of the entire proteome. There were eight hypothetical protein hits and eight hits from proteins associated with different aspects of metabolism. The chip also allowed us to readily determine the IgG subclass bias, towards individual or multiple antigens, in protected and unprotected animals. These data give insight into the protective immune response and have potentially important implications for the rational design of non-living vaccines for tularemia and other intracellular pathogens.

2025, Vaccine

Nanotechnology promises a revolution in medicine including through new vaccine approaches. The use of nanoparticles in vaccination has, to date, focused on attaching antigen directly to or within nanoparticle structures to enhance antigen uptake by immune cells. Here we question whether antigen incorporation with the nanoparticle is actually necessary to boost vaccine effectiveness. We show that the immunogenicity of a sub-unit protein antigen was significantly boosted by formulation with silica nanoparticles even without specific conjugation of antigen to the nanoparticle. We further show that this effect was observed only for virus-sized nanoparticles (50 nm) but not for larger (1000 nm) particles, demonstrating a pronounced effect of nanoparticle size. This non-attachment approach has potential to radically simplify the development and application of nanoparticle-based formulations, leading to safer and simpler nanoparticle applications in vaccine development.

2025, Vaccine

2024, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Infrared and Raman spectroscopy have been used to characterize synthetic hydrotalcites of formula Cu x Zn 6-x Al 2 (OH) 16 (CO 3 ).4H 2 O . The spectra have been used to assess the molecular assembly of the cations in the hydrotalcite structure. The spectra may be conveniently subdivided into spectral features based (a) upon the carbonate anion (b) the hydroxyl units (c) water units. The Raman spectra of the hydroxyl-stretching region enable bands to be assigned to the CuOH, ZnOH and AlOH units. It is proposed that in the hydrotalcites with minimal cationic replacement that the cations are arranged in a regular array. For the Cu x Zn 6- x Al 2 (OH) 16 (CO 3 ).4H 2 O hydrotalcites, spectroscopic evidence suggests that 'islands' of cations arte formed in the structure. In a similar fashion the bands assigned to the interlayer water suggest that the water molecules are also in a regular well-structured arrangement. Bands are assigned to the hydroxyl stretching vibrations of water. Three types of water are identified (a) water hydrogen bonded to the interlayer carbonate ion (b) water hydrogen bonded to the hydrotalcite hydroxyl surface and (c) interlamellar water. It is proposed that the water is highly structured in the hydrotalcite as it is hydrogen bonded to both the carbonate anion and the hydroxyl surface.

2024, Polyolefins Journal

The article presents the results of studies of the influence of aluminum hydroxide concentration on the crystallization process regularities of nanocomposites based on compatibilized polypropylene random copolymer and aluminum hydroxide (PP-R/PPH-g-MAH/Al(OH)3). The isothermal crystallization kinetics of compatibilized polypropylene random copolymer composites containing 1, 3, 5, 10, 20, 30 and 50 wt. % of aluminum hydroxide was determined by the stepwise dilatometry method using the Kolmogorov-Avrami equation. The crystallization behaviors of composites were investigated on an IIRT-1 device converted into a dilatometer, in the process of stepwise cooling of samples under a load of 5.3 kg. In this study, maleic anhydride functionalized homopolypropylene (PPH-g-MAH) was employed as a compatibilizer to enhance the compatibility between the PP-R and Al(OH)3. Considering the dependence of specific volume and free specific volume on temperature, the first-order phase transition was established and the glass transition temperature values of the composites were determined. The mechanism of formation and development of crystallization centers in the region of the first-order phase transition was investigated. The obtained values of “n” prove that the mechanism or nature of the growth of crystallization centers changes into three-dimensional spherulitic - two-dimensional disc-shaped - one-dimensional rod-shaped with an increase in the amount of aluminum hydroxide in composite. The study of the temperature dependence of the specific volume for the studied samples showed that the first order phase transition occurs at a temperature of 125°C. It was determined that the second order phase transition temperature (the glass transition temperature determined by the dilatometric method) increases with the increase in the amount of filler.

2024, Vaccine

Thirty-three HIV-seronegative adults were recruited into a Phase I safety and immunogenicity HIV-1 vaccine trial. The immunogens were as follows: a synthetic, monovalent, octameric HIV-1 MN V3 peptide in aluminum hydroxide (alum) adjuvant administered by intramuscular delivery; and a similar product encapsulated in biodegradable micro-spheres composed of co-polymers of lactic and glycolic acids, administered by the oral route. These were administered in three sequential oral doses, followed by a parenteral boost. No serious adverse experiences were observed. Oral administration of this vaccine, alone or in combination with parenteral boosting, resulted in no significant humoral, cellular, or mucosal immune responses.

2024, Journal of Immunotoxicology

The adjuvanticity of aluminum hydroxide and calcium phosphate on the antibody response in mice towards the venom of the snake Bothrops asper was studied. It was found that, in vitro, most of the venom proteins are similarly adsorbed by both mineral salts, with the exception of some basic phospholipases A 2 , which are better adsorbed by calcium phosphate. After injection, the adjuvants promoted a slow release of the venom, as judged by the lack of acute toxicity when lethal doses of venom were administered to mice. Leukocyte recruitment induced by the venom was enhanced when it was adsorbed on both mineral salts; however, venom adsorbed on calcium phosphate induced a higher antibody response towards all tested HPLC fractions of the venom. On the other hand, co-precipitation of venom with calcium phosphate was the best strategy for increasing: (1) the capacity of the salt to couple venom proteins in vitro; (2) the venom ability to induce leukocyte recruitment; (3) phagocytosis by macrophages; and (4) a host antibody response. These findings suggest that the chemical nature is not the only one determining factor of the adjuvant activity of mineral salts.

2024, Zentralblatt für Bakteriologie

Rabies vaccine containing aluminium hydroxide and oil adjuvant were compared for their efficacy in inducing serological response in 11-12 months old calves. The serum antibody titres were estimated at 0,21,90, 180 and 360 dpv by RFFIT. Both groups of calves responded serologically in a similar way and there was no significant varia tion in serum antibody titres in animals between both groups of animals. The serum antibody titres in both groups of animals were above protective levels on 360 dpv.

2024

The soils in index 4 have relatively high soil P concentrations. Such concentrations are not of economic benefit to the farmer. These sites are also likely to be more at risk of P loss from soil to water compared to sites in the lower index categories (Sharpley and Rekolainen, 1997). Discussion The linear relationship between CaCl 2 P and Morgan P indicates that both of these tests provide comparable results for the soil types examined in this experiment. In the UK, Williams and Cooke (1962) found that the Morgan and CaCl 2 tests tended to be closely correlated. The absence of a linear relationship between Morgan or C a C l 2 tests with the Olsen P test indicates that the Olsen test provided a comparatively low estimation of soil P levels at the higher soil P concentrations included in this study. The relationship between the CaCl 2 test and the Olsen test, presented in this study, is similar to that demonstrated by Johnston and Poulton (1993).

2024, Chemosphere

Nitrate-intercalated MgAl layered double hydroxide (LDH) was successfully delaminated in water by a facile and effective method upon reflux at 120 °C for 24 h followed by sonication at 40 °C for 5 h. This process is environmentally friendly since water is the only solvent used. The delaminated nanosheets were characterized by microscopic, spectroscopic, and particle size analyses. The delamination process successfully produced octahedron-shaped single-layer nanosheets 50-150 nm in size. X-ray photoelectron spectroscopy (XPS) data confirmed that the surface elements and their chemical status are consistent with the basic layer of MgAl LDH. The delaminated nanosheets displayed higher adsorption capacity for removing heavy metals from waste water than the original powdered LDH. After treating the waste water, a sharp and intense peak in the X-ray powder diffraction (XRD) pattern of the precipitate confirms the restacking of the LDH nanosheets.

2024, Vaccine

Novel adjuvants that contain immunoenhancer molecules are now present in human vaccines either registered or in clinical trials. These adjuvants have the potential to provide clear benefits in improving the magnitude and duration of various aspects of the adaptive immune response. However, the use of immunoenhancers in vaccine formulations may be perceived as introducing theoretical safety risks that need to be addressed during the course of vaccine development. In addition to classical clinical safety evaluation, the licensing authorities recommend that novel adjuvants should be evaluated in non-clinical toxicology studies, both as separate entities and as part of the final vaccine formulation. We present here our approach for the safety evaluation of adjuvanted vaccines using AS04-adjuvanted vaccines as example. This evaluation consists of three tiers: non-clinical toxicology, adjuvant mode-of-action investigations and clinical safety assessment in controlled clinical trials and post-marketing surveillance. We also discuss how the knowledge of adjuvant mode of action can support the current practice of safety evaluation.

2024

Boron removal by raw and aluminum modified pumice from Bigadiç colemanite mine wastewaters in Turkey were investigated. At Bigadiç mine, the colemanite ore is waited in water pools for swelling of attached clays (382 mg Boron/L) and then washed. The general wastewater of mine is stored in Çam Köy dam (608.1 mg Boron/L). The influence of pH (3-9), dilution ratio (1-10) and adsorbent dosage (1-05 g/50 mL) was studied for waiting pool wastewater. The maximum adsorption capacities of modified and raw pumice were calculated as 1.06 mg/g and 0.607 mg/g for waiting pool wastewater. In the experimental design for waiting pool wastewater, low and high parameter levels were pH (3 and 7), dilution fold (1 and 10) and adsorbent dosage (1 and 5 g/50 mL). According to confidence level (p<0.1) (2 3 factorial design), the statistically important sequence of factors for modified pumice were model constant, adsorbent amount, dilution, adsorbent amount-dilution ratio, pH-dilution ratio, pH, pH-adsorbent amount. The pseudo second order kinetic model described the boron adsorption. The isotherm data of study fitted to the Langmuir isotherm than Freundlich isotherm. As the adsorption capacity of aluminum modified pumice was not so high, the in-situ formed aluminum hydroxide was tested and provided about %75.35 boron removal from Çam Köy dam wastewater (608.1 mg Boron/L).

2024, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Raman spectroscopy has been used to study the nitrate hydrotalcite mbobomkulite NiAl 2 (OH) 16 (NO 3 ).4H 2 O. Mbobomkulite along with hydrombobomkulite and sveite are known as 'cave' minerals as these hydrotalcites are only found in caves. Two types of nitrate anion are observed using Raman spectroscopy namely free or non-hydrogen bonded nitrate and nitrate hydrogen bonded to the interlayer water and to the 'brucite-like' hydroxyl surface. Two bands are observed in the Raman spectrum of Ni-Mbobomkulite at 3576 and 3647 cm -1 with an intensity ratio of 3.36/7.37 and are attributed to the Ni 3 OH and Al 3 OH stretching vibrations. The observation of multiple water stretching vibrations implies that there are different types of water present in the hydrotalcite structure. Such types of water would result from different hydrogen bond structures.

2024, Vaccine

Leptospirosis is an important zoonotic disease worldwide. Subunit vaccines are an attractive intervention strategy against this disease, but potent, non-toxic adjuvants are necessary components to any effective vaccine. Among various adjuvant candidates, liposomes have garnered recent attention for their capacity as carriers of vaccines. In the present study we prepared novel liposomes using total polar lipids from the nonpathogenic bacterium, Mycobacterium smegmatis (designated smegmosomes). The potential for smegmosomes as a vaccine delivery/adjuvant system was evaluated with novel leptospira protective antigens (Lp0607, Lp1118, Lp1454) and compared with conventional aluminum hydroxide adjuvant (alum) in a hamster model of leptospirosis. Four-week-old hamsters were immunized subcutaneously twice at three weeks intervals and either bled at various time points to evaluate antibody responses, sacrificed to isolate splenocytes for lymphocyte proliferation and cytokine profiles in response to recall antigen, or challenged intraperitoneally with a modified lethal dose (10X MLD 50 ) of virulent Leptospira interrogans serovar Pomona. Our results demonstrate that smegmosomes carrying antigens are better adjuvants than alum as revealed by enhanced and long term antibody response, lymphocyte proliferation and significant enhancement in both Th1 (IFN-␥) and Th2 (IL-4, IL-10) cytokine production. Additionally, smegmosomes were found to induce memory responses that are significantly higher than those of alum. Above all, smegmosomes were observed to impart a significantly higher level of protection than alum as revealed by enhanced survival, reduced histopathological lesions and bacterial load in vital organs. Taken together, the data of the present study suggests that smegmosomes will serve well as a promising delivery vehicle/adjuvant system that can induce both Th1 and Th2 type immune responses and provide a novel tool in development of improved vaccines for leptospirosis and other infectious diseases.