Immunization
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
In addition to the antigenic components to be described below, vaccine preparations usually contain other constituents, some active and some inert. Among the most important are adjuvants, i.e., agents which increase immunogenicity. Adjuvants are proving to be especially important in recombinant subunit vaccines which as a group tend to be poorly immunogenic. It is now appreciated that bacterial whole cell vaccines may owe at least a portion of their immunogenicity to naturally occurring materials such as lipid A which act as natural adjuvants. Their particuiate nature may aiso be a contributing factor, since the immune system processes particulate and soluble antigens differently. Currently, the only adjuvant licensed in the United States is alum. Alum consists of either aluminum hydroxide or aluminum phosphate and is an insoluble substance with the property of adsorbing protein to its exposed surfaces. The efficacy of alum in promoting the immune response is poorly understood, but may be related to the concentration on the particles of alum of many molecules of antigen, thus presenting to the immune system particles covered with multiple epitopes. As occurs with cellular vaccines, so with alum-containing vaccines, the persistence of antigen at the injection site due to the decreased solubility of the complex may also play a role in increasing immunogenicity.
Ofloxacin
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Ofloxacin absorption is not significantly impaired by the co-administration of calcium carbonate or aluminum phosphate, although it may be delayed and possibly slightly reduced by co-administration of magnesium–aluminum hydroxide; nevertheless, this effect is somewhat less than that observed with other fluoroquinolones (Maesen et al., 1987; Flor et al., 1990; Akerele and Okhamafe, 1991; Sánchez Navarro et al., 1994; Lode, 2001; Sultana et al., 2007). Regardless of these findings, separating the administration of ofloxacin and antacids or multivalent cation–containing preparations by at least 2 hours would seem prudent (Hooper, 2000). The antiretroviral didanosine (ddI) buffered pediatric oral solution contains antacid, so the same care should be exercised, although this drug is now used uncommonly (AHFS, 2015). The absorption of ciprofloxacin, norfloxacin, and ofloxacin is significantly reduced by the co-administration of ferrous sulfate, although ofloxacin is less affected than the other agents, with a reduction in AUC and peak plasma concentrations of 25% and 36%, respectively. Thus ferrous sulfate and these fluoroquinolones should not be administered together (Lehto et al., 1994a; Sultana et al., 2007). Co-administration with the other metal cations chromium, manganese, nickel, copper, zinc, and cadmium also slightly reduced bioavailability (Sultana et al., 2007). Concurrent administration of sucralfate and ofloxacin reduces ofloxacin bioavailability by about 61%, but no such reduction occurs if the ofloxacin is given 2 hours prior to sucralfate (Kawakami et al., 1994; Lehto and Kivisto, 1994b).
A
Caroline Ashley, Aileen Dunleavy, John Cunningham in The Renal Drug Handbook, 2018
Aluminum hydroxide or oxide is slowly solubilised in the stomach and reacts with hydrochloric acid to form aluminium chloride and water. In addition to forming aluminium chloride, dihydroxyaluminium sodium carbonate and aluminium carbonate form carbon dioxide, and aluminium phosphate forms phosphoric acid. About 17–30% of the aluminium chloride formed is absorbed and is rapidly excreted by the kidneys in patients with normal renal function.
Aluminum reproductive toxicity: a summary and interpretation of scientific reports
Published in Critical Reviews in Toxicology, 2020
The primary source of Al intake in the general human population is from foods and beverages, with over 95% most commonly from food. Daily Al intake by adults from 70 English-language published studies since 1990 averaged 7.4 mg, with a median of 5.3 mg (calculated by the author). Assuming 70 kg body weight, 7.4 mg/day results in a daily intake of 106 μg/kg. Assuming 0.1% Al absorption, the daily systemic Al exposure would be ∼0.1 μg/kg, or 0.5 to 1% of that calculated for the mouse and rat. However, some people consume much more dietary Al than these averages. The highest average reported in these studies is 28.5 mg/day (Gharib 2004) and one individual’s daily consumption was reported to be 176 mg (Aung et al. 2006). Major contributors to Al in food are the approved food additives acidic sodium aluminum phosphate as a leavening agent, resulting in high Al levels in baked goods; basic sodium aluminum phosphate as an emulsifying agent in cheese; and sodium aluminosilicate as an anticaking agent, in non-diary creamer and single packets of salt (Yokel 2013). In China, fried bread, and in Japan jellyfish treated with alum, often contain very high Al levels. Tea beverage typically contains 1–4 mg/L and can significantly increase daily Al intake. Consumption of Al-containing pharmaceuticals, such as antacids/phosphate binders, can result in ingestion of up to 5000 mg Al/day (Yokel and McNamara 2001). Because >90% of Al is eliminated by the kidneys, reduced renal function and end-stage renal disease can increase Al accumulation and the risk of Al-induced adverse effects.
Beyond the amyloid hypothesis: how current research implicates autoimmunity in Alzheimer’s disease pathogenesis
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Miyo K. Chatanaka, Dorsa Sohaei, Eleftherios P. Diamandis, Ioannis Prassas
Aluminum was deemed another antigen that can trigger autoimmunity, due to its increased prevalence in water, processed foods, such as bread, ice cream, and chocolate, and various pharmacological products, such as antiperspirants and vaccines (diphtheria, tetanus, polio, etc.) [204,315]. Aluminum salts (aluminum phosphate, aluminum hydroxide) are used in vaccines to enhance the activation of immune responses, resulting in higher antibody production and T/B cell immunological memory [316]. Due to its high positive charge, it can bind to proteins, act as a cross-linker between proteins, induce protein oligomerization, and conformational changes that hinder degradation by proteases [204]. Specifically, in AD, aluminum has been linked to the oligomerization of Aβ [317,318]. Vodjani et al. examined the immune response to complexes that included aluminum hydroxide (AH-HSA), aluminum citrate (AC-HSA), and aluminum potassium sulfate bound to human serum albumin (HSA) (APS-HSA) in 94 HC, 47 AD, 47 Crohn’s disease, 47 celiac diseases and 47 mixed connective tissue disease (MCTD) patients using ELISA [204]. The results showed that the percentage of samples with elevated anti-AH-HSA, anti-AC-HSA, and anti-APS-HSA was higher in the non-control sera [204], including AD. The percentage of AD patients with increased anti-AH-HSA was 29%, for anti-AC-HSA 53%, and for anti-APS-HSA 63%, whereas for controls it was 10% [204]. This could indicate that aluminum binds to proteins that contain amino acids like histidine, tyrosine, and arginine in the brain, which form neoantigens that can then be targeted by the immune system [317–320].
Evaluation of 28-day repeated oral dose toxicity of aluminum chloride in rats
Published in Drug and Chemical Toxicology, 2022
Je-Oh Lim, Tae-Yang Jung, Se-Jin Lee, So-Won Park, Woong-Il Kim, Sung-Hyeuk Park, Je-Hein Kim, Jeong-Doo Heo, Yong-Bum Kim, In-Sik Shin, Jong-Choon Kim
Aluminum and its compounds are major constituents of the Earth’s crust, comprising approximately 8% of the minerals found on the Earth’s surface (ATSDR 2008, Willhite et al. 2014). Aluminum is light in weight and is durable because the surfaces of products made from this element are oxidized to form a thin protective coating of aluminum oxide. Aluminum metal and its alloys are used extensively in construction, transportation, packaging, and electrical equipment. Several chemical compounds containing aluminum are extensively used in various products and processes associated with human activities. These compounds are aluminum chloride, aluminum hydroxide, aluminum nitrate, aluminum phosphate, aluminum sulfate, aluminum potassium sulfate, aluminum ammonium sulfate, and aluminum silicate (Igbokwe et al. 2019). Owing to the increased production and widespread use of aluminum and its compounds, human exposure to aluminum products has steadily increased, which may result in adverse health effects. Aluminum has not been classified with respect to carcinogenicity; however, ‘aluminum production’ has been classified as carcinogenic to humans (Group I) by the International Agency for Research on Cancer (IRIS 1999, ATSDR 2008).
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