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Structure and properties of aluminum-containing adjuvants.

This chapter is concerned with the identification, characterization, and behavior of aluminum-containing adjuvants with proteins and anions similar to those occurring in vaccines and interstitial fluid. Aluminum-containing adjuvants referred to commercially as aluminum hydroxide have been identified as poorly crystalline aluminum oxyhydroxide with the structure of the mineral boehmite. Relevant properties of this material include its high surface area and its high pI, which provide the adjuvant with a high adsorptive capacity for positively charged proteins. Aluminum phosphate and alum-precipitated adjuvants may be classified as amorphous aluminum hydroxyphosphate with little or no specifically adsorbed sulfate. Variations in the molar PO4/A1 ratio of amorphous aluminum hydroxyphosphates result in PI values that range from 5 up to 7; the materials are negatively charged at a physiological pH of 7.4. The amorphous nature of these compounds gives them high surface area and high protein adsorptive capacity for positively charged proteins. Observations on the interactions of anions and charged proteins with charged adjuvant surfaces have provided a framework for predicting behavior of complex systems of vaccines and for designing specific combinations of adjuvants and antigens to optimize the stability and efficacy of vaccines.

Adjuvants, Immunologic↗

Removal of nitroaromatics from synthetic wastewater using two-step zero-valent iron reduction and peroxidase-catalyzed oxidative polymerization.

Degradation of nitroaromatics, which are significant environmental pollutants, is difficult to achieve. Zero-valent iron reduction of nitroaromatics coupled with peroxidase-catalyzed capture of the resulting anilines as a two-step strategy for removing nitroaromatics from wastewater and process water is investigated here. The concentration range of nitroaromatics studied was that which would be present in industrial wastewater streams. Studies were done in continuous-flow columns. The enzymatic treatment following zero-valent iron reduction was carried out in a plug-flow reactor using a crude preparation of the enzyme soybean peroxidase extracted from soybean hulls. The complete reaction time for the two steps was 5 to 5.5 hours. Operating parameters including pH, peroxide/substrate ratio, enzyme concentration, and alum concentration were optimized. Optimum conditions obtained were approximately neutral pH with a hydrogen peroxide/substrate molar ratio of 1.5 for all of the nitroaromatics tested. Alum concentrations between 50 and 100 mg/L were useful in removing the apparent color from the treated water.

Hydrocarbons, Aromatic↗

Penetrating the conjunctival barrier. The role of molecular weight.

Dinitrophenyl (DNP) derivatives of various molecular weights were tested for their ability to elicit ocular anaphylaxis after topical application to the eye of immunized animals. Adult male Sprague-Dawley rats were immunized by intraperitoneal injection of DNP-Ascaris suum extracts and alum and were then skin-tested with DNP-bovine serum albumin on day 13 post-immunization to assess their sensitivity to the DNP hapten. On day 14, animals were challenged topically with DNP derivatives in one eye; PBS was applied to the contralateral, control eye. Animals were evaluated clinically, and ocular tissues were processed for histologic evaluation. The compounds used for topical ocular challenge included the DNP derivative of egg albumin (MW 43,500 D), soybean trypsin inhibitor (MW 20,080 D), insulin (MW 5733 D), B-chain insulin (MW 3496 D), and lysine (MW 478 D). Only di-DNP-lysine elicited clinical signs of redness, edema, and tearing and histologic evidence of mast cell degranulation. None of the other compounds, tested in solutions of either equal numbers of milligram per milliliter or equimolar concentrations, elicited ocular anaphylaxis after topical application. A compound of low molecular weight, less than 3496, is needed to elicit ocular anaphylaxis when applied topically.

Administration, Topical↗

Rapid and economical indicator for evaluating arsenic removal with minimum aluminum residual during coagulation process.

Detection of various types of contaminants in water treatment plant by sophisticated analytical methods such as inductively coupled plasma/mass spectrometry and gas chromatography/mass spectrometry requires hours to days to provide the results. Because naturally occurring ultraviolet (UV) active compounds are commonly present in almost all source waters and can be rapidly monitored by UV absorbance at 260 nm (E260), the extent of correlation between the removal efficiency of E260 and the removal efficiency of As(V) with minimum soluble residual Al by coagulation process was investigated. Percentage removals for E260 were well correlated to those of As(V). When sufficient alum or polyaluminum chloride (PACl) was added for 60-65% removal of E260, 90-95% removal of As(V) was achieved with minimum soluble residual Al regardless of the initial level of turbidity, E260, and As(V). As E260 analysis is precisely available even by an unskilled plant operator in a few minutes, E260 removal efficiency appears to be the promising economical indicator for monitoring the effectiveness of the coagulation process for the removal of contaminants with minimum residual Al.

Aluminum↗

Aluminum compounds used as adjuvants in vaccines.

The structure of nine commercially manufactured aluminum-containing adjuvants was investigated by X-ray diffraction, infrared spectroscopy, transmission electron micrography, and energy dispersive spectrometry. Seven samples which were labeled as aluminum hydroxide were identified as boehmite, a crystalline aluminum oxyhydroxide [AlO(OH)]. However, the degree of crystallinity varied between the samples. Two samples which were labeled as aluminum phosphate were found to be amorphous aluminum hydroxyphosphate. Buffer anions and sulfate anions substitute for hydroxyls in the amorphous aluminum hydroxide formed by the in situ alum precipitation method. Finally, the aluminum-containing adjuvant in diphtheria and tetanus toxoid, U.S.P., produced by three manufacturers was characterized.

Adjuvants, Pharmaceutic↗

[The effect of aluminum on the structure and metabolism of collagen].

BACKGROUND: Aluminium is considered to be the etiopathogenetic factor in various pathological conditions. It was demonstrated already previously that metals even under conditions in vivo link with collagen structures and influence the protein metabolism. Therefore the authors investigated the effect of aluminium (Al) on collagen and its metabolism. METHODS AND RESULTS: In the described trial aluminium was used as potassium alum, oxalate alum or aluminium chloride. The effect of aluminium was investigated in rats, chick embryos or fibroblast cultures. Using electron microscopy of collagen from the tail tendons, the development of transverse striation following 15 weeks of i.m. Al administration was revealed. At the same time also an increase of temperature of contraction of this collagen by 1.5 to 3.7 degrees C occurred, depending on the Al compound used. On fibroblast cultures an inhibitory effect of Al on their proliferation was found. In chick embryos Al caused a decline of the radioactive hydroxyproline concentration and thus also a reduced collagen synthesis practically in all investigated tissues. Similarly the negative effect of Al was manifested in the incorporation of radioactive glucosamine into proteoglycans of granulation tissue of rats. In cartilaginous collagen enhanced proline hydroxylation caused by Al was observed. CONCLUSIONS: Although it is not possible, with regard to Al chemistry, to make an unequivocal statement on the nature of the compound which causes a particular reaction in biological systems, it may be said, based on the achieved results, that Al has an effect on biological systems due to its bond with collagen structures and by influencing their metabolism.

Aluminum↗

Determining the effectiveness of conventional and alternative coagulants through effective characterization schemes.

Polymeric forms of metal coagulants in water treatment have become increasingly used due to their wider availability and reduction in cost. These specialized coagulant forms and products are claimed by manufacturers to be superior to conventional coagulants in particulate and/or organic removal with inherent advantages of lower alkalinity consumption and lesser sludge production. However, due to their proprietary nature, little is known about their chemical composition. To determine and understand the effectiveness of these alternative coagulants, a comprehensive study was undertaken to characterize metal coagulants, and to comparatively evaluate them on a well-characterized source water. The objective of this study was to provide a scheme for utilities that could be employed as a screening process and a method of selecting an appropriate coagulant based on raw water characteristics and insight into the coagulatability of the source water. Characterizations of coagulants included: (i) active metal content, (ii) anion content, (iii) acidity, (iv) alkalinity consumption, (v) charge reversal by colloidal titration, and (vi) molecular weight determination. A total of five poly-aluminum chlorides (PACl), along with a conventional coagulant (aluminum sulfate or alum) were evaluated. Results show that through the characterization scheme, an effective coagulant (conventional versus alternative) and coagulant type (among various PACl) can be chosen before undertaking time-consuming bench or pilot-scale evaluation.

Aluminum Compounds↗

Systematic investigations of the contrast results of histochemical stainings of neurons and glial cells in the human brain by means of image analysis.

The investigation of neurohistological specimens by image analysis has become an important tool in morphological neuroscience. The problems which arise during the processing of these images are non-trivial, especially if a pattern recognition of cells in the imaged tissue is intended. One of the major problems faced concerns the segmentation of structures of interest, whether cells or other histologic structures. The segmentation problem is often the result of an inappropriate staining procedure. For serious image analysis to be performed, the material under investigation must be optimally prepared. Spatially complex patterns, e.g. fuzzy-like neighbouring neurons, are easy to recognize for humans. But the integrative and associative performance of current artificial neuronal network schemes is too low to achieve the same recognition quality as humans do. Therefore, a general analysis of staining characteristics was performed, especially with respect to those stains which are relevant to object segmentation. Although most image analytical investigations of tissues are based on stained samples, a study of this type has not been previously conducted. Of the stains and procedures evaluated, the gallocyanin chrome alum combination staining provided the best stain contrast. Furthermore, this staining method shows sufficient constancy within different parts of the human brain. Even the fine nuclear textures are differentiable and can be used for further pattern recognition procedures.

Adult↗

Management of wastewater from soap and food industries: a case study.

This paper presents the wastewater management of an industrial complex which produces different products, i.e. soap, perfume extract, macaroni, jam and juices. A continuous monitoring programme for departmental as well as final effluents was carried out for almost 3 months. Characterization of the composite wastewater from both soap and food processing plants indicated that the waste was highly contaminated with organic compounds as indicated by COD and BOD values. Moreover, effluent from the soap manufacturing plant contains significant concentrations of oil and grease amounting to 563 mg l-1. Soap manufacturing effluent and the combined wastes discharged from the whole industrial complex were subjected to different treatment processes, namely dissolved air flotation, chemical coagulation-sedimentation, and biological treatment via a completely mixed activated sludge process. Although coagulation using alum followed by sedimentation removed 52% of COD, residual values did not comply with the regulatory standards. Biological treatment of the composite combined wastewater significantly removed the organic contaminants in wastewater. Average residual BOD, COD, oil and grease values were 30, 92 and 8.3 mg l-1 respectively. Based on the laboratory results a final process design was developed.

Egypt↗

A simple method for the use of gallocyanin-chrome alum as an electron strain.

A method has been elaborated for the demonstration of DNA in the electron microscope. The method uses glutaraldehyde fixed tissue pieces from which RNA has been removed by incubation with RNase. DNA is stained by gallocyanin-chrome alum in the tissue block. Embedding and cutting is done in the usual manner. The method is based on histochemical observations at the light microscope level which show sufficient specificity and a good stoichiometry of the staining reaction.

Animals↗

DDA adjuvant induces a mixed Th1/Th2 immune response when associated with BBG2Na, a respiratory syncytial virus potential vaccine.

Human respiratory syncytial virus (hRSV) is one of the most common causes of respiratory infection in infants and the elderly. Previous attempts to vaccinate children against RSV failed and the induction of an aberrant Th2-type immune response was shown to induce severe to fatal pulmonary disease characterised in part by eosinophilia. BBG2Na is a promising human RSV subunit vaccine candidate which successfully passed phase II clinical trials in adults in association with Adju-Phos((R)). However, this formulation is not the most suitable for use in children since aluminium salts are known to induce a Th2-based immune response. In this study, we describe a potent and safe adjuvant formulation for BBG2Na in dimethyldioctadecylammonium bromide (DDA) that induces a mixed Th1/Th2 immune response in BALB/c mice. Furthermore, BBG2Na showed the same protective efficacy against RSV challenge when formulated either in DDA or in alum in mice and cotton rats.

Adjuvants, Immunologic↗

Preliminary oxidation in histochemical staining methods for cholesterol.

The need for preliminary oxidation with histochemical methods for cholesterol was investigated on silica-coated sheets and in tissue sections. The techniques used were the Schultz reaction, perchloric acid-naphthoquinone (PAN), Lewis & Lobban's ferric alum-sulphuric acid reagent and Okamoto's iodine-sulphuric acid. The oxidants assessed were ferric chloride, ferric alum, potassium permanganate, ammonium sulphamate and ultraviolet light. The best combinations amongst those tested in order of reactivity were FeCl3-PAN, ferric alum-Schultz, Lewis-Lobban (no additional oxidant), iodine-sulphuric acid (no additional oxidant). Authentic preparations of cholesterol oxidation products were stained with these methods, but the nature of the oxidized product in the preliminary stage could not be determined.

Cholesterol↗

Irreversible and reversible adhesion between virus particles and hydrolyzing-precipitating aluminium: a function of coagulation.

The infectivity of viruses (Qbeta, MS2, T4, and P1) after dosing virus-contaminated water with 4 types of aluminium coagulant was investigated. The concentrations of infectious viruses were determined after dissolving aluminium hydroxide flocs in alkaline solution. The concentration of infectious viruses did not recover to the initial value after a short floc-dissolution time (5 s). Although the infectious virus concentration increased as the floc-dissolution time was extended to 5 h, it did not recover fully. Irreversible adhesion between virus particles and aluminium coagulant is responsible for the insufficient recovery. We interpret this phenomenon as a virucidal activity of the aluminium coagulant. All tested aluminium coagulants (PACl, alum, and reagent grade aluminium chloride and aluminium sulfate) inactivated all types of viruses tested. PACl had the highest virucidal activity. The virucidal activity of aluminium coagulants was lower in river water, presumably owing to the presence of natural organic matter.

Adsorption↗

Adjuvant activity of incomplete Freund's adjuvant.

The water-in-oil emulsion adjuvants developed by Jules Freund and coworkers have been, and continue to be, used in research and veterinary vaccines. Incomplete Freund's Adjuvant (IFA) has also been widely tested in humans where it was shown to augment antibody responses greater than other adjuvants, such as alum, and to be well tolerated. Toxicity associated with the use of IFA has been controlled by the use of high grade oils and purified surfactants and clinical testing is ongoing to day. One potential limitation of IFA is that it does not augment the types of cellular immune responses that thought to be critical to the control of many viral infections and tumors. However, IFA can be mixed with or used in conjunction with other adjuvant-active compounds, such as saponins and cytokines. These mixed formulations or vaccine protocols have proved successful in animal testing and may soon be tested in clinical trials. Thus, the toxicity and potential limited adjuvant activity of IFA can be controlled or corrected making IFA a useful product in the vaccine industry.

Journal Article↗

Haemolytic activity and adjuvant effect of notoginsenoside K from the roots of Panax notoginseng.

Notoginsenoside K (1), a saponin isolated from the roots of Panax notoginseng (Burk.) F. H. Chen, was evaluated for its haemolytic activity and adjuvant potential on specific antibody and cellular response to ovalbumin (OVA) in mice. Compound 1 showed a slight haemolytic effect, its concentration inducing 50% of the maximum haemolysis (HD50 value) being 318+/-13 microg/ml, on a 0.5% suspension of red blood cells. Compound 1 significantly increased the concanavalin A (Con A)-, lipopolysaccharide (LPS)-, and OVA-induced splenocyte proliferation in OVA-immunized mice (P<0.05, P<0.01, or P<0.001). The OVA-specific serum IgG, IgG1, and IgG2b antibody levels were also significantly enhanced by 1, especially at a dose of 25 mug compared to an OVA control group (P<0.001). Moreover, the enhancing effect of 1 on the OVA-specific IgG2b antibody responses to OVA in mice was more significant than that of Alum (AlOH gel; P<0.01). These results suggest that 1 exhibits a slight haemolytic activity and a significant adjuvant effect on specific antibody and cellular response against OVA in mice.

Adjuvants, Immunologic↗

Adjuvants recognized by toll-like receptors inhibit the induction of polarized type 2 T cell responses by natural attachment (G) protein of respiratory syncytial virus.

Immunization with native fusion (F) protein from respiratory syncytial virus (RSV) adsorbed to alum adjuvant generates greater than fourfold rises in serum neutralizing antibody titers in approximately 50% of seropositive humans. Using BALB/c mice we demonstrate herein that enhanced neutralization titers and accelerated clearance of virus from the lungs after challenge are possible if the attachment (G) glycoprotein is added to F protein-based vaccines. We further reveal for the first time that polarized type 2 T cell responses and immunopathology associated with G protein are inhibited by adjuvants recognized by toll-like receptors (TLR). Co-formulation with compounds that targeted TLR-2, TLR-3, TLR-4, or TLR-9 elicited significantly diminished type 2 T cell responses that caused granulocytic inflammation and eosinophilia in the airways after challenge. These results were not observed with recombinant IL-12 or QS-21. The data are important for improving combination vaccines for RSV.

Adjuvants, Immunologic↗

The use of waterworks sludge for the treatment of dye wastes.

Water treatment works using coagulation/flocculation in the process stream will generate a waste sludge. The works in Adana, Turkey uses ferric chloride. The potential for using this sludge for the treatment of reactive, direct, disperse, acidic, and basic dyestuffs by coagulation and sorption has been investigated. The sludge acted as a coagulant and removed colour with excellent removal efficiencies being obtained for basic, disperse and direct dyes. The optimum conditions were a pH value of 5 and a sludge dose of 2000 mg l(-1). Mediocre results were obtained for acidic and reactive dyes. The efficiency of the sludge was also compared with alum and ferric chloride for the same group of dyes. The sludge was also used as a coagulant to treat the wastewater from a textile factory. At doses of 2000-4000 mg l(-1), the sludge was as effective as ferric chloride and alum at removing COD. Sorption tests showed that the disperse and reactive dyes did not bind to the sludge. Langmuir and Freundlich constants were determined for the other three types of dye. Rate constants for the adsorption were determined using the Lagergren equation.

Adsorption↗

Protection from genital herpes simplex virus type 2 infection by vaccination with cloned type 1 glycoprotein D.

Guinea pigs were vaccinated with truncated herpes simplex virus type-1 (HSV-1) glycoprotein D produced in the genetically engineered mammalian cell line gD10.2. Vaccinated animals formed antibodies that neutralized both HSV-1 and herpes simplex virus type 2 (HSV-2) in an in vitro neutralization assay. Vaccinated animals were challenged with HSV-2 by intravaginal infection. Animals that received the immunogen in Freund's complete adjuvant were completely protected from the clinical manifestations of genital HSV-2 infection. Animals that received the immunogen incorporated in alum adjuvants were partly protected from clinical disease; the infections that did develop were significantly less severe than those that occurred in control animals injected with adjuvant alone. The results demonstrate that immunization with a purified viral protein can provide significant protection against primary genital infection by HSV-2 in guinea pigs.

Adjuvants, Immunologic↗