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[A 13-week toxicity study of simultaneous administration of cochineal and aluminum potassium sulfate in rats].

Cochineal (C), a scarlet material extracted from the powdered pregnant insect, Dactylopius Coceus Costa, is used as a color food additive in the form of aluminum lakes. A 13 week subchronic toxicity study was conducted to investigate the effects of simultaneous administration of C and aluminum potassium sulfate (A). Male and female Wistar rats (5-weeks-old, 15 rats/group) were given diets containing 0.75%A and 0.75%C (1.5%AC), 1.5%A and 1.5%C (3%AC), 3%C alone or 3%A alone. The following results were obtained. 1) No toxic symptoms or death occurred in any treated group. Body weight gain in male rats of the 3%A group decreased significantly. 2) Serum levels of phospholipids, triglycerides (TG) and total cholesterol in male rats and TG in female rats fed 3%C, 3%A or 3%AC were significantly decreased at the 13th week. The serum level of glutamate dehydrogenase (GIDH) in male rats treated with 1.5% or 3%AC was increased at the 4th week but no difference from control was observed at the 13th week. 3) No histopathological changes attributable to A and/or C administration were observed. In this 13-week oral toxicity study, no dose-dependent synergistic effects of simultaneous administration of C and A were found except for an increase in serum GIDH.

Administration, Oral↗

Comparison of IL-2- and IL-4-transfected B16-F10 cells with a novel oil-microemulsion adjuvant for B16-F10 whole cell tumour vaccine.

The use of whole cell tumour vaccines in the treatment of malignant melanoma has given mixed results. Cytokine-transfected tumour cells as vaccine have shown efficacy in animal models but need to be compared with other means of enhancing a systemic anti-tumour immune response. A new generation of immunological adjuvants claimed to be more effective than the conventional adjuvants is now available for assessment. We have investigated the action of an oil-microemulsion adjuvant formulation (IDEC antigen formulation (IDEC-AF)) in the B16-F10 murine melanoma model. After standardisation of the whole cell tumour vaccination protocol we showed that mice vaccinated with whole irradiated cells combined with IDEC-AF produced a significant inhibition of tumour growth, following a challenge with live tumour cells, when compared with mice vaccinated with whole cell vaccine alone. IDEC-AF was superior to two conventional adjuvants, namely alum and incomplete Freund's adjuvant and a more reliable response was achieved with the oil-microemulsion adjuvant compared with IL-2-transfected cells. In addition, the adjuvant was comparable in efficacy to IL-4-transfected B16-F10 cells. Given the practical difficulty in using cytokine-transfected tumour cells and the limited therapeutic range of some cytokines, a cheap and easy to deliver adjuvant formulation proved equally or more effective than some of the currently clinically used transfected cytokines.

Alum Compounds↗

Effect of supervised use of an alum mouthrinse on dental caries incidence in caries-susceptible children: a pilot study.

Aluminum salts have demonstrated anticaries activity in a number of laboratory and animal studies. The aim of this double-blind, pilot, clinical trial was to evaluate the effect of an alum (Al) mouthrinse on dental caries formation both by itself and in combination with an ADA-approved sodium fluoride (F) dentifrice. A total of 260 caries-prone children residing in a low-F area were preselected for the study and scored independently for caries by two experienced examiners. After using gender, age, and initial DMFT(S) scores for baseline stratification, the subjects were assigned to one of three treatment regimens: (1) placebo mouthrinse and F dentifrice, (2) Al mouthrinse and placebo dentifrice, and (3) Al mouthrinse and F dentifrice. The alum mouthrinse contained 500 ppm Al and the sodium fluoride dentifrice contained 1100 ppm F. Rinsing was supervised at school on weekdays for 30 sec/day, while the dentifrices were used ad libitum at home. Subjects were reexamined for caries and oral health after six and twelve months. Both examiners found that children who used Al mouthrinse, in conjunction with either placebo or F dentifrices, had lower caries incidence than those who used placebo mouthrinse/F dentifrice combination; but the differences were statistically significant for only one of the examiners. No evidence of deleterious effects to the oral tissues was observed. The results of this pilot clinical trial demonstrated that daily supervised use of an alum mouthrinse inhibited caries development in decay-prone children at least as effectively as a F dentifrice.

Alum Compounds↗

Evaluation of an alum containing mouthrinse on plaque and gingivitis inhibition over 2 weeks of supervised use.

The present study was carried out on 40 municipal school children in the age group of 12-14 years to evaluate the effectiveness of daily supervised rinsing with specially formulated alum containing mouthrinse on plaque and gingivitis inhibition. The results of this 2 week study demonstrate that a mouthrinse containing 0.02 M Aluminium has significant effect on plaque inhibition. There was a reduction in gingivitis but it was not significant statistically.

Adolescent↗

Ovalbumin-specific, MHC class I-restricted, alpha beta-positive, Tc1 and Tc0 CD8+ T cell clones mediate the in vivo inhibition of rat IgE.

In the following study, we demonstrate that medium responder PVG rats immunized i.p. with OVA complexed to the adjuvant aluminum hydroxide exhibit a moderate IgE response (400-1000 ng/ml). In these rats, we demonstrate that underlying the MHC class II-restricted CD4+ T cell response, there is an MHC class I-restricted CD8+ T cell component that plays an important role in restricting the magnitude and duration of the IgE response. We show that in vivo depletion of CD8+ T cells effects a massive increase in IgE (20-fold), and that they are MHC class I-restricted, OVA-specific, cytolytic cells that universally produce IFN-gamma (25-69 ng/ml) and IL-2 (7.6-22 U/ml), and occasionally secrete IL-4 (68-81 U/ml IL-4), and when adoptively transferred into CD8-depleted recipients, can effect a significant reduction in IgE (3- to 50-fold). We also demonstrate that this in vivo inhibition of IgE is dependent on the Ag-specific activation of the CD8+ T cells, and that the activated CD8+ T cells will suppress total/bystander IgE in an Ag-nonspecific manner. These data are consistent with a growing literature demonstrating sensitization of MHC class I-restricted CD8+ T cells by exogenous protein Ags delivered to mucosal sites, and may represent a mechanism whereby a selective pressure can be applied on the functional outcome of an immunoglobulin response to environmental allergens.

Adoptive Transfer↗

CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen.

Unmethylated CpG dinucleotides in bacterial DNA or synthetic oligodeoxynucleotides (ODN) cause B cell proliferation and Ig secretion, monocyte cytokine secretion, and activation of NK cell lytic activity and IFN-gamma secretion in vivo and in vitro. The potent immune activation by CpG ODN suggests possible utility for enhancing immune responses to vaccines. Mice immunized with recombinant hepatitis B virus surface Ag and a CpG ODN as an immune enhancer have titers of Abs against HBsAg (anti-HBs) that are five times higher than those of mice immunized with HBsAg and the standard adjuvant, aluminum hydroxide (alum). Ab titers in mice immunized with HBsAg and both CpG ODN plus alum were 35 times higher than the titers in mice immunized with alum alone, indicating a strong synergistic interaction between the CpG ODN and alum. ODN without CpG motifs had little or no immune-enhancing activity at the doses used herein. Alum induces a Th2 humoral response (mostly IgG1) and no CTL. In contrast, CpG ODN gives a strong Thl response with predominantly IgG2a Abs and CTL, even when mixed with alum. In vitro studies to determine possible mechanisms of CpG immune-enhancing effects show that CpG ODN induce expression of costimulatory molecules on Ag-presenting cells and drive B cell isotype switching in the appropriate cytokine milieu. These studies demonstrate that CpG ODN are promising new immune enhancers for vaccination applications.

Adjuvants, Immunologic↗

Ovalbumin coupled either with murine red blood cells or liposome induces IgG but not IgE antibody production.

Ovalbumin (OVA) was coupled with murine red blood cells (MRBC) using glutaraldehyde. The OVA-MRBC conjugate induced anti-OVA IgG antibody in mice at almost the same level as OVA in alum. However, no IgE antibody production specific for OVA was observed in OVA-MRBC-injected mice. A significant increase in IGG2a production was obtained with OVA-MRBC immunization, whereas the production of IgG1 predominated in OVA in alum immunization. Am OVA-liposome conjugate induced IgE-specific unresponsiveness in mice in the same manner as OVA-MRBC. Similar results were obtained when antigens other than OVA, such as tetanus toxoid or diphtheria toxoid, were coupled to liposome. These results show the potential of antigen-liposome conjugates for the development of vaccine that induces sufficient IgG antibody production without IgE synthesis.

Alum Compounds↗

Th2-type CD4+ cells neither enhance nor suppress antitumor CTL activity in a mouse tumor model.

Many cervical cancers express the E7 protein of human papillomavirus 16 as a tumor-specific Ag (TSA). To establish the role of E7-specific T cell help in CD8+ CTL-mediated tumor regression, C57BL/6J mice were immunized with E7 protein or with a peptide (GF001) comprising a minimal CTL epitope of E7, together with different adjuvants. Immunized mice were challenged with an E7-expressing tumor cell line, EL4.E7. Growth of EL4.E7 was reduced following immunization with E7 and Quil-A (an adjuvant that induced a Th1-type response to E7) or with GF001 and Quil-A. Depletion of CD8+ cells, but not CD4+ cells, from an immunized animal abrogated protection, confirming that E7-specific CTL are necessary and sufficient for TSA-specific protection in this model. Immunization with E7 and Algammulin (an alum-based adjuvant) induced a Th2-like response and provided no tumor protection. To investigate whether a Th2 T helper response to E7 could prevent the development of an E7-specific CTL-mediated protection, mice were simultaneously immunized with E7/Algammulin and GF001/Quil-A or, alternatively, were immunized with GF001/Quil-A 8 wk after immunization with E7/Algammulin. Tumor protection was observed in each case. We conclude that an established Th2 response to a TSA does not prevent the development of TSA-specific tumor protective CTL.

Adjuvants, Immunologic↗

Effect of an alum-containing mouthrinse in children for plaque and salivary levels of selected oral microflora.

The purpose of the study was to assess the effect of daily supervised rinsing with a specially formulated, alum-containing mouthrinse on plaque and salivary levels of S. mutans, S. mitis and S. salivarius in caries susceptible children (12-14 years old) and to monitor the effect on the oral tissues and acceptability to subjects. Forty-five subjects were divided into 3 groups (n = 15). Group I received an experimental group with a mouthrinse containing hydrated aluminum potassium sulfate (alum). Group 2 received a vehicle control group containing the same mouthrinse, but without alum and Group 3 had a treatment control with distilled water. All subjects continued normal oral hygiene habits during the study. Salivary and plaque levels were obtained at base line, 2 weeks and 4 weeks and evaluated for microbiologic procedures. Also, potential adverse effects on oral tissues were performed during every visit. The mean plaque and salivary levels of oral Streptococcus (S. mutans, S. mitis, S. salivarius) for the experimental group were significantly reduced after 2 weeks and 4 weeks compared with baseline. The plaque and salivary levels of oral Streptococcus of experimental and vehicle control group differed statistically from each other after 4 weeks, with the strongest reduction in the experimental group and there was statistically difference between treatment control and vehicle control or experimental groups at each time interval. No evidence of deleterious effects to the oral tissues was observed. Daily use of an alum-containing mouthrinse was safe and produced significant reduction effect on plaque and salivary levels of oral Streptococcus and can be used in children for the preventive dentistry.

Adolescent↗

[Orthogonal experiment design in the optimization of processing technology for Rhizoma Pinelliae by ginger and alum].

Based on the L9(3)1 orthogonal design with the amount of ginger, amount of alum and decocting time as working factors, and using the method of recording comprehensive scores, an experimental study has been made on the optimization of processing technology for Rhizoma Pinelliae by ginger and alum as stipulated in the Pharmacopoeia. The result shows that the best process is to use 15 kg of ginger juice and 8 kg of alum per 100 kg of Pinellia ternata and decoct them together for 2-3 hours till the juice is fully absorbed by Rhizoma Pinelliae.

Alkaloids↗

Mechanisms of adjuvancy: I--Metal oxides as adjuvants.

The exact mechanism of how immune adjuvants function still remains largely unknown, despite their long history of use. This work reports the properties of alum and the related compounds Al(OH)3 or Al2O3. Experiments were performed in rats to determine the relative adjuvancy of silica, talc, ground glass, Al2O3, SnO2, ZrO2, hematite and magnetite. Antibody response and cell-mediated immunity (CMI) to ovalbumin (OVA) were determined and were found to be significantly enhanced by silica and talc. Antibody response to OVA was moderately enhanced by Al2O3, hematite, and magnetite, while CMI to OVA was not affected, SnO2, ZrO2, and ground glass only gave a slight adjuvant effect. The magnitude of adjuvancy appeared to correlate with the magnitude of the inflammatory response produced by each metal oxide and also correlated with their surface area. No correlation could be drawn between the hydrophilicity or hydrophobicity of the metal oxides and the magnitude of their adjuvancy.

Adjuvants, Immunologic↗

Effect of NOM, turbidity and floc size on the PAC adsorption of MIB during alum coagulation.

The effect of natural organic material (NOM) and turbidity on the powdered activated carbon (PAC) adsorption of the odour compound 2-methylisoborneol (MIB) was evaluated during alum coagulation. The character of the flocs, in terms of their size and fractal dimensions (Df), was used to interpret the observed adsorption behaviour of MIB during the coagulation process. As the alum dose was increased, the adsorption of MIB decreased. This was determined to be due to the size of the flocs, with larger flocs incorporating PAC into their structure, reducing the efficiency of mixing, and the bulk diffusion kinetics for the MIB molecule. The presence of turbidity also reduced MIB adsorption due to the formation of larger flocs. The character of NOM was found to have a greater influence on the adsorption of MIB than the floc structure.

Adsorption↗

Effects of chemically amended litter on broiler performances, atmospheric ammonia concentration, and phosphorus solubility in litter.

The effects of 6 different litter amendments on broiler performance, level of atmospheric ammonia (NH3) concentration, and soluble reactive phosphorus (SRP) in litter was determined. Through 3 experiments conducted on 2 different commercial farms, one chemical amendment was added to the litter and then was compared with a control. Broiler performance was not affected by any of the amendments except the ferrous sulfate amendment for which mortality was 25.5%. Application of aluminum chloride (AlCl3 x 6H2O) to the litter lowered atmospheric ammonia concentrations at 42 d by 97.2%, whereas ferrous sulfate (FeSO4 x 7H2O) lowered it by 90.77%. Ammonia concentrations were reduced by 86.18, 78.66, 75.52, and 69.00% by aluminum sulfate [alum or Al2(SO4)3 x 14H2O)], alum + CaCO3, aluminum chloride + CaCO3, and potassium permanganate (KMnO4), respectively, when compared with each control at 42 d. Each amendment except KMnO4 significantly reduced SRP contents. Alum and aluminum chloride were the effective compounds evaluated on the commercial farms with respect to reducing ammonia contents, phosphorus solubility, and mortality.

Air Pollution↗