[Usefulness of alginate impression isolation by 2% alum solution].
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The feet of sheep which had been given two doses of oil adjuvant foot rot vaccine were completely resistant to direct challenge with a virulent homologous culture of Bacteroides nodosus four weeks after vaccination, partially resistant after eight weeks but completely susceptible after 12 weeks. Sheep given two doses of alum precipitated vaccine, or a dose of oil emulsion vaccine followed by a dose of alum precipitated vaccine, were resistant four weeks but not eight weeks later. Foot rot in affected, vaccinated sheep was more severe in those which had received the alum precipitated vaccine than in those given the oil emulsion vaccine, but vaccinated sheep were always less severely affected than controls. Where oil emulsion vaccine provided the primary stimulation, agglutinin titres were 18,000 four weeks after revaccination with either vaccine, falling to 4000 after a further four weeks. Significantly poorer titres were observed when two doses of alum precipitated vaccine only were given.
Stingose, an aqueous solution of 20% aluminum sulphate and 1.1% surfactant, has been developed as a wide-acting and effective first-aid treatment designed to counteract the venoms of insects, bees, marine stingers and stinging plants. Rapid application to prevent further systemic abosorption is necessary. As virtually all characterized insect, marine, and spiked-fish venoms contain a protein component, it is proposed that the Al3+ ion in Stingose interacts with proteins and long-chain polysaccharide components to denature and inactivate the venoms. It is also proposed that an osmotic fluid movement towards the high ionic strength solution could account for part of the action of the product. In an extensive field trial which involved 1003 cases, the over-all success of first-aid treatment with Stingose in 997 cases and partial success in six cases was extremely high. Further work is to be undertaken to study the range of envenomations against which Stingose is active.
Aluminum sulfate, potash alum, ammonium alum, purified and unpurified nephelinic coagulant are assigned to the 3rd jeopardy class (moderately dangerous chemicals), sodium alum--to the 4th jeopardy class (slightly dangerous chemicals) at the single exposure. Local irritation of rabbit's skin was not revealed, but instillation into the eye results in conjunctivitis and purulent ophthalmitis. Aluminum sulfate and coagulants afflict the nervous system, liver and heart. The recommended MAC in the air of workplace for aluminum sulfate, potash alum, sodium alum and coagulants based on them is equal to 0.5 mg/m3.
Twenty-one male rabbits were administered with alum (aluminum potassium sulfate) for 32 weeks to study the accumulative toxic effects of aluminum in food additives on central nervous system. Results showed aluminum levels in blood and brain tissue of the animals increased significantly with intake of alum (P < 0.01). Blood zinc levels, and activities of superoxide dismutase (SOD) and monoamine oxidase B (MAO-B) correlated negatively with aluminum levels in blood and brain, and SOD activity correlated negatively to accumulative aluminum deposit and positively to lipid oxide level in brain. Pathological examinations showed lesions in gyrus centralis anterior, gyrus hippocampi and spinal cord of the animals got more severely and extensively with aluminum intake and brain aluminum content, with disarrangement of neurofilaments and neurotubule, and deformation of synaptic structures.
The effect of adjuvant and immunization schedule on the immunogenicity of HIV-1 envelope glycoprotein, MN rgp120, was optimized by using baboons. The novel adjuvant QS21 elicited earlier seroconversion than alum adjuvant, and the antibody titers to MN rgp120 for animals treated with QS21 were significantly greater than the titers obtained in animals treated with alum. The use of QS21 shifted the dose-response curve, resulting in less MN rgp120 required to achieve equivalent titers to those in the alum formulations. The in vitro virus neutralizing (VN) titers from animals treated with QS21 were 3- to 10-fold higher than with alum. The data presented herein point to the superiority of QS21 as adjuvant in primates for MN rgp120.
The successful development of an AIDS vaccine will require formulations that not only invoke the desired immunological response, but also are stable and easy to administer. A single shot MN rgp120 vaccine formulation comprised of MN rgp120 encapsulated in poly (lactic-coglycolic) acid (PLGA) microspheres was developed to provide an in vivo autoboost of antigen. These formulations were designed to yield an in vivo autoboost at 1, 2, 3 or 4-6 months. In addition, PLGA microspheres containing the adjuvant, QS21, were also prepared to provide an in vivo autoboost concomitant with antigen. In guinea pigs, these formulations yielded higher anti-MN rgp120 and anti-V3 loop antibody titers than alum formulations that were administered at higher antigen doses. Different doses of encapsulated MN rgp120 provided a clear and well-defined dose response curve for both anti-MN rgp120 and anti-V3 loop antibody titers. When soluble QS21 was mixed with the encapsulated MN rgp120, the antibody titers were increased by a factor of 5 over the titers with encapsulated MN rgp120 alone. An additional fivefold increase in antibody titers was observed for guinea pigs immunized with encapsulated MN rgp120 and QS21 on the same microspheres. These results suggest that the adjuvant properties of QS21 can be increased by microencapsulation in PLGA. Furthermore, antibodies induced by these preparations neutralized the MN strain of HIV-1. The neutralization titers for sera from animals immunized with MN rgp120-PLGA and soluble QS21 were greater than the titers obtained from guinea pigs that were treated with MN rgp120 and soluble QS21 at the same dose. Overall, these studies validate the in vivo autoboost concept, reveal a method for improving the adjuvant properties of QS21, and indicate the potential of future single shot vaccine formulations.
Groups of NIH and C57BL/10 (B10) mice were vaccinated subcutaneously with excretory/secretory material from the nematode parasite Trichinella spiralis using a variety of different adjuvants, i.e. complete Freund's adjuvant (CFA), 'TiterMax', alum and ISCOMs. ISCOMs were also given orally. NIH mice, known to be rapid responders to T. spiralis, expelled their worms earlier than usual with vaccination. The slow-responder B10 mice did not expel worms any earlier, no matter which adjuvant was used. The antibody isotype response profiles following vaccination with the four adjuvants did not differ significantly; however NIH mice generally produced higher levels of antibody than B10 and CFA induced the highest overall response. NIH cells yielded stimulation indices far in excess of the B10 following in vitro stimulation with T. spiralis antigen. Secretion of interleukin-5 (IL-5) and interferon-gamma (IFN-gamma) by these cells followed similar trends, i.e. higher levels from NIH than B10. A high IL-5 level in the NIH strain was accompanied by low-level IFN-gamma production following infection, whereas the IFN-gamma response was not observed in B10 supernatants. This study shows that vaccination using these adjuvants did not appear to modify the immune response qualitatively, but the magnitude of the response was affected greatly.
The ability of freshly derived T cells to produce interleukin-4 (IL-4) remains controversial. Many groups report that freshly derived antigen-, allogen- or mitogen-activated CD4 T cells produce almost exclusively IL-2, acquiring the capacity to produce a spectrum of cytokines following culture, rest and restimulation. In contrast, it is demonstrated here that in vivo exposure to protein allergens induces rapid, co-ordinate activation of IL-4 and interferon-gamma (IFN-gamma) gene expression. Overnight culture of spleen cells obtained from mice immunized with ovalbumin (OVA) or ragweed extract (RAG) in alum adjuvant elicits strong IL-2 and IL-4 responses within 14 hr of culture. T cells from mice immunized with allergen in complete Freund's adjuvant (CFA) generate strong IL-2 and IFN-gamma production, but virtually no IL-4, while unimmunized mice do not respond detectably to allergen in vitro (< 1 U). Unlike the differential pattern of cytokine synthesis observed following antigen-specific in vitro restimulation, cultures derived from naive and allergen-primed animals yield virtually equivalent IL-4, IL-2 and IFN-gamma synthesis upon polyclonal restimulation with anti-CD3 mAb 145-2C11 or concanavalin A (Con A), a finding which underlines the importance of the experimental conditions selected for in vitro analysis of in vivo cytokine gene expression. Collectively, the results indicate that the mode of immunization is critical to the pattern of cytokine response elicited and consequently to the type of antibody response which develops.(ABSTRACT TRUNCATED AT 250 WORDS)
The involvement of aluminium in the aetiology of a number of human pathological diseases has altered its status from being a nontoxic, nonabsorbable, harmless element. This maybe of particular concern to the developing foetus which is more susceptible to agents and at lower levels than the adult. Little attention has been given to aluminium's potential reproductive toxicity until recently and further research is required for a full evaluation of its toxicity. Our preliminary results demonstrate behavioural and neurochemical alterations in the offspring of mice exposed to aluminium during gestation. Further, the effects of such exposure are also present in the adult animal suggesting persistent changes in behaviour following prenatal exposure.
To evaluate the effectiveness of potash alum in purifying household water, this study was carried out in a suburban community in Yangon, Myanmar. It was designed to test whether the application of potash alum (0.05%) regularly into household water storage vessels during water replenishment was capable of decontaminating household water in homes using shallow well water. It was conducted in 100 households (50 each in intervention and control groups). After alum (0.05%) was added, the contamination level of water decreased on the 2nd and 3rd days. The alum-treated water was well tolerated by the users; only one member complained of a metallic taste. We conclude that potash alum was effective and acceptable in this community in decontaminating household water.
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The effects of the thyroid hormone triiodothyronine (T3), nerve growth factor (NGF) and stress (exposure to heat or aluminum sulfate) on growth, development and ageing of human neuroblastoma cells were studied in vitro. Differentiation of cells using retinoic acid and NGF inhibits cell growth and proliferation; simultaneously, it promotes acquisition of neuronal phenotype, down-regulation of T3 receptors, and an increase in catecholaminergic tyrosine hydroxylase activity and microtubule assembly. The actions of T3 on neuronal differentiation resemble those of NGF and suggest the existence of NGF-T3 interactions. Exposure to stress inhibits cell growth and proliferation, increases immunoreactivity to the microtubule-assembling protein tau (which occurs in paired filaments of neurofibrillary tangles in the aged human brain), and facilitates formation of tau-ubiquitin complexes (which also occur in the aged brain). Stress does not prevent the inhibition of cell proliferation by high doses of T3; however, T3 doses that are equivalent to physiological levels reduce stress-induced inhibition of growth. Previous studies have shown that stress may also induce in these cells facsimile lesions of normal and abnormal ageing, such as accumulation of lipofuscin pigments, formation of paired helical filaments and increased immunoreactivity to tau, beta-amyloid proteins, and ubiquitin. These lesions may represent cellular and molecular manifestations of increased vulnerability and susceptibility to genetic and extrinsic factors (e.g. hormones and environmental influences) with ageing. It is proposed that neuroblastoma cells may serve as a model to study mechanisms of neuronal ageing and to identify agents and conditions capable of preventing, delaying or reducing metabolic abnormalities leading to age-associated disorders.
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Serum phosphorus concentrations are maintained within narrow limits in humans. In the extracellular fluid most of the phosphorus is present in the inorganic form and at the level of the glomerulus greater than 90% of PO4 is ultrafilterable. The kidney plays a key role in PO4 homeostasis. Micropuncture experiments have demonstrated that 60 to 70% of the filtered PO4 is reabsorbed in the proximal tubule; however, there is evidence that a significant amount of PO4 is reabsorbed in the distal tubule. Phosphate secretion probably plays a minor role in the overall renal regulation of phosphate. In normal individuals the amount of PO4 ingested plays a key role in the amount that ultimately will be excreted in the urine. The reabsorption of PO4 along the nephron is regulated by a series of factors of which parathyroid hormone is the most important one. Hyperphosphatemia is seen frequently in clinical medicine and by far, the most common cause is a decrease in urinary PO4 excretion secondary to renal failure. From the practical point of view, the most effective way to treat hyperphosphatemia is to decrease PO4 absorption in the GI tract by the use of PO4 binders.
The current studies evaluate granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant. An important issue for developing vaccine therapy for human malignancy is identifying adjuvants that can elicit T-cell responses to proteins and peptides derived from "self" tumor antigens. GM-CSF, in vitro, stimulates the growth of antigen-presenting cells such as dendritic cells and macrophages. Initial experiments examined whether GM-CSF injected into the skin of rats could affect the number or character of antigen presenting cells, measured as class II major histocompatability complex expressing cells, in lymph nodes draining the injection site. Intradermal (id) inoculation of GM-CSF every 24 hours for a total of five inoculations resulted in an increase of class II+ fluorescing cells that peaked at the fourth inoculation. Subcutaneous (sq) inoculation resulted in an increase of class II+ fluorescing cells that peaked following the second inoculation, then decreased over time. Using this schema for "conditioning" the inoculation site, GM-CSF was administered id or sq for five injections and a foreign antigen, tetanus toxoid (tt), was given at the beginning or the end of the immunization cycle. Id immunization was more effective than sq at eliciting tt specific immunity. In addition, GM-CSF id, administered as a single dose with antigen, compared favorably with complete Freund's adjuvant (CFA) and alum in eliciting tt specific antibody and cellular immunity. We have shown that immunity to rat neu (c-erbB-2) protein, an oncogenic self protein, can be generated in rats by immunization with peptides derived from the normal rat neu sequence plus CFA. The current study demonstrates that rat neu peptides inoculated with GM-CSF could elicit a strong delayed type hypersensitivity reaction (DTH) response, whereas peptides alone were non-immunogenic. GM-CSF was as effective as CFA in generating rat neu specific DTH responses after immunization with a neu peptide based vaccine. Soluble GM-CSF is a potent adjuvant for the generation of immune responses to foreign proteins as well as peptides derived from a self tumor antigen.
Aluminum salts have demonstrated activity against oral bacteria and also have shown indications of inhibiting plaque and gingivitis. The aims of this clinical trial were to determine the effects of daily supervised rinsing with a specially formulated, alum-containing mouthrinse on existing plaque and gingivitis in children and to monitor its effect on the oral tissues and its acceptability to subjects. Using a double-blind, parallel design, 48 sixth-graders rinsed once daily for 30 sec under supervision with either a placebo or a mouthrinse containing 0.02 M alum while continuing their normal oral hygiene habits. Plaque and gingivitis were assessed and intraoral examinations were performed at 0, 2 and 4 weeks. The alum mouthrinse significantly (P < 0.05) reduced the amount of plaque relative to the placebo after both 2 and 4 weeks. Gingivitis and plaque thickness also were decreased, but the differences did not attain significance. No evidence of deleterious effects to the oral tissues was observed and the alum mouthrinse was well accepted by the children. This trial demonstrated that daily use of an alum-containing mouthrinse was safe and produced a significant effect on plaque that supplemented the benefits of daily toothbrushing. Thus, topically applied aluminum may have potential applications in preventive dentistry for controlling plaque.
This study reports the bactericidal activity of potash alum when added to water, against various epidemic causing enteric pathogens like Vibrio cholerae 01, V. cholerae 0139 and Shigella dysenteriae 1 by lowering the pH of water (from 6.0 to 4.0). Growth of the enteric pathogens was monitored in vitro by inoculating broth cultures of the different organisms in distilled water containing increasing concentrations of potash alum and quantitatively determining the concentration of viable organisms over a 48 h period by the standard plate count method. Controls constituted cultures of each organism grown in the absence of potash alum. The pH of alum administered water was measured in each test tube before inoculation of organisms. Potash alum was found to inhibit growth (10(5) viable count per ml) of most of the organisms examined, particularly V. cholerae 01 and V. cholerae 0139 in a dose dependent fashion. Reduction of colony forming units was observed in presence of 0.25 g/dl of alum after 5 h and no growth was noticed after 24 h.