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Selective regulation of chemotactic lymphokine production by monocytes and macrophage cell line cells.

Effects of lipopolysaccharides (LPS) on the production of chemotactic lymphokines for eosinophils and monocytes (ECF and MCF) from antigen- or mitogen-stimulated T cells were examined. Supernatants from monocytes stimulated with various LPS regulated concanavalin A (Con A)- and purified protein derivative (PPD)-induced ECF or MCF production. The regulation varied with LPS used for monocyte stimulation. The supernatant from monocytes stimulated with LPS from Escherichia coli, J-5 strain, selectively potentiated ECF production, whereas that from Salmonella minesota potentiated MCF production. In contrast, supernatant from monocytes stimulated with LPS from Salmonella typhimurium potentiated both ECF and MCF production, whereas that from Vibrio cholerae failed to potentiate production. The supernatants from monocytes stimulated with lipid A of S. typhimurium, S. minesota, and E. coli, however, failed to potentiate ECF and MCF production. The potentiating activity for each lymphokine was recovered from fractions ranging in molecular weight between 10 and 20 kD. Further purification with isoelectric electrophoresis revealed that the potentiating activity for the production of chemotactic lymphokine for eosinophils has a pI value of about 4-5, and that the activity for MCF production is detected in two fractions of pI about 5-6, and 7-8. Macrophage lineage cell line cells, such as THP-1 and U-937, also release similar factors after differential stimulation.

Alum Compounds↗

Aluminum uptake and inhibition of enamel dissolution by sequential treatments with aluminum solutions.

The effects of sequentially applied solutions containing aluminum (Al) on enamel uptake and inhibition of acid dissolution were investigated. Following 10 consecutive 5-min treatments with seven Al solutions varying in concentration from 0.15 to 2.0 mmol/l, the subsequent acid dissolution of enamel was progressively reduced from 0 to over 70%. Teeth treated with 1.5 mmol/l Al from 1 to 30 consecutive 5-min periods demonstrated a stepwise increase in the reduction of enamel acid dissolution ranging from about 10 to 90%. Following the same treatment regimen, the amount of Al deposited in the enamel varied from 2,500 ppm after a single 5-min application to approximately 9,000 ppm after 20 or 30 consecutive treatments. These experiments showed that teeth repeatedly exposed to low concentrations of Al solutions (i.e. < 2 mmol/l) progressively accumulated significant amounts of Al in the surface enamel, which was associated with a concomitant decrease in the acid dissolution rate of enamel.

Acetates↗

Investigation of the effects of aluminum mouthrinses on rat dental caries and plaque.

The effects of topically applied mouthrinses containing AlCl3, or AlK(SO4)2 on dental caries and plaque were investigated in a rat model. For comparison, NaF and a two-step treatment of AlCl3 and NaF were also tested. Six groups of 20 weanling rats were inoculated with Streptococcus sobrinus 6715 and provided a caries-inducing diet and distilled water ad libitum. Test agents were topically applied twice daily 5 days per week at a concentration of 0.037 mol/l in a mouthrinse vehicle and were compared with a vehicle control rinse and a distilled water control. After 10 weeks none of the treatments reduced plaque amounts relative to the controls. The AlCl3 and AlK(SO4)2 rinses significantly reduced both smooth-surface and sulcal caries by approximately 40%. The cariostatic activity of the aluminum rinses was equivalent to an equimolar NaF mouthrinse on smooth surface lesions, but was statistically less than NaF on sulcal caries. The two-step treatment with AlCl3 and NaF indicated numerically additive effects, but the results were not statistically better than with NaF alone. Dentine caries progression paralleled the enamel caries prevalence results. No deaths, toxicologic effects, or inhibition of growth rates were observed in any treatment group. This study confirmed that topically applied solutions of aluminum salts inhibited caries formation in the rat caries model and showed that the cariostatic activity of aluminum was maintained in a compatible mouthrinse vehicle.

Alum Compounds↗

Comparative three-year caries protection from an aluminum-containing and a fluoride-containing toothpaste.

In the present study, 2,087 fifth-graders (mean age: 12 years) from two cohorts entered a 3-year clinical toothpaste trial. The study subjects were randomly allocated to two groups: one group was a positive control using a 0.83% NaFPO3 toothpaste, while the other group brushed with a test toothpaste containing 1.77% KAl(SO4). Both toothpastes were used unsupervised at home. One set of bite-wing radiographs was obtained at the beginning of the trial and another at the 3-year follow-up. Clinical registrations of caries were performed by the municipal dentists responsible for the child's dental care. After 3 years, the mean caries increment was significantly higher in the group using the aluminum-containing toothpaste measured both clinically and radiographically.

Alum Compounds↗

Evaluation of intravesical alum irrigation for massive bladder hemorrhage.

The efficacy of intravesical alum irrigation was analyzed after application to 9 patients with continuous and severe bladder hemorrhage. Causes of bleeding were radiation cystitis in 4 patients, vesical invasion by cervical cancer in 3, bladder cancer in 1 and cyclophosphamide-induced cystitis in 1. Though alum treatment was initially effective for control of massive bladder hemorrhage in all patients, it eventually failed to suppress a subsequent hemorrhage in 2 patients (78% success rate). No significant side effects directly related to this therapy were observed. In conclusion, alum irrigation is effective for controlling massive bladder hemorrhage for a rather short time. Therefore, additional treatment modalities should also be considered for primary diseases.

Administration, Intravesical↗

Inhibitors of the polymerase chain reaction in Papanicolaou stain. Removal with a simple destaining procedure.

OBJECTIVE: To identify inhibitors of the polymerase chain reaction (PCR) within Papanicolaou stain and to develop a method of removal. STUDY DESIGN: PCR was performed on cellular digests of archival, Papanicolaou-stained cervical smears and unstained cervical smears using primers to the human beta-globin gene to determine if Papanicolaou stain inhibited the reaction. Next, in order to identify the specific reagents responsible for inhibition, components of the Papanicolaou stain were added to PCRs performed on purified human genomic DNA. Finally, PCR was performed on cellular digests of cervical smears that had been destained using 1% HCl to determine if the inhibitors of PCR were removed. RESULTS: Cellular digests from Papanicolaou-stained cervical smears did not yield products from PCR, whereas cellular digests from unstained cervical smears always yielded PCR products. Analysis of individual Papanicolaou stain reagents revealed inhibition of PCR by hematoxylin and aluminum sulfate. These inhibitors could be removed from Papanicolaou-stained cervical smears by destaining the slides with 1% HCl. CONCLUSION: The hematoxylin and aluminum sulfate within Papanicolaou stain inhibit PCR but can be removed from Papanicolaou-stained cytologic specimens using a simple destaining procedure.

Alum Compounds↗

Role of prostaglandin I2 in airway remodeling induced by repeated allergen challenge in mice.

Recently, we demonstrated that prostaglandin (PG)I2 has a regulatory role in allergic responses through the receptor, IP; however, the role of PGI2 in airway remodeling associated with chronic airway inflammation has not been elucidated. In the present study, we examined the role of PGI2 in allergen-induced airway remodeling using IP gene-deficient mice. Mice were sensitized to ovalbumin (OVA) with alum, and exposed daily for 3 wk to aerosolized OVA. Twenty-four hours after the final antigen inhalation, bronchoalveolar lavage, biochemical, and histopathologic examinations were performed. In wild-type mice, prolonged allergen exposure in sensitized animals induced the increases in the numbers of inflammatory leukocytes (including eosinophils and lymphocytes), levels of T helper type 2 (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13), levels of OVA-specific immunoglobulin (Ig)E and IgG1 in serum, and amount of hydroxyproline in the right lungs associated with transforming growth factor-beta1 levels in bronchoalveolar lavage fluid. Moreover, goblet cell hyperplasia and subepithelial fibrosis were also appreciated after repeated allergen challenge. In contrast, the disruption of IP gene significantly augmented all these parameters. These findings suggest that PGI2 has a regulatory role in allergen-induced airway remodeling as well as airway eosinophilic inflammation, Th2 cytokine production and IgE production, and that a PGI2 agonist is a therapeutic approach for the treatment of airway remodeling in allergic asthma.

Allergens↗

Uptake and retention of aluminum by dental enamel.

The uptake, depth of penetration, and retention of aluminum (Al) in sound and acid-etched dental enamel were determined following in vitro applications of solutions containing 0.005 M or 0.037 M Al. Compared with controls, significant amounts of Al uptake (approximately 2000 to 6000 ppm) were detected in both sound and etched enamel, with significantly more Al deposited in the latter. Analysis of successive layers of treated enamel demonstrated that Al was located predominantly within the first 20 microns of surface enamel. Only slight reductions in Al retention occurred following one week of water-soaking or one minute of brushing with water or dentifrice, indicating that Al was firmly bound by enamel.

Acid Etching, Dental↗

Acute encephalopathy due to aluminum toxicity successfully treated by combined intravenous deferoxamine and hemodialysis.

Acute aluminum intoxication is uncommon in clinical practice but can be fatal. This limited experience is reflected in the paucity of data assessing a viable approach to the treatment of these patients. In this report, the authors describe the clinical course and successful, pharmacokinetic-based deferoxamine-hemodialysis treatment regimen of a patient with severe aluminum encephalopathy following alum bladder irrigation. The combined use of deferoxamine and appropriately timed hemodialysis appears to be a very reasonable means of treating patients with severe acute aluminum intoxication.

Acute Disease↗

Impairment of ciprofloxacin absorption by calcium polycarbophil.

The effect of calcium polycarbophil on the absorption of ciprofloxacin, a broad-spectrum antibacterial agent, was evaluated in an in vitro and in vivo study. In the in vitro study, the release of ciprofloxacin from the cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, male ST Wistar rats and male volunteers were employed. First, 20 mg/kg of ciprofloxacin alone (Rat Study 1) or 20 mg/kg of ciprofloxacin in combination with 64 mg/kg of calcium chloride (Rat Study 2) was administered orally to 3 rats. Second, a volunteer study was employed and a randomized crossover design with twophases was used. In onephase, volunteers received 400 mg of ciprofloxacin alone (Study 1); in the other phase, they received 400 mg of ciprofloxacin and 1200 mg of fine calcium polycarbophil granules concomitantly (Study 2). The plasma and serum concentrations of ciprofloxacin were measured by high-performance liquid chromatography. The release of ciprofloxacin from the cellulose membrane in the presence of aluminum, calcium, or iron ions was slower than that in the absence of these metal ions. The AUC0-4 and Cmax in Rat Study 2 were lower than those respective values in Rat Study 1. AUC0-4 was approximately 60% lower in Rat Study 2 than Rat Study 1. In the volunteer study, the AUC0-12 and Cmax in Study 2 were lower than those respective values in Study 1. In particular, AUC0-12 was approximately 50% lowerin Study 2 than in Study 1. These findings suggest that when ciprofloxacin and calcium polycarbophil were coadministered concomitantly, a decrease of ciprofloxacin absorption was observed, and this action was caused by the formation of chelate complexes. Therefore, it seems clear that we should avoid the concomitant administration of ciprofloxacin and calcium polycarbophil.

Absorption↗

Leaching behaviour of elements and evaluation of pre-treatment methods for municipal solid waste incinerator residues in column leaching tests.

Two new pre-treatment methods (water-washing/carbonation and carbonation/phosphate stabilization) of municipal solid waste (MSW) incinerator residues were evaluated by column leaching tests under aerobic conditions and anaerobic conditions (which were changed to aerobic conditions after 10 months). A mixture of bottom ash and fly ash (5:1 ratio) was pre-treated using each method. Shredded incombustible residues (SIR) were added to each ash preparation in proportions similar to the ratios present in landfills. For comparison, landfill wastes typical of Japan, namely, a mixture of bottom ash, chelating-pre-treated fly ash, and SIR, were also examined. Leachate samples were collected periodically and analysed over a 15-month period. When compared with chelating pretreatment, both water-washing/carbonation and carbonation/ phosphate stabilization reduced the leaching of Pb, Al, and Cu by about one to two orders of magnitude. Moreover, the initial concentrations of Ca and Pb in leachates from column of water-washing/carbonation were 56-57% and 84-96% less than those from the column of carbonation/phosphate stabilization. Therefore, water-washing/carbonation was considered to be a promising approach to obtain early waste stabilization and to reduce the release of heavy metals to near-negligible levels. The leaching behaviour of elements was also discussed.

Alum Compounds↗

Physico-chemical treatment of Merida landfill leachate for chemical oxygen demand reduction by coagulation.

In order to determine the optimal dosage and type of coagulant for the physico-chemical treatment of leachate from the sanitary landfill of Merida, Mexico, a total of 864 jar tests were performed. Four metallic coagulants (ferric chloride, ferric sulphate, aluminium polychloride and aluminium sulphate) with doses ranging between 50 and 300 mg L(-1) and two polyelectrolytes (high-density anionic and cationic reagents) with doses from 2 to 12 mg L(-1) were tested. Neither an adequate type of coagulant nor an optimal dose could be found. The removal of contaminants was measured as total and dissolved chemical oxygen demand (COD). Soluble COD removal efficiencies were low, from 0 to 47%, with a 4% average value only. These low values of organic material removal were attributed to the particular characteristics of the Merida landfill leachate (low suspended solids concentration), so even with sweep-floc coagulation (300 mg L(-1) dose) only low COD removal efficiencies were obtained. A study of the suspended particle size distribution of the leachate was conducted in order to explain the poor performance. The particle size distribution ranged from 0.375 to 948.2 microm, with an average value of 22.97 microm. In a second step the optimal pH for physico-chemical treatment of these leachates was determined. Finally a greater than 90% removal of organic material, measured as suspended COD, was obtained at pH 2, which was considered as the optimal value.

Alum Compounds↗

Camelford water poisoning accident: serial neuropsychological assessments and further observations on bone aluminium.

The serial cognitive assessment of ten individuals made between 8 and 26 months after the water at Camelford in Cornwall was accidentally contaminated with aluminium sulphate, showed consistent evidence of impairment of information processing and memory. There was no obvious relationship between these impairments and measurements of anxiety and depression. Serial bone biopsies in two individuals showed that the aluminium which was present 6 and 7 months after the accident had disappeared by 19 months. In the eight individuals biopsied 12-17 months after the accident the bone showed no stainable aluminium. Thus, aluminium deposited in the bone of normal individuals can disappear within 18 months. After an accident such as that at Camelford important evidence of toxicity is likely to be missed if an investigation is delayed. The abnormal neuropsychological findings indicate cognitive impairment, but whether this was caused by an acute episode of brain damage, or other causes such as the psychological effects of stress resulting from the accident, is uncertain.

Accidents↗

Renal filtration and excretion of aluminium in the rat: dose-response relationships and effects of aluminium speciation.

The known toxicity of aluminium, and the toxicity of agents (such as desferrioxamine) used to remove aluminium from the body, has prompted us to investigate whether there may be ways of enhancing aluminium excretion by exploiting the normal renal handling of aluminium. Aluminium (as sulphate or citrate) was administered intravenously to conscious rats at doses ranging from 25 micrograms (0.93 mumol) to 800 micrograms (29.6 mumol) aluminium, and aluminium excretion was monitored over the following 2 h. Measurements of the filterability of aluminium from the rat plasma, and the glomerular filtration rate (inulin clearance), enabled us to calculate the filtered load of aluminium, and hence determine aluminium reabsorption. At all doses of administered aluminium, that administered as sulphate was excreted less effectively than that administered as citrate. This difference was attributable to the much greater filterability of aluminium administered as citrate. However, for any given filtered load, the excretion of aluminium administered as citrate was not significantly different (in either fractional or absolute terms) from the excretion of aluminium administered as sulphate. It seems likely that, following aluminium sulphate administration, the filtered aluminium may be an aluminium citrate form which is then reabsorbed in the same way as aluminium administered as citrate. It is thus apparent that aluminium removal from the body could be further enhanced if it were possible to prevent the tubular reabsorption of the aluminium species which is so effectively filtered following aluminium citrate administration.

Absorption↗

Renal excretion of aluminium in the rat: effect of citrate infusion.

When aluminium is administered intravenously to rats, the speciation of the aluminium has a major effect on its renal excretion. Aluminium administered as citrate is much more effectively excreted than that administered as chloride or sulphate. This suggests that citrate could be therapeutically useful in patients who have been exposed to aluminium. Accordingly, we have performed two series of experiments in rats, in which a citrate infusion (intravenous), was begun either immediately after, or one hour after, the administration of an intravenous aluminium sulphate bolus. Both protocols led to markedly enhanced aluminium excretion compared to controls in which only 0.7% NaCl was infused. The enhancement of aluminium excretion was 783% if citrate infusion was begun immediately after aluminium administration, and 335% if the citrate infusion began after an hour delay. The increased excretion was due to an increase in the freely filterable fraction of aluminium. In the control experiments, in which aluminium sulphate administration was followed by 0.7% NaCl infusion, aluminium was found to be deposited in the liver. Administration of citrate one hour after the aluminium bolus did not reduce this liver deposition. The results indicate that a fraction of the plasma aluminium is accessible to the citrate infused and can thereby be converted into a filterable form which can be excreted. It appears that, for maximum therapeutic effect, citrate should be infused as rapidly as possible after an aluminium load, to limit aluminium binding to ligands which allow it to enter cells.

Alum Compounds↗

Water contamination in North Cornwall: a retrospective cohort study into the acute and short-term effects of the aluminum sulphate incident in July 1988.

IN JULY 1988 the drinking water supply of part of Cornwall was contaminated with 20 tons of aluminum sulphate solution. Emergency measures ensured that aluminum sulphate levels in most parts of the water distribution system were rapidly reduced, but residents were supplied with water containing raised concentrations of aluminum and other metals for at least a few days. A retrospective cohort study compared 480 individuals in the exposed area with 532 individuals resident in an area served by a different water supply. The exposed group were more likely to complain of all 18 symptoms in the questionnaire enquiry. They had a significantly higher relative risk of experiencing painful joints. These symptoms were reported by less than a quarter of the respondents exposed to contaminated water. This may represent a previously unrecognised acute effect of water contamination with aluminum sulphate, but the study does not exclude the possibility that the threshold for symptom reporting was lowered by anxiety and by the publicity associated with the incident. The overall response rate of the study was low (45%) and reflects the difficulties in both carrying out and interpreting environmental epidemiological studies of acute incidents.

Accidents, Occupational↗

Safety and immunogenicity of a candidate vaccine for visceral leishmaniasis (Alum-precipitated autoclaved Leishmania major + BCG) in children: an extended phase II study.

BACKGROUND: Untreated visceral leishmaniasis (VL) is an inevitably fatal childhood disease. First-generation candidate vaccines for VL [autoclaved Leishmania major (ALM) + BCG] have been found to be safe and immunogenic but not superior to BCG alone. Modulation of ALM by adsorption to Alum significantly increases the immunogenicity. The Alum-adsorbed ALM vaccine was found to be safe and strongly immunogenic in healthy adult volunteers in a non-VL-endemic area. This study aimed at establishing the safety and immunogenicity of Alum-precipitated autoclaved L. major + BCG vaccine in children under field conditions. METHODS: A total of 544 healthy, leishmanin non-reactive children (<15 y) were randomly allocated to receive either a single intradermal injection of Alum/ALM + BCG or vaccine diluent (placebo). Volunteers were closely followed for 2 years at 6-month intervals for vaccine safety and immunogenicity. RESULTS: The vaccine was well tolerated with minimal side-effects. Leishmanin skin test conversion (>or=5 mm) was seen in 56%, 50%, 25% and 31% at 6, 12, 18 and 24 months post-vaccination, respectively; conversion in the placebo group was 4%, 12%, 3% and 13% at the same follow-up visits. There was no significant increase in anti-leishmanial antibodies in either study arm at any of the follow-up visits. During the study, four patients in the placebo arm developed parasitologically confirmed VL. CONCLUSION: Alum/ALM + BCG vaccine is safe and immunogenic in children under field conditions. Multiple injections might be needed to obtain results similar to those obtained in healthy volunteers.

Adolescent↗