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New sodium hydroxide digestion method for measurement of renal tobramycin concentrations.

Because of the known propensity of the cationic aminoglycosides to interact with a variety of anionic tissue constituents, it was postulated that present elution methods fail to detect a substantial proportion of the aminoglycoside that accumulates in the kidney. After preliminary experiments documented the pH and temperature stability of tobramycin, a new sodium hydroxide (NaOH) tissue digestion method was applied to renal tissue collected from rats given tobramycin at 80 mg/kg (body weight) per day in two divided doses for 3, 7, 10, 14, and 17 days. Compared with elution with buffer from the renal homogenate, digestion with 1.0 N NaOH at 70 degrees C for 15 min significantly increased the amount of assayable tobramycin (P less than 0.001). The absolute increase varied between 37 and 96%, depending on the number of days of in vivo drug administration. A single trichloroacetic acid (TCA) treatment of the homogenate altered the amount of assayable tobramycin over a range which varied from a decrease of 6% to an increase of 32%. After TCA treatment, it was possible to increase the amount of measurable tobramycin by 17 to 22% by treatment of the TCA-induced precipitate with 1.0 N NaOH. Digestion of renal homogenates with 1.0 N NaOH significantly increases the amount of tobramycin detectable by immunoassay.

Animals↗

Improved sodium hydroxide digestion method without homogenization for extraction of gentamicin from renal tissue.

Recovery of gentamicin from renal cortical tissue (assayed by fluorescence polarization immunoassay) was highest (P less than 0.05) when using a sodium hydroxide (NaOH) digestion procedure without homogenization (90.0 +/- 5.4%), followed by homogenization with NaOH digestion (85.8 +/- 7.7%) and homogenization with trichloroacetic acid precipitation (84.4 +/- 3.3%). Simple homogenization recovered the least gentamicin (59.0 +/- 5.2%; P less than 0.05).

Animals↗

Concentration of viruses from water by using cellulose filters modified by in situ precipitation of ferric and aluminum hydroxides.

Untreated cellulose filters adsorbed only small amounts of poliovirus 1, echovirus 5, coxsackievirus B5, or bacteriophage MS2 that were added to tap water or to solutions of imidazole-glycine buffer at pH 5 to 7. Modification of filters by in situ flocculation of ferric and aluminum hydroxides greatly increased the ability of the filters to adsorb viruses. Viruses adsorbed to the modified filters could be recovered by treating the filters with 3% beef extract (pH 9.5). Greater than 60% of the enteroviruses and greater than 55% of the MS2 added to tap water or buffer could be recovered in the beef extract eluate.

Aluminum Hydroxide↗

Direct comparison of the N-acetyl-l-cysteine-sodium hydroxide and the trisodium phosphate digestion methods for the culture of mycobacteria.

Comparison of sputum digestion procedures utilizing acetylcysteine-sodium hydroxide (AC) and trisodium phosphate for the isolation and culture of mycobacteria indicated that the AC procedure provides faster growth, thus permitting the earlier detection of positives. Also, in untreated patients and those in whom treatment has been recently instituted, the number of positives was slightly larger with the use of the AC procedure. However, of greater interest was finding that the AC procedure provided a larger quantity of positive cultures with sputum from subjects who had been intensively treated with antimicrobials and other drugs. Contamination was higher with the AC procedure, but when the sputa were diluted 1:10 this interference due to contamination was decreased.

Bacteriological Techniques↗

Liposomes, lipid A, and aluminum hydroxide enhance the immune response to a synthetic malaria sporozoite antigen.

A liposome-encapsulated cloned protein (R32tet32) containing sequences from the tetrapeptide repeat region of the circumsporozoite protein of Plasmodium falciparum sporozoites was examined for immunogenicity with rabbits and monkeys. Effects of adjuvants were tested by encapsulation of the antigen in liposomes either lacking or containing lipid A and adsorption with aluminum hydroxide (ALUM). When rabbits were immunized with R32tet32 alone, a primary antibody response was not seen and a secondary response did not appear until 32 to 36 weeks after boosting. Immunization with ALUM-adsorbed R32tet32 resulted in a minimal primary antibody response. A moderate secondary antibody response was detected within 2 weeks after boosting, but antibody levels decreased to preimmunization levels 8 weeks after boosting. When R32tet32 was encapsulated in liposomes containing lipid A, strong primary and secondary antibody responses were observed. Strong primary and secondary responses also were obtained when R32tet32 was encapsulated in liposomes either containing or lacking lipid A and the liposomes were adsorbed with ALUM. The strongest antibody response was obtained by immunization with ALUM-adsorbed liposomes containing lipid A and R32tet32, suggesting that the adjuvant effects of liposomes, lipid A, and ALUM were additive or synergistic.

Adjuvants, Immunologic↗

Improved immunogenicity and efficacy of the recombinant 19-kilodalton merozoite surface protein 1 by the addition of oligodeoxynucleotide and aluminum hydroxide gel in a murine malaria vaccine model.

Vaccination of mice with yeast-secreted Plasmodium yoelii-derived 19-kilodalton merozoite surface protein 1 (yMSP1(19)) has been shown to afford protection from challenge with a lethal strain of P. yoelii. Sterile immunity can be achieved when MSP1(19) is emulsified in Freund adjuvant but not when it is adsorbed to aluminum hydroxide gel (alum). Because complete Freund adjuvant is not an acceptable adjuvant for use in humans, alternative adjuvants must be identified for formulating MSP1(19) as a vaccine for use in humans. To determine whether oligodeoxynucleotides with CpG motifs (ODN), reported to be a powerful new class of adjuvants, could enhance the immunogenicity of yMSP1(19), C57BL/6 mice were vaccinated either with yMSP1(19) formulated with Freund adjuvant, with alum, or with ODN plus alum and challenged intravenously with P. yoelii 17XL asexual blood-stage parasites. Adsorption of immunogen and adjuvant to alum was optimized by adjusting buffer (phosphate versus acetate) and pH. We found that the adjuvant combination of ODN plus alum with yMSP1(19), injected intraperitoneally (i.p.), increased immunoglobulin G (IgG) yMSP1(19)-specific antibody production 12-fold over Freund adjuvant given i.p., 3-fold over Freund adjuvant given subcutaneously (s.c.), 300-fold over alum given i.p., and 48-fold over alum given s.c. The predominant antibody isotype in the group receiving alum-ODN-yMSP1(19) was IgG1. Increased antibody levels correlated to protection from a challenge with P. yoelii 17XL. Supernatant cytokine levels of gamma interferon in yMSP1(19)-stimulated splenocytes were dramatically elevated in the alum-ODN-yMSP1(19) group. Interleukin-10 (IL-10) levels were also elevated; however, no IL-5 was detected. The cytokine profile, as well as the predominant IgG1 antibody isotype, suggests the protective immune response was a mixed Th1/Th2 response.

Adjuvants, Immunologic↗

Suppression of secondary hyperparathyroidism in children with chronic renal failure by high dose phosphate binders: calcium carbonate versus aluminium hydroxide.

Secondary hyperparathyroidism was suppressed over a period of one year in 12 children with chronic renal failure by using a regimen of mild dietary phosphate restriction and high dose phosphate binders. The patients were randomised to receive either aluminium hydroxide or calcium carbonate by mouth for six months and then crossed over to the other medication. Vitamin D (dihydrotachysterol) dosage was unchanged. Serum parathyroid hormone concentrations were reduced to within the normal range, urinary cyclic adenosine monophosphate values fell, plasma phosphate concentrations decreased, and the theoretical renal phosphate threshold increased significantly. Transiliac bone biopsy findings improved in four patients with adequate suppression of parathyroid hormone concentrations, deteriorated in two patients who were not compliant, and did not change in five patients in whom initial bone disease was mild. Growth velocity improved significantly. There was no difference in the clinical response, biochemical changes, or incidence of complications during treatment with the two agents. In view of the risk of aluminium toxicity the use of high dose calcium carbonate with dietary phosphate restriction and vitamin D supplementation is recommended in the control of secondary hyperparathyroidism in children with chronic renal failure.

Adolescent↗

Obstructive airway disease associated with occupational sodium hydroxide inhalation.

Sodium hydroxide (NaOH) is well known for its corrosive properties and its ability to generate heat on contact with water. The respiratory effects of industrial exposure to NaOH have, however, never been reported. A 63 year old man worked daily for 20 years cleaning large industrial jam containers by boiling lye (NaOH) solution without using respiratory protective equipment. Physical examination, chest x ray film, pulmonary function tests, and arterial blood gases were all compatible with severe obstructive airway disease with significant air trapping. It is probable that this massive and prolonged occupational exposure to the corrosive effect of NaOH mists induced irritation and burns to the respiratory system, eventually leading to severe obstructive airway disease.

Humans↗

Use of sodium hydroxide treated selenium deficient barley to induce vitamin E and selenium deficiency in yearling cattle.

Selenium deficient barley grown in Northern Ireland was treated with sodium hydroxide to deplete it of vitamin E. Housed cattle fed a complete diet based on this treated barley developed nutritional degenerative myopathy, showing that spontaneous myopathy in yearling cattle can be the result of vitamin E and selenium deficiency alone. The diet used is as effective and cheaper than others presently in use for inducing degenerative myopathy.

Animal Feed↗

Viruses in sewage: effect of phosphate removal with calcium hydroxide (lime).

During calcium hydroxide (lime) treatment (pH 9.6 to 10.5) of wastewaters for phosphate removal there was also a two-log removal of added poliovirus (type I, Sabin) from effluents. A similar virus reduction was seen in the sludge generated in these experiments. However, in view of the limitations of techniques for virus recovery from sludge, only a small portion of the infectious virus present in lime sludge may have been detected. Storage of lime sludge at 28 degrees C for up to 48 h produced no appreciable reduction in the virus titre. Five sets of field samples of sewage, effluents, and sludge from a sewage treatment plant (Kemptville, Ont.) which utilizes lime for phosphate removal were also examined for indigenous viruses being BS-C-1 cells. All of the sample of lime sludge and 80% of the samples of both sewage and lime-treated effluent revealed virus; after chlorination only 20% of the lime-treated effluent samples were positive for virus. In contrast, in an earlier study with essentially the same experimental set up, 76% of the sample of chlorinated primary effluent were found to contain virus. Because of the easily detectable quantities of infectious virus in lime sludge and due to the lack of virus inactivation during storage of such sludge, caution must be exercised in its handling and disposal.

Antiviral Agents↗

Preformed magnesium hydroxide precipitate for second-step concentration of enteroviruses from drinking and surface waters.

A method is described for the second-step concentration of viruses from large volumes of drinking and surface waters. Seeded viruses present in the first eluate, performed with 50 mM glycine buffer, pH 11.5, were adsorbed on a preformed magnesium hydroxide precipitate. After low-speed centrifugation they were desorbed and adjusted to pH 7 with McIlvaine citrate-phosphate buffer. In these experimental conditions 90% of the viruses present in the 300-mL first eluate were reconcentrated in a final volume of 40 mL. The recovery efficiency was independent of either virus concentration or water quality.

Chemical Precipitation↗

Immunotherapy with an aluminum hydroxide-adsorbed Juniperus ashei foreign pollen extract in seasonal indigenous cypress pollen rhinoconjunctivitis. A double-blind, placebo-controlled study.

BACKGROUND: The efficacy of standardized Juniperus ashei extract was assessed in patients with allergic rhinoconjunctivitis due to European cypress pollens. METHODS: Forty adults with European cypress-allergic rhinoconjunctivitis were randomized to receive immunotherapy or a matched placebo. Specific immunotherapy was performed with a standardized, aluminum hydroxide-adsorbed J. ashei extract with a potency of 100 IR (arbitrary index of reactivity) containing 54 microg of Jun a 1/ml (Alustal, Stallergenes, France). Subcutaneous injections started in October 2000. The maintenance dose was 0.30 ml of the 100-IR concentration per month. Rhinitis and conjunctivitis symptoms were rated according to a 4-point score. RESULTS: Seventeen patients from the treated group and 15 patients from the placebo group completed year 2001; 14 in each group completed year 2002. A statistically significant improvement (41%, p < 0.02) in the conjunctivitis symptom score was observed in actively treated patients compared to the placebo group at the peak of the 2001 pollen season. Improvement in rhinitis (17%) was not significant. This significant improvement was greater at the peak of the 2002 pollen season (63%, p < 0.01). CONCLUSIONS: This study therefore indirectly validates the concept of treatment by major allergen because J. ashei is absent from the region in which this study was conducted.

Adsorption↗

Beneficial effect of aluminum hydroxide on progress of adriamycin-induced nephropathy in rats.

To investigate the effect of phosphate binder on adriamycin (ADR)-induced nephropathy, serial changes in renal histology and renal hemodynamics were compared between ADR rats treated with aluminum hydroxide (ADR-AH group) and those without AH (ADR group) for 24 weeks. Urinary protein excretion was less marked in the ADR-AH group than in the ADR group. Serum creatinine in the ADR group increased progressively from week 20, while in the ADR-AH group the increase was less. There were no significant differences in glomerular filtration rate or renal plasma flow between the both groups until week 12 but these parameters decreased to the significantly lower levels at week 24 in the ADR group. Vacuolative degeneration in glomerular epithelium, which was determined as an initial renal lesion, was more marked in the ADR group compared to the ADR-AH group. Glomerular sclerosis and tubulointerstitial changes developed progressively in the ADR group at the later stages. These changes were lessened in the ADR-AH group. In conclusion, AH prevents the progress in ADR-induced nephropathy. The beneficial effects appeared as the preservation of glomerular epithelial cells.

Aluminum Hydroxide↗

Substitution of calcium carbonate for aluminum hydroxide in patients on hemodialysis. Effects on acidosis, on parathyroid function, and on calcemia.

Substitution of calcium carbonate for aluminum hydroxide in patients on dialysis: effects on acidosis, parathyroid function, and calcemia. We studied the effects of substituting CaCO3 for aluminum-containing gels on metabolic acidosis and on the response of the parathyroid glands in 11 patients treated with chronic hemodialysis. The 8 men and 3 women were clinically stable, were known to be compliant, and had no clinical evidence of aluminum overload; they were not receiving vitamin D supplements; and they had been on dialysis for an average of 65.6 months (range: 13-188 months). After 3 weeks of CaCO3 administration plasma phosphate concentration remained well controlled, and plasma calcium concentration increased from 9.2 +/- 0.2 (2.3 +/- 0.1 mmol/l) to 10.1 +/- 0.2 mg/dl (2.5 +/- 0.1 mmol/l). Predialysis plasma bicarbonate concentration increased from 19.7 +/- 0.6 to 21.9 +/- 0.6 mmol/l. Plasma aluminum concentration decreased from 78.7 +/- 12.5 to 48.5 +/- 3.9 micrograms/l. Plasma PTH level increased from 2.0 +/- 0.7 to 3.3 +/- 0.8 ng/ml despite the concurrent increase in plasma calcium levels. All values returned to control levels following discontinuation of CaCO3 and resumption of aluminum gels. We conclude: (1) In addition to controlling hyperphosphatemia and increasing plasma calcium concentration, CaCO3 ameliorates metabolic acidosis. (2) Avoidance of oral aluminum intake is followed by prompt lowering of plasma aluminum levels. (3) PTH levels paradoxically increase despite the increment in plasma calcium concentration. The hypercalcemia seen with CaCO3 administration may be due, in part, to transient parathyroid hypersecretion that develops when aluminum administration is discontinued.

Acidosis↗

Absorption of factor VIII by aluminium hydroxide.

The absorption of factor VIII from gel filtration fractions, concentrates and plasma by aluminium hydroxide has been studied. Significant quantities of factor VIII could be removed when the protein concentration was low; the percentage absorbed increased with decreasing initial protein concentration. Factor VIII R:Ag and VIII:C were removed in parallel, but absorption of a high purity concentrate resulted in selective absorption of the lower molecular weight forms of factor VIII. Elution of the absorbed proteins gave a poor yield of VIII R:Ag, with no detectable VIII:C. Absorption of plasma showed no detectable loss of VIII R:Ag, but an apparent decrease of VIII:C of about 10%.

Absorption↗

An exfoliated polyamide-6/layered double hydroxide nanocomposite via in situ intercalative polymerization between positively charged inorganic platelets.

An exfoliated polyamide 6 (PA6)/layered double hydroxide (LDH) nanocomposite has been successfully prepared via an in situ intercalative polymerization procedure. The original LDH surface is hydrophilic. After an ion exchange reaction of LDH with sodium stearate (SS), the organic anions intercalated into the interlayer space of LDH, adopting a double-layer inclined structure, and the surface of the organic-modified LDH became hydrophobic. An exfoliated PA6/LDH nanocomposite has been obtained via in situ intercalative polymerization. Its microstructure was characterized by a combination of wide-angle X-ray diffraction (WAXD) and transmission electron microscopic (TEM) techniques. The positively charged inorganic platelets of LDH were dramatically exfoliated and homogeneously dispersed in the PA6 matrix.

Caprolactam↗

The effects of calcium hydroxide on dentin permeability.

Calcium hydroxide paste was applied to human dentin in vitro to determine its effects on dentin permeability. Discs of dentin were acid-etched on both sides to permit determination of their maximum permeability. Smear layers were then applied to the enamel sides of the discs, thereby reducing dentin permeability 99%. Topical application of Ca(OH)2 paste to the smear layer reduced dentin permeability further, to levels 48% below that of untreated smear layers. When the Ca(OH)2-treated smear layers were exposed to 6% citric acid for two min, dentin permeability returned to the initial acid-etched value, demonstrating that Ca(OH)2 offers little protection to acid challenge. Treatment of acid-etched dentin with Ca(OH)2 produced a similar reduction in dentin permeability, which was restored to normal following acid challenge. Thus, Ca(OH)2 is effective at reducing the permeability of both the smear layer and of acid-etched dentin, in vitro.

Acid Etching, Dental↗

Immunolocalization of fibronectin during reparative dentinogenesis in human teeth after pulp capping with calcium hydroxide.

Exposed dental pulp is known to possess the ability to form a hard-tissue barrier (dentin bridge). The exact mechanisms by which pulp cells differentiate into odontoblasts in this process are unknown. Fibronectin has been demonstrated to play a crucial role in odontoblast differentiation during tooth development. This study tested the hypothesis that fibronectin is involved in the initial stages of replacement odontoblast differentiation and reparative dentin formation. We observed its immunohistochemical localization during dentin bridge formation in human teeth, after pulp was capped with calcium hydroxide [Ca(OH)2]. One day after the capping, precipitation of crystalline structures was observed at the TEM level in association with cell debris at the interface between the superficial necrotic zone and underlying pulp tissue. This layer of dystrophic calcification showed positive reaction for fibronectin, and pulp cells appeared to be closely associated with this layer, seven to ten days post-operatively. At 14 days, an alignment of cells, some of which were elongated and odontoblast-like, was observed adjacent to the fibronectin-positive irregular matrix. Between the cells, corkscrew fiber-like fluorescence was visible. At 28 days, the irregular fibrous matrix was followed by the formation of tubular dentin-like matrix lined with odontoblast-like cells. Therefore, it would seem that fibronectin associated with the initially formed calcified layer might play a mediating role in the differentiation of pulp cells into odontoblasts during reparative dentinogenesis, after pulp was capped with Ca(OH)2.

Adult↗