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CHARACTERISTICS OF AVERSIVE THRESHOLDS MEASURED BY A TITRATION SCHEDULE.

Three variables were studied for their single and joint effects on aversive thresholds obtained by a titration schedule with electric shock as the aversive stimulus. One variable was the interval between the periodic increments in shock amplitude. Another was the size of this increment. The third was the size of the decrement produced when the subject responded. Both monkeys and humans tolerated more shock at the shorter increment-to-increment intervals than at the longer ones, confirming rat data previously obtained. Reducing the decremental step size also led to an increase in the amount of shock tolerated by monkeys. In addition, simply reducing both incremental and decremental step size without changing the interval between increments led monkeys to tolerate more shock. The attempt to explain these data was based on the changes that such manipulations might produce in the amount of avoidance behavior elicited.

Animals↗

Neutralising antibody titration in 25,000 sera of dogs and cats vaccinated against rabies in France, in the framework of the new regulations that offer an alternative to quarantine.

Regulations governing international movements of domestic carnivores from rabies-infected to rabies-free countries have recently been loosened, with the adoption of a system that combines vaccination against rabies and serological surveillance (neutralising antibody titration test with a threshold of 0.5 UI/ml). Since 1993, the Research Laboratory for Rabies and Wild Animal Pathology in Nancy, France, has analysed over 25,000 sera from dogs and cats using a viral seroneutralisation technique. The statistical analyses performed during this time show that cats respond better than dogs. Although no significant difference in titres was observed between primovaccinated and repeat-vaccinated cats, repeat-vaccinated dogs had titres above 0.5 IU/ml more frequently. In primovaccinated dogs, monovalent vaccines offered a better serological conversion rate than multivalent ones. Finally, the results of these analyses showed a strong correlation between antibody counts and the time that elapsed between the last vaccination and the blood sampling.

Animals↗

Simultaneous determination of cationic surfactants and nonionic surfactants by ion-association titration.

A simultaneous determination of cationic and nonionic surfactants has been developed using ion-association titration. Tetrabromophenolphthalein ethyl ester (TBPE) was used as an indicator. Benzalkonium reacted with TBPE to form a blue ion-associate in the organic phase. When tetrakis(4-fluorophenyl)borate was added dropwise to the solution, the color of the organic phase turned to yellow at the equivalence point. In addition, when a large amount of potassium ion was added to a solution including Triton X-100, Triton X-100 could be determined by the same technique as described above because of formation of the K+-Triton X-100 cation. The proposed method is available for the stepwise determination of cationic and nonionic surfactants in mixtures.

Journal Article↗

A nonaqueous potentiometric titration study of the dissociation of t-butyl methacrylate-methacrylic acid copolymers.

The dissociation of t-butyl methacrylate-methacrylic acid copolymers in dimethyl sulfoxide was analyzed by a nonaqueous potentiometric titration technique. The negative logarithm of the dissociation constant of the monomer unit of a methacrylic acid (MAA) monotonously increased with the increasing degree of dissociation corresponding to the titrant/MAA amount ratio, and was highly influenced by the copolymerization ratio. The results are discussed in terms of the suppression of the dissociation of MAA by a neighboring charged methacrylate anion unit.

Journal Article↗

Electrooxidation of iodide in the presence of 4-hydroxycoumarin: application to a simple coulometric titration of 4-hydroxycoumarin.

The electrochemical oxidation of iodide ion in the presence of 4-hydroxycoumarin (1) was studied using cyclic voltammetry and controlled-potential coulometry. The result indicates that the resulting iodine takes part in a halogenation reaction and reacts with 4-hydroxycoumarin (1). According to the obtained results, a new and simple coulometric titration method with potentiometric end-point detection for the determination of 4-hydroxycoumarin (1) is presented. In the presented method, 2-200 micromol of 4-hydroxycoumarin (1) was successfully determined.

4-Hydroxycoumarins↗

Redox titration of antioxidant mixtures with N-bromosuccinimide as titrant: analysis by non-linear least-squares with novel weighting function.

Equations are presented by which potential-volume data from redox titrations can be analyzed. Mixtures of analytes as well as of titrants may be analyzed, yielding for each component its concentration, number of electrons, and reduction potential. A novel weighting function ensures endpoint accuracy in fitting. Standard deviation of each parameter is obtained. The equations can be readily implemented in Microsoft Excel. Agreement with true values and good precision of fit parameters is demonstrated for a number of test cases. Use of these exact equations enables analysis of analyte mixtures without prior separation using single titrant or titrant mixtures. The equations were used to demonstrate that N-bromosuccinimide, a useful oxidant for organic analytes, undergoes hydrolysis.

Algorithms↗

A dose titration of triamcinolone acetonide on insulin-like growth factor-1 and interleukin-1-conditioned equine cartilage explants.

REASONS FOR PERFORMING STUDY: Previous in vitro pilot studies have defined a potentially beneficial effect of insulin-like growth factor-1 (IGF-1) and triamcinolone acetonide (TA) on interleukin-1 (IL-1)-conditioned equine cartilage. Furthermore, an optimal dose for IGF-1 treatment alone has been documented previously using the same test system as in the current project. OBJECTIVES: To perform a dose titration of TA on IL-1-conditioned equine articular cartilage explants in the presence of an optimised IGF-1 dose, in order to optimise a triamcinolone concentration for use in combination with IGF-1 for future investigations. METHODS: Cartilage explants were harvested from the distal femur of a normal horse. The effect of a clinically relevant TA dose range was evaluated in the presence of IL-1 and IGF-1 through measurement of proteoglycan (PG) matrix metabolism (synthesis and degradation). RESULTS: TA and IGF-1 in combination inhibited the IL-1-induced release of PG matrix components (glycosaminoglycan or GAG) from the articular cartilage, as well as producing a significant increase in GAG synthesis. CONCLUSIONS: This experiment provided proof of principle that a combination treatment appears to be able to combat the IL-1-induced matrix depletion, while enhancing anabolic metabolism within the articular cartilage. POTENTIAL RELEVANCE: The use of IGF-1 in conjunction with TA in vivo has the potential to provide beneficial anabolic effects not seen with TA alone.

Animals↗

Food-stimulated acid secretion measured by intragastric titration with bicarbonate in patients with duodenal and gastric ulcer disease and in controls.

Gastric acid secretion stimulated by a normally eaten beefsteak meal was measured for 4 h in 16 patients with duodenal ulcer disease (DU), in 9 patients with gastric ulcer disease (GU), and in 14 controls by intragastric titration with bicarbonate to a constant pH 5.5. Reproducibility of the method investigated in 6 DU and in 5 controls gave similar acid secretory values (var. coeff. = 7.5%). DU produced acid on a higher level and with longer duration after food than controls and GU (p less than 0.001). Apart from the second half of the first hour after food, when the acid secretion was higher in controls than in GU (p less than 0.025), there was no significant difference in acid output after food between GU and controls. Maximum gastrin values and 'total gastrin output' after food were significantly higher in GU than in controls, but these differences were not significant between GU and DU and between DU and controls. Fasting gastrin and gastrin levels after food were not correlated to basal acid output or acid output after pentagastrin or food in any of the groups. The maximal acid output after food was higher than the peak acid output after pentagastrin in controls, DU and GU. The relation between food- and pentagastrin-stimulated acid output was not statistically significantly different between the three groups. Instead, acid secretion after food was well correlated to acid secretion after pentagastrin in controls, DU and GU (r = 0.85).

Adult↗

Inhibition of food-stimulated acid secretion (intragastric titration) by roxatidine acetate. Dose-response study.

In 10 healthy male volunteers a dose-response study was carried out with roxatidine acetate, 75, 150, 300, and 600 mg, and placebo on food-stimulated gastric acid secretion (intragastric titration (IGT]. The design of the study, with drug intake 150 min before starting IGT, enabled stable inhibition over the 90-min observation period of the test. Cumulative secretory results showed a dose-related acid secretion inhibition (67% for 75 mg; 87.6% for 150 mg; 98.8% for 300 mg; 99.6% for 600 mg). The results were statistically significantly different from placebo and from each other, except for 300 mg versus 600 mg. With a Lineweaver-Burk plot, the ED50 was 41 mg and r = 0.98. Peak concentrations of roxatidine were observed either at T 150 or T 180. Significant correlation (r = 0.7; p less than 0.001) was obtained for the percentage inhibition with 75 mg and 150 mg together versus peak concentrations. Antisecretory potency with the IGT model applied to normal subjects appears to be of the same order for roxatidine acetate and for ranitidine.

Adult↗

Chicken (Gallus gallus) hemolytic complement: optimal conditions for its titration.

The effect of pH, ionic strength, cation concentration, ethylenediaminetetraacetic acid trisodium salt (Na3EDTA), time and temperature were studied to determine the optimal conditions for titrating the hemolytic complement (C) activity in sera of chicken (Gallus gallus). Swine erythrocytes (E) sensitized with rabbit antibodies were the most sensitive, while chicken serum had a smaller amount of "natural" antibody against them than against red blood cells from other five species tested. The highest titers of chicken C, when tested with swine sensitized E, were detected when isotonic NaCl-barbital buffer was used as diluent, having the ionic strength of 0.15, conductance of 11 millimhos/cm at 20 degrees C. However, maximal chicken C titers detected with sensitized rabbit E were obtained at ionic strength of 0.07 to 0.11 depending on pH. A final concentration of 1 X 10(-3) M of Mg2+ and 3 X 10(-4) M of Ca2+ and pH 8 were optimal in both cases. The temperature of 30 degrees C and time of 60 minutes were appropriate to reveal the maximal titers..

Animals↗

[Titration method for determination of carcinine (beta-alanyl-histamine). Application to the heart of Carcinus maenas (L.)].

1.--Carcinine was isolated by ion-exchange chromatography and titrated spectrophotometrically. The technique used was based on formation of an azo derivative of carcinine with sulfanilamide at basic pH. It allowed detection of carcinine at 1 microgram/ml concentration. 2.--Histamine could be detected simultaneously with the same technique, provided its concentration was greater than 1 microgram/ml. 3.--The mean amount of carcinine in cardiac tissues of Carcinus maenas was 22.1 micrograms/ml dry cardiac tissue. 4.--The technique described above did not allow detection of histamine in the heart of Carcinus maenas. If present, histamine must be at a concentration smaller than 0.1 microgram/ml dry cardiac tissue.

Animals↗

A simple novel method for determination of an inhibition constant by isothermal titration microcalorimetry. The effect of fluoride ion on urease.

A simple novel method was introduced for determination of an inhibitor binding constant (Ki) and enthalpy of binding by isothermal titration microcalorimetry technique. This method was applied to the binding of fluoride ion, as an inhibitor, with the active sites of jack bean urease at pH = 7.0 (Tris 30 mM) and T = 300 degrees K. The dissociation equilibrium constant measured by this method was markedly consistent with the inhibition constant obtained from assay of enzyme activity in the presence of fluoride ion.

Binding Sites↗

Comparison of titratable acid/alkaline reserve and pH in potentially caustic household products.

Exposure to caustic agents is a common problem, affecting thousands of individuals annually. Despite this incidence, the factors responsible for the production of injury remain poorly defined. Although extremes of pH seem to correlate well with the production of esophageal lesions, pH alone fails to explain the damage resulting from exposure to agents with near neutral pH, such as soldering flux containing zinc chloride. We determined titratable acid/alkaline reserve (TAR) in 38 potentially caustic household agents. A subset of these products was evaluated in an in-vitro canine esophageal model to determine whether TAR correlated with esophageal injury. The results indicate that for the products evaluated TAR correlated better than pH with the production of caustic esophageal injury.

Animals↗

Dose titration of sustained-release recombinant bovine somatotropin in lactating dairy cows.

Lactating dairy cows (n = 264) were used in seven dose titration experiments at four geographic locations in the United States. A sustained-release formulation of recombinant bST was evaluated for a 30-wk treatment period that began 14 wk postpartum. The first series of four experiments evaluated doses of 0, 140, 350, or 700 mg of bST/14 d (series A); the second series evaluated doses of 0, 56, 140, or 350 mg of bST/14 d (series B). Milk yield, DMI, milk composition, body condition, health, and reproductive parameters were measured. Multiparous cows in series A that were administered 700 mg of bST/14 d yielded 3.0 kg/d more milk and 3.5% FCM than control cows. When all seven experiments were combined, multiparous cows that were administered 350 mg of bST/14 d yielded 2.7 and 2.6 kg/d more milk and 3.5% FCM than control cows. Dry matter intake was not significantly affected by bST administration. In series A, an increase in milk yield with no increase in DMI resulted in lower adequacy of dietary NEL and CP to meet maintenance and yield requirements among multiparous cows administered 700 mg of bST/14 d. Primiparous cows that were administered bST in series A and both parity groups in the combined seven experiments were not different from control cows in the adequacy of dietary NEL or CP to meet maintenance and yield requirements. No adverse effects of bST on health parameters were significant, and doses of 350 mg of bST/14 d or less caused no changes in reproductive parameters. Conception rate was decreased by administration of 700 mg of bST/14 d. These data suggest that 350 mg of bST/14 d increased yields of milk and FCM with no adverse effects on DMI, health, or reproduction in dairy cows.

Animals↗

In vivo titration of white spot syndrome virus (WSSV) in specific pathogen-free Litopenaeus vannamei by intramuscular and oral routes.

White spot syndrome virus (WSSV) is a devastating pathogen in shrimp aquaculture. Standardized challenge procedures using a known amount of infectious virus would assist in evaluating strategies to reduce its impact. In this study, the shrimp infectious dose 50% endpoint (SID50 ml(-1)) of a Thai isolate of WSSV was determined by intramuscular inoculation (i.m.) in 60 and 135 d old specific pathogen-free (SPF) Litopenaeus vannamei using indirect immunofluorescence (IIF) and 1-step polymerase chain reaction (PCR). Also, the lethal dose 50% endpoint (LD50 ml(-1)) was determined from the proportion of dead shrimp. The median virus infection titers in 60 and 135 d old juveniles were 10(6.8) and 10(6.5) SID50 ml(-1), respectively. These titers were not significantly different (p > or = 0.05). The titration of the WSSV stock by oral intubation in 80 d old juveniles resulted in approximately 10-fold reduction in virus titer compared to i.m. inoculation. This lower titer is probably the result of physical and chemical barriers in the digestive tract of shrimp that hinder WSSV infectivity. The titers determined by infection were identical to the titers determined by mortality in all experiments using both i.m. and oral routes at 120 h post inoculation (hpi), indicating that every infected shrimp died. The determination of WSSV titers for dilutions administered by i.m. and oral routes constitutes the first step towards the standardization of challenge procedures to evaluate strategies to reduce WSSV infection.

Animals↗

Adhesion mechanism of polyelectrolyte cements to tooth structure--polyelectrolyte behavior of the cement polymers obtained by potentiometric titration in the presence of calcium ion.

Potentiomeric titration of aqueous solutions of polyacrylic acid and commercial polyelectrolyte cement polymers with sodium hydroxide solution was carried out in the presence of different concentrations of Ca2+. Polyelectrolytes all behave as weak acids without the coexisting Ca2+. However, in the presence of Ca2+, in amounts over one-half of the equivalent amount to the carboxyl group in the polymer, they have a strong acid-like behavior. This means that the carboxyl groups in the polymer chain tend to react strongly with coexisting Ca2+ as they are partially neutralized by the alkaline solution. This is also strong evidence supporting polyelectrolyte cement as an adhesion mechanism to tooth structure during cementation.

Acrylic Resins↗

Costimulation blockade, busulfan, and bone marrow promote titratable macrochimerism, induce transplantation tolerance, and correct genetic hemoglobinopathies with minimal myelosuppression.

Mixed hemopoietic chimerism has the potential to correct genetic hemological diseases (sickle cell anemia, thalassemia) and eliminate chronic immunosuppressive therapy following organ transplantation. To date, most strategies require either recipient conditioning (gamma-irradiation, depletion of the peripheral immune system) or administration of "mega" doses of bone marrow to facilitate reliable engraftment. Although encouraging, many issues remain that may restrict or prevent clinical application of such strategies. We describe an alternative, nonirradiation based strategy using a single dose of busulfan, costimulation blockade, and T cell-depleted donor bone marrow, which promotes titratable macrochimerism and a reshaping of the T cell repertoire. Chimeras exhibit robust donor-specific tolerance, evidenced by acceptance of fully allogeneic skin grafts and failure to generate donor-specific proliferative responses in an in vivo graft-versus-host disease model of alloreactivity. In this model, donor cell infusion and costimulation blockade without busulfan were insufficient for tolerance induction as donor-specific IFN-gamma-producing T cells re-emerged and skin grafts were rejected at approximately 100 days. When applied to a murine beta-thalassemia model, this approach allows for the normalization of hemologic parameters and replacement of the diseased red cell compartment. Such a protocol may allow for clinical application of mixed chimerism strategies in patients with end-stage organ disease or hemoglobinopathies.

Animals↗

Selegiline transdermal system for the treatment of major depressive disorder: an 8-week, double-blind, placebo-controlled, flexible-dose titration trial.

OBJECTIVE: This study investigated the efficacy, safety, and tolerability of the selegiline transdermal system (STS) administered in a dose range of 6 mg/24 hours to 12 mg/24 hours for treating major depressive disorder (MDD). METHOD: Patients meeting DSM-IV criteria for MDD (N = 265) were randomly assigned to blinded treatment with STS or a matching placebo patch for 8 weeks. Patients failing to meet or maintain protocol-defined therapeutic response criteria at predetermined time points had their STS (or placebo) dose increased. Assessments were conducted at weeks 1, 2, 3, 5, 6, and 8. Patients were not required to follow a tyramine-restricted diet. The study ran from September 2001 through August 2002. RESULTS: Selegiline transdermal system treatment resulted in significantly greater improvement (p < or = .05) compared with placebo treatment on the 3 depression rating scales: the 28-item Hamilton Rating Scale for Depression (HAM-D28) (primary outcome measure), the Montgomery-Asberg Depression Rating Scale, and the Inventory for Depressive Symptomatology-Self Rated. The treatment effect measured by the HAM-D28 was modest, primarily due to insomnia side effects. The antidepressant efficacy of STS was substantiated further by the significantly greater improvement in core depression symptoms (HAM-D Bech-6 subscale). The side effects of highest incidence were application site reactions and insomnia. There were no safety concerns based on routine clinical laboratory and electrocardiogram monitoring, and there were no occurrences of hypertensive crisis. CONCLUSION: Results of this double-blind, placebo-controlled, dose titration trial provide evidence of short-term efficacy, safety, and tolerability of STS in the dose range of 6 mg/24 hours to 12 mg/24 hours for treatment of MDD. Selegiline transdermal system has an improved margin of safety compared with oral monoamine oxidase inhibitors and represents a useful addition to the existing array of antidepressants.

Administration, Cutaneous↗