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Hepatitis C virus antibody titration in patients with chronic hepatitis C, before and after interferon treatment.

We measured hepatitis C virus antibody titers in 13 patients with chronic hepatitis C to determine whether titration of hepatitis C virus antibody was useful or not, to predict and evaluate the efficacy of interferon (IFN) treatment. During administration of IFN, hepatitis C virus titers declined in all patients. Antibody titers performed before treatment as well as just at the end of treatment did not correlate with change of the alanine aminotransferase levels during administration of IFN. Antibody titers declined continuously after treatment in 5 patients with normal alanine amino-transferase levels for over 6 months after discontinuation of IFN. Antibody titers rose again in 6 patients whose alanine aminotransferase levels fluctuated after treatment. An exceptional pattern of change occurred in 2 patients whose antibody titers declined continuously although their alanine aminotransferase levels fluctuated after treatment. Repeated titration of hepatitis C virus antibody appears to be useful for evaluating the long-term efficacy of IFN treatment.

Adult↗

Titration schedule with rats in a restraining device.

In a restraining device, providing a constant localization and easy placement of stimulating electrodes, rats were conditioned to push a front panel in order to reduce the intensity of a shock which otherwise increased regularly every 10 sec. Rapid conditioning was obtained from all subjects. They showed a very stable behavior, with negligible inter- or intra-individual variability throughout very long experimental sessions. The operant nature of the response was demonstrated further in extinction, where no shock was delivered, and in situations where the animal could not change the predetermined intensity of the shock. The interpretation of the obtained threshold was discussed with reference to previous studies on titration schedule. It was suggested that, with the parameters used, the shock intensity at which it was maintained by the rats' behavior, had the value of a warning signal, and that, in this particular case, the titration schedule generated mainly discriminative avoidance behavior rather than escape behavior.

Journal Article↗

Stepwise determination of quaternary ammonium salts and aromatic amines in pharmaceuticals by ion association titration.

A stepwise titrimetric method has been developed for the simultaneous determination of pharmaceutical quaternary ammonium salts (R4N+) and aromatic amines (R3N). The method is based on the solvent extraction of R4N+ and R3NH+ with an ion association reagent. Sodium tetrakis(4-fluorophenyl)borate and sodium tetraphenylborate were used as titrants and potassium tetrabromophenolphthalein ethyl ester (TBPE) was used as an indicator. The ion associate which formed between R4N+ ion and TBPE made a blue color in 1,2-dichloroethane, while the ion associate formed between R3NH+ and TBPE showed a red-violet one. Sample solutions containing quaternary ammonium and/or amine compounds were titrated with sodium tetrakis(4-fluorophenyl)borate or sodium tetraphenylborate. When one drop of excess titrant was added, the color of the organic phase turned from blue or red-violet to yellow at the equivalence point. On the other hand, in the mixture of R4N+ and R3N, the color changed from blue to red-violet at the first equivalence point, and then its color turned to yellow at the second equivalence point. The quaternary ammonium compound and aromatic amine in pharmaceuticals could be simultaneously and successfully determined by the proposed titration method.

Journal Article↗

Determination of glyphosate in water samples by alternating-current oscillopolarographic titration.

This paper describes a novel, simple and sensitive method for the determination of glyphosate in water samples by alternating-current oscillopolarographic titration. Under an acidic condition, glyphosate can be transferred into a nitrosocompound by reacting with NaNO2. The titration end-point was obtained by the formation of a sharp cut in the oscillopolarographic with infinitesimal NaNO2 on double platinum electrodes. The results showed that glyphosate had an excellent linear relationship over the range of 7.16 x 10(-6) - 4.14 x 10(-3) mol L(-1), the RSD of the proposed method was lower than 3%, and the spiked recoveries of three real water samples were in the range of 97.7 - 100.2%.

Glycine↗

Colloidal titration of aqueous zirconium solutions with poly(vinyl sulfate) by potentiometric endpoint detection using a toluidine blue selective electrode.

Zirconium oxy-salts were hydrolyzed to form positively charged polymer or cluster species in acidic solutions. The zirconium hydrolyzed polymer was found to react with a negatively charged polyelectrolyte, such as poly(vinyl sulfate), and to form a stoichiometric polyion complex. Thus, colloidal titration with poly(vinyl sulfate) was applied to measure the zirconium concentration in an acidic solution by using a Toluidine Blue selective plasticized poly(vinyl chloride) membrane electrode as a potentiometric end-point detecting device. The determination could be performed with 1% of the relative standard deviation. The colloidal titration stoichiometry at pH < or = 2 was one mol of zirconium per equivalent mol of poly(vinyl sulfate).

Journal Article↗

Spectrophotometric titration of cobalt(II) with CaCl2 in mixed solvents of 2-propanol and water for the analysis of the extraction mechanism of cobalt(II) by salting-out in the presence of CaCl2.

The spectrophotometric titration of cobalt(II) with CaCl2 was carried out in mixed solvents of 2-propanol and water at different solvent compositions of 2-propannol, water and CaCl2 to analyze the salting-out extraction mechanism of Co(II) by the addition of CaCl2 from the mixed solvents. The formation constants of betaCoCl4(2-) = [CoCl4(2-)][Co2+](-1)[Cl-](-4) in both the organic and aqueous phases were determined thorough non-linear regression of the spectrophotometric titration data by a computer program SPECFIT/32. The values of log betaCoCl4(2-) in the aqueous phases were -4.26 +/- 0.03, -4.03 +/- 0.07, -3.83 +/- 0.04, -3.69 +/- 0.03 and -3.46 +/- 0.01 at mole fractions of 2-propanol of 0.026, 0.023, 0.017, 0.014 and 0.012, respectively, and at [CaCl2]/mol dm(-3) values of 3.555 (I = 10.6), 4.276 (I = 12.8), 4.916 (I = 14.7) and 5.444 (I = 16.3), respectively. The formation constants of [CoCl4(2-)] in the organic phase were 5.70 +/- 0.06, 5.44 +/- 0.03, 5.36 +/- 0.06, 5.10 +/- 0.04 and 4.84 +/- 0.05 at mole fractions of water of 0.431, 0.441, 0.444, 0.447 and 0.451, respectively, and at [CaCl2]/mol dm(-3) of 0.941 (I = 2.8), 0.943 (I = 2.8), 1.013 (I = 3.0), 1.090 (I = 3.3) and 1.165 (I = 3.5), respectively. These results suggest the formation of [CoCl4(2-)] of 23-90% in the aqueous phase at the above mole fractions and the quantitative formation of [CoCl4(2-)] in the organic phase. The extraction percentage of [CoCl4(2-)] increased with an increase in [CaCl2]. The distribution constant, KD (= [CoCl4(2-)]org/[CoCl4(2-)]aq), however, decreased and became constant with [CaCl2]. The detailed extraction mechanism of Co(II) is discussed.

2-Propanol↗

Determination of sulfur compounds in hydrotreated transformer base oil by potentiometric titration.

A method was developed to analyze the distribution of sulfur compounds in model sulfur compounds by potentiometric titration, and applied to analyze hydrotreated transformer base oil. Model thioethers were oxidized to corresponding sulfoxides by tetrabutylammonium periodate and sodium metaperiodate, respectively, and the sulfoxides were titrated by perchloric acid titrant in acetic anhydride. The contents of aliphatic thioethers and total thioethers were then determined from that of sulfoxides in solution. The method was applied to determine the organic sulfur compounds in hydrotreated transformer base oil.

Journal Article↗

SBR on-line monitoring by set-point titration.

The applicability of set-point titration for monitoring biological processes has been widely demonstrated in the literature. Based on published and on-going experiences, some operating procedures have been specifically developed to be applied to SBRs, so that real-time information about the process and/or the influent can be obtained. This, in turn, would allow plant operators to select the most appropriate actions properly and timely. Five operating modes are described for the monitoring of (1) influent toxicity, (2) influent N-content, (3) nitrification capacity, (4) end of the nitrification reaction, and (5) nitrate effluent concentration, and are currently tested on the on-line titrator TITAAN (TITrimetric Automated ANalyser) which is in operation on a pilot scale SBR.

Bacteria↗

Adipocyte lipid-binding protein complexed with arachidonic acid. Titration calorimetry and X-ray crystallographic studies.

The association of the adipocyte lipid-binding protein (ALBP) with arachidonic acid (all cis, 20:4 delta 5,8,11,14) and oleic acid (cis, 18:1 delta 9) has been examined by titration calorimentry. In addition, the crystal structure of ALBP with bound arachidonic acid has also been obtained. Crystallographic analysis of the arachidonic acid.ALBP complex along with the previously reported oleic acid-ALBP structure (Xu, Z., Bernlohr, D. A., and Banaszak, L. J. (1993) J. Biol. Chem. 268, 7874-7884) provides a framework for the molecular examination of protein-lipid association. Isothermal titration calorimetry revealed high affinity association of both unsaturated fatty acids with the protein. The calorimetric data yielded the following thermodynamic parameters for arachidonic acid: Kd = 4.4 microM, n = 0.8, delta G = -7370 cal/mol, delta H = -6770 cal/mol, and T delta S = +600 cal/mol. For oleic acid, the thermodynamic parameters were Kd = 2.4 microM, n = 0.9, delta G = -7770 cal/mol, delta H = -6050 cal/mol, and T delta S = +1720 cal/mol. The identification of thermodynamically dominating enthalpic factors for both fatty acids are consistent with the crystallographic studies demonstrating the interaction of the fatty acid carboxylate with a combination of Arg106, Arg126, and Tyr128. The crystallographic refinement of the protein-arachidonate complex was carried out to 1.6 A with the resultant R factor of 0.19. Within the cavity of the crystalline binding protein, the arachidonate was found in a hairpin conformation. The conformation of the bound ligand is consistent with acceptable torsional angles and the four cis double bonds in arachidonate. These results demonstrate that arachidonate is a ligand for ALBP. They provide thermodynamic and structural data concerning the physical basis for protein-lipid interaction and suggest that intracellular lipid-binding proteins may mediate the biological effects of polyunsaturated fatty acids in vivo.

Adipocytes↗

Differences in humoral insulin-antibody response among inbred Lou/M rats and epitope presentation differences in ELISA and radioimmune titration.

Insulin antibodies were not detected in an insulin-capture enzyme-linked immunosorbent assay (ELISA), but they were easily detected in an insulin-copolymer-capture ELISA. Thus, there is a high degree of steric hindrance because of the proximity of the epitopes on the insulin monomer. This is circumvented by substituting an insulin copolymer for insulin in the capture ELISA. A regression analysis comparing the titers of 28 Lou/M rat insulin antiserums measured by liquid-phase radioimmune titration (RIT) with titers obtained in the direct insulin ELISA was not significant (P greater than .05). Thus, epitopes on insulin available and/or masked for antibody binding in the RIT differ from those available and/or masked in the direct insulin ELISA. As more of the epitopes become available when an insulin copolymer is substituted for monomeric insulin in the ELISAs, a significant positive correlation (P less than .05) with the RIT was observed with these 28 insulin antiserums. Twenty-five percent (7 of 28) of these antiserums contained more antibodies that bound to epitopes available in the ELISAs that were masked in the RIT. Conversely, two antiserums contained more antibodies that bound to epitopes that were available in the RIT but were masked in the ELISAs. Thus, the amount of insulin antibodies measured in a given antiserum can vary substantially, depending on which epitopes are made available or are masked in the particular antibody-titration method used. These results demonstrate that the humoral immune response to insulin among inbred Lou/M rats can vary in insulin-antibody levels as well as the epitopes on insulin to which the antibodies bind.

Animals↗

Diclazuril, a new broad spectrum anticoccidial drug in chickens. 1. Dose titration studies and pilot floor pen trials.

Diclazuril, a new anticoccidial drug, was tested in poultry against six Eimeria species either in single species infections in dose titration studies or in mixed species infections in floor pen trials. The dose titration studies in cockerels indicated that diclazuril at dosages of 10, 5, 1, and .5 ppm was highly active against all major pathogenic species: E. tenella, E. acervulina, E. necatrix, E. brunetti, E. maxima, and E. mitis and effective in terms of weight gain and suppression of mortality, dropping scores, and oocyst counts. In two floor pen trials diclazuril was fed for 6 wk to broiler chickens experimentally infected either with E. tenella and E. acervulina or with E. necatrix and E. brunetti. Dose levels of 10, 5, and 1 ppm suppressed mortality and lesion scores. Even at 1 ppm the mean terminal body weight, feed conversion, and productivity index of treated birds were comparable to results for the uninfected, unmediated controls. In these pilot studies, involving 1,020 Hisex and 1,000 Hubbard broiler chickens, it has been demonstrated that diclazuril at the dose level of 1 ppm in the diet is an excellent anticoccidial without any adverse effects.

Animals↗

Anticoccidial efficacy of semduramicin. 1. Evaluation against field isolates by dose titration in battery tests.

Semduramicin (AVIAX), a novel polyether ionophore, was titrated in a series of five battery tests at 20, 25, and 30 ppm in feed to determine the optimum level for use. Twelve-day-old broiler chicks were medicated for 48 h prior to inoculation in each 9-day test. The inocula included monospecific field isolates of Eimeria tenella, Eimeria brunetti, Eimeria necatrix, and Eimeria maxima, and a mixture of these species with Eimeria acervulina and Eimeria mitis. The numbers of oocysts inoculated were selected after titration of each species and the mixture of species. All three concentrations of semduramicin significantly (P < .05) reduced coccidiosis mortality and lesion scores and achieved lower feed:gain ratios and greater weight gains than the infected, unmediated treatments. A concentration of 25 ppm semduramicin was determined to be optimal based on improved lesion control compared with 20 ppm and improved weight gain compared with 30 ppm.

Animals↗

Titration of botulinum toxins for lethal toxicity by intravenous injection into mice.

Clostridium botulinum type A - F toxins can be titrated by the time-to-death method by iv injection into mice. The time to death is not dependent upon the molecular size, but upon the immunological type of the toxin. It is necessary to assure complete activation of the activable toxin produced by nonproteolytic as well as a certain proteolytic strains before subjecting to titration by the iv injection method.

Animals↗

Titration of varicella-zoster virus DNA in throat swabs from varicella patients by combined use of PCR and microplate hybridization.

We devised a simple procedure for titration of varicella-zoster virus (VZV) DNA in throat swabs from varicella patients. DNA which was extracted from throat swabs, together with known copy numbers of a cloned VZV DNA fragment, were 10-fold serially diluted and used as template in PCR. The PCR products, after heat denaturation, again serially diluted in 1.5 M NaCl and adsorbed to microplate wells. Then, biotin-labeled DNA probes were hybridized with the immobilized DNA. The hybridization signal was produced by streptavidin-conjugated beta-galactosidase and a fluorogenic enzyme substrate. By comparing the titration curves of a clinical specimen with those of the cloned fragment, of which detection limit was about 10 copies, we estimated the copy numbers of VZV DNA in the specimen. With this technique, we evaluated the degree of potential contagiousness of the patient along the course of infection: we found that varicella patients possessed highest quantity of VZV DNA in the throat on the first day of illness.

Chickenpox↗

Development and usefulness of the gelatin-particle-agglutination test for titration of antibodies against diphtheria, pertussis and tetanus toxins.

The gelatin-particle-agglutination (PA) test for titrating antibodies against diphtheria, pertussis and tetanus toxins was developed and used for assaying 65 sera from healthy children to assess the antitoxin acquisition in relation to the administration of adsorbed diphtheria-purified pertussis-tetanus (DPT) combined vaccine. The antitoxin titers obtained by the PA test and the conventional methods were correlated well; the correlation coefficient of the diphtheria antitoxin titers between the PA test and the cell culture method was 0.908, that of the tetanus antitoxin titers between the PA test and the passive hemagglutination test 0.968, and that of anti-pertussis toxin titers between the PA test and polystyrene-ball ELISA 0.885. The PA test was shown to be useful in both developed and developing countries, since it is simple to perform, sensitive and specific, and the three antitoxins can be titrated by the same procedure.

Agglutination Tests↗

[The CAPITOL study (Captopril Post Infarction Tolerance). A trial of progressive titration of captopril after myocardial infarct with left ventricular dysfunction].

The objective of CAPITOL (Captopril Post Infarction Tolerance) multicentre open trial was to study the tolerance of a protocol of titration of Captopril in patients with recent myocardial infarction complicated by left ventricular dysfunction. Five hundred and four patients, with a mean age of 62 +/- 12 years, were included during the hospital period in the 74 participating intensive care units, 9 +/- 6 days after myocardial infarction (ejection fraction 34 +/- 6%). After a 6.25 mg test dose of Captopril, the dosage was progressively increased to the target dose of 150 mg at the end of the first month. Of the 504 patients included, 343 finished the trial and 161 stopped the trial prematurely. At the end of the hospital period, 73% received 75 mg/day: at the first follow-up visit (27 +/- 16 days after inclusion), 59% had attained 150 mg/day, this proportion increasing to 71% at the end of the trial (79 +/- 33 days after inclusion). There was no significant change in blood pressure for the whole study population. However, the systolic blood pressure of the patients receiving 150 mg/day of Captopril at the end of the trial was slightly higher than that observed at the end of the hospital period (126 +/- 17 mmHg and 116 +/- 17 mmHg respectively, p = 0.006). Severe Intercurrent events were observed in 89 patients: 24 deaths, 7 recurrent infarctions, 58 hospital admissions (21 for cardiac failure, 15 for recurrence of angina, 11 aorto-coronary bypass operations, 7 coronary angioplasties, 2 cerebro-vascular accidents, 2 systemic emboli). Of the benign complications, hypotension was observed in 25% of patients, nearly half of which occurred during the hospital admission. The drugs prescribed in association with Captopril were Aspirin (78%), betablockers (57%), nitrate derivatives (42%) and diuretics (27%). Multivariate analysis showed 3 factors associated with good tolerance of the 150 mg dosage of Captopril: Killip Class I or II on admission, an ejection fraction > 30% and an initial systolic blood pressure > 100 mmHg. In conclusion, in this trial of dose titration, 3 out of 4 patients with myocardial infarction and left ventricular dysfunction, tolerated the 150 mg/day dosage of Captopril. Patients in the trial could also be treated with drugs recommended after myocardial infarction, in particular the betablockers. Arch Mal Coeur 1999: 92: 395-403.

Adrenergic beta-Antagonists↗

Intratympanic gentamicin titration therapy for intractable Meniere's disease.

OBJECTIVE: This study aimed to assess the efficacy and morbidity of intratympanic gentamicin titration therapy on patients with intractable unilateral Meniere's disease. STUDY DESIGN: The study design was a retrospective chart review and patient interviews. SETTING: The study was conducted at a tertiary referral ambulatory dizziness clinic at the London Health Sciences Centre, University Campus, from July 1992 to June 1997. INTERVENTION: Eighty-three patients received weekly intratympanic gentamicin injections in their diseased ear. Treatments were terminated after four injections or sooner if patients met clinical or audiologic criteria. Sixty-eight patients were available for detailed follow-up. MAIN OUTCOME MEASURES: Vertigo frequency, hearing status, personal disability ratings, tinnitus level, and caloric responses before and after gentamicin therapy were measured. RESULTS: Eighty-four percent of patients showed complete, and an additional 6% showed substantial, vertigo control. At 24 months, 17% of patients demonstrated a clinically significant (10-dB) reduction in hearing, but 26% showed a significant hearing improvement. Overall, the group showed no combined statistically significant changes in any of the hearing parameters. No patients had an "extreme" drop in hearing (>30 dB). CONCLUSIONS: Intratympanic gentamicin titration therapy provides excellent vertigo control with a low incidence of hearing loss.

Adult↗

Efficacy and safety of cerivastatin in primary hypercholesterolemia: a long term comparative titration study with simvastatin.

OBJECTIVE: To compare cerivastatin with simvastatin in their long term safety and efficacy in reducing low density lipoprotein cholesterol (LDL-C). DESIGN: Multicentre, randomized, double-blind, parallel group study. SETTING: Thirteen Canadian centres. PATIENTS AND METHODS: A total of 387 patients with primary hypercholesterolemia received treatment with either cerivastatin (0. 05 to 0.3 mg/day) or simvastatin (5 to 40 mg/day) to achieve plasma LDL-C levels below 3.36 mmol/L (130 mg/dL) for an initial 32-week dose-titration phase and a subsequent 72-week extension phase. MAIN RESULTS: Cerivastatin and simvastatin produced clinically significant reductions in LDL-C of 28.4% and 35.4%, respectively, at the end point for the 32-week study, and reductions of 32.8% and 35. 0%, respectively, at the end of the extension phase of the study. Response rates (a greater than 15% drop in LDL-C) were comparable for the two treatments (88.9% cerivastatin versus 93.2% simvastatin) at the 32-week end point. Response rates were 100% for both treatments at the end of the 72-week extension phase. Both treatments also reduced total cholesterol, apolipoprotein B and very low density lipoprotein cholesterol levels. Cerivastatin and simvastatin increased HDL-C levels significantly by 8.8% and 11.0%, respectively, at the end point for the 32-week study, and by 8.6% and 12.1%, respectively, at the end of the extension phase of the study. Treatments were well tolerated, and the incidence of adverse effects was similar in both groups. CONCLUSIONS: This forced titration study demonstrates that cerivastatin, given once daily at doses up to 0.3 mg/day, is effective and well tolerated. The results of this study support further investigation of higher doses of cerivastatin given the excellent safety profile at doses up to 0.3 mg.

Anticholesteremic Agents↗