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Biomedical subjects

J Popović

Publications and source records attributed to J Popović.

At least 19 recordsLinked to original sources
PubMed2005

The effects of acute and chronic lithium treatment on rat submandibular salivation.

OBJECTIVE: Acute and chronic actions of lithium on salivation induced by agonists associated with receptor-linked hydrolysis of membrane inositol phospholipids (carbachol and phenylephrine) and by agonist linked to activation of adenylate cyclase (isoproterenol) were investigated. MATERIAL AND METHODS: In anaesthetized rats, submandibular salivation induced by intravenous injection of carbachol, phenylephrine and isoproterenol, was measured and expressed as volume of fluid (microl) elicited per 100 mg wet weight of each gland per minute. The experiments were repeated after acute and chronic treatment of lithium (7 mg kg(-1)). The results were analysed with unpaired t-test. RESULTS: Chronic, but not acute lithium treatment significantly decreases carbachol- and phenylephrine-induced salivation while isoproterenol-induced salivation was not changed neither after acute nor after chronic administration of lithium. CONCLUSION: The results suggest that hyposalivation during chronic lithium therapy could be mediated by alterations in the phosphatidylinositol cycle and a consequent lack of inositol after agonist stimulation.

Acute Disease↗
PubMed2005

Laparoscopy treatment of adnexal sterility.

A total of 113 patients who were examined and treated for matrimonial infertility underwent surgical laparoscopy at the Sterility and Infertility Department, Clinic of Gynecology and Obstetrics, Clinical Center of Nis. Age distribution in the group of patients who were subjected to surgical laparoscopy after diagnosis was 31.39 +/- 6.1 years, out of whom 74.3% were treated for primary sterility. Out of corrective interventions in laparoscopy, the following procedures were performed: adnexiolysis, salpingo-ovariolysis, fimbrioplasty, terminal salpingoneostomy, cyst puncture and ovarian incision. During any surgical laparoscopy, ovarian biopsy was performed for evaluation of ovarian potency and verification of probable histopathological findings. The most commonly used technique was salpingo-ovariolysis--in 22.88% of cases, followed by fimbrioplasty--18.81%. A total of 42 pregnancies were verified: 36 intrauterine (29 completed at full term) and 6 extrauterine pregnancies. Average conception rate in our patients was 37.17%, while rate of parturition was 25.66%. The rate of pregnancy in different corrective laparoscopic procedures ranged from 18.18%-61.54%. The rate of intrauterine pregnancy was the highest after bilateral fimbrioplasty (47.83%), and the lowest after bilateral neosalpingostomy--9.09%. The rate of delivery after adhesiolysis was 30.8%, after salpingo-ovariolysis--28.8%, after fimbrioplasty--18.3%, and after neostomy--12.5% of the time.

Adnexal Diseases↗
PubMed1999

Derivation of Laplace transform for the general disposition deconvolution equation in drug metabolism kinetics.

This paper presents some very simplified general treatments which will allow workers to derive equations for any linear kinetic metabolic process. This is done through the use of the Laplace transforms. A general equation is presented to describe the disposition function in Laplace operators for the central compartment of a linear n compartment mammillary model with elimination occurring from any of the compartments. Input functions describes IV bolus, zero-order infusion, intramuscular injection or GI absorption. The Laplace transform for the amount of drug or metabolite in the central compartment is given by the products of the input and disposition functions.

Kinetics↗
PubMed1990

Screening of newborns for congenital hypothyroidism in Croatia--organization and first results.

In 1985 a newborn screening programme for the detection of congenital hypothyreosis was introduced in Croatia in addition to the already existing one for phenylketonuria. The paper delineates the organization of the screening programme, the method used, and the first results. Clinical manifestations, somatic and mental development, as well as laboratory findings of the first eleven children with congenial hypothyroidism detected by the screening programme and followed-up regularly are presented in more detail.

Congenital Hypothyroidism↗
PubMed1987

Interaction of metabolism of aspartate and inosine and energy state of malignant cells.

1. Oxidation of glutamine in Ehrlich ascites-carcinoma cells results in a large accumulation of aspartate. 2. The addition of inosine causes a marked decrease in aspartate production from glutamine. This may be related to the resynthesis of AMP from aspartate and IMP, the latter being produced from inosine via the salvage pathway for purine nucleotides. In accordance with this assumption, a significant production of lactate was observed, which comes probably from the ribose moiety of inosine. Since lactate is known to inhibit production of aspartate from glutamine, this may explain the effect of inosine. 3. Addition of glutamine together with inosine increased cellular ATP content. This was not the case if glutamine or inosine was present separately or if inosine was added together with lactate, pyruvate or glucose. The effect did not occur if amino-oxyacetate, an inhibitor of transaminases, was added. These findings suggested again that production of aspartate is important for resynthesis of ATP from IMP via the purine nucleotide cycle. 4. If the cells were exposed to prolonged anaerobic incubation, addition of glutamine and inosine markedly increased O2 uptake and [ATP], suggesting the crucial importance of aspartate production by glutamine oxidation for the recovery of energy metabolism in the cells.

Adenosine Triphosphate↗
PubMed1984

High-pressure liquid chromatographic method for determination of metoclopramide in serum, urine, and saliva, with a pharmacokinetic study in patients.

A method for determination of metoclopramide in serum, urine, and saliva is described that can be applied to both pharmacokinetic and clinical studies. Metoclopramide was extracted from alkalinised plasma into dichloromethane and chromatographed on a Micro-Pak Si-5 column using a mobile phase of dichloromethane/methanol/diethylamine (89:10:1, by volume). The column was maintained at 25 degrees C and the eluate monitored at 308 nm. The retention time for metoclopramide was 4.7 min. The limit of sensitivity in serum and urine was 15 nmol/L and 3 mumol/L, respectively, with coefficients of variation of 5.4 and 3.84%, respectively. Recovery was in the range of 93-110% for serum and 94-103% for urine. The limit of sensitivity in saliva was 15 nmol/L. In more than 210 samples analyzed to date, the only drugs known to have interfered with the assay are beta-adrenoceptor blockers (e.g., propranolol). The metabolites of metoclopramide did not interfere with the quantitation of the parent drug.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Pharmacokinetic analysis of a new acenocoumarol tablet formulation during a bioequivalence study.

The pharmacokinetics of a new tablet formulation of acenocoumarol racemate, an oral anticoagulant agent, has been investigated in 8 normal healthy subjects. The drug was given as a single oral dose of 12 mg. 12 blood samples were collected after administration Plasma acenocoumarol concentrations were determined by a sensitive HPLC method. Areas under the plasma level-time curves for each subject were evaluated by means of the trapezoidal rule. The peak plasma concentration of 244.19-644.23 micrograms/l was reached 1-4 h after drug administration. The terminal phase half-life was 6.29-14.22 h and a systemic clearance was 1.86-5.62 l/h. The new table formulation of acenocoumarol seems to be bioequivalent when compared to the one used so far. For the prediction of systemic availability and estimation of the first-pass metabolism, from plasma level data, a hepatic blood flow rate limited model were used. The systemic availability was 94.22-98.01% and the elimination of the drug on its first-pass through the liver was 1.99-5.78%.

Acenocoumarol↗
PubMedDate not supplied

Cubic spline functions and polynomials for calculation of absorption rate.

A model-independent method for calculation of the absorption rate based on an exact mathematical solution to the deconvolution problem of systems with linear pharmacokinetics and a polyexponential impulse responses has been examined. Theoretical analysis shows how a noninteracting primary input can be precisely evaluated when data on blood levels from a known source such as an i.v. bolus or zero-order infusion are available. This work compares the use of a Lagrange 3rd degree polynomial with that of a cubic spline function (special 3rd degree polynomial) for calculation of the absorption rate. The method is compared to another using simulated data (12 data points) containing various degrees of random noise.The accuracy of the methods is determined by how well the estimates represent the true values. It was found that the accuracy of the two methods was not significantly different, and that it was of the same order of magnitude as the noise level of the data.

Absorption↗
PubMedDate not supplied

Pharmacokinetics of carbamazepine derived from a new tablet formulation.

The pharmacokinetics of a new tablet formulation of carbamazepine, an antiepileptic agent, have been investigated in 9 normal healthy subjects. The drug was given as a single oral dose of 400 mg. Ten blood samples were collected after administration. Plasma carbamazepine concentrations were determined by a sensitive method (HPLC). Areas under the plasma level-time curves for each subject were evaluated by means of the trapezoidal rule. The peak plasma concentration of 3.96-8.25 mg/l was reached 4-24 h after drug administration. The terminal phase half-life was 22.19-39.61 h and a systemic clearance was 1.05-2.06 l/h. The new tablet formulation of carbamazepine seems to be bioequivalent when compared to the one used so far. For the prediction of systemic availability and estimation of the first-pass metabolism, from plasma level data, a hepatic blood flow rate limited model were used. The systemic availability was 97.8-98.9% and the elimination of the drug on its first-pass through the liver was 1.13-2.20%.

Administration, Oral↗
PubMedDate not supplied

Spline functions in convolutional modeling of verapamil bioavailability and bioequivalence. I: conceptual and numerical issues.

A cubic spline function for describing the verapamil concentration profile, resulting from the verapamil absorption input to be evaluated, has been used. With this method, the knots are taken to be the data points, which has the advantage of being computationally less complex. Because of its inherently low algorhythmic errors, the spline method is less distorted and more suitable for further data analysis than others. The method has been evaluated using simulated verapamil delayed release tablet concentration data containing various degrees of random noise. The accuracy of the method was determined by how well the estimates of input rate and extent represented the true values. It was found that the accuracy of the method was of the same order of magnitude as the noise level of the data. Spline functions in convolutional modeling of verapamil formulation bioavailability and bioequivalence, as shown in the numerical simulation investigation, are very powerful additional tools for assessing the quality of new verapamil formulations in order to ensure that they are of the same quality as already registered formulations of the drug. The development of such models provides the possibility to avoid additional or larger bioequivalence and/or clinical trials and to thus help shorten the investigation time and registration period.

Biological Availability↗
PubMedDate not supplied

Spline functions in convolutional modeling of verapamil bioavailability and bioequivalence. II: study in healthy volunteers.

The pharmacokinetics of a new verapamil retard tablet formulation have been investigated in a randomized cross-over bioequivalence study on 12 healthy subjects. The drug was given orally at a single new or standard retard tablet dose of 240mg and at a single intravenous dose of 5mg. Plasma verapamil concentrations were determined by HPLC. New retard tablets produced peak plasma verapamil concentrations of 81.34+/-5.69microg/l, time to peak plasma concentrations of 4.91+/-0.89h and an AUC (0-24h) of 1291+/-103.4h x microg/l, with a terminal phase half-life of 55.1+/-14.9h. After intravenous administration verapamil exhibited biphasic elimination kinetics with a terminal plasma half-life of 2.36+/-0.42h and systemic clearance of 34.32+/-5.81 l/h. Bioavailability of the new peroral retard formulation ranged from 19.49+/-4.41% to 67.69+/-11.70%. Absorption rates and amounts were evaluated by means of the spline-convolutional method. Input rates for the new verapamil retard formulation ranged from 0.77+/-0.20mg/h to 5.57+/-1.58mg/h. The cumulative amount of verapamil input was 39.17+/-9.71% for the new retard tablets. All pharmacokinetic parameters for the new verapamil retard tablet formulation, were in reasonable agreement with the data obtained on already registered verapamil retard formulations, indicating their bioequivalence.

Administration, Oral↗