Adipocytokines during pregnancy and postpartum in women with gestational diabetes and healthy controls.

BACKGROUND: This study aims to explore the changes in maternal serum adipocytokines during pregnancy and post partum in normal and complicated with gestational diabetes (GDM) pregnancies and to investigate the relationship between serum adipocytokines and some of major metabolic parameters. MATERIALS AND METHODS: 236 pregnant women (127 with GDM and 109 control group) and 50 postpartum women (30 with GDM during pregnancy and 20 controls). Using ELISA and EIA kits, serum levels of adipocytokines were tested during pregnancy and post partum. Maternal adipocytokines levels were correlated with some metabolic parameters. RESULTS: Women with GDM had lower values of adiponectin and higher values of leptin during pregnancy (p<0.001; 0.0001) and post partum (p<0.002; 0.0001). Serum apelin was significantly lower in GDM group (p<0.009). However, we did not find significance for resistin (p<0.317) and apelin (p<0.218). Positive correlation for leptin and negative for adiponectin was found for pre-pregnancy and pregnancy body mass index, glycated hemoglobin and homeostasis model assessment of insulin resistance index. Using cut point of 8.2 µg/ml for adiponectin and 28.7 ng/ml for leptin could exclude GDM with a sensitivity of 83.6%/81.2% and specificity of 56.6%/64.2% (area under the curve 0.702 and 0.827). CONCLUSION: There are constant differences in adiponectin and leptin levels between GDM and control group during pregnancy and post partum. Apelin was decreased in our GDM group and no differences were found for resistin and visfatin. Further studies are required to verify the mechanism of this alteration and whether the adipocytokines can be predictors for GDM at an early stage of pregnancy.

[Sperm disorder in males with obesity and metabolic syndrome--pilot study].

UNLABELLED: The aim of the study was to compare the semen quality in men with metabolic syndrome /MS/ and controls. MATERIALS AND METHODS: Semen samples were collected from 42 males (mean age--27.69 +/- 7.98 years). 21 of them had the features of the metabolic syndrome according to the IDF definition and 21 were healthy volunteers. The semen samples were analyzed according to the World Health Organization 1999 guidelines. RESULTS: The patients with MS had similar age, ejaculate volume, percentage of spermatozoa with normal morphology, sperm concentration (in million per milliliter), and total sperm count (in million) compared to controls. However, they had lower percentage of motile spermatozoa (p = 0.002). Men with obesity (BMI > 30) had significantly lower sperm concentration and total sperm count in comparison to normal- or overweight males (BMI < 30). CONCLUSION: reduced semen quality could be established in patients with obesity and MS. Further investigations are necessary to clarify the changes in the exocrine testicular function in males with MS and their consequences for the reproduction.

An estimate of the influence of the measurement procedure on patient and phantom doses in breast imaging.

This work is aimed to study the variability of dosimetry results owing to various measurement methodologies for breast dosimetry. This is performed in the frame of the development of a national protocol for breast dosimetry. Doses for standard phantom and group of patients were calculated for two mammography systems from the tube output measured with a calibrated ionisation chamber. The backscatter from the phantom under the chamber contributes to an increase in dosimeter readings of approximately 0.8-1.5%, whereas the proximity of the compression plate to the chamber causes increase in the measured air kerma value by 6.5-7%. High value layer (HVL) measured with solid-state detector without corrections for energy dependence was 17% higher than the one measured with ionisation chamber, which causes corresponding overestimation of average glandular dose (AGD). The use of conversion factors based on typical but not measured HVL values leads to 3.5-5.6% overestimation of AGD. Although the sources of uncertainty were taken into account, the difference between the phantom and patient doses was 24%. Some practical recommendations to be included in the national dosimetry protocol are summarised.

[Effect of 6-month treatment with oral antiandrogen alone and in combination with insulin sensitizers on body composition, hormonal and metabolic parameters in women with polycystic ovary syndrome (PCOS) in order to determine therapeutic strategy].

UNLABELLED: PCOS is a complex disorder with variability of phenotypes, characterized by hyperandrogenic, anovulatory and metabolic components. The later is a result of specific insulin resistant state with compensatory hyperinsulinaemia. Oral hormonal contraceptives (OHC) are a treatment of first choice in hyperandrogenic PCOS women who do not desire conception. Addition of insulin sensitizers might counteract unfavourable metabolic consequences of OHC monotherapy and could result in additional benefits for treated PCOS women. AIM: To compare the effects of 3 therapeutic regimens widely used in practice--OHC alone and in combination with metformin or rosiglitazone on body weight and anthropometric proportions, hormonal and metabolic alterations. MATERIAL AND METHODS: The study comprised of 44 women with proven PCOS, divided in 3 therapeutic groups: 1st group--with Diane35 alone; 2nd group--with Diane35 + metformin; 3rd group--with Diane35 + rosiglitazone. Body weight, fat mass and distribution, hormonal levels, metabolic parameters (insulin and blood glucose during oGTT lipid profile) were studied before and after a 6-month treatment. RESULTS: Monotherapy with Diane35 did not lead to changes in body weight, fat mass and distribution; had beneficial influence on some of the hormonal alterations in PCOS, but did not achieved significant antiandrogenic effect; did not induce changes in carbohydrate tolerance while having mild negative effect on insulinaemia; had an unfavourable although mild influence on lipid parameters including atherogenic indices except the HDL-cholesterol; did not show side effects on liver and vascular function. Combined treatment with Diane35 and metformin led to reduction of weight, fat mass and abdominal fat distribution; possessed significant antiandrogenic effect; did not decrease blood glucose levels; supressed glucose-stimulated insulin levels; had beneficial effect on HDL-cholesterol and neutral effect on other lipid parameters and atherogenic indices; decreased diastolic blood pressure. Combined treatment with Diane 35 and rosiglitazone did not induce changes in body weight, fat mass and abdominal fat distribution; possessed significant antiandrogenic effect; did not influence fasting and postchalange glucose levels; suppressed fasting hyperinsulinaemia and HOMA-index, respectively; had neutral effect on the levels of lipid parameters and atherogenic indices.

Pharmacokinetic variability of nimodipine disposition after single and multiple oral dosing to hypertensive renal failure patients: parametric and nonparametric population analysis.

OBJECTIVES: To explore the contribution of renal failure to nimodipine overall pharmacokinetic variability after single and multiple oral dosing and to develop a population pharmacokinetic model by means of the nonparametric expectation maximization (NPEM2) algorithm based on sampled individual drug concentrations close to the estimated patients' C(SS)avs (NPEM2-C(SS)av). PATIENTS, MATERIALS AND METHODS: 24 hypertensive patients with normal and reduced renal function, without clinical and laboratory data for hepatic dysfunction, were enrolled in the study and their nimodipine plasma levels were analyzed by means of a parametric and nonparametric population pharmacokinetic modeling using a maximum a posteriori Bayesian (MAPB) estimator in an iterative two-stage Bayesian population modeling program and NPEM2-algorithm. RESULTS: Comparison of parameter dispersion revealed higher variability of nimodipine disposition after the first dose than at steady-state except for apparent volume of distribution at steady-state, V(SS)/F, whose variability increased from 98% to 223%. The most variable was mean residence time, MRT, whose coefficient of variation (CV) was 288% after the first dose and decreased by more than 2 times at steady-state, followed by terminal elimination half-life, t(1/2el), with CV = 171% after the first dosing and decreasing by more than 3 times at steady-state. Concerning the impact of renal failure on disposition parameters variability, patients with slightly to moderately reduced renal function, creatinine clearances between 51 to 80 and 25 to 50 ml/min, resp., stated higher variation than patients with more definitively altered renal function. The validation of NPEM2-C(SS)av population model was performed by using a set of 272 individual plasma drug concentrations, including trough levels as well as concentrations belonging to mono-exponential elimination phases after single and multiple dosing. Bayesian forecasting, using 4 trough levels per patient as Bayesian priors, revealed highly significant correlation between observed and population model predicted drug concentrations (r = 0.526, p < 0.0001). The predictive performance of NPEM2-C(SS)av population model was characterized by low bias (mean error = -0.48 microg/l, 95% CI = -0.99-0.04 microg/l), and good precision (root mean squared error = 4.32 microg/l, 95% CI = -2.53-11.17 microg/l). CONCLUSIONS: As predicted for high hepatic clearance drugs [Rowland 1985], nimodipine parameters variability decreased after reaching steady-state. NPEM2-C(SS)av population model demonstrated high accuracy and precision in predicting drug levels from terminal exponential phase including trough levels at steady-state.

Average bioequivalence of two oral formulations of fluconazole in healthy subjects after multiple dosing.

OBJECTIVES: To assess the average bioequivalence of two oral dosage forms of fluconazole--test (Fungolon, Antibiotic Co.) and reference (Diflucan, Pfizer)--in 18 healthy volunteers in a multiple dose-balanced, two-period, crossover study design. MATERIALS AND METHODS: The dosage regimen consisted of seven days treatment (first day 100 mg and 50 mg thereafter for six days given orally) and a washout period of two weeks between different treatments. Plasma samples were taken at regular time intervals according to the study protocol for measuring of plasma fluconazole concentrations. The primary and secondary parameters AUC(168-192), Cav, %PTF, Cmax, %Swing, %AUCF, 100 Cmax/AUC, T above Cav, and Tmax were estimated. RESULTS: The point estimates--geometric means of the ratios test (T)/reference (R) and the 90% confidence intervals (CI) for the ratios of expected medians (T)/(R), assuming a multiplicative model, estimated by parametric and nonparametric analysis--were in the defined ranges for accepting of bioequivalence for two of the primary metrics. The point estimates and the 90% CIs after parametric analysis of AUC(168-192) were 1.00 (0.98-1.02) and for the metric %PTF exceeded the accepted range for bioequivalence after parametric analysis the point estimate and 90% CI were 0.93 and (0.799-1.08). CONCLUSION: The two preparations were considered to be bioequivalent in the rate and extent of absorption with significant variability across subjects.

Population pharmacokinetics of ciprofloxacin in patients with liver impairments analyzed by NPEM2 algorithm--a retrospective study.

In order to develop a population pharmacokinetic model for ciprofloxacin after single oral dosing in patients with liver impairments, a retrospective population analysis of already published data was undertaken. The purpose of the study was to compare the population model parameter estimates for ciprofloxacin obtained with the non-parametric expectation maximization (NPEM2) algorithm based on a full data set (NPEM2-FULL) with those based on a set of 3 randomly chosen time/concentrations data (NPEM2-3RPs). Parameter values generated by the standard two-stage (STS) approach using traditional data-rich situation were used as a "gold standard" for comparative purposes. There was no significant difference between parameter means at p < 0.05 for Gauss-Newton and maximum a posteriori Bayesian (MAPB) estimators. The values of k(s) (min/ml/h) as estimated by STS and NPEM2-FULL models, on the one hand, and by STS and NPEM2-3RPs population models on the other hand (0.001, 0.00095, and 0.001, respectively), were not significantly different (p = 0.1457, respectively p = 0.6276). The population models values of k(s) suggest that good approximation between ciprofloxacin renal clearance and creatinine clearance could be expected for most of the patients and support previous observations that creatinine clearance is a meaningful predictor for ciprofloxacin elimination from the body. The 3 population models estimated Vs/F (l/kg) without significant difference. The predictive performance of these population models was subsequently assessed using internal validation approach. The 3 population models demonstrated comparable accuracy and precision in Bayesian forecasting of drug plasma levels of validation group patients based on 1 random and 2 suboptimal prior drug concentrations. There was, however, a one-order of magnitude decrease in population models bias when 2 suboptimal data points were used as Bayesian priors.

Antiepileptic drug utilization in out-patients--a prescribing pattern study.

Antiepileptic drug utilization for the treatment of different epileptic seizures had been investigated for 10 years in Bulgaria (1985-1994). The data were collected from ambulatory cards of 10,132 epileptic out-patients as well as from pharmacists' sales records. The results were expressed in DDD/1,000 inhabitants/year. During the period 1985-1989 the drug mostly prescribed had been phenobarbital both in mono- and polytherapy, but during the second period (1990-1994) it had been replaced to a high extent by carbamazepine and valproates. Polytherapy had given up its place to monotherapy in all forms of epileptic seizures during the 10-year period of investigation.

Nitric oxide synthase inhibition and acute renal ischemia: effect on systemic hemodynamics and mortality.

This study was designed to examine if acute systemic blockade of nitric oxide (NO) production by inhibition of nitric oxide synthase (NOS) with N-omega-nitro-L-arginine methyl ester (L-NAME) would worsen the severity of ischemic acute renal failure (ARF). Initially three groups of rats, were studied: 45 min of bilateral renal ischemia (I) alone, Group I; L-NAME (L; 10 mg/kg BW, i.v.) alone, Group L; and L-NAME administered 15 min before renal ischemia, Group L+I. We observed, however, a 60% mortality in Group I+L during the first 4 h of reflow. Captopril, administered acutely 15 min before L-NAME in an attempt to offset any detrimental effects of increased angiotensin II generation in response to renal ischemia, failed to obviate the mortality because 67% of rats in this group (Group C+L+I) also died. Therefore, additional studies were performed in rats instrumented for cardiovascular studies to evaluate the acute hemodynamic responses during the first 90 min of reperfusion following renal ischemia in rats pretreated with L-NAME. As expected, L-NAME injection was accompanied by a 25-30 mm Hg increase in mean systemic arterial pressure (SAP) (p < 0.05), a bradycardia (p < 0.02), and a decrease in cardiac output (CO) (p < 0.02). The increase in SAP was due exclusively to an increase in systemic vascular resistance (SVR) (p < 0.01). Ischemia and reflow in the L-NAME-treated rats were attended by a progressive increase in SVR and a progressive decrease in CO such that by the end of 45 min of reperfusion SVR had increased 10-fold and CO had decreased to one third of its initial rate (both p < 0.02). Pulmonary artery pressure (PAP) increased promptly following L-NAME injection. Total pulmonary resistance (PRT) increased significantly by the end of reperfusion. L-NAME in combination with renal ischemia and reflow induces a large increase in both SVR and PRT, and is accompanied by a 70% reduction in CO and substantial mortality.

Investigation on antibiotics in a hospital for a one-year period.

Defined daily dose (DDD) units were used to analyze the antibiotic utilization in a University Military Hospital for a one-year period. The data were collected from hospital records. The mostly prescribed drug groups were penicillins (broad-spectrum), systemic sulfonamides and combinations and tetracyclines. Amoxycillin, doxycycline and co-trimoxazole were most frequently used. Circannual variations were observed only in the utilization of amoxycillin and doxycycline during the year.

Pharmacokinetic and pharmacodynamic approach for comparing two therapeutic regimens using amikacin.

The efficiencies of two dosage schedules of amikacin (2 x 10 mg/kg of body weight per 24 h and 1 x 20 mg/kg/24 h intramuscularly for 5 days) against Pseudomonas aeruginosa sepsis in rabbits were compared. Blood samples were drawn at various times after the first application, and amikacin concentrations in serum were assayed microbiologically. The dynamics of the bactericidal effect of amikacin was simulated in vitro with the same strain of P. aeruginosa. No regrowth was found with the 20-mg/kg dose when the bacterial inoculum was in contact with experimental and theoretically predicted serum amikacin concentrations. The killing effect was present even when the drug levels decreased considerably below the MIC. The interrelationship between simulated amikacin concentrations in serum and the corresponding average killing rates was described appropriately by the standard Emax model. The higher amikacin dose performed its bacterial effect faster and the drug persisted longer in the blood. The two amikacin regimens were therapeutically equivalent, but the once-daily schedule had some advantages over the twice-daily drug administration which became evident when both the pharmacokinetic and the pharmacodynamic parameters of the drug were considered.

Utilization of some NSAID's and a H2-blocker in two hospitals.

The method of DDD (defined daily dose) was used to determine the drug utilization of NSAIDs and H2-blockers in two randomly chosen hospitals in Sofia during the last year period. The data were collected from hospital records. Seasonal variations in DDDs were compared for two groups of drugs. The utilization of diclofenac in the university hospital was higher than that in the city hospital. The utilization of indomethacin in the city hospital was higher in summer than in winter. The derivatives of propionic and acetic acids, piroxicam and sulindac, were mostly utilized in the university hospital. The overall ranitidine utilization and its autumn consumption in the city hospital were considerably higher in comparison with the university hospital.

Atrial natriuretic peptide and dopamine in a dog model of acute renal ischemia.

Atrial natriuretic peptide (ANP) has been shown to reverse functional impairment in ischemic acute renal failure (ARF). To prolong and/or to enhance the effects of peptide, in this investigation dopamine (D) (3 micrograms/kg BW/min) was applied together with ANP (100 ng/kg BW/min) after 90 min unilateral renal artery occlusion in anesthetized dogs. ANP significantly increased creatine clearance, filtration fraction, diuresis, sodium excretion, sodium reabsorption, and free water clearance, as in postinfusion period only V remained elevated. D alone did not effect renal function beneficially. ANP+D improved kidney function impairment to a level comparable with that of ANP alone, but V and UNa.V remained increased in the postinfusion period. MAP was elevated during ANP+D infusion as compared to ANP alone and was sustained to the end of the experiment. We conclude that D does not potentiate the positive effects of ANP on postischemic kidney, but prolongs its action on UNa.V, possibly by maintenance of high MAP after renal ischemia.

[The clinical and microbiological study of the preparation perfloxacin in treating urologic infections]. / Klinichno i mikrobiologichno prouchvane na preparata pefloksatsin pri lechenie na uroinfektsiite.

Experience with Pefloxacin treatment of thirty-nine patients presenting urinary tract infection, over the period 1992-1993, is shared. The drug is administered per os at dosage--800 mg, divided in two doses given at 12-hour intervals. As shown by the results of assaying the clinical symptoms, laboratory indicators and microbiological findings in the urine, the therapeutic effect is very good. A clinical cure is recorded in 76 cases (92 per cent), and healing of the bacteriological agent--in 92.31 per cent. Side effects are rarely observed and mildly manifested. The results of Pefloxacin treatment warrant the assumption that the drug synthesized is encouraging, suitable for both out- and inpatient treatment of urinary tract infections, and therefore it should be introduced in the daily routine practice.

Atrial natriuretic factor infusion following acute renal ischemia in anesthetized dogs.

Atrial natriuretic factor (ANF) has been shown to be effective in reversing renal functional impairments following renal ischemia. We studied the effects of a nonhypotensive intravenous ANF infusion (100 ng/min x kgBW, 60 min) after 90 min unilateral renal arterial occlusion in anesthetized dogs with an intact contralateral kidney. ANF plasma levels remained unchanged in controls (group 1) and increased in ANF-infused animals (group 2) from 22 +/- 3 to 552 +/- 124 pg/ml. Blood pressure increased in both groups during renal ischemia, but returned to control values in group 2 when ANF infusion was started. Plasma vasopressin did not change in group 1, but increased in group 2 (0.77 +/- 0.29 vs. 1.10 +/- 0.49 pg/ml) after terminating ANF infusion. The postischemic fall in creatinine clearance (CCr), filtration fraction (FF) and renal blood flow (RBF) was prevented by infusion of ANF (CCr: group 1, 0.16 +/- 0.05 vs. group 2, 1.01 +/- 0.25 ml/min x kgBW; FF: group 1, 4.0 +/- 1.6 vs group 2, 14.1 +/- 4.1%; RBF: group 1, 6.0 +/- 1.2 vs. group 2, 9.2 +/- 1.6 ml/min x kgBW); however, the effects were limited to the time of infusion and the postischemic increase in urinary excretion of the proximal tubular enzyme N-acetyl-beta-D-glucosaminidase (NAG; group 1, 317.7 +/- 163.6 vs. group 2, 672.4 +/- 245.7 microU/min x kgBW) was not improved by ANF. Our data suggest that infusion of ANF transiently reverses postischemic renal impairment. However, the failure to demonstrate a sustained postischemic improvement of renal functional parameters and to ameliorate massive NAG excretion casts doubt on the benefit of ANF infusion in preventing cellular damage.

Intact kidney function during contralateral renal artery clamping in dogs.

Experiments were carried out on 32 Nembutal anaesthetized mongrel dogs from both sexes. After 45 min control period unilateral renal ischemia was achieved by clamping the left renal artery for 90 min. In part of the experiments (n = 8) after clamp removal 3 consecutive 45 min periods were performed. The function of the intact right kidney was investigated. Mean arterial pressure (MAP), heart rate (HR), glomerular filtration rate (GFR), urine flow rate (V), fractional excretions of sodium (FENa), potassium (FEK) and chloride (FECl) and plasma levels of atrial natriuretic peptide, dopamine and antidiuretic hormone were evaluated. During ischemia MAP was elevated from 122.5 +/- 3.1 to 140.2 +/- 2.7 mmHg (p < 0.001), HR decreased from 119 +/- 4 to 102.5 +/- 3.9 beats/min (p < 0.01) as compared to the control period. GFR did not change significantly, while all excretory parameters increased: V from 8.7 +/- 1.2 to 14.5 +/- 1.7 microliters/min/gr kidney tissue (p < 0.05); FENa from 2.3 +/- 0.2 to 3.6 +/- 0.3% (p < 0.01); FEK from 40.0 < 3.5 to 51.2 < 2.8% (p < 0.05); FECl from 1.8 < 0.3 to 2.6 < 0.3% (p < 0.05). MAP remained elevated in the first and the second postischemic periods and was paralleled by the sustained increase in FENa and FECl, while FEK remained higher to the end of the experiment. ANP was significantly elevated during ischemia: on 75 min--p < 0.01 and on 105 min.--p < 0.05. AVP and dopamine showed no statistically significant changes during the investigated periods.(ABSTRACT TRUNCATED AT 250 WORDS)