PubMed Health⌕ Search

Biomedical subjects

D Jovanović

Publications and source records attributed to D Jovanović.

At least 19 recordsLinked to original sources
PubMed2006

A comparative bioavailability study of a generic capsule formulation containing carbocysteine.

The bioequivalence of two carbocysteine capsulae preparations was assessed in 18 healthy volunteers who received a single 750 mg dose of each carbocysteine formulation, and a new sensitive method for the quantification of carbocysteine in human plasma was developed. The study was conducted using an open, randomized, two-sequence, two-period crossover design with a week washout period between the succesive treatments. Plasma samples were obtained over a 12-hour period and analyzed by high performance liquid chromatography coupled to electrospray ionization-mass spectrometry. Either a multiplicative statistic model for concentration-dependent parameters or an additive approach for time-related parameters were used for the comparison of pharmacokinetic parameters describing both the early and total exposure to carbocysteine. The respective 90% confidence limits [CL] of the individual ratios of geometric means were 0.898 to 1.112 [point estimate 0.999] for Cmax and 0.923 to 1.210 [point estimate 1.057] for AUC(0-infinity), while the difference between times elapsed to reach Cmax was insignificant [p = 0.4497]. Since both 90% CL for the log-transformed AUC(0-infinity) and Cmax geometric mean ratios were included in the proposed 0.80-1.25 interval, test drug (Bronchobos capsules) was considered bioequivalent to the reference one (Mucopront capsules).

Antitussive Agents↗
PubMed2005

[The role of endoscopic ultrasound(EUS) in differential diagnosis of subepithelial oesophago-gastric lesions].

BACKGROUND: Endoscopic ultrasonography(EUS) allows high-resolution demonstration of the entire gut wall. The aim of the study was to clarify the usefulness of the EUS in differential diagnosis of upper gastro-intestinal subepithelail lesions(SEL). METHODS: From September 1998- March 2005, EUS was performed in 1600 patients. Among them, in 206pts (13%), this examination was carried out due to previous upper endoscopy, which revealed the suspicion to SEL or extraluminal compression. We studied the location, the size, echo pattern and originating layer of SEL. The results were compared with CT, angiography and operation with histology when possible. All EUS examinations were performed using Olympus GIF-130 videoecho-endoscope with 7,5/12MHz switchable radial probe. RESULTS: EUS accuracy in separating intramural masses from extraluminal compression was 96%(44/46). Among 160 pts with true SEL, in 95(59.3%), EUS revealed the existence of a stromal tumor arising from muscularis propria (92) or muscularis mucosae (3). The size of the tumor varied from 5-75mm; depth: 8-40mm. 33 patients were operated on. In 14/16(87%), the EUS diagnosis of benign stromal tumor was confirmed on operation. In 18/19(95%), EUS correctly disclosed the malignant tumor. EUS accuracy in predicting malignancy was 91.5%(32/35). Findings suggestive for malignancy were: size 40mm; inhomogenicity with microcysts and irregular outer margin. In 12 pts, EUS revealed lypoma. Abberant pancreas was correctly diagnosed in all 22pts. In 16 persons, EUS disclosed submucosal cysts: 6 of them were operated on and EUS diagnosis was confirmed in all. In 10 patients EUS visualized varices. The finding was confirmed on angiography. CONCLUSION: The EUS appears to be very effective in differential diagnosis of SEL in upper gastro-intestinal tract. Tumour size greater than 40mm, inhomomogenous echo pattern and irregular outer margin are very suggestive for malignancy.

Diagnosis, Differential↗
PubMed2004

Influence of dissolution media composition on drug release and in-vitro/in-vivo correlation for paracetamol matrix tablets prepared with novel carbomer polymers.

The influence of dissolution media composition on drug release kinetics and in-vitro/in-vivo correlation (IVIVC) for hydrophilic matrix tablets based on Carbopol 971P and Carbopol 71G was investigated. A number of buffered and unbuffered media differing with respect to their pH value, ionic strength and ionic species was evaluated. The observed in-vitro drug release profiles were compared with the hypothetical drug release profiles in-vivo calculated by numerical deconvolution from the results of an in-vivo study. The obtained IVIVC plots were examined using linear and non-linear (proportional odds, proportional hazards and proportional reversed hazards) mathematical models. Although the studied sustained release agents were chemically identical, they exhibited pronounced differences in drug product behaviour both in-vitro and in-vivo. The use of non-linear modelling resulted in an improved level of correlation, especially in the case of Carbopol 71G matrices. The obtained results indicated the susceptibility of drug release kinetics and hence IVIVC in the case of anionic polymer matrices to media composition, and emphasized the need for thorough evaluation of applied media during the development of biorelevant dissolution methodology. Although the use of non-linear modelling could be advantageous, the need for a simple and meaningful non-linear relationship is pointed out.

Acetaminophen↗
PubMed2004

Effects of X-ray irradiation on the overexpression of HER-2/Erb-B2 on breast cancer cell lines.

Irradiation is the conventional treatment modality for cancer patients. However, besides its cytotoxic effects on malignant cells it might also affect the biology of surviving cells. Since overexpression of HER-2 receptors on malignant cells is a prerequisite for the therapeutic efficacy of Herceptin, it seems important to know whether previous irradiation changes their overexpression. The experiments performed in this work were aimed to determine whether X-ray irradiation of MDA-MB-361 and MDA-MB-453 breast carcinoma cell lines, besides its cytotoxic action, affects the overexpression of HER-2 protein. Determination of the cytotoxic effect of X-ray irradiation was done using trypan blue test. The breast carcinoma cell responsiveness to herceptin treatment in the presence of 10% fresh human serum (from healthy volunteer's) in the presence or absence of 25 microg/ml of herceptin, in vitro before and after cell-irradiation, was evaluated by MTT test. The degree of HER-2 overexpression was determined by immunocytochemistry, using DAKO HercepTest. Preliminary results obtained in this work showed that X-ray irradiation, besides its cytotoxic effect on malignant cells, could lead to overexpression of HER-2 receptors on (initially by immunocytochemistry, HER-2 negative) tumor cells, indicating change in biology of treated tumor cells. Further investigation in this direction will probably be helpful to elucidate this task in order to improve the selection of irradiated patients for Herceptin therapy.

Antibodies, Monoclonal↗
PubMed2003

Guiding center theory for ion holes in magnetized plasmas.

A drift-kinetic theory for ion phase-space vortices in magnetized plasmas is developed, taking into account the effects of the ion polarization and anisotropic heating by ion beams. It provides a theoretical explanation for the bipolar electrostatic structures in the auroral zone of the Earth's magnetosphere and their spatial and temporal scales, as observed by S3-3, Viking, FREJA, Polar, and FAST spacecrafts. Several types of quasi-three-dimensional ion holes are obtained analytically, in the form of either cylinders or ellipsoids. Although topologically different, they produce similar signals on the spacecraft and cannot be distinguished on the basis of the existing satellite data.

Journal Article↗
PubMed2002

Local recurrence and five year survival after abdominoperineal resection of the rectum due to rectal carcinoma.

In the period 01.01.1991-12.31.1996, 523 operations due to rectal carcinoma were performed on the First Surgical Clinic, the Third Department for Colorectal Surgery. Most common localization of tumor was in the distal third of the rectum 65.2%. In the middle third, there were 28.9% and in the upper, intraperitoneal third 5.9%. We performed 286 low anterior stapled resections, 93 anterior resections with hand-sewn anastomosis and 144 Abdominoperineal excisions of rectum (Miles procedure). Pathohistological examination revealed adenocarcinoma in all cases. In this study we analyzed local recurrence and five-year survival after long-term follow-up in the group where Miles procedure was carried out as a potentially curative procedure (except 4.9% cased with Dukes D stage). There were 74.3% males and 23.7% females median age 59.2 years. According to Dukes classification there were 4.9% in stage A, 47.2% in stage B, 43.1% stage C, and 4.9% stage D. There were 4(2.7%) postoperative deaths. Recurrence of the disease was registered in 44 (30.5%) patients. Local recurrence alone was found in 14 (9.7%) patients, while distant spread was registered in 30 (20.8%) patients. At present, the median follow-up is at 72.9 months. Analysis by the Kaplan-Meier's test shows cumulative survival of 61%, and disease free survival of 63.4% at 60 months of the follow-up. Dukes C is associated with a very poor prognosis; survival after 60 months of follow up shows cumulative Survival of 0.35 while Dukes B has far better prognosis (0.86). Analysis of disease free survival by Dukes stage shows that Dukes C has the worst prognosis (disease free survival 0.36 after 60 months), while stage B has much better prognosis (0.84). Local recurrence analysis by the Kaplan-Meier's test shows disease free survival of 84.9% at 60 months of follow-up. Analysis of local recurrence by Dukes stage shows 1.00% disease free survival for cases in stage A, 0.94 for Dukes B and 0.66 for Dukes C, while overall comparison between groups regarding local recurrence using the Wilcoxon (Gehan) statistic shows statistically significant difference (p-0.005). There is no statistical difference between Dukes A and Dukes B cases in distribution of local recurrence.

Adenocarcinoma↗
PubMed2001

A bioavailability/bioequivalence study of two oral lansoprazole formulations after single administration to healthy volunteers.

Two oral lansoprazole formulations, containing encapsulated microgranules, Lasoprol (test formulation) and Lanzor (reference), were administered to 12 healthy volunteers of both sexes in a single dose of 30 mg lansoprazole in order to investigate their comparative bioavailability. No statistically significant differences, at the probability level of 90%, were observed neither for the maximal serum concentrations (1.12:1.22 micrograms/ml) nor for the area under the concentration-time curves (5.01:5.77 micrograms/ml.h), the parameter to which the inhibition of acid secretion induced by lansoprazole is directly related. The similar holds true for the value of time to reach the maximal concentration of lansoprazole in serum, although this parameter was previously described as less sensitive in comparative bioavailability studies. The terminal elimination half-lives were 4.56 h for Lasoprol and 4.57 h for the reference formulation. The results indicate the bioequivalence and good tolerability of both lansoprazole formulations. The overall pharmacokinetic profile of the drug was comparable with the data previously reported by other investigators.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Prevention and recovery of CuSO4-induced inhibition of Na+/K+ -ATPase and Mg2+ -ATPase in rat brain synaptosomes by EDTA.

Enzymatic activities of Na+/K+-ATPase and Mg2+ -ATPase from rat brain synaptic plasma membrane were studied in the absence and presence of EDTA. The aim of the study was to examine the ability of this strong chelator to prevent and recover the CuSO4-induced inhibition. The influence of experimentally added CuSO4 and EDTA on MgATP2- complex and 'free' Cu2+ concentrations in the reaction mixture was calculated and discussed. CuSO4 induced dose-dependent inhibition of both enzymes in the absence and presence of 1 mM EDTA. In the absence of EDTA, the IC50 values of Cu2+, as calculated from the experimental curves, were 5.9x10(-7) M for Na+/K+ -ATPase and 3.6x10(-6) M for Mg2+ -ATPase. One millimolar EDTA prevented the enzyme inhibition induced by CuSO4, but also reversed the inhibited activity, in a concentration-dependent manner, following exposure of the enzymes to the metal ion, by lowering 'free' Cu2+ concentration. Kinetic analysis showed that CuSO4 inhibits both the Na+/K+ -ATPase and Mg2+ -ATPase, by reducing their maximum enzymatic velocities (Vmax), rather than apparent affinity for substrate MgATP2- (K0.5), implying the noncompetitive nature of enzyme inhibition induced by the metal. The kinetic analysis also confirmed two distinct Mg2+ -ATPase subtypes activated in the presence of low and high MgATP2- concentrations. K0.5 and Vmax were calculated using a computer-based program. The results of calculation showed that MgATP2- concentration in the kinetic experiments exceeded three times the apparent K0.5 value for the enzyme activation.

Animals↗
PubMed1999

Fungus-like hyphochytrids associated with human disease.

We report two cases, with liver and brain abscess, respectively, where fungus-like organisms belonging to the Hyphochytriomycota were found at the site of inflammation together with Peptococcus in the first and Cysticercus cellulosae in the second case. This is the first time these groups of organisms have been reported in human material. The role of hyphochytrids in human pathology remained uncertain as they were found together with already known human pathogens.

Adult↗
PubMed1998

Cathepsin D: association between TN-stage and steroid receptor status of breast carcinoma.

PURPOSE: To assess whether the expression of estrogen-induced protease, cathepsin D, might facilitate biological subgrouping of patients with breast carcinomas, and accordingly, its potential applicability in clinical oncology. PATIENTS AND METHODS: This study includes 70 patients with histologically confirmed breast carcinoma. Pathological findings were classified according to tumor size (T) and the presence or absence of metastases in regional lymph nodes (N). Steroid hormone receptor (SR) density as well as cathepsin D concentrations were assayed in the cytosol of breast carcinomas in accordance with the recommendation of the EORTC. RESULTS AND DISCUSSION: Statistically significant direct correlations were observed between cathepsin D expression and axillary node status as well as SR status. However, it is important to point out that in spite of these statistically significant findings, there were no biologically significant associations due to a wide range of individual cathepsin D values. Baseline levels of cathepsin D expression were found in patients with SR-negative status and node-negative tumors as well as in patients with SR-negative status and tumors of </=2 cm. Accordingly, a clinical significance of cathepsin D expression may be assumed.

Biomarkers, Tumor↗
PubMed1997

Prognostic factors: classification approaches in patients with lung cancer.

With the proliferation of potential prognostic factors for lung cancer, it is becoming increasingly more difficult to integrate the information provided by these factors into a single accurate prediction of clinical outcome. Here we reviewed five classification methods for their capabilities in classification of 200 patients with lung cancer into distinct prognostic groups using survival outcome as a criteria. The source of patient data for this study is a Lung Tumour Registry from Institute for Lung Diseases, University Clinical Hospital, Belgrade. Almost all developed classification algorithms determined prognostic groups according to biochemical tumour markers LDH and alkaline phosphatase, producing most significant split, instead of commonly used staging variables. The choice of which approach to use for a given classification problem depends not only on statistical properties of method, but also on medical considerations, such as whether more differential findings are given greater weight and the applicability of a classification rule.

Alkaline Phosphatase↗
PubMed1996

Oxime-induced reactivation of acetylcholinesterase inhibited by phosphoramidates.

The reaction of human erythrocyte acetylcholinesterase (AChE) with a set of structurally related phosphoramidates was studied in order to investigate the properties of phosphorylated enzyme and the effects of 4 oximes PAM-2, TMB-4, HI-6 and BDB-106 on the reactivation of inhibited AChE. Second-order rate constant of the phosphorylation reaction of the compounds towards the active site of AChE range between 5.0 x 10(2) and 4.9 x 10(6) M-1min-1 and their inhibitory power (I50) was from 7.3 x 10(-5) to 5.7 x 10(-9) M for 20 min incubation at 37 degrees C. The oximes used were weak reactivators of inhibited AChE except for (C4H9O)(NH2)P(O)DCP (DCP, -O-2,5-dichlorphenyl group) and (C6H13O)(NH2)P(O)SCH3 where we have obtained good reactivation. Imidazole oxime BDB-106 proved to be a potent reactivator of tabun-inhibited AChE.

Acetylcholinesterase↗
PubMed1996

[Radiographic changes in the sella turcica in female patients on chronic hemodialysis].

The bone disease in chronic renal failure patients with secondary hyperparathyroidism is usually termed renal osteodystrophy. Radiographic methods have been applied in renal bone disease mainly to discover lesions on long bones, hands and fee. During the evaluation of hormonal disturbances of hemodialysed chronic renal failure female patients, roentgenograms of sella turcica were taken. Findings that were detected were most probably the consequences of renal osteodystrophy. Osteoporosis of clinoid processes posteriores and dorsum sellae and intrasellar calcifications were confirmed in 25 percent of investigated patients. Lateral view of the sellae turcica demonstrated a "double floor".These pathological findings in sella turcica region could be of practical importance because of well known anatomophysiological position of this sceletal structure.

Adult↗
PubMed1996

[Hemostatic system parameters in patients with chronic renal insufficiency and arteriovenous fistula thrombosis].

Functional disturbances among different tissues and organic systems are associated with chronic renal failure. The most common problems following the disturbances in complex hemostatic changes in uremic patients are prolonged bleeding time ant the increased thrombosis tendency. As the patients vascular access is critical to the treatment of the chronic haemodialysis patient, we performed an investigation of causes of repeated vascular access thrombosis with purpose of detecting any consistent abnormality of the haemostatic system. Research has been conducted on a group of 29 patients (14 males and 15 females), age 21 to 61 (x = 45), on regular haemodialysis from 1 to 6 years (x = 2.2); 23 of them having one episode of thrombosis of vascular access, and 6 having two episodes. Partial thromboplastin time was among the normal ranges in all investigated subjects, three of them had low prothrombine time and thrombine time was prolonged in two cases. The high fibrinogen value was found in 19 patients. Mean value of platelet count was normal, though seven patients had thrombocytopenia. Absence of coagulum retraction was found in three patients. Assessment of blood coagulation in this study could not explain the development of repeated thrombotic events affecting arterio-vein fistula in chronic renal failure patients receiving haemodialysis. That points out the necessity to analyze functional status of natural coagulation inhibitors, fibrinolytic system and platelet function.

Adult↗
PubMed1996

[Peritonitis in patients on continuous ambulatory peritoneal dialysis].

We analysed 27 patients (15 women and 12 men) on CAPD treatment longer than 6 months at the Clinic of Nephrology, CCS, in Belgrade. Pts were between 22 and 72 years old (57.77 +/- 12.21 years). These pts had 47 episodes of peritonitis: 6 pts (22.22%) were without peritonitis, but 21 pts (78.22%) had between 1 and 5 episodes of peritonitis. We found 1 peritonitis /pts/year. Causes of peritonitis were mostly unknown (27/47) because treatment had began before taking culture of the peritoneal dyalisate. The most common causes of peritonitis were coagulase negative staphylococci: Staphylococcus aureus (8) and Staphylococci epidermidis (8). Laboratory showed: leucocytosis, hyperfibrinogenaemia, hypoproteinaemia and accelerated ESR. There was no connection between causes of chronic renal failure and frequency or peritonitis. During treatment of peritonitis in 2 pts we had to replace the peritoneal catheter and 5 pts went on haemodialyses. The other were recovered and continued CAPD treatment.

Adult↗
PubMed1996

[Pulmonary complications in patients on continuous ambulatory peritoneal dialysis].

We analysed 27 patients (15 women and 12 men) on CAPD treatment, between 6 months and 7 years at the Clinic of Nephrology, Clinical Center of Serbia, in Belgrade. Patients were between 22 and 72 years old. The main causes of pulmonary abnormalities were infections (5), hypervolaemia, hypoproteinaemia and heart failure (13). We had 11 patients (40.74%) with 18 pulmonary abnormalities: bronchopneumonia (2 pts), pleuritis sicca (1 pt), pleural effusion (10 pts): unilateral (4) and bilateral (7). Three patients had recurrent pulmonary infections and pulmonary abnormalities. All patients recovered and continued treatment with CAPD.

Adult↗
PubMed1996

[Distribution of renal diseases at the Ambulatory Nephrologic Clinical Center in Serbia].

At the nephrologic offices of the Clinical Centre of Serbia Polyclinic 2,451 patients (975 males and 1,476 females) were examined over a period of four years (1987-1990). Out of these 647 (26.40%) were suffering from chronic renal failure. Hypertension as the principal diseases was diagnosed in 432 patients (17.62%), being somewhat more frequent in women. Two hundred patients were suffering from glomerulonephritis. Pyelonephritis was diagnosed in nearly the same number of patients (199). Out of the 129 patients suffering from urinary tract infections 112 (86.82%) were women. Women appeared in large numbers in other diagnostic groups as well. Quite a number of patients (14.08%) reported only once for functional examination of the kidneys. It may be concluded that among the examined patients the most numerous were those with chronic renal failure, while many were suffering from chronic nephropathy which points to the comparatively late diagnosing of nephrological disorders.

Female↗