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S Pavlovic

Publications and source records attributed to S Pavlovic.

At least 19 recordsLinked to original sources

2,9-Dimethyl-beta-carbolinium, a neurotoxin occurring in human brain, is a potent inducer of apoptosis as 1-methyl-4-phenylpyridinium.

The causes of neurodegeneration are not well understood. However, the role of environmental and endogenous toxins is receiving much attention. In this study, we compared the synthetic neurotoxin 1-methyl-4-phenyl-pyridinium with beta-carbolines occurring in human brain. Methylation of both nitrogens is necessary to convert a beta-carboline into a potent inhibitor of mitochondrial complex I. The respective beta-carboline, 2,9-dimethyl-beta-carbolinium ion is neurotoxic in rats. To investigate the underlying mechanisms, we incubated mouse neuroblastoma 2A cells with 2,9-dimethyl-beta-carbolinium ion, and compared the findings with effects of norharman, the precursor beta-carboline of methylated derivatives, and with 1-methyl-4-phenyl-pyridinium. 2,9-Dimethyl-beta-carbolinium ion caused a significant increase of reactive oxygen species (higher efficiency than 1-methyl-4-phenyl-pyridinium) and of mitochondrial membrane potential within the first minutes. After 60 min, the membrane potential dissipated. Concomitantly, the levels of glutathione increased in 2,9-dimethyl-beta-carbolinium ion but not in 1-methyl-4-phenyl-pyridinium treated cells. After 24 h effector caspases 3 and 7 were activated and the number of apoptotic cells increased as revealed by fluorescence-activated cell sorting cytometry. When incubated longer (48 h), cells underwent late apoptosis/secondary necrosis as shown by fluorescence-activated cell sorting analysis and confirmed qualitatively by an electron microscopy study. The effects of 2,9-dimethyl-beta-carbolinium ion on apoptotic changes were similar to those induced by 1-methyl-4-phenyl-pyridinium(,) while norharman showed only a weak potency at the very high doses. To investigate whether 2,9-dimethyl-beta-carbolinium ion is neurotoxic under in vivo conditions and whether only dopaminergic neurones are affected we conducted a dose-response study. Three weeks after injection of 2,9-dimethyl-beta-carbolinium ion in the substantia nigra we found a dose-dependent decrease of dopamine and its metabolites in the striatum of rats. The levels of 5-hydroxytryptamine were diminished although the decrease was less. The levels of noradrenaline increased after some doses. The findings strongly suggest an important role of endogenous beta-carbolines in neurodegeneration with apoptosis as the predominant mechanism.

1-Methyl-4-phenylpyridinium↗

[Long-term results after epilenticular intraocular lens implantation following traumatic cataract].

BACKGROUND: The purpose of this study was to analyze the late postoperative outcome and complication rate after lensectomy with primary epilenticular intraocular lens (IOL) implantation for traumatic cataract. MATERIAL AND METHODS: We retrospectively reviewed the data of 11 patients who were operated on for traumatic cataract after penetrating or blunt ocular trauma between 1997 and 2002. One patient developed cataract due to a large rupture of the posterior capsule after blunt trauma. Ten patients sustained a penetrating ocular injury with (7 eyes) or without (3 eyes) intraocular foreign body (IOFB). In all patients the IOL was implanted at the beginning of the operation into the ciliary sulcus in front of the opaque lens followed by pars-plana lensectomy and vitrectomy. RESULTS: The mean follow-up was 27.4 months. Eight eyes (72.7 %) achieved a final visual acuity of 0.5 or better. Major causes of limited visual acuity were central corneal scars causing irregular astigmatism. In all patients the IOL was safely and easily implanted into the ciliary sulcus. During the subsequent pars-plana lensectomy and vitrectomy as well as during the follow-up period all IOLs remained anatomically stable and well centered. In one patient PVR retinal detachment had to be treated by pars-plana vitrectomy with silicone oil tamponade. CONCLUSIONS: Epilenticular IOL implantation followed by pars-plana lensectomy is an easy and safe method to treat traumatic cataract in the setting of penetrating ocular trauma repair. It is associated with a favorable visual outcome and a low rate of postoperative complications.

Adult↗

Molecular and phenotypic characteristics of patients with phenylketonuria in Serbia and Montenegro.

Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism in Caucasians. PKU is caused by mutations in the gene encoding phenylalanine hydroxylase (PAH) enzyme. Here, we report the spectrum and the frequency of mutations in the PAH gene and discuss genotype-phenotype correlation in 34 unrelated patients with PKU from Serbia and Montenegro. Using both polymerase chain reaction-restriction fragment length polymorphism and 'broad-range' denaturing-gradient gel electrophoresis/DNA sequencing analysis, 19 disease-causing mutations were identified, corresponding to mutation detection rate of 97%. The most frequent ones were L48S (21%), R408W (18%), P281L (9%), E390G (7%) and R261Q (6%), accounting for 60% of all mutant alleles. The genotype-phenotype correlation was studied in homozygous and functionally hemizygous patients. We found that the most frequent mutation, L48S, was exclusively associated with the classical (severe) PKU phenotype. The mutation E390G gave rise to mild PKU. For the mutation R261Q, patients had been recorded in two phenotype categories. Considering allele frequencies, PKU in Serbia and Montenegro is heterogeneous, reflecting numerous migrations over the Balkan Peninsula.

Genotype↗

Re-emergence of trichinellosis in southeastern Europe due to political and economic changes.

The countries of southeastern Europe including the Balkan region and bordering countries - Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Greece, Hungary, Macedonia, Romania, Serbia and Montenegro, Slovenia, and the European part of Turkey - occupy a very important strategic position and represent a land bridge between Europe and Asia. In the majority of southeastern European countries, cases of trichinellosis among the human and animal populations were described in the late 19th or early 20th centuries. Trichinella infections among wildlife were also described in the aforementioned countries. Today, the prevalence of trichinellosis is different between the Balkans and bordering countries. A high prevalence of trichinellosis in domestic animals and humans has been reported in Bulgaria, Serbia and Montenegro, Romania and Croatia. A moderate prevalence was found in Bosnia and Herzegovina. In Hungary, human trichinellosis has not been present for a long period of time. However, sporadic cases were recorded in swine over the last 2 years. Trichinellosis has not been found among domestic animals and humans in Greece and Macedonia in recent years while in Turkey and Slovenia human trichinellosis is sporadic. The re-emergence of trichinellosis is connected with the changes in the social and political systems in Bulgaria and Romania. In Serbia and Montenegro as well in Croatia, however, a re-emergence of trichinellosis was due not only to political and social changes but also to wars that took place in these countries during the last years of the 20th century. Social, economic and political factors responsible for the re-emergence of trichinellosis in southeast European countries are discussed in this communication.

Animals↗

The need for implementation of International Commission on Trichinellosis recommendations, quality assurance standards, and proficiency sample programs in meat inspection for trichinellosis in Serbia.

Implementation of methods to control inspection for Trichinella in meat recommended by International Commission on Trichinellosis (ICT), particularly the introduction of the quality assurance standards and proficiency panels for certified analysts is extremely important in Serbia and other countries where Trichinellosis is endemic. In spite of existing regulations, including the inspection of 0.5 g samples of diaphragm by the compression method or by artificial digestion of 1g samples, in Serbia 280 people were diagnosed with clinical trichinellosis after consumption of inspected meat during the period 2001--2002. These outbreaks, which occurred in the municipalities of Kumane, Surcin and Bogatic, were a consequence of inadequate application of inspection methods and insufficient education of some veterinary inspectors. The problem of inadequate veterinary inspection in Serbia can be overcome by strict application of the ICT recommendations for the control of Trichinella with specific emphasis on implementing the quality assurance system (QAS) and proficiency sampling (PS/--PP/panel).

Animals↗

Cyclosporine in the treatment of myasthenia gravis.

Cyclosporine A (CsA) treatment was evaluated in 52 patients with severe generalized myasthenia gravis (MG) whose illness was not controlled by anticholinesterase drugs, thymectomy, corticosteroids, and azathioprine. The efficacy of CsA treatment was expressed by mean disability score quotient (MDSQ), which was obtained by comparing mean disability score (MDS) at the beginning of the treatment with the MDS at the end of the follow-up period. For the entire group of patients MDSQ was 53.3%, indicating moderate improvement. Analyzing individual cases, eight patients (15%) did not improve, 17 (33%) showed moderate improvement, 20 (38%) showed remarkable improvement, and seven patients (14%) achieved complete remission. The most common side effects were rise of serum creatinine (seven), hypertension (two), gingival hyperplasia (two), hypertrichosis (six), myalgia (10), and 'flu-like' symptoms (10 patients). The results of this study suggest that CsA is efficacious and safe treatment in severe and resistant forms of MG.

Adult↗

Molecular basis of thalassemia syndromes in Serbia and Montenegro.

This study reports the molecular characterization of thalassemia syndromes in Serbian and Montenegrin populations. We identified eight beta-thalassemia mutations [codon 39 (C-->T), IVS-I-110 (G-->A), IVS-II-745 (C-->G), codon 44 (-C), -87 (C-->G), IVS-II-1 (G-->A), IVS-I-6 (T-->C), IVS I-1 (G-->A)] in 70 members of 29 families using polymerase chain reaction, reverse dot blot, amplification refractory mutation system and direct sequencing analysis. Hemoglobin (Hb) Lepore was found to be the most common cause of the thalassemia phenotype. Hb Sabine and alpha-thalassemia were detected as well. We also studied beta-globin gene cluster haplotypes and their association with the most common mutations. A novel haplotype associated with the Hb Lepore gene was identified. The results presented herein allowed the implementation of a prenatal diagnosis program in Serbia and Montenegro.

Codon↗

C-fiber activation exacerbates sleep-disordered breathing in rats.

We reported previously that activation of vagal feedback by protoveratrines or serotonin exacerbates sleep apnea in rats, but each of these agents activates multiple afferent fiber types. To elucidate the specific impact of C-fiber activity on sleep apnea, the present study utilized capsaicin (CAP), which stimulates C-fibers via the CAP receptor. Nine adult Sprague-Dawley rats were instrumented for chronic polysomnography and recorded for 6 hours on four occasions. Prior to each recording, the animals received an intraperitoneal injection of either saline (control), or CAP 0.1, 1.0, or 10.0 mg/kg. Respiration was monitored by single-chamber plethysmography and apneas were scored as breaths longer than 2.5 seconds not preceded by a sigh. CAP increased apneas during non-rapid eye movement (NREM) sleep (p < 0.05 vs control) and reduced respiratory minute ventilation by about 15% in all behavioral states (waking, NREM, and REM sleep). We conclude that selective pharmacological activation of C-fibers produces a diathesis of sleep-disordered breathing specific to NREM sleep in rats.

Animals↗

The strong inhibition of triosephosphate isomerase by the natural beta-carbolines may explain their neurotoxic actions.

The natural beta-carbolines (BC) closely resemble the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in structure. The N-methylated beta-carbolinium ions (BC+) are potent inhibitors of mitochondrial respiration and are nigrostriatal neurotoxins. Utilizing [3H]BC, we have identified several proteins to which BC binds with high affinity (e.g. the chaperone member glucose regulated protein 78, the enzyme carboxylesterase, the cytochrome P450 2E1, the enzyme monoamine oxidase B and a small G-protein of the Rho subfamily). In the present study we isolated a protein from bovine brain to which [3H]BC binds with high affinity and identified it being the enzyme triosephosphate isomerase (TPI; EC 5.3.1.1.). 2,9-Dimethyl-BC+ was the most potent inhibitor of TPI, clearly more potent than the known inhibitors. TPI deficiency is a rare disorder in humans characterized by a severe progressive extrapyramidal course. Thus, TPI inhibition could contribute to neurodegeneration observed after injection of BCs into substantia nigra. Furthermore, the findings fit into the hypothesis of BCs as endogenous toxins responsible for neurodegeneration.

Animals↗

[Phacogenic uveitis with luxation of of Soemmering's ring formation in the vitreous body 63 years after cataract surgery].

BACKGROUND: After extracapsular cataract extraction, the remaining epithelial cells near to the equator may lead to the formation of a Soemmerings ring. Only 4 cases of dislocation of the ring in the vitreous are reported in the literature. A spontaneous dislocation associated with a phacolytic uveitis has not been described before. HISTORY AND SIGNS: In 1999 a 68-year-old man attended our clinic with a vision loss from 0.3 to hand movements in his left eye. For some years his right eye had been blind after unsuccessful retinal detachment surgery. In his left eye conjunctival inflammation, anterior chamber flare and complete occlusion of the pupil were found. Intraocular pressure was normal under hypotensive medication. Ophthalmoscopy was not possible and ultrasound revealed a ring-like dense structure in the vitreous cavity. THERAPY AND OUTCOME: Pars plana vitrectomy showed a Soemmerings ring, which was successfully removed by pars plana fragmentation. Forty-eight months postoperatively the patient had a visual acuity of 0.2 in a healthy and normotensive eye. CONCLUSIONS: Even years after cataract extraction a spontaneous dislocation of Soemmerings ring is possible.

Cataract Extraction↗

[Primary implantation of posterior chamber lenses after traumatic cataract peneration].

PURPOSE: To analyze the postoperative outcome and complication rate after phacoemulsification, lens aspiration or lensectomy with primary intraocular lens (IOL) implantation after traumatic cataract penetration. METHODS: We retrospectively reviewed the data of 15 patients who were admitted to our hospital from 1997 to 2001 because of traumatic cataract with corneal laceration with and without intraocular foreign body (IOFB). In all patients phacoemulsification, lens aspiration or lensectomy and primary IOL implantation were performed. Removal of IOFB was performed in 6 patients. RESULTS: The mean follow-up was 19.6 months, 8 eyes (53%) achieved a final visual acuity of 20/40 or better and 12 eyes achieved 20/100 or better final visual acuity. One patient (final visual acuity=1/40) had an additional macular pathology. Due to irregular astigmatism two patients achieved a final vision of less than 20/100. Major causes of limited visual acuity were central corneal scars and in one patient a photopic maculopathy. Four eyes (25%) developed secondary cataract and underwent YAG laser capsulotomy. In one patient PVR retinal detachment had to be treated by pars-plana vitrectomy with silicone oil tamponade. CONCLUSIONS: Primary implantation of posterior chamber lenses after penetrating ocular trauma is associated with a favourable visual outcome and a low rate of postoperative complications.

Adult↗

Prognostic value of myocardial viability determined by a 201Tl SPECT study in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction.

The prognostic meaning of myocardial viability is most important in patients with severe left ventricular dysfunction and ischaemic heart disease, but its prognostic significance in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction is uncertain. The aim of this study was to assess the prognostic value of a 201Tl single photon emission computed tomography (SPECT) rest-redistribution study in patients with previous myocardial infarction, ischaemic heart disease and mild-to-moderate myocardial dysfunction. Myocardial viability was assessed in 55 patients (50 male; mean age 58+/-9 years) by 201Tl SPECT rest-redistribution (after 4 h) scintigraphy. All patients had previous myocardial infarction (>3 months) and angiographically documented coronary artery disease, with the mean ejection fraction of 43+/-10%. Out of 55 patients, 20 were medically treated and 35 were revascularized. The follow-up period for adverse cardiac events, including death and non-fatal myocardial infarction, was 12 months. 201Tl SPECT study was positive for myocardial viability in 36 patients (65%) and negative in 19 patients (35%). Sensitivity, specificity, positive and negative predictive values for functional improvement in the follow-up period were 85%, 75%, 92% and 60%. Out of seven (13%) cardiac events in the follow-up period (four cardiac deaths and three reinfarctions), five occurred in 20 medically treated patients and two in 35 revascularized patients (25% vs 6%, P <0.05). Absence of myocardial viability was the only variable associated with adverse cardiac events (P =0.02). Survival at 12 months, as determined by using Kaplan-Meier analysis, was 56% for medically treated and non-viable patients, 80% for revascularized and non-viable patients, 91% for medically treated and viable patients, and 100% for revascularized and viable patients (P =0.0034). These findings suggest that in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction, the absence of myocardial viability as determined by the 201Tl SPECT study was the only variable associated with adverse cardiac events. The best 12 month survival was observed in revascularized viable patients, whereas the worse prognosis was found in non-viable, medically treated patients.

Female↗

A new radionuclide approach for the quantification of left ventricular volumes: the 'geometric count based' method.

A new radionuclide method, called the 'geometric count based' (GCB) method, has been developed for the quantification of absolute left ventricular volume. As the method is based on planar radionuclide ventriculography, it is non-invasive and simple, and avoids the relatively cumbersome and longer lasting, dynamic procedure using single photon computed emission tomography, which can be used for achieving the same goal. The purpose of this study was to describe the exactness of the theoretical approach to the method and validate its accuracy both by physical experiments and the initial clinical trial, as compared to contrast ventriculography. Count based data were combined with the geometric based data assuming an ellipsoid left ventricular shape with identical short axes. The following equation for computing left ventricular end diastolic volume, EDV (in ml) was developed: EDV=2cMCtot/Cmax, where c is the manually drawn short axis (one row pixel ROI) of the prolate ellipsoid in LAO 45 degrees (cm), M is the calibrated pixel size (in cm2), Ctot is the total counts in LV ROI, and Cmax is the maximum pixel counts in the LV ROI. Physical experiments with two different 'heart shaped' phantoms were used to compare the results obtained by the GCB method with the true phantom volumes and with the method assuming LV ball shape (BLV), developed by other authors. The true volumes of cylindrical and ellipsoid phantoms of 112.5 ml and 190.5 ml were computed to be 114 ml and 196 ml by the GCB and 168 ml and 180 ml by the BLV methods, respectively. In a clinical study, GCB volumes were compared to volumes measured by using single plane contrast ventriculography in 38 coronary patients. A good correlation between the GCB method and contrast ventriculography was obtained both for EDV and end systolic ventricular volumes (r=0.94, r=0.90). Both phantom and initial clinical studies indicate that the GCB method is an accurate, non-invasive and simple radionuclide method for measuring left ventricular volumes. Additionally, it could be used even in the smallest nuclear medicine units, for example in intensive care units where there are mobile cameras.

Algorithms↗

Trends and patterns of tuberculosis: interpretations and prospects of tuberculosis control in Vojvodina, Yugoslavia, 1987-2000.

AIM: To assess the trends and pattern of tuberculosis in Vojvodina, Yugoslavia. METHODS: Using a retrospective design, data on 393 diagnosed TB cases were investigated for the years 1987, 1993 and 2000. RESULTS: TB case notification has been increasing in Vojvodina. The number of reported TB cases was 146 in 1987, 101 in 1993 and 146 in 2000; cases were predominantly in the age group 20-39 years (44.5%) in 1987, compared to the 40-59 year age group in 1993 and 2000 (38.6% and 45.9%, respectively). The majority of patients belonged to lower socio-economic groups. Manifestations of TB such as cough, weight loss and exhaustion were common. With the increasing trend of alcoholism from 1987 to 2000, delays in reporting were noticed. TB-related mortality was 1.4% in 1987 and 4.1% in 2000. Resistance to TB drugs among previously treated cases was 2.7% in 1987, 0.9% in 1993 and 2.7% in 2000. With respect to the increasing resistance, the levels of detection and surveillance were poor. The implementation of the DOTS strategy remained fairly low. CONCLUSION: TB is a chronic problem in Vojvodina. Prompt community-oriented actions need to be taken to improve case detection and cure rates through DOTS.

Directly Observed Therapy↗

Results of combined vitreoretinal surgery and phacoemulsification with intraocular lens implantation.

PURPOSE: To assess the outcome and complications after combined pars plana vitrectomy and phacoemulsification with intraocular lens implantation in patients with concomitant cataract and vitreoretinal abnormalities. METHODS: This retrospective study consisted of 113 eyes of 109 patients with various vitreoretinal abnormalities and visually significant cataract. Vitreoretinal surgery was combined with clear corneal phacoemulsification and intraocular mplantation. RESULTS: The combined surgery resulted in minimal complications, and postoperative visual acuity was improved in 83 eyes (71.6%). Visual acuity was improved by two or more lines in 26 eyes (66.6%) with proliferative diabetic retinopathy, 22 eyes (73%) with proliferative vitreoretinopathy, eight eyes (30.7%) with macular abnormalities, four eyes (55.5%) with trauma and two eyes (40%) with retinal vein occlusion. CONCLUSIONS: The combined vitreoretinal surgery and phacoemulsification with intraocular lens implantation was safe and effective in treating vitreoretinal abnormalities coexisting with cataract. Combined surgery is recommended for all patients having simultaneous vitreoretinal pathological changes and cataract. The addition of phacoemulsification does not prolong vitreoretinal operative time notably nor increase the risk of intraoperative and postoperative complications significantly

Adult↗

Present status of trichinellosis in Yugoslavia: Serbia.

Trichinellosis was recognized almost one century ago as a health and animal husbandry problem in Serbia. In the last 10 years, trichinellosis has been expanding from three endemic regions (Srem, Macva and Negotinska Krajina) to neighbouring regions. The infection rate detected by veterinary inspection in 1999 year was 0.17% in slaughtered swines. Simultaneously, the number of infected humans increased three-five times in comparison with the period 1980-1990. For instance, 555 individuals were registered in 1999 as infected after the consummation of non-inspected pork from domestic swine or wild boar. Prevalence of trichinellosis in wild animals was examined more than a 20 years ago. The trichinellosis in horses has not been detected in the country, but infected horses imported from Serbia were detected in France and Italy.

Abattoirs↗

Infectivity of Trichinella spiralis larvae in pork buried in the ground.

Time of survival and infectivity of Trichinella spiralis larvae in pig muscle tissue, buried at various depths in the ground were assessed. In the pork pieces the number of infective larvae was 250 ML/g. Meat originated from pig halves was divided in 39 equal pieces, 0.7 kg each, disposed in three groups of 13, and buried in depths of 30, 50, and 100 centimeters respectively. The pork was dug up at 13 intervals, approximately every week, until 91st day of the experiment. After each time interval, infectivity of larvae was assessed by bioassay on rats. The artificially infected rats were sacrificed on 42nd day after the infection and meat was examined by the following methods--artificial digestion and trichinoscopy. It was found that the larvae during all 90 days preserved infectivity in each depth.

Animals↗