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Biomedical subjects

M Markovic

Publications and source records attributed to M Markovic.

At least 19 recordsLinked to original sources
PubMed2005

[Correlation between glaucomatous hemifield scotomas and measurements of nerve fiber layer thickness using scanning laser polarimetry].

BACKGROUND: The purpose of the present study was to investigate wether a reduction of the retinal nerve fiber layer (RNFL) in patients with hemifield scotoma can be measured with scanning laser polarimetry and wether regional RNFL parameters can be correlated with the corresponding visual field indices. PATIENTS AND METHODS: We included one eye from each of 40 normal subjects and one eye from each of 40 glaucoma patients. Automated perimetry was performed and the RNFL was analyzed. RESULTS: HMD values obtained by white-white (W/W) and blue-yellow (B/Y) perimetry failed to correlate significantly with most of the corresponding RNFL parameters obtained with the GDx. Significant correlations were only shown for the inferior HMD (W/W and B/Y) and the superior ratio, superior average, and deviation superior. Furthermore, we found a high correlation between differences of upper and lower GDx parameters and differences of upper and lower visual field indices of W/W and B/Y perimetry. CONCLUSIONS: Scanning laser polarimetry can detect differences in RNFL sectors in patients with functional hemifield differences and carries the potential to detect changes in RNFL thickness at an early stage.

Diagnosis, Differential↗
PubMed2004

Inducible nitric oxide synthase inhibition by mycophenolic acid.

The focus of this review is the influence of an immunosuppressive xenobiotic drug mycophenolic acid on the induction of nitric oxide production in various cell types. The potential therapeutic significance of the cell-specific fine-tuning of nitric oxide release by mycophenolic acid, as well as the mechanisms behind the drug action are discussed.

Animals↗
PubMed2003

Regulation of inducible nitric oxide synthase by cAMP-elevating phospho-diesterase inhibitors.

Among the numerous genes controlled by cyclic adenosine monophosphate (cAMP)/protein kinase A signalling machinery is the gene encoding the inducible nitric oxide synthase (iNOS), an enzyme catalyzing the synthesis of a highly reactive free radical nitric oxide (NO). While being a major microbicidal and tumoricidal molecule, iNOS-derived NO has also been implicated in tissue destruction, as well as in regulation of inflammatory/immune cell function in various disorders associated with excessive inflammation. A feasible way for cAMP-dependent therapeutic control of inflammation, including iNOS-mediated NO synthesis, could involve the administration of drugs that block the enzymatic activity of cAMP-degrading phosphodiesterases (PDE). Indeed, cAMP-elevating PDE inhibitors can influence iNOS activation in different cell types in vitro, and their potent anti-inflammatory effects in experimental disease models and clinical studies were frequently accompanied with profound modulation of NO production. A set of conflicting data has been generated over the years, ranging from strong suppression to marked enhancement of NO release by cAMP-increasing PDE inhibitors, depending on cell-type, iNOS stimuli, and/or the agents used. The present review summarizes the data on iNOS modulation by cAMP-elevating PDE inhibitors and possible mechanisms behind it, speculating on its contribution to the therapeutic effects of these drugs.

Animals↗
PubMed2001

Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes.

The effect of interleukin-17 (IL-17) on production of nitric oxide (NO) in rodent astrocytes was investigated. While IL-17 by itself did not induce NO production, it caused a dose-dependent enhancement of IFN-gamma-triggered NO synthesis in both mouse and rat primary astrocytes. In contrast, IL-17 was unable to stimulate NO synthesis in either murine or rat macrophages. IFN-gamma-triggered expression of mRNA for iNOS, but not for its transcription factor interferon regulatory factor-1 (IRF-1), was markedly elevated in IL-17-treated astrocytes. The induction of iNOS mRNA by IL-17 in IFN-gamma-pretreated astrocytes was abolished by antagonists of nuclear factor-kappaB (NF-kappaB) activation--a proteasome inhibitor MG132 and an antioxidant agent PDTC, as well as with specific p38 MAP kinase inhibitor SB203580. While IL-17 stimulated both IL-1beta and IL-6 production in astrocytes, only IL-1 was partly responsible for IL-17-induced NO release. Finally, IL-17 synergized with exogenous IL-1beta and TNF-alpha for astrocyte NO production. Having in mind a well-known neurotoxic action of NO, these results suggest a possible role for IL-17 in the inflammatory diseases of the CNS.

Animals↗
PubMed2001

Morphological and phase characterizations of retrieved calcium phosphate cement implants.

A self-hardening calcium phosphate cement (CPC), consisting of equimolar amounts of tetracalcium phosphate and dicalcium phosphate anhydrous, hardens when mixed with water and forms a resorbable hydroxyapatite (HA) as the end-product. The objective of this study was to investigate the changes of the phase and morphology of the CPC during hardening and aging under in vivo conditions. CPC samples retrieved 12 h after hardening in vivo had already contained carbonated HA (type B), even though the initial cement mixture did not contain carbonate as one of the solid components. The mass fraction of carbonate in the 12-h sample was about 1%. The results suggested that under in vivo conditions carbonate is readily available and this allows formation of carbonated HA in favor of carbonate-free HA. The carbonate content of the CPC samples retrieved 3 months after implantation was similar to that of the 12-h samples, and the exterior surfaces of the 3-month samples appeared less crystalline than that of the 12-h samples.

Animals↗
PubMed2001

Amphotericin B potentiates the activation of inducible nitric oxide synthase and causes nitric oxide-dependent mitochondrial dysfunction in cytokine-treated rodent astrocytes.

Because the neurotoxic effects of the antifungal drug amphotericin B (AMB) closely resemble those ascribed to the highly reactive gaseous free radical nitric oxide (NO), we investigated the effect of AMB on NO production in rodent astrocytes. AMB caused a dose-dependent increase of NO generation in interferon-gamma (IFN-gamma)-stimulated rat and mouse astrocytes, as well as in IFN-gamma + tumor necrosis factor-alpha (TNF-alpha)-activated rat astrocytoma cell line C6. Treatment of rat astrocytes with AMB markedly potentiated IFN-gamma-triggered expression of mRNA for iNOS, but not for its transcription factor IRF-1. The activation of transcription factor NF-kappaB was apparently required for AMB-induced iNOS mRNA expression, as the latter was abolished by NF-kappaB inhibitors: pyrrolidine dithiocarbamate and MG132. AMB-mediated enhancement of astrocyte NO production was partly dependent on endogenous IL-1, as shown by partial inhibition of AMB effect with IL-1 receptor antagonist. IFN-gamma + AMB treatment led to reduction of astrocyte mitochondrial respiration (measured by MTT assay) that has been completely reverted by selective iNOS inhibitor aminoguanidine. AMB toxicity toward IFN-gamma-stimulated astrocytes was dependent on both AMB and NO action, since AMB and NO-releasing substance SNP synergized in inducing astrocyte mitochondrial dysfunction. These results suggest that the enhancement of cytokine-induced iNOS activation in astrocytes and the subsequent release of high amounts of NO might be at least partly responsible for AMB neurotoxicity.

Amphotericin B↗
PubMed2001

Declarative memory in early Parkinson's disease: serial position learning effects.

This study tested the question of whether executive failure associated with frontal lobe deficit is associated with, and therefore, may influence declarative memory dysfunction in Parkinson's disease (PD). A variety of memory and 'frontal sensitive' tasks were used. The 'frontal lobe dysfunction' hypothesis was tested in part, by examining the serial position effects (SPE) of word list learning across five successive trials. The relationship between memory and 'frontal sensitive' task scores was tested also. A total of 39 PD patients early in the course of the disease and 31 matched controls were included in the study. The PD subjects showed mild memory deficits in comparison to the healthy control group. In the face of any hypothesized selective 'dysexecutive' syndrome in PD group, the latter groups learning strategy across five trials did not differ from that of the control group. Also, the expected interrelation between memory and 'frontal sensitive' scores was not obtained. Therefore, the hypothesis that frontal dysfunction alone may account for memory impairments in PD is not fully supported.

Case-Control Studies↗
PubMed2000

Visuomotor skill learning on serial reaction time task in patients with early Parkinson's disease.

This study tested the role of basal ganglia in visuomotor skill learning. Thirty-nine patients early in the course of Parkinson's disease (PD) and 30 patients after operation for an aneurysm of the anterior communicating artery (ACoA) were compared with 31 matched control subjects on a Serial Reaction Time test (SRTt). The patients with PD showed impaired visuomotor skill learning across the repeating blocks, in the presence of preserved declarative knowledge of embedded sequences, in contrast to the ACoA group in whom the reverse pattern was observed. The significant correlation in patients with PD between the standard neuropsychological and motor measures and the performance observed in the skill acquisition test, in the ACoA group and control subjects was not observed. The suggestion that this learning impairment could not be attributed to a motor deficit per se was also confirmed more directly for patients with PD. Accuracy of performance after the initial learning phase on the SRTt in patients with PD was associated predominantly with visual span capacity measures. Declarative knowledge of the embedded sequence of the SRTt was correlated to general cognitive and verbal span abilities in the PD group. The impairment observed in the PD group was not the result of a general decline in cognitive functioning, mood disturbances, or the severity of the motor symptoms.

Adult↗
PubMed1998

Reappraisal of the quantity and nature of renal calcifications and mineral metabolism in the magnesium-deficient rat. Effects of treatment with potassium citrate or the combination magnesium citrate and potassium citrate.

There is an urgent need for drugs capable of inhibiting renal calcifications, nephrocalcinosis and stones included, in humans. Current anticalcification medication is based mainly on alkalinization of the metabolism using potassium-containing citrate alone, despite the fact that calcium stone patients suffer marginally from both magnesium and potassium deficiency. We investigated the anticalcification efficacy of oral potassium citrate versus the combined administration of this drug and magnesium citrate in the magnesium-deficient rat developing corticomedullary nephrocalcinosis and luminal microliths in the long term. Among other things we employed specific stains for calcium and oxalate, light microscopy and element analysis for renal tissue and calcifications, respectively. In addition, minerals in renal tissue, urine and plasma were determined, as well as the state of extracellular calcium homeostasis. Magnesium deficiency caused pure calcium phosphate tissue deposits, containing no magnesium, but no deposition of calcium oxalate in the tubular lumen; tissue magnesium, calcium and phosphorus were increased, and there was marked potassium wastage via urine; despite mild hypercalcemia other signs of hyperparathyroidism were not found. Alkalinization with the two kinds of medication evoked an increase in urinary pH, citrate, and potassium; however, potassium citrate alone tended to aggravate renal concretions, whereas the combination of this drug with magnesium citrate completely prevented concretions. It was concluded that: (1) magnesium deficiency-induced calcifications are oxalate-free and are not sensitive to mobilization by alkalinization with potassium citrate, which might explain the failure of the drug to prevent stone recurrence in clinical stone patients, and (2) the combination of potassium citrate and magnesium citrate, which shows enormous anticalcification efficacy, deserves high priority in clinical trials aimed at evaluating strategies for the prevention of stones.

Animals↗
PubMed1995

Thermophysical properties of some pharmaceutical excipients compressed in tablets.

PURPOSE: Thermophysical properties of three tableting excipients; microcrystalline cellulose, lactose and dicalcium phosphate dihydrate were observed to evaluate their ability to resist temperature induced changes in tablet form. METHODS: Two thermophysical parameters, thermal diffusivity and specific heat, were measured by a pulse heating method. The materials were also evaluated by differential scanning calorimetry (DSC). RESULTS: Microcrystalline cellulose in tablet form was found to be rather insensitive to heating and cooling treatments, even though the tablets seemed to remain in a stressed state four weeks after tableting. This stress, indicated by low temperature anomalies, was observed by the pulse method, but not by DSC. When magnesium stearate was incorporated as a lubricant within the microcrystalline cellulose powder, the thermophysical parameters indicated that the internal structure of the tablets changed with heating and cooling. Magnesium stearate eliminated the low temperature anomalies as well. The heat treatment changed the thermophysical properties of tablets made of the crystalline excipients lactose and dicalcium phosphate dihydrate, permanently causing irreversible structural changes. CONCLUSIONS: The melting of the lubricant together with enhanced stress relaxation in the structure of microcrystalline cellulose most probably caused the improved thermal diffusivity. The observed thermophysical changes with the crystalline excipients were due to changes in tablet's structure and material. The combination of methods used was found to be an accurate and reliable way to obtain useful information on the structural changes and material relaxations of intact tablets during temperature treatment and age-related changes in material properties.

Calcium Phosphates↗
PubMed1994

'Therapeutic window's for multiple drug treatment of experimental cerebral ischemia in gerbils.

The effects of the following drugs: nimodipine (1 mg/kg b.w., i.p.), 2-amino-5-phosphonovaleric acid (4 mg/kg b.w., i.p.) and propentofylline (25 mg/kg b.w., i.p.), administered (alone or in combination) at the end of 15 min bilateral ischemia in gerbils were evaluated on mitochondrial superoxide dismutase (SOD), glutathione reductase (GR), glucose-6 phosphate dehydrogenase (G6PD), monoamine oxidase (MAO) activities, and thiobarbituric acid reactive material (TBARM), and brain water content at 1 hour of reperfusion. The combined treatment virtually abolished early postischemic brain edema (4.1% v.s. 0.6%) and efficiently counteracted ischemia-induced changes [decreased SOD (79% v.s. 98%), GR (52% v.s. 105%) and MAO (25% v.s. 79%), and increased TBARM (198% v.s. 108%)]. The same combination of drugs administered 15 min before ischemia had a similar effect (e.g., reduced brain swelling and lipid peroxidation) as when given at the end of ischemia, whereas a limited or absent impact was seen when the drugs were given 15 min or 1 hour after ischemia, respectively. The data suggest that (post)ischemic brain swelling and mitochondrial dysfunction can be reduced by drugs which synchronously prevent processes induced in the early stages of reperfusion.

2-Amino-5-phosphonovalerate↗
PubMed1994

Liposome-entrapped superoxide dismutase reduces ischemia/reperfusion 'oxidative stress' in gerbil brain.

Bilateral common carotid artery occlusion (15 min.) followed by two hours of recirculation reduced mitochondrial superoxide dismutase (SOD) and glutathione reductase (GR) activities, and increased susceptibility of mitochondrial membranes to in vitro lipid peroxidation in brain regions (i.e., cortex, striatum and hippocampus) of Mongolian gerbil. Intraperitoneal bolus injection (2 mg/kg b.w.) of liposome-entrapped CuZn superoxide dismutase (1-SOD) increased the endogenous SOD activity in normal brain tissue and, when given at the end of ischemia, counteracted both the ischemic reduction of endogenous SOD and the increased peroxidation of mitochondrial membranes. 1-SOD treatment was ineffective in reducing brain swelling, suggesting that superoxide radicals are not a main participant in the process of (post)ischemic brain edema formation.

Animals↗
PubMed1989

A simple and fast method for iron determination with ferrozine after proteolytic disruption of iron-transfer in complex.

A direct method for iron determination with ferrozine in blood serum is described. Iron is liberated and proteins degraded by pepsin in hydrochloric acid medium. At appropriate pH the iron-ferrozine complex forms and stabilizes in five minutes. Accuracy of the method is 99.3-101.4%, precision within run and day to day 0.73 and 1.1% respectively, and linearity till 72 mumol/L iron.

Adult↗
PubMed1986

Microbial growth in clinically used enteral delivery systems.

Potential contamination of enteral formulas has led to the development of policies limiting formula hangtimes. However, enteral administration bags can easily become contaminated during formula refilling. We prospectively studied enteral formula contamination when the hangtime of a prefilled 1000 ml pouch was compared with the standard 4-hour hangtime of a refilled enteral administration bag. Samples of formula collected from different locations along the enteral delivery system were cultured during 57 days of enteral hyperalimentation in 19 patients. The overall enteral formula contamination rate was 61%, where the greatest microbial growth occurred in reconstituted enteral formulas. The presence of microbial growth did not differ between canned formulas administered according to a 4-hour hangtime and the prefilled pouch. Greatest growth in all cases was at the distal tubing hub, where contamination during system manipulation or from the patient probably occurred. Use of prefilled enteral administration bags may delay formula contamination in the administration reservoir. A change in equipment design that would decrease the need to manipulate feeding sets or feeding tube connections should be further investigated.

Aged↗
PubMed1986

The role of the orthodontist in the treatment of adolescents with orofacial clefts.

In the orthodontic treatment of patients with clefts the main aim is to maximize the growth and development of the maxillary complex and, at the same time, to improve functional efficiency and facial aesthetics. The commonest malocclusions found in adolescents with lip and palate clefts are: frontal or anterior crossbite; posterior or buccal crossbite which is either unilateral or bilateral; retrusion of the middle third of the face to a greater or a lesser degree; open bite; and finally malformation and displacement of the teeth adjacent to the cleft. Treatment may be divided into: correction of malocclusions in the transverse plane; correction in the antero-posterior plane; vertical corrections; and correction of misplaced individual teeth. Posterior (lateral) crossbite can be corrected by both gradual and rapid (forced) expansion using various removable appliances. Following this, correction of anterior crossbite and restoration of vertical occlusal relationships will be necessary. Finally, misplaced individual teeth will need to be repositioned. Traumatic surgery and consequent scar tissue affects the growth of the maxillary arch and the development of the occlusion. This was demonstrated in a comparative analysis of monozygotic and dizygotic twins discordant for clefts as well as in twin pairs whose clefts were non-identical in type and extent. The adolescents who still have unoperated clefts have special problems.

Adolescent↗