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Biomedical subjects

D Marinkovic

Publications and source records attributed to D Marinkovic.

17 recordsLinked to original sources

Genetic variability in the group of patients with congenital hip dislocation.

Our study of genetic homozygosity degree includes an analysis of the presence, distribution and individual combination of 20 selected genetically controlled morpho-physiological traits in the group of patients (N = 93) with congenital hip dislocation (CDH) and in control sample consisting of school children from Belgrade (N = 200). Assuming that CDH is genetically controlled disease, we made a hypothesis that an increased homozygosity level, as well as the changed variability among the patients, could be population-genetic parameter for the prediction of the illness. Taking into consideration our experience, as well as the experience of numerous scientists who studied the nature of the inheritance of mono- and oligo-genically controlled qualitative traits, we applied a methodology to estimate the proportion of such homozygously recessive characters (HRC-TEST). This population-genetic study did not only show statistically significant difference of the middle values of genetic homozygosity (CDH-7.1+/-0.2; control - 5.2+/-0.1), but of the differences in the type of distribution too, as well as the differences in the presence of certain individual combinations of such traits. The described methodology can be used in further analyses, with hope that it can be applied as an early prognosis for decreased resistance to different diseases. The frequencies of ABO blood types in the sample of CDH patients were similar to the average value of Serbian population, while the percentage of blood group A is slightly increased. Comparing frequencies of Rh blood groups, there is no difference between tested samples.

ABO Blood-Group System↗

[Micronuclei and ageing in a sample of Yugoslavian population].

OBJECTIVE: Instability in the organization and expression of the genetic material has been hypothesized as the basic mechanism of ageing. Aim of this study was to quantify the effect of ageing on spontaneous micronuclei (MN) frequency in peripheral blood lymphocytes. METHOD: Analysis of Yugoslavian population sample (164 tested individuals, age 0-62 years) has performed by application of cytokinesis-block technique (CB). RESULTS: There was an increase of MN frequency with age, from newborns to 40-year-old persons. The total average of MN frequency per 1000 analyzed binuclear cells amounts to 8.03 +/- 0.42, with variation from 0 to 26 MNs. In a sample of 29 newborns the recorded average MN frequency was 6.91 +/- 0.81, while among 69 persons 25-39 years old, the MN frequency was 9.16 +/- 1.00. The lowest average MN frequency, however, was noted in the sample of 34 tested individuals 40 to 62 years of age. CONCLUSION: An increase with age in MN frequency has been observed in samples of studied individuals from newborns to 40-year-old persons. A decrease of MN frequency in older groups could be explained by a gradual decrease of proliferative cell capacities.

Adolescent↗

Genetic load and coadaptation of chromosomal inversions. II. O-chromosomes in Drosophila subobscura populations.

We have analysed the inversion polymorphism and genetic load of O-chromosomes in three populations of D. subobscura from southeastern Europe. As expected for a central populations the inversion polymorphism was extensive. In a like fashion, the genetic load, in particular the frequency of lethals, was heavy in all three populations. There were significant differences in the frequency of moderately deleterious genes. These differences in viability can be attributed to balancing selection. A comparison of these two kinds of genetic polymorphism indicates that there are differences in mean viability among different gene arrangements of O-chromosomes in the three populations. The differences observed are due to an unequal distribution of various viability classes among O-chromosome gene arrangements. We here show for the first time a specific distribution of lethal genes among these arrangements within the Palearctic distribution area of D. subobscura. The lethal allelism test showed lethals are non-randomly associated with the Ost gene arrangement. The amount of genetic load is heavy in gene arrangements with a high frequency, in comparison with the ones with a low frequency. Lethal genes may be protected in combinations of low and moderate frequency gene arrangements that harbor more lethal genes, as the Ost in the one population. Some arrangements that are less protected against recombination have a higher load than ones that are more protected against recombination. This can be taken as evidence for coadaptation.

Animals↗

Analysis of background-dependent genetic interactions without inbred strains.

Experimental analysis of background dependent effects of genetic interactions can be designed using strains generated by introgression of small genetic regions containing identical genotypes at loci in question into different inbred strains. We use a novel multilocus paradigm, denoted conditional intergenic functional association (CIFA), to simulate this procedure, with the trade-off of power for convenience that is affordable when sufficiently strong effects are present. We analyze nine enzyme loci at three chromosomes in groups of D. melanogaster with different developmental rates that showed similar allelic frequencies at individual loci. Results obtained suggest the presence of adaptive interaction between particular alleles at two loci when genetic variation at seven background loci is eliminated. Biochemical considerations show that, in the resulting developmental context, strong interaction between these genes may emerge from shifted control of the pentose phosphate pathway, with cascading effects on the glycolysis, TCA cycle, and biosynthetic pathways: one gene may assume control of the irreversible rate-limiting step in the pentose phosphate pathway, whereas the other gene may assume control of the NADP+ level that regulates the same rate-limiting step as an electron acceptor. The newly developing functional genomics research and the absence of inbreeding make CIFA directly applicable to complex human traits in large samples.

Animals↗

The side-effects of clozapine: a four year follow-up study.

Clozapine, as the model agent for the atypical antipsychotic drugs, is currently recommended as effective regarding negative symptoms of schizophrenia and treatment-resistant schizophrenic patients. This study focuses on the clozapine-induced side-effects in 100 hospitalized schizophrenic patients (negative and therapy-resistant forms), followed-up for a four year period. Clinically relevant side-effects occurred in 73% of all patients. Tachycardia (67%), the increase of liver enzymes (36%), hypotension (29%) and sedation (27%) were most frequent. Tachycardia, hypotension and sedation disappeared during the initial phase of treatment (i.e. 4-6 weeks), as tolerance developed with continuation of therapy. The increase of liver enzymes appeared to be dose related, since the reduction of daily clozapine dose led to the normalization of transaminases values. The other side-effects (constipation, nausea and vertigo) were rare and transient. Leucopenia was not registered in any patient during the follow-up period. Therefore, clozapine is efficient and, with some precautions concerning hepatotoxicity, is safe for in- and outpatient long-term treatment in appropriately selected patients.

Adult↗

Plasma lipid peroxides in murine sepsis--sex differences and effect of antioxidative/anti-inflammatory therapy.

In order to investigate the influence of antioxidative/anti-inflammatory combination therapy (AACT) with dimethyl sulfoxide (DMSO), chlorpromazine (CPZ) and vitamin E upon the activity of the inflammation, plasma lipid peroxide was measured as thiobarbituric acid reactive substance (TBARS) 12 hrs postoperatively in the modified cecal ligation sepsis model in the mouse. Significantly higher TBARS levels were found in the male control group (13.7 +/- 0.7 nmol MDA/ml) than in the female control group (11.6 +/- 0.6 nmol MDA/ml). The operated male group had significantly higher TBARS levels (16.2 +/- 0.6 nmol MDA/ml) than the unoperated male control group (13.7 +/- 0.7 nmol MDA/ml). No increase of TBARS levels was observed in the operated female group. Both male and female operated group, when postoperatively treated with AACT had the same TBARS level as the not operated male or female control group. Survival curves of operated male and female group did not demonstrate any significant difference. The survival was better in an operated male and an operated female group, when postoperatively treated with AACT. It was concluded that the applied TBARS test is too insensitive to follow the activity of the inflammation and has no predictive value for the outcome of sepsis in this model.

Animals↗

Models of exogenous and endogenous sleep perturbation as diagnostic and therapeutic predictors in depression.

In a group of 60 samples divided into three subgroups: a) healthy, b) exogenic (non-psychotic) and c) endogenic (psychotic) depressives, nocturnal sleep (10 p.m. to 6 a.m.) was registered according to accepted standards. 130 parameters (variables) of hypnograms were exposed to exact statistical testing. Mathematical modes were formed through satisfactory conditions of N-distribution by the method of discriminative analysis ("step by step"). These models were called "The Discriminative Profile of Sleep" (DPS). The Model of Exogenic Perturbation of Sleep is characteristic of exogenic (reactive) depressive disturbances. The dominant discriminative factors of this model are: increased number of nocturnal awakenings (NAW) and fragmentation of nocturnal sleep. The Model of Endogenic Perturbation of Sleep is formed by: shortened REM-latency, reduction of delta-sleep, increase of the Index of Endogenic Periodicity/Perturbation (IEP). These models contribute not only to the problem of correct differential diagnosis, but also to the accurate choice of therapy, the appraisal of therapeutic sensitivity-insensitivity following the course of illness, and a more precise final result. According to these models, depression in relation to the structure of nocturnal sleep is defined as: hypnofragmentic exogenic (reactive) depression, and hypnodisrrhythmic endogenic depression (or where endogenic perturbation developed during the illness).

Adjustment Disorders↗

Roentgenological monitoring of the position of subclavian catheters introduced by the infraclavicular approach.

Roentgenological monitoring of 684 central venous catheters introduced by the infraclavicular route showed that in 11% of cases positioning was incorrect. In particular, deviation into the right internal jugular vein after catheterisation on this side occurs in 9% of the cases. Roentgenological monitoring of the position of a central venous catheter is a necessary measure and should never be omitted. In addition, other complications such as pneumothorax can be detected in this manner. Catheters without X-ray marker should no longer be used.

Catheterization↗

Selection for higher fitness in populations of Drosophila pseudoobscura.

Four laboratory populations, each consisting of flies homozygous for a wild second chromosome, were maintained in population cages. Three of them were initially characterized by low fecundity of the females; the fourth was a control. After 15 months, in all three populations with low fecundity this character was much improved; two of them, have reached the control level. The changes observed were presumably due to mutation and selection under highly competitive conditions.

Animals↗

Lithium ion influence on N-acetyl-beta-glucosaminidase isoenzymes serum level.

N-acetyl-beta-glucosaminidase (NAG) is a lysosomal enzyme found in most human cells, including those from the nervous system and kidneys. There are several different NAG forms in human tissues and fluids, but isoenzymes A and B are the most abundant, presenting about 98% of the whole NAG activity in normal serum. The paper is dealing with the total NAG serum level, main isoenzymes (A and B) activity, their ratio and possible lithium ion influence in affectively disordered patients. The sample consisted of thirteen bipolar-euthymic patients who had been receiving lithium for more than two years. The results pointed out reduction in total serum NAG activity, the lithium ion influence absence on total serum NAG activity, but at the same time the important modifying effects on isoenzyme NAG activities.

Acetylglucosaminidase↗