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Biomedical subjects

V Savić

Publications and source records attributed to V Savić.

At least 19 recordsLinked to original sources
PubMed2005

Acidity constants of cefetamet, cefotaxime and ceftriaxone; the effect of the substituent at C3 position.

Ionization constants of three cephalosporin antibiotics, cefetamet (CEF), cefotaxime (CFX) and ceftriaxone (CFTR) are determined using pH-potentiometric titrations at I=0.1 M (NaCl) and t=25 degrees C. Cefetamet and cefotaxime have three ionization groups: carboxylic, amide and aminothiazole. Besides those three, ceftriaxone possesses an hydroxytriazinone group as new and additional ionization center. In acid medium two overlapping acid-base processes are occurring with acidity constants being: pK1 2.93 (COOH) and pK2 3.07 (aminothiazole) for cefetamet, and pK1 2.21 (COOH) and pK2 3.15 (aminothiazole) for cefotaxime. In the case of ceftriaxone the situation is even more complicated, three overlapping processes coexist with pK1 2.37 (COOH), pK2 3.03 (aminothiazole) and pK3 4.21 (hydroxytriazinone). Protolysis of amide group is happening in the alkaline medium as completely separated process from those in acid medium. The acidity constants which correspond to amide group are pK3 10.65 (CEF), pK3 10.87 (CFX) and pK4 10.74 (CFTR). The influence of the C3 substituent on the dissociation process of the neighboring ionization group, particularly carboxylic group, was considered. The differences in acidity of CEF, CFX and CFTR (pK1: 2.93, 2.21 and 2.37, respectively) are likely to be caused by the stereoelectronic properties of substituents in the beta-position to the carboxylic group due to the combined inductive, hyperconjugative and resonance effects.

Carbon↗
PubMed2005

Repair of bone tissue affected by osteoporosis with hydroxyapatite-poly-L-lactide (HAp-PLLA) with and without blood plasma.

The aim of this study is to examine the reparatory ability of the synthetic biomaterial hydroxyapatite-poly-L-lactide (HAp-PLLA), the replacement of alveolar ridge, and rehabilitation of bone defects caused by osteoporosis, in an experimental group of animals. The experiments are performed on syngeneic Sprague Dawley rats. Osteoporosis is induced by glucocorticoids in rats during a 12-week period. After this, the experimental group of animals is divided into five subgroups. An artificial defect is made in the alveolar bone on the left side of the mandible. In one group of animals, the defect is left to heal by itself, while in other groups, pure HAp-PLLA or one mixed with plasma is implanted. The best results are achieved by the implantation of the HAp-PLLA composite biomaterial mixed with autologous plasma. Formation of a new mandibular bone is seen, growing intensely, leading to rapid osteogenesis.

Animals↗
PubMed2003

Genetic analysis of Newcastle disease virus strains isolated in Bosnia-Herzegovina, Croatia, Slovenia and Yugoslavia, reveals the presence of only a single genotype, V, between 1979 and 2002.

Newcastle disease (ND) epizootics in some European countries after the World War II were caused by ND virus (NDV) of multiple genotypes (IV-VIIa) occurring sequentially and/or simultaneously. This study was carried out to characterise the genetic composition of NDV strains during the outbreaks in the territory of the former Yugoslavia in order to enhance our understanding of the relationships of past epizootics in Europe. Sixty-eight NDV strains isolated between 1979 and 2002 were analysed by restriction enzyme digestion and partial sequencing of the fusion protein gene. All isolates were placed in genotype V, an exotic type, that was introduced to western Europe in 1970. Residue substitution analysis has allowed the recognition of four genetic variants, Vb1-Vb4, and the tracing of their movements. Vb1, a dominant variant in Bulgaria from the late 1970s, was also wide spread in the former Yugoslavia throughout the period under investigation. Vb2, a variant occurring in the neighbouring countries in the early 1970s could be the founder of the epidemic in Yugoslavia and it was present up to the late 1980s. Variants Vb3 and Vb4 could be found only after 1987. In conclusion, the ND outbreaks in Yugoslavia were part of the epizootic wave due to genotype V viruses that started in western Europe in 1970 and became endemic in the region. Inter-country transmission occurred for all variants, and Vb3 and Vb4 might have evolved during the endemic period.

Amino Acid Sequence↗
PubMed2002

[Use of fibrin glue in the prevention of leakage in pancreatico-jejunal anastomoses].

The aim of this study was to test the protective effects of fibrin sealing on the pancreatico-jejunostomy (PJA), the high-risk anastomosis following pancreas head resection. Experimental study was performed on the mongrel dogs, divided in two groups (20 animals each): Experimental group-with end to end "dunking" PJA, protected by temporary occlusion of the pancreatic duct with fibrin sealant/Tissucol/Immuno Ag/, while control group was without any protective procedure. The animals were followed 5 months in order to study: protective effects of such procedure on the PJA quantified with the percent of anastomotic leakage, effects of the exocrine secretion and effects the endocrine function Results: PJA leakage occurred in 13.33% in control group. No leakage was registered in experimental group. Biochemical, histological and electron microscopic study showed slight transitory elevation of amylase levels. Fibrin glue plug was dissolved and pancreatic juice output was reestablished 12th days postoperatively. Long term follow-up showed no damages of the endocrine and exocrine pancreas. Pancreatic duct occlusion with fibrin glue appeared to be an useful method in the prevention of pancreatico-jejunostomy leakage, without negative effects on the exocrine and endocrine pancreas.

Anastomosis, Surgical↗
PubMed2001

A study of HAp/PLLA composite as a substitute for bone powder, using FT-IR spectroscopy.

Chemically synthesized hydroxyapatite/poly-L-lactide (HAp/PLLA) composite biomaterial was studied in vivo. The biocomposite was implanted into Balb/c Singen mice and after 1 and 3 weeks removed from their organisms and analyzed by the FT-IR spectroscopy. After 1 week of testing in vivo the implanted sample gave a spectrum in which absorption bands arising from newly formed functional groups of amine and peptide can be seen. After 3 weeks, a spectrum with pronounced absorption bands at 3420 and 1650cm(-1) assigned to newly generated collagen, a component of the extracellular connective-tissue matrix, was registered. Also, decrease of the intensity absorption band at 1760cm(-1) originating from the C=O group of PLLA indicates bioresorption of the PLLA used. Analysis of the microstructure of the sample surface by scanning electron microscopy before and after implantation revealed bioresorption of the PLLA polymer phase and generation of collagen fibers at the sites of implanted bioresorptive PLLA. A mixture of autologous bone powder and HAp/PLLA biocomposite was also examined. After implantation, the same final products as in the case of HAp/PLLA composite biomaterial used alone were found.

Animals↗
PubMed2001

Immune status assessment by abundance of IFN-alpha and IFN-gamma mRNA in chicken blood.

Avian diseases, including such viral infection as infectious bursal disease, infectious anemia, and Marek's disease, often cause immunosuppression, leading to more severe infection, problems with secondary infection, and inadequate responses to vaccination. Immunosuppression thus causes serious economic losses in commercial poultry production. To date, methods for assessing immune status have been too slow to be of practical help. Reasoning that immunosuppression should be reflected by reduced production of interferons (IFN) in response to a viral antigen, we have developed competitive nucleic acid hybridization microtiter plate assays for chicken IFN-alpha (ChIFN-alpha) and ChIFN-gamma mRNA. To evaluate the assay, chickens were challenged with inactivated Newcastle disease virus (iNDV). Whole blood samples were collected at various times subsequently and preserved with a cationic detergent. Later, total RNA was extracted, and mRNA for both ChIFN-alpha and ChIFN-gamma was measured. Both rose from undetectable levels to reach a peak by 4 h, remained high for about 3 days, and fell to undetectable levels by day 5. Results were similar in chickens aged between 1 and 28 days. In later experiments, blood was collected 4 h after viral challenge. When chickens were immunosuppressed by administering 4-5 mg cyclophosphamide (CY) daily for 3 days and challenged with iNDV, they transcribed less ChIFN-alpha and ChIFN-gamma mRNA, and their antibody response was impaired. Our results suggest that suspected immunosuppression in a commercial flock could be assessed within 2-3 days by challenging birds with iNDV and measuring the amounts of ChIFN-alpha and ChIFN-gamma mRNA in blood obtained 2-4 h later.

Aging↗
PubMed2000

Pulmonary blast injury increases nitric oxide production, disturbs arginine metabolism, and alters the plasma free amino acid pool in rabbits during the early posttraumatic period.

Plasma nitrate + nitrite (nitrates), as final NO products, and free amino acid pool (FAAP) characteristics, as indicators of protein/amino acid metabolism, were analyzed in the early (30 min) period following blast injury. The experiments were performed on 27 rabbits subjected to pulmonary blast injury (experimental group) or not exposed to overpressure (controls). We report that pulmonary blast injury (PBI) induces prompt NO overproduction within a very early period. Increased arginine utilization via NO synthase, presumably associated with its cleavage by arginase, leads to the depletion of the arginine level in arterial plasma 30 min following PBI. Impaired balance between arginine utilization and release/resynthesis from endogenous sources causes disturbed nutritional status and urea cycle activity. Early identification and appropriate management of the changes in amino acid metabolism should be included in the evaluation of patients with blast injury. Furthermore, the results suggest that depleted arterial levels of arginine and NO overproduction may be helpful in diagnosis and prognosis of blast injury.

Amino Acids↗
PubMed1998

Quantitative analysis of the renal changes in Balkan endemic nephropathy.

The volume densities of the cortical interstitium (CI), glomeruli and proximal tubular epithelium have been investigated on a sample involving 18 patients suffering from Balkan endemic nephropathy (BEN), classified into three groups with regard to the clearance of 99mTc-DTPA. In comparison with the control group, the evolution of the disease is marked by a significant increase of the CI volume (p<0.001), as well as a significant reduction of glomerular (p<0.01) and tubular volume densities (p<0.001). The most intensive changes of CI and glomerular volumes are characteristic of the initial stage of the disease when glomerular filtration (GF) has shown no signs of deterioration yet. On the other hand, a significant reduction of the tubular epithelium volume density is characteristic of the advanced stages. The specified changes, particularly those taking place at the level of interstitium bear the key responsibility for the BEN progression. However, a number of links constituting the chain of BEN morphogenesis remained insufficiently clarified. This urges for a precise quantification of all histological changes taking place in different stages of the disease, starting from the earliest, in order to get a better insight into the order and dynamics of their occurrence.

Balkan Nephropathy↗
PubMed1998

Kidney ectopeptidases in gentamicin and mercuric chloride-induced acute renal failure.

The clinical use of gentamicin is associated by nephrotoxicity in over 10% of patients. However, the biochemical events responsible for proximal tubular injury and acute renal failure (ARF) are still unclear. In the present study, effects of gentamicin and, comparatively, of mercuric chloride upon rat kidney cortex ectopeptidases were studied. Gentamicin was given i.p., 100 mg/kg daily for up to 6 days, mercuric chloride i.p. once 2.5 mg/kg to rats studied after 3 days. Kidney cortex aminopeptidase N decreased significantly after 3 and 6 days' treatment (p < 0.01), however, angiotensinase A significantly decreased after 3 (p < 0.01), and much more after 6 days of gentamicin treatment (p < 0.001). Dipeptidylpeptidase IV activity was significantly decreased only after 6 days of treatment with gentamicin. In mercuric chloride-induced ARF all three peptidase activities were markedly decreased (p < 0.001). These results suggest that gentamicin-induced decrease in ectopeptidase activities could compromise vasoactive and other biologically active peptides handling, with important consequences upon renal function and metabolism.

Acute Kidney Injury↗
PubMed1997

Effects of ethane dimethanesulfonate on the structure of adult male rat adrenal cortex.

The influence of ethane dimethanesulfonate (EDS), a specific toxicant for Leydig cells, on the morphometric characteristic of adult male rat adrenal cortex was examined on day 15 after administration. As expected, the dose of 75 mg kg-1 of EDS produced drastic reduction in serum testosterone levels followed by a decrease in testis and seminal vesicle weight. However, a considerable drop (over 50%) in adrenal weight was also found. Stereological analysis of the adrenal cortex, performed under light microscope, revealed atrophy of all adrenocortical zones. The changes were most prominent in the inner zones. Thus, in the zona fasciculata the number of parenchymal cells was markedly decreased. In the zona reticularis a layer consisting mostly of atrophic parenchymal cells was localised at the border between zona reticularis and zona fasciculata. The remaining small number of cortical cells in this zone displayed a notable hypertrophy. It is concluded that EDS at a dose that destroys Leydig cells has a strong deleterious effect on steroidogenic cells of adult male rat adrenal cortex.

Adrenal Cortex↗
PubMed1996

[Lupus glomerulonephritis--clinico-morphologic correlation].

In a period of 10 years we performed renal biopsies in 13 patients with systemic lupus erythematosis, the results showed mild changes and focal glomerulonephritis in 30%, diffuse glomerulonephritis in 23% and membranous nephropathy and sclerotic glomerulonephritis in 15% of patients. In the follow-up period three patients died. Prognosis of severe lupus nephritis is better nowadays because of improved therapy. Adverse effects of the applied therapy should not be overlooked while arterial hypertension should be suppressed.

Adolescent↗
PubMed1995

Effects of growth factors on the enzymes of purine metabolism in culture of regenerating rat liver cells.

Hepatocytes are affected by many cytokines and growth factors during liver regeneration. In regenerating rat liver cells cultures, liver cell growth factor (LCGF), hepatic stimulator substance (HSS), interleukin-1 beta (IL-1 beta), as well as their combination, were tested for their ability to activate the enzymes involved in purine metabolism. The enzymes tested were 5' nucleotidase, AMP deaminase, adenosine deaminase and xanthine oxidase. The cytokines alone or in combination, activated 5' nucleotidase and adenosine deaminase. Activity of AMP deaminase was stimulated by IL-1 beta associated with LCGF, HSS and IL-1 beta. Xanthine oxidase was stimulated by IL-1 beta but not with HSS and LCGF. Associated with IL-1 beta these two substances decreased its activity. A novel approach to the understanding of the mechanisms involved in the regulation of purine metabolism during liver regeneration, is proposed.

5'-Nucleotidase↗
PubMed1995

Effect of glomerular cells interaction with macrophages on surface 5'-nucleotidase activity.

Interaction of cultured rat mesangial cells with macrophages induces a marked increase in surface 5'-nucleotidase activity of these mesangial cells. A significant increase in surface 5'-nucleotidase was also observed upon interaction of rat fibroblast with macrophages, both in cocultures and after treatment of fibroblasts with macrophage conditioned medium. Interaction of glomerular epithelial cells in primary culture with macrophages had no effect on surface 5'-nucleotidase activity. No significant effect on enzyme activity was observed after interaction of mesangial-epithelial cells, mesangial cells-fibroblasts, and epithelial cells-fibroblasts.

5'-Nucleotidase↗