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Biomedical subjects

S Petrovic

Publications and source records attributed to S Petrovic.

At least 19 recordsLinked to original sources

Development of a dermal cancer slope factor for benzo[a]pyrene.

Polycyclic aromatic hydrocarbons (PAHs) are commonly found at environmentally impacted sites in both Canada and the United States, and also occur naturally. Typically, benzo[a]pyrene (B[a]P) is selected as a standard to which the cancer potencies of other carcinogenic PAHs are compared. Cancer potency estimates for B[a]P have been published for the oral and inhalation routes of exposure, however, no such estimate has been established by a regulatory agency for dermal exposure. The main objectives of the current investigation were to: evaluate approaches used to examine the relative carcinogenicity of PAHs; to conduct a review of mammalian dermal carcinogenicity studies for B[a]P; and derive a cancer slope factor for dermal exposure to PAHs using B[a]P as a surrogate for other PAHs. The toxicological database of dermal B[a]P studies was examined for relevant animal bioassays. Seven relevant studies were identified. A cancer slope factor for B[a]P was developed using the benchmark dose approach and the linearized multistage model. The upper 95th CI at the 5% effect level above background incidence was used as the point of departure for low-dose linear extrapolation. An average slope factor of 0.55 (microg/animal day)(-1) was calculated for mice, which was converted to a dose-equivalent slope factor of 25 (mg/kg day)(-1). This latter slope factor is proposed for application to human health risk assessment with no scaling adjustment. Dermal potency equivalency factor values were identified which may be used with other carcinogenic PAH in the calculation of total B[a]P equivalent dermal cancer risk estimates. An identified area for further investigation is the consideration of scaling in extrapolating the calculated dermal cancer slope factor from mice to humans.

Administration, Cutaneous↗

Radon concentrations in a spa in Serbia.

The paper presents the results of indoor radon concentration survey in 201 homes and offices in Niska Banja (the Spa of Nis), a well-known health resort and a spa in the South-East of Serbia. Radon indoor concentrations were determined by active charcoal method, according to standard EPA procedure. The indoor radon concentrations were in the range of up to 200 Bq/m(3) (47%), from 200-600 Bq/m(3) (26%) and over 600 Bq/m(3) (27%). Three areas of extremely high average radon concentrations were found (1,340-4,340 Bq/m(3)), with a maximum above 13,000 Bq/m(3). The content of natural radionuclides ((226)Ra, (214)Pb, (214)Bi, (235)U, (228)Ac, (212)Pb, (212)Bi, (208)Tl, (40)K) and (137)Cs, as well as the content of total uranium, thorium and potassium in mud used in peloidotherapy in the Health Institute "Niska Banja" was determined, too. The activities of the radionuclides were determined on an HPGe detector, by standard gamma spectroscopy. The results indicated considerably high amounts of total uranium and thorium (0.021 g/kg mud and 0.003 g/kg mud, respectively), due to the karsts origin of the soil.

Air Pollutants, Radioactive↗

Validation of liquid chromatographic method for analysis of lidocaine hydrochloride, dexamethasone acetate, calcium dobesilate, buthylhydroxyanisol and degradation product hydroquinone in suppositories and ointment.

In this paper, there was developed a sensitive, precise and accurate reversed-phase liquid chromatographic (RP-HPLC) method and validated for simultaneous determination of lidocaine hydrochloride, dexamethasone acetate (DA) and calcium dobesilate (CD) in suppositories and ointment. Also there was achieved a parallel analysis of buthylhydroxyanisol, as a preservative, and hydroquinone, as a degradation product of calcium dobesilate, present in these dosage forms. The relative standard deviation (RSD) values for all five compounds indicated a good precision and accuracy of the RP-HPLC method. Method is selective, sensitive and reproducible with good recovery values and can be applied in simultaneous determination of all mentioned compounds.

Butylated Hydroxyanisole↗

Developmental potentials of hematopoietic and neural stem cells following injection into pre-implantation blastocysts.

Pluripotent embryonic stem (ES) cells are able to differentiate in vivo into all cell types of the fetal and adult organism and in vitro they can differentiate into a variety of cell types. In contrast, multipotent somatic stem cells (SSCs) isolated from fetal and adult tissues differentiate into mature effector cells of their tissue. However, recent studies imply that SSCs can also generate cell types of heterologous tissues indicating unexpected broad differentiation potentials. In order to examine and compare the developmental potentials of SSCs, we exposed hematopoietic stem cells (HSCs) and neural stem cells (NSCs) to an environment that is permissive for the development of all cell types of the embryo, namely the mouse preimplantation blastocyst. Using this approach we were able to detect progeny of HSCs and NSCs frequently in developing chimeric animals. Analysis of 18 different adult tissues revealed minor preferences of HSCs for hematopoietic tissues, while progeny of NSCs were mostly detected in neural tissues. Furthermore we observe that human cord blood-derived CD34+ and CD34+/CD38- HSCs also engraft murine embryos and that human donor contribution persists into adulthood. Our studies show the existence of tissue specific engraftment preferences of HSCs and NSCs and that both stem cell types are non-ES cell-like.

ADP-ribosyl Cyclase↗

Abc protein transport of MRI contrast agents in canalicular rat liver plasma vesicles and yeast vacuoles.

The mechanism of excretion into bile of hepatospecific magnetic resonance imaging (MRI) contrast media employed labeled Gd-reagents EOB.DTPA, BOPTA, B 20790 (iopanoate-linked), and B 21690 (glycocholate-linked) for measurement in rat liver canalicular plasma membrane vesicles and yeast vacuoles. The presence of ATP gave threefold greater transport of B 20790 and B 21690 than of EOB.DTPA and BOPTA. In yeast vacuoles the ATP stimulatory effect was eightfold with B 20790 and fivefold greater for B 21690, whereas in YCF1- or YLLO115w-deleted yeast cells the transport was significantly reduced and absent from double mutants, YCF1 and YLLO15w. The transport was similar in wild-type and deletant cells for B 21690; taurocholate gave 85% inhibition. These data suggest that bilary secretion of structurally related MRI agents depend on molecular structure. The findings are suggestive as of possible value for clinical diagnosis of inherited hyperbilirubinemias and other liver disorders.

ATP-Binding Cassette Transporters↗

Mouse Na+: HCO3- cotransporter isoform NBC-3 (kNBC-3): cloning, expression, and renal distribution.

BACKGROUND: Na+:HCO3- cotransporters mediate the transport of HCO3- into or out of the cell. We recently reported the partial cloning and characterization of a new human Na+:HCO3- cotransporter (referred to as NBC-3 or kNBC-3). The purpose of the present studies was to clone the mouse kNBC-3 and to examine its properties and expression in the kidney. METHODS: Using primers from human kNBC-3 cDNA and 5' and 3' rapid amplification cDNA end polymerase chain reaction (RACE PCR), the mouse kNBC-3 full-length cDNA was cloned from inner medullary collecting duct (mIMCD-3) cells. The tissue distribution and functional properties of NBC-3 was determined using established methods. RESULTS: The coding region of the mouse kNBC-3 has 1089 amino acids and shows 73 and 56% identity to human NBC-2 and NBC-1, respectively. The renal distribution of kNBC-3 demonstrated a unique expression pattern: Whereas kNBC-1 is predominantly expressed in the cortex and is absent in the inner medulla, kNBC-3 shows an intense expression level in the inner medulla and is absent in the cortex. Expression studies in oocytes indicated that NBC-3 mediates Na-dependent HCO3- cotransport. Electrophysiological experiments demonstrated that unlike kNBC-1, which is electrogenic, kNBC-3 is electroneutral. CONCLUSIONS: Based on its distribution and electroneutrality, we propose that kNBC-3 mediates the transport of HCO3- into the cells.

Amino Acid Sequence↗

Role of basolateral carbonic anhydrase in proximal tubular fluid and bicarbonate absorption.

Membrane-bound carbonic anhydrase (CA) is critical to renal acidification. The role of CA activity on the basolateral membrane of the proximal tubule has not been defined clearly. To investigate this issue in microperfused rabbit proximal straight tubules in vitro, we measured fluid and HCO(3)(-) absorption and cell pH before and after the extracellular CA inhibitor p-fluorobenzyl-aminobenzolamide was applied in the bath to inhibit only basolateral CA. This inhibitor was 1% as permeant as acetazolamide. Neutral dextran (2 g/dl, molecular mass 70,000) was used as a colloid to support fluid absorption because albumin could affect CO(2) diffusion and rheogenic HCO(3)(-) efflux. Indeed, dextran in the bath stimulated fluid absorption by 55% over albumin. Basolateral CA inhibition reduced fluid absorption ( approximately 30%) and markedly decreased HCO(3)(-) absorption ( approximately 60%), both reversible when CA was added to the bathing solution. In the presence of luminal CA inhibition, which reduced fluid ( approximately 16%) and HCO(3)(-) ( approximately 66%) absorption, inhibition of basolateral CA further decreased the absorption of fluid (to 74% of baseline) and HCO(3)(-) (to 22% of baseline). CA inhibition also alkalinized cell pH by approximately 0.2 units, suggesting the presence of an alkaline disequilibrium pH in the interspace, which would secondarily block HCO(3)(-) exit from the cell and thereby decrease luminal proton secretion (HCO(3)(-) absorption). These data clearly indicate that basolateral CA has an important role in mediating fluid and especially HCO(3)(-) absorption in the proximal straight tubule.

Absorption↗

Pendrin: an apical Cl-/OH-/HCO3- exchanger in the kidney cortex.

The identities of the apical Cl-/base exchangers in kidney proximal tubule and cortical collecting duct (CCD) cells remain unknown. Pendrin (PDS), which is expressed at high levels in the thyroid and its mutation causes Pendred's syndrome, is shown to be an anion exchanger. We investigated the renal distribution of PDS and its function. Our results demonstrate that pendrin mRNA expression in the rat kidney is abundant and limited to the cortex. Proximal tubule suspensions isolated from kidney cortex were highly enriched in pendrin mRNA. Immunoblot analysis studies localized pendrin to cortical brush-border membranes. Nephron segment RT-PCR localized pendrin mRNA to proximal tubule and CCD. Expression studies in HEK-293 cells demonstrated that pendrin functions in the Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange modes. The conclusion is that pendrin is an apical Cl-/base exchanger in the kidney proximal tubule and CCD and mediates Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange.

Analysis of Variance↗

The products of YCF1 and YLL015w (BPT1) cooperate for the ATP-dependent vacuolar transport of unconjugated bilirubin in Saccharomyces cerevisiae.

Since bilirubin-like pigments are present in the environment as degradation products of heme-containing proteins, yeast could have developed a detoxifying system to transport these compounds into their vacuoles. Vacuoles from Saccharomyces cerevisiae showed an ATP-dependent, saturative transport of unconjugated bilirubin (UCB) that was reduced by 60% and 40% in YCF1 and YLL015w-deleted cells, respectively; the double deletant showed no UCB uptake. Conversely, the transport of bile acids (taurocholate) was comparable in wild and deleted stains. These data identify YCF1 and YLL015w, named BPT1 (Bile Pigment Transporter), as the genes responsible for ATP-dependent UCB transport in yeast. Since YCF1 and YLL015w are rather homologous with multidrug resistant proteins (MRPs), they also suggest the involvement of this class of transporters in the ATP-dependent transport of unconjugated bilirubin.

ATP-Binding Cassette Transporters↗

Effects of cumene hydroperoxide on cellular cation composition in frog kidney proximal tubular cells.

Effects of cumene hydroperoxide were studied on the peritubular membrane potential and cellular cation composition in frog kidney proximal tubular cells. After perfusion of isolated frog kidneys for 30 min with 1.3x10(-4) mol l(-1) cumene hydroperoxide Ringer solution, the peritubular membrane potential gradually declined. The ouabain-like effects were demonstrated on cell Na and K activities after 1 h of perfusion with cumene hydroperoxide. The peritubular apparent transference number for potassium was decreased. Intracellular pH was not altered in the presence of cumene hydroperoxide. Intracellular free Ca(2+) concentration increased slowly and moderately. The concentration of the malondialdehyde in the kidney homogenates, measured as an index of lipid peroxidation, was increased. A previously observable effect of cumene hydroperoxide on the peritubular membrane potential was prevented by oxygen radical scavengers.

Animals↗

[Treatment and reconstruction of bullet wounds of the calf].

The paper describes complete management of bullet wounds of the crus. After thorough primary surgical treatment and fixation of the fracture the authors recommend the method of muscle flap of the soleus muscle and anterior tibial muscle and the method of musculocutaneous flap of the gastrocnemius muscle to achieve reconstitution of soft tissues. In fractures with tissue loss, after healing of the reconstituted areas of soft tissues, they advocate plastics with sponge and corticosponge grafts. Of the 12 bullet wounds of the extremities treated 3 were injuries of the crus.

Humans↗

[Treatment and reconstruction of open fractures of the forearm with tissue loss].

The importance of the forearm calls for attempts to preserve it and to restore its function even in severe injuries with extensive tissue loss. At early and comprehensive first surgical treatment providing sufficient perfusion good results can be achieved also in cases that do not appear promising at first sight. After treating the soft tissues fixation of the fracture is to be ensured externally and reconstitution surgery is to proceed according to the management plan. Of the reported series of 11 severe compound fractures the functional result of management was not favorable only in a single case.

Forearm Injuries↗

[Reconstruction of open fractures of the leg associated with extensive loss of skin and soft tissues using muscular and cutaneo-muscular flaps].

The author draws attention to the serious character of open fractures of the leg with extensive losses of the skin and soft tissues. He emphasizes the need of high standard primary surgical treatment and osteosynthesis of the fracture by external fixation device according to a therapeutic plan. To ensure an undisturbed consolidation of the fracture in indicated cases, the author implements the reconstruction of acute skin losses and soft tissue losses by a muscular flap of the m. soleus or m. tibialis ant. and by dermatomuscular flaps of the gastrocnemius muscle. Of 42 casualties with open fractures of the leg with losses of soft tissues the author made in 9 reconstructions of acute losses by muscular and dermatomuscular flaps. The author presents the documentation of two patients with open fractures of the leg who were treated by muscular and dermatomuscular flaps.

Fracture Fixation, Internal↗

Expression of modified rye ribosomal RNA genes in wheat.

Several wheats (Triticum aestivum L. em Thell.) containing the short arm of chromosome 1R from rye (Secale cereale L.) translocated to the long arm of wheat chromosome 1B were examined, by in situ hybridization with a biotinylated probe, for the expression of rye rRNA genes located in the nucleolus-organizing region (NOR) present on the short arm of 1R. The wheats analyzed contain a reduced rye NOR band, identified by a C-banding technique, that was assumed to have resulted from a deletion that reduced the number of rRNA genes and spacer units. Genes being actively transcribed could be recognized as dispersed label on DNA within the nucleolus, while those genes that were inactive were seen as condensed label. After in situ hybridization with a biotinylated rye NOR spacer probe, no evidence of rye rRNA gene activity was detected in the plants containing a reduced rye NOR band. Biotin-labeling of chromosomes containing a normal-sized rye NOR locus showed a degree of rye activity consistent with the results of a previous study that used a radioactive probe detected by autoradiography. It was determined previously that rye rRNA genes in a wheat background show significantly less activity than in diploid rye because the spacer units between the rRNA genes of rye are smaller than those of wheat, and in cereals the ribosomal locus with the larger spacer unit is preferentially transcribed. The present results indicate that the number of spacer units is also important in determining which NOR locus (i.e., rye or wheat) will be expressed when several ribosomal loci are present in a wheat background.

Journal Article↗