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Biomedical subjects

P Kowalski

Publications and source records attributed to P Kowalski.

At least 19 recordsLinked to original sources

Capillary electrophoretic determination of thiamphenicol in turkeys serum and its pharmacokinetic application.

The pharmacokinetics of thiamphenicol were investigated in 12 healthy turkeys of both sexes, following intravenous (i.v.) and intragastric (p.o.) administration of a single dose of 30 mg/kg body weight (bw). Serum drug concentrations were determined by capillary electrophoresis technique on blood samples collected over 24 h following treatment. The method was statistically validated for its linearity, accuracy, precision and selectivity. The linear range was from 0.2 to 500 microg/ml with correlation coefficients greater than 0.999. The limit of detection of drug was 70 ng/ml, while the quantitative limit was 200 ng/ml, using 0.5 ml sample size. Pharmacokinetic variables of the drug were calculated after both administration routes.

Administration, Oral↗

Pharmacokinetics and bioavailability study of L-ornithine-L-aspartate in healthy volunteers--a comparative study of two oral formulations.

The aim of the evaluation was to establish bioequivalence between two oral 3.0 g sachet forms of L-ornithine-L-aspartate (LOLA). It was designed as randomised, two-way crossover study with a 1-week washout interval. Blood samples were collected throughout a 12 h period after administration of reference and test product to 12 fasting healthy male volunteers. Plasma were analyzed by sensitive, reproducible, accurate and rapid capillary electrophoresis (CE) method with UV detection. Many pharmacokinetic parameters including AUC0-t, AUC0-infinity, Cmax, Tmax, T1/2 and Kel were determined from plasma concentration. First three of them after log-transformation of data were examined for bioequivalence. Based on ANOVA with 90% confidence level no significant difference was found. All of tested parameters were found to be within the bioequivalence acceptance range of 80-125%. Based on these and other statistical tests it was concluded that Hepatil is bioequivalent to Hepa-Merz granulate.

Administration, Oral↗

Validated method for L-ornithine-L-aspartate analysis in human plasma by capillary electrophoresis.

A rapid capillary electrophoresis method for routine determination of two amino acids, L-ornithine and L-aspartic acid, in human plasma is reported. The method runs automatically, requires a minimum of sample preparation and moreover includes no extensive extraction and no gradient or derivatization procedure. Analyses were performed on an uncoated silica capillary using buffer solution composed with 10 mM sodium tetraborate and 1 M sodium hydroxide (pH=10.0). A capillary electrophoresis P/ACE system equipped with UV detection (200 nm), an automatic injector, a fluid cooled cartridge and System Gold data station was used in this study. The total analysis time under these conditions was 8.0 min. The calibration curve was linear in the range 10-280 microg mL-1 for L-aspartic acid and 20-280 microg mL-1 for L-ornithine (for both amino acids, r=0.999). The method was validated by inaccuracy (bias) and precision (RSD) studies by analysing samples. The method was successfully applied to the quantitative determination of L-ornithine-L-aspartate in human plasma and could be useful for clinical and bioavailability investigations.

Aspartic Acid↗

Capillary electrophoresis in analysis of veterinary drugs.

Antibiotics are extensively applied in veterinary medicine for the treatment of various bacterial infections. Because of their use in food producing animals, the risk of occurrence of unwanted residues in edible products exists. To ensure human food safety, The European Union has defined maximum residue limits (MRLs) for veterinary drug residues in food products. Analytical methods need to be developed to confirm the presence of antibiotics at the MRL level. A capillary electrophoresis (CE) method with UV detection is proposed for the quantitative determination of residues from poultry and porcine tissues. Eight of the most frequently used antibiotics and nifursol, which routinely used as poultry coccidiostat, were analysed. CE technique permitted analysing substances to be separated from muscle, liver, kidney and skin with fat after a simple extraction with acetonitrile or ethyl acetate under basic conditions. Proposed method is capable to identify drug residues in tissues at level below 20 microg/kg.

Animals↗

Wetland management to reduce Baltic Sea eutrophication.

Seven regions with coastal eutrophication problems in the Baltic Sea, including the Kattegat, constitute the BERNET project (Baltic Eutrophication Regional Network). To counteract eutrophication and associated severe biological conditions the countries around this large brackish water body must all cooperate. The regions are characterized by large differences in land use, e.g. agricultural intensity, and losses of retention capacity in the catchments due to wetland reclamation. Initially it has been necessary to identify nutrient sources--especially nitrogen--and technical, economical and even administrative obstacles to initiate eutrophication management measures. Nitrogen retention in different types of wetlands in the Baltic Sea Region has been analysed. The wetlands generally have a positive effect on reduced nitrogen transport to aquatic environments and it is generally accepted that measures leading to decreased losses of nutrients to the aquatic environment must be combined with measures leading to increased retention of nutrients in catchments. Data analysed in the BERNET project show that the potential for such a measure is large. Therefore, conservation and restoration initiatives for wetlands is an essential part of the work in the BERNET project. Wetlands have been drained or totally eliminated due to intensive agriculture in some regions while large scale rehabilitation of wetlands occurs in regions with less intensive agriculture. Based on land use data from the seven regions, the working group for wetland management within the BERNET project has identified the possible use of wetlands as building blocks as a contribution to the management of the Baltic Sea eutrophication. Several recommendations are presented on the wise use of existing and constructed wetlands for water quality management in relation to non-point nutrient pollution.

Agriculture↗

Benzolactam derivatives and their affinity for alpha 1- and alpha 2-adrenoreceptors.

A series of benzolactam derivatives has been evaluated for their affinity for alpha 1 and alpha 2-adrenoreceptors. The influence of terminal amine and amide fragments on the affinity and selectivity has been investigated. It has been found that derivatives containing 1,2,3,4-tetrahydroisoquinoline (THIQ) as the basic component can form potent alpha 1 and/or alpha 2 ligands, and that their alpha 1/alpha 2 selectivity depends on the benzolactam fragment.

Animals↗

Selection and characterization of a high-activity ribozyme directed against the antineoplastic drug resistance-associated ABC transporter BCRP/MXR/ABCG2.

Breast cancer resistance protein (BCRP) is a recently identified new member of the superfamily of ATP-binding cassette transporters. BCRP is a "half transporter" that may homo- or heterodimerize to form an active transport complex. A considerable overexpression of BCRP was reported from various atypical multidrug-resistant tumor cell lines, in particular from those which were established by treatment with mitoxantrone. Thus, BCRP represents a very interesting candidate molecule for reversal of a drug-resistant phenotype. Six hammerhead ribozymes directed against the BCRP-encoding mRNA were designed and tested for their ability to cleave their target molecule. The anti-BCRP ribozymes were in vitro synthesized using bacteriophage T7 RNA polymerase and oligonucleotide primers whereby one primer contains a T7 RNA polymerase promoter sequence. BCRP-encoding substrate RNA molecules were created by a reverse transcription polymerase chain reaction using total RNA prepared from the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV exhibiting a high BCRP mRNA expression level. One anti-BCRP ribozyme was found to show a very high endoribonucleolytic cleavage activity at physiologic pH and temperature. This ribozyme was characterized in a cell-free system with regard to its specific kinetic parameters using large target molecules.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

Metastases to the products of conception from a maternal bronchial carcinoma. A case report and review of literature.

The association of mother's malignancy with metastases to the products of conception is rarely reported. We present 8th case reported in the literature of oat-cell lung carcinoma complicated by an aggressive clinical course and documented placental metastases. Review of all published cases of lung cancer metastasizing to the placenta is also presented. A 44-year-old white pregnant woman at an estimated gestational age of 30 weeks presented with cervical incompetence symptoms and multiple tumors of 2-4 cm in diameter located in the subcutaneous tissue of the chest, including both breasts. The biopsy revealed a metastatic oat-cell carcinoma. Cesarean section was performed immediately. During the procedure, micronodular metastatic infiltration of the liver was noted. Microscopic examination of placenta showed clusters of oat-cell carcinoma calls within the intervillous spaces; no infiltration of villi themselves was noted. The malignant cells were morphologically identical as those of the subcutaneous metastases. The woman succumbed to cancer and died on the 16th postoperative day. Lung cancer metastasizing to the placenta is relatively rarely reported. In all cases only placental metastases were found; the fetus in all cases was spared. Only in one out of 8 reported cases outcome of mother was not fatal. It should be emphasized that not in all cases of maternal malignancy the histological examination of the placental was made Therefore it is possible that the incidence of placental involvement is more often than it is reported.

Adult↗

Accelerating discoveries in the proteome and genome with MALDI TOF MS.

Recent developments in mass spectrometry (MS) provide scientists with an established analytical tool that addresses the demands for rapid, accurate and cost effective analyses of biomolecules. These advances clearly accelerate the rate and success of protein identification, genetic sequencing, determining biological variances and drug discovery. This review is intended to illustrate how matrix-assisted laser desorption/ionisation (MALDI) time-of-flight (TOF) MS is typically used to generate information about biomolecules under investigation. Additionally, examples will be used to describe the steps involved in preparing samples for MALDI TOF and obtaining answers through data management.

Animals↗

Ki-67 reactivity in primary fallopian tube cancers.

Forty-four cases of primary cancer of the fallopian tube (PFTC) were analyzed as to Ki-67 expression, grade, stage and the cancer histological type. Among patients with an average age of 57.5 years (range 38-70 years), 27 patients were FIGO I, 7 were FIGO II and 10 were FIGO III. Histological classification of PFTC revealed 18 cases of endometrioid type, 9 serous, 7 undifferentiated, 6 urothelial, 2 clear-cell and 2 of other type. Histological grading revealed 11 cases of G1, 16 of G2 and 17 of G3 tumors. The quantity of Ki-67 positive cells was counted on 300 cancer cells in random high-power fields (10 x 40) and recorded as the labeling index (LI, %). Positive staining for Ki-67 was shown in the nuclei in all cases. Ki-67 LI values ranged from 14.2 to 97.2% (median 36.1). Ki-67 LI values were graded as > or = 36.1% as high and <36.1% as low. We did not find any significant differences in Ki-67 LI values among tumors of various clinical stages, histological grades and histological types. The p value was statistically significant only for stage as a prognostic factor.

Adult↗

Structure-activity relationship studies of CNS agents. Part 38. Novel 1,4-benzoxazin-3(4H)-one, 1,2-benzoxazolin-3-one and 1,3-benzoxazolin-2,4-dione arylpiperazine derivatives with different 5-HT1A and antagonistic 5-HT2A activities.

New 1-arylpiperazine (series d-f) and 1,2,3,4-tetrahydroisoquinoline (series g) derivatives of 1,4-benzoxazin-3(4H)-one 1, 1,2-benzoxazolin-3-one 2, and 1,3-benzoxazolin-2,4-dione 3 with an n-butyl chain were synthesized in order to explore the effect of spacer elongation on their binding affinity and in vivo functional activity at 5-HT1A and 5-HT2A receptors in comparison with trimethylene analogues (a, bc). 5-HT1A receptor binding constants of derivatives 1d-g, 2d-f, and 3d-f were very high (Ki = 1.25-54 nM), and 5-HT2A affinities were maintained at a similar, high level (Ki = 27-85 nM) for series d and e, and moderate (Ki = 246-495 nM) for series f. In respect of a spacer, the obtained results showed either no effect or a slight increase in the 5-HT1A/5-HT2A affinity in case of derivatives of 1 and 2, respectively. A striking effect was observed for derivatives 3d and 3f, whose 5-HT1A affinity was reinforced by two orders of magnitude with a simultaneous decrease in 5-HT2A binding constants in comparison with trimethylene analogues. As shown by X-ray crystallography, this phenomenon may be attributed to the position of non-carbonyl oxygen atom in the amide moiety. In vivo studies demonstrated that compounds 1e-g, 2d-f, and 3f behaved like typical postsynaptic 5-HT1A receptor antagonists, whereas 3d and 3e might be qualified as their potential partial agonists. Moreover, 1e, 2e, and 3e demonstrated 5-HT2A receptor antagonistic properties. Of the tested compounds, two derivatives showed some very outstanding properties: 3e may be regarded as a potential anxiolytic and/or antidepressant agent, while 3f as a new potent 5-HT1A antagonist.

Animals↗

Determination of piracetam in human plasma by capillary electrophoresis.

A capillary electrophoresis (CE) procedure has been developed for the determination of piracetam in human plasma. Analyses were performed on an uncoated silica capillary using borax buffer modified with the addition of alpha-cyclodextrin. The detection was UV, operated at 200 nm. The detection limit of the authentic samples was 1 microg/ml. The calibration curve was linear over a range of 4 to 24 microg/ml (r=0.997). Inter-assay R.S.D. was below 9.3%. The described method has been successfully applied to the quantitative determination of piracetam in human plasma and should be useful for clinical and bioavailability investigations.

Electrophoresis, Capillary↗

Helicobacter pylori in kidney allograft recipients: high prevalence of colonization and low incidence of active inflammatory lesions.

Since kidney transplant recipients are at enhanced risk for developing severe upper gastrointestinal disease and Helicobacter pylori (Hp) is an important pathogen in active gastritis and peptic ulcer, we performed gastroduodenoscopic examination, coupled with assessment of Hp colonization in 29 renal allograft recipients complaining of recurrent dyspepsia. Results were compared with those of 25 chronically hemodialyzed patients and 16 subjects free from renal disease, also suffering from upper gastrointestinal symptoms of similar severity. We found that while transplant recipients have had a high prevalence of Hp infection (62 vs. 34.6% in dialysis and 43.6% in control dyspeptic patients), active gastritis was clearly less frequently seen in these patients than in control subjects (transplant group: 6.9%, dialysis 3.8%, control 31.3%) and peptic ulceration was totally absent. Prevalence of Hp colonization was even higher in renal graft recipients on triple posttransplant immunosuppression (82%). In dyspeptic transplant and dialysis patients, colonization with Hp did not account for development of active inflammatory lesions, an association frequently seen in subjects free from renal disease and immunosuppressive therapy.

Adolescent↗

Influence of mesna on urotoxic effects of selected bromosubstituted analogs of ifosfamide.

Bromofosfamides, the group of novel compounds closely related to ifosfamide, are currently in the stage of advanced preclinical evaluation. Ifosfamide, although itself the effective antineoplastic drug useful in situations which have proved refractory to cyclophosphamide therapy, has the side-effect toxicities caused by its metabolities that pose clinically a very real problem. One of their manifestations is the severe urinary tract toxicity which now could be adequately managed by conjunctive administration of mesna (sodium 2-mercaptoethane sulphonate). In this study we have compared the magnitude of urotoxic effects elicited by ifosfamide and two bromofosfamide compounds--racemate and S(-) isomer of chlorobromofosfamide (ClBrs)--selected previously on the base of their superior antitumor activity in advanced animal tumor models. The urotoxic effects, expressed by the increase of urinary bladder weight and histopathologically defined organ wall edema, were estimated in healthy mice 24 h following single intraperitoneal or oral administrations of tested compounds which were applied in amounts equal to curative, sublethal or lethal doses. It was found that the expression of toxic effects revealed by both ClBrs was statistically significantly lower as compared to ifosfamide. Mesna coadministration prevented urotoxic effects almost completely in mice treated with ifosfamide or racemic ClBr. Somewhat lower efficacy of uroprotection with mesna was observed in the case of S(-) isomer of ClBr.

Administration, Oral↗

5-HT1A and 5-HT2A receptor affinity and functional profile of some N-[3-(4-aryl-1-piperazinyl)propyl] derivatives of indolin-2(1H)-one, quinolin-2(1 H)-one and isoquinolin-1(2H)-one. Part 30: Structure-activity relationship studies of CNS agents.

A series of new 1-aryl-4-propylpiperazines containing the modified terminal amide fragment 9, 15-19, 21, 23 and 25 were synthesized and their 5-HT1A and 5-HT2A receptor affinities were determined. All the compound were highly potent 5-HT1A receptor ligands with a diverse 5-HT2A receptor affinity. It was found that the 5-HT2A receptor affinity depends on the dipole moment and lipophilicity of amide moiety. Compound 9b was found to be a 5-HT2A receptor antagonist and a weak 5-HT1A receptor agonist.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

NMR relaxation time studies of large bowel neoplasms.

The purpose of the study was to determine if measurements of the NMR relaxation times could be useful in distinguishing healthy from neoplasmatic tissue in in vitro study of the slices from the large bowel obtained during surgery before histological examination. Tissue samples taken from the center of the tumor and from the distal part of the excised large bowel segment were stored at 4 degrees C in closed tubes not longer than 24 hours. The measurements were performed at 37 degrees C using a pulse spectrometer operating at 27 MHz. After NMR investigation all the tissue samples were preserved and carefully examined by conventional histopathological techniques. Both for the T1 and the T2 the mean values of the relaxation time for the respective neoplasmatically changed group and normal, non-changed group, were statistically different. However, the differences in measured relaxation times are too small to use the NMR method alone for diagnosis. The NMR method can be useful only for an initial selection of tissue samples with possible cancer changes but histopathological examination is required to verify that cancer is present in the tissue.

Colon↗

[Conservative treatment of hepatic amebic abscesses].

A case is presented of hepatic amebic abscesses in a young man after return from India. After establishing of the aetiology of the disease conservative treatment was started which was completed with success. The authors point to the possibility of transmission of amoeba dysentery to Poland due to journeys to tropical or subtropical countries.

Adult↗