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1.
J Physiol Pharmacol ; 69(2)2018 Apr.
Article En | MEDLINE | ID: mdl-30045004

Green tea extract exerts favorable influence on the lipid profile and insulin resistance in the high-sodium intake arterial hypertension. A high-sodium diet (HSD) was introduced to thirty Wistar rats to create a model of hypertension. Rats were randomized into three groups, 10 animals each. The SK group consumed HSD. The SH2 group consumed HSD with 2 g of green tea extract in kg of diet. The SH4 group was fed HSD with 4 g of green tea extract in kg of diet. After six-week trial blood samples were collected. The serum concentrations of glucose, insulin and lipids were estimated, and insulin sensitivity was calculated using homeostatic model assessment (HOMA). Neither the high-sodium diet nor supplementation with green tea extract had any significant influence on the body mass of the animals in either group. Total cholesterol (TCH) and low-density lipoproteins (LDL) cholesterol serum concentrations were significantly smaller in both supplemented groups than in the SK group. The insulin level in the SH2 rats and HOMA in SH2 and SH4 groups were found to be significantly smaller than in the SK group. There were no differences in glucose concentrations between groups. Within the whole population, statistically significant positive correlations between HOMA and LDL, TCH were found. We conclude that in NaCl-induced hypertensive Wistar rats, supplementation with green tea extract produced a dose-independent beneficial and parallel effect on the lipid profile and insulin resistance.


Blood Glucose/drug effects , Camellia sinensis , Hypertension/blood , Insulin/blood , Lipids/blood , Plant Extracts/pharmacology , Animals , Blood Pressure/drug effects , Disease Models, Animal , Hypertension/chemically induced , Hypertension/physiopathology , Insulin Resistance , Male , Rats, Wistar , Sodium Chloride
2.
Bioact Mater ; 3(3): 213-217, 2018 Sep.
Article En | MEDLINE | ID: mdl-29744459

The study is focussing towards Metal Injection Moulding (MIM) of Mg-alloys for biomedical implant applications. Especially the influence of the sintering processing necessary for the consolidation of the finished part is in focus of this study. In doing so, the chosen high strength EZK400 Mg-alloy powder material was sintered using different sintering support bottom plate materials to evaluate the possibility of iron impurity pick up during sintering. It can be shown that iron pick up took place from the steel bottom plate into the specimen. Despite the fact that a separating boron nitrite (BN) barrier layer was used and the Mg-Fe phase diagram is not predicting any significant solubility to each other. As a result of this study a new bottom plate material not harming the sintering and the biodegradation performance of the as sintered material, namely a carbon plate material, was found.

3.
J Physiol Pharmacol ; 69(5)2018 Oct.
Article En | MEDLINE | ID: mdl-30683825

A range of studies showed confusing data about the relationship between obesity, weight reduction and circulating total insulin-like growth factor -1 (IGF-1). The aim of the study was to compare the influence of orlistat (IO), metformin (IM), or calorie-restricted diet (LC) on IGF-1, with special respect to insulin-resistance status. One hundred and fourteen obese women aged from 18 to 40 years were divided into insulin sensitive (IS) and insulin resistant (IR) groups and received a low calorie diet (LC), or an isocaloric diet and 500 mg metformin twice daily (IM), or isocaloric diet with 120 mg orlistat three times daily (IO). Before and after the intervention anthropometric parameters, serum lipid profile, serum concentrations of alanine aminotransferase, aspartate aminotransferase, insulin, glucose, IGF-1, HOMA-IR (homeostatic model assessment), and visceral adiposity index (VAI), and their changes were registered. Although the reductions in weight and body fat were comparable in IS and IR groups, only women with IR showed a significant increase in IGF-1 concentration as a result of all interventions. We found significant positive correlations of ΔIGF-1 with initial and Δ values of: HOMA-IR, triglyceride/high-density cholesterol ratio, VAI. IR premenopausal women show significant increase in IGF-1 serum concentrations regardless the method of intervention. The increase in IGF-1 was parallel to the improvement of insulin resistance parameters.


Anti-Obesity Agents/therapeutic use , Caloric Restriction , Hypoglycemic Agents/therapeutic use , Insulin Resistance , Insulin-Like Growth Factor I/analysis , Metformin/therapeutic use , Obesity/therapy , Orlistat/therapeutic use , Adult , Diet , Female , Humans , Intra-Abdominal Fat , Obesity/blood , Premenopause/blood
4.
J Proteomics ; 164: 43-51, 2017 07 05.
Article En | MEDLINE | ID: mdl-28583384

Microorganisms can support environmental restoration by biodegradation of hydrocarbons but the mechanism of this process has been not described in detail yet. We present the effect of benzene derivatives on Raoultella ornithinolytica M03 cell composition. Comparison of the cell response after short-term and long-term stress revealed significant differences in surface properties, fatty acid composition and proteins profile. R. ornithinolytica M03 after long-term stress was characterized by lower cell surface hydrophobicity and much higher inner membrane permeability. Also decrease in the content of branched and unsaturated fatty acids was observed. Cells after short- and long-term stress were characterized by analyses of changes related to thirty-nine proteins participating in various metabolic pathways. The presence of benzene derivatives resulted in modifications in the abundance of proteins involved in determination of cell shape and ability to ion transport, lipid biosynthesis, amino-acid biosynthesis, tRNA ligases, chaperone and TCA cycle proteins, gluconeogenesis, transcription and nucleotide synthesis. Uptake and transport associated proteins, cell properties and membrane stability were also found to differ in the cells after short- and long-term stress suggesting the use of different mechanisms for transport and biodegradation of benzene derivatives and modification of cell response depending on the length of exposure to the stressor. BIOLOGICAL SIGNIFICANCE: This is the first comprehensive study whose results may contribute to a better understanding of the changes occurring during short- and long-term contact with benzene derivatives. After long term stress R. ornithinolytica M03 was characterized by lower cell surface hydrophobicity and much higher inner membrane permeability and decrease in the content of branched and unsaturated fatty acids. We identified changes related to multiple proteins engaged in various metabolic pathways such as biogenesis of cell membrane/wall, amino-acid biosynthesis, nucleotide and protein synthesis, gluconeogenesis and tRNA ligases. Changes in proteins participating in uptake and transport associated proteins, cell properties and membrane stability indicate modifications in transport and biodegradation of benzene derivatives, connected with the length of exposure to the stressor. The provided results seem to constitute an important aspect of remediation techniques.


Bacterial Proteins/metabolism , Benzene Derivatives/metabolism , Enterobacteriaceae/metabolism , Fatty Acids/metabolism , Biodegradation, Environmental
5.
Eur Rev Med Pharmacol Sci ; 20(18): 3868-3876, 2016 09.
Article En | MEDLINE | ID: mdl-27735028

OBJECTIVE: We compared the effects of three weight loss interventions on serum concentrations of adiponectin and leptin in obese premenopausal women. PATIENTS AND METHODS: 114 obese Caucasian women were randomized into three groups receiving a low-calorie diet (LC; n = 39), an isocaloric diet with 500 mg of metformin twice a day (IM; n = 38), and an isocaloric diet with 120 mg of orlistat three times a day (IO; n = 37), for three months. Serum concentrations of adiponectin and leptin were evaluated, along with anthropometric and body composition parameters, at baseline and after the study. RESULTS: Both IO and LC, but not IM, caused an increase in serum adiponectin concentration (p < 0.01, p < 0.05 respectively). A decrease in serum leptin level was documented in the LC (p < 0.001), IM (p < 0.01), and IO group (p < 0.01). Beneficial changes in anthropometric and body composition values were observed following all interventions with the greatest advantage seen in the IO group. The strongest correlations, of Δadiponectin with Δbody weight (r = -0.54), ΔBMI (r = -0.49), ΔFAT [%] (r = -0.48), ΔFAT [kg] (r = -0.48), and Δlean [%] (r = 0.48); and of Δleptin with Δbody weight, ΔBMI, Δwaist, Δfat, and Δlean, were documented in the IO group. CONCLUSIONS: Beneficial effects were observed on serum leptin concentration, weight loss, and body composition for all interventions and in all examined groups, with the greatest advantage being associated with the orlistat treatment. Improvements in serum adiponectin concentrations resulted from the low-calorie and isocaloric diets with orlistat, but not from the isocaloric diet with metformin. We find these strategies more promising for the treatment of obesity and its related complications in obese premenopausal women.


Adiponectin , Caloric Restriction , Leptin/blood , Obesity , Aged , Diet, Reducing , Female , Humans , Hypoglycemic Agents/therapeutic use , Lactones/therapeutic use , Metformin/therapeutic use , Middle Aged , Orlistat , Postmenopause , Prospective Studies , Weight Loss/drug effects
6.
Amino Acids ; 47(4): 825-38, 2015 Apr.
Article En | MEDLINE | ID: mdl-25583605

Transglutaminases (E.C. 2.3.2.13) catalyze the post-translational modification of proteins by establishing ε-(γ-glutamyl) lysine isopeptide bonds and by the covalent conjugation of polyamines to endo-glutamyl residues of proteins. In light of the confirmed role of transglutaminases in animal cell apoptosis and only limited information on the role of these enzymes in plant senescence, we decided to investigate the activity of chloroplast transglutaminases (ChlTGases) and the fate of chloroplast-associated polyamines in Hordeum vulgare L. 'Nagrad' leaves, where the senescence process was induced by darkness (day 0) and continued until chloroplast degradation (day 12). Using an anti-TGase antibody, we detected on a subcellular level, the ChlTGases that were associated with destacked/degraded thylakoid membranes, and beginning on day 5, were also found in the stroma. Colorimetric and radiometric assays revealed during senescence an increase in ChlTGases enzymatic activity. The MS/MS identification of plastid proteins conjugated with exogenous polyamines had shown that the ChlTGases are engaged in the post-translational modification of proteins involved in photosystem organization, stress response, and oxidation processes. We also computationally identified the cDNA of Hv-Png1-like, a barley homologue of the Arabidopsis AtPng1 gene. Its mRNA level was raised from days 3 to 10, indicating that transcriptional regulation controls the activity of barley ChlTGases. Together, the presented results deepen our knowledge of the mechanisms of the events happened in dark-induced senescence of barley leaves that might be activation of plastid transglutaminases.


Cellular Senescence/radiation effects , Hordeum/enzymology , Plant Leaves/physiology , Plant Proteins/metabolism , Plastids/enzymology , Transglutaminases/metabolism , Darkness , Hordeum/genetics , Hordeum/physiology , Hordeum/radiation effects , Plant Leaves/enzymology , Plant Leaves/genetics , Plant Leaves/radiation effects , Plant Proteins/genetics , Plastids/genetics , Plastids/radiation effects , Transglutaminases/genetics
7.
J Math Biol ; 71(3): 713-33, 2015 Sep.
Article En | MEDLINE | ID: mdl-25266056

Density dependent Markov population processes with countably many types can often be well approximated over finite time intervals by the solution of the differential equations that describe their average drift, provided that the total population size is large. They also exhibit diffusive stochastic fluctuations on a smaller scale about this deterministic path. Here, it is shown that the individuals in such processes experience an almost deterministic environment. Small groups of individuals behave almost independently of one another, evolving as Markov jump processes, whose transition rates are prescribed functions of time. In the context of metapopulation models, we show that 'individuals' can represent either patches or the individuals that migrate among the patches; in host-parasite systems, they can represent both hosts and parasites.


Models, Biological , Population Density , Animals , Computer Simulation , Host-Pathogen Interactions , Humans , Markov Chains , Mathematical Concepts , Population Dynamics , Stochastic Processes
8.
Transplant Proc ; 43(8): 2991-3, 2011 Oct.
Article En | MEDLINE | ID: mdl-21996207

OBJECTIVE: Urinary tract infection (UTI) is among the most common infections in solid organ transplantation, especially in kidney transplantation. PATIENTS AND METHODS: This study included 295 adult patients undergoing KTx between September 2001 and December 2007. All patients were followed prospectively for UTI during the first 4 weeks after surgery. Samples of urine were investigated by bacteriological cultures to identify microorganisms in accord with standard procedures. Susceptibility testing was performed using Clinical and Laboratory Standards Institute procedures. RESULTS: Urine specimens (n=582) were obtained from 84.5% of 245 recipients during the first month after transplantation. Among the isolated bacterial strains (n=291), the most common were Gram-negative bacteria (56.4%) predominantly Serratia marcescens (32.3%) and Enterobacter cloacae (14.6%). Extended- spectrum beta-lactamase (ESBL+) strains were isolated in 52.5% of cases. Gram-positive bacteria comprised 35.7%; most commonly, high-level aminoglycoside resistant (HLAR; 87.8%) and vancomycin-resistant (VRE; 11%) Enterococci. There were fungal strains in 23 cases (7.9%). CONCLUSION: Our study showed predominantly Gram-negative rods from the Enterobacteriaceae family comprising (84.8%) of Gram-negative isolates: 52.5% ESBL and resistant enterococci (87.5%) in Gram-positive isolates. The increased proportion of isolates of multi-drug-resistant bacterial agents which can cause severe UTIs may be due to our frequent use of ceftriaxone for perioperative bacterial prophylaxis.


Kidney Transplantation/adverse effects , Urinary Tract Infections/etiology , Adult , Bacteriuria/drug therapy , Bacteriuria/etiology , Bacteriuria/microbiology , Drug Resistance, Multiple, Bacterial , Enterobacter cloacae , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/etiology , Enterobacteriaceae Infections/microbiology , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mycoses/drug therapy , Mycoses/etiology , Mycoses/microbiology , Prospective Studies , Risk Factors , Serratia Infections/drug therapy , Serratia Infections/etiology , Serratia Infections/microbiology , Serratia marcescens , Time Factors , Urinary Tract Infections/drug therapy , Urinary Tract Infections/microbiology
9.
Transplant Proc ; 43(8): 3052-4, 2011 Oct.
Article En | MEDLINE | ID: mdl-21996222

BACKGROUND: We performed an analysis of etiologic agents for urinary tract infections in the early posttransplant period after orthotopic liver transplantation (OLT) in adult recipients. PATIENTS AND METHODS: The study covered the first 4 weeks after OLT of 190 patients from September 2001 to the end of 2007. Immunosuppression consisted of steroids and tacrolimus. Antimicrobial prophylaxis was piperacillin/tazobactam, fluconazole, and SBD. Urine samples were cultured to identify microorganisms in accord with standard microbiological procedures and to test susceptibility using Clinical Laboratory and Standards Institute guidelines. RESULTS: Urine specimens (n=539) examined from 185 recipients (97.4%) showed 210 microbial strains. The most common were Gram-negative (n=131; 62.4%) with predominance of Escherichia coli (28.2%), Enterobacter cloacae (19.1%), and Acinetobacter baumannii (11.4%). Extended-spectrum ß- lactamases (ESBL(+)) strains were isolated in 38.5% of cases. Gram-positive bacteria comprised 28.6% (n=60): The most common strains were enterococci (85% including HLAR 80.4% and VRE 17.6%] and staphylococci 11.8% [MRSA/MRCNS; 100%]. There were 19 (9%) fungal strains. CONCLUSIONS: In general, the identification in urine samples of multi-drug-resistant bacterial and fungal strains in patients after OLT such as ESBL(+) 38.5%; HLAR 80.4%; VRE 17.6%; and MRSA/MRCNS 100% requires better infection control.


Liver Transplantation/adverse effects , Postoperative Complications/etiology , Urinary Tract Infections/etiology , Adult , Bacterial Infections/etiology , Bacterial Infections/microbiology , Drug Resistance, Multiple, Bacterial , Drug Resistance, Multiple, Fungal , Female , Humans , Male , Middle Aged , Mycoses/etiology , Mycoses/microbiology , Postoperative Complications/microbiology , Prospective Studies , Risk Factors , Time Factors , Urinary Tract Infections/microbiology
10.
Int J Mol Med ; 25(5): 777-83, 2010 May.
Article En | MEDLINE | ID: mdl-20372822

Human papillomavirus (HPV)-mediated transformation of human epithelial cells has been recognized as a multi-step process in which additional unknown factors and (epi)genetic events are required. The tumor susceptibility gene 101 (TSG101) was discovered in mouse NIH3T3 fibroblast cells as a gene whose functional knockout leads to transformation. TSG101 protein is involved in a variety of important biological functions, such as ubiquitination, transcriptional regulation, endosomal trafficking, virus budding, proliferation and cell survival. It is suggested that TSG101 is an important factor for maintaining cellular homeostasis and that perturbation of TSG101 functions leads to cell transformation. Interestingly, a recent report showed up- or down-regulation of TSG101 in several human malignancies. At present, the role of TSG101 in cervical tumorigenesis is unexplained. TSG101 expression in tumors, where carcinogenesis is connected with viral infection, and a mechanism of TSG101 expression regulation in cancer cells are also unknown. The aim of our study was to estimate the TSG101 mRNA and protein level in cervical cancer and non-tumor epithelial cells. We also analyzed the TSG101 coding and promoter sequence using the PCR-SSCP technique and methylation pattern of the TSG101 promoter. Our real-time PCR and Western blot analysis showed decreased TSG101 mRNA and protein level in cervical cancer tissue in comparison to normal (non-tumor) HPV(-) and HPV16(+) epithelial cells. Our results suggest that TSG101 down-regulation in cervical cancer cells is not regulated by genetic or epigenetic events. However, we detected novel single nucleotide polymorphisms in the promoter of this gene.


DNA-Binding Proteins/genetics , Endosomal Sorting Complexes Required for Transport/genetics , Transcription Factors/genetics , Uterine Cervical Neoplasms/genetics , Adult , Aged , Animals , Cell Transformation, Neoplastic/genetics , DNA-Binding Proteins/metabolism , Endosomal Sorting Complexes Required for Transport/metabolism , Female , Gene Expression Regulation, Neoplastic , Human papillomavirus 16/genetics , Humans , Mice , Middle Aged , NIH 3T3 Cells , Polymorphism, Single Nucleotide , Polymorphism, Single-Stranded Conformational , Promoter Regions, Genetic , Transcription Factors/metabolism , Uterine Cervical Neoplasms/virology , Young Adult
11.
Transplant Proc ; 41(8): 3143-7, 2009 Oct.
Article En | MEDLINE | ID: mdl-19857697

OBJECTIVE: This study evaluated the frequency of microbial isolates and their susceptibility profiles among cultures from the "surgical site" of 26 simultaneous pancreas-kidney (SPKT) recipients in the early posttransplant period. PATIENTS AND METHODS: Data on microbiologic cultures of 26 adult patients undergoing SPKT were collected prospectively from 2001 to the end of 2006. The isolation and identification of cultured micro-organisms was performed according to standard microbiological procedures and commercially available tests. Susceptibility of the strains to antibacterial agents was made by the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: All patients were followed prospectively for the first 4 weeks after surgery yielding 168 microbial isolates from the surgical site. The most commonly isolated organisms were Gram-positive bacteria (65.5%) with domination of staphylococci (52.7%) as methicillin-resistant S aureus and methicillin-resistant coagulase-negative staphylococci. The second most common were enterococci (33.6%) with the presence of an high level aminoglycoside-resistant strains (64.9%) and vancomycin-resistant strains (2.7%). Gram-negative bacteria comprised 19% of positive cultures; among them were isolated extended spectrum beta-lactamase producers and carbapenem-resistant strains. Yeast-like fungi comprised 15.5% of positive cultures. In conclusion, we observed predominantly Gram-positive bacteria, comprising 65.5% of isolates. The increased proportion of multi-drug-resistant bacterial isolates may be due to the frequent prophylaxis of bacterial infections in patients.


Kidney Transplantation/adverse effects , Pancreas Transplantation/adverse effects , Postoperative Complications/microbiology , Surgical Wound Infection/drug therapy , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Cadaver , Drug Resistance, Multiple , Female , Gram-Positive Bacterial Infections/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Infusions, Intravenous , Kidney Transplantation/immunology , Male , Methicillin-Resistant Staphylococcus aureus , Middle Aged , Pancreas Transplantation/immunology , Postoperative Complications/drug therapy , Postoperative Complications/epidemiology , Staphylococcal Infections/drug therapy , Surgical Wound Infection/epidemiology , Tissue Donors
12.
Transplant Proc ; 41(8): 3148-50, 2009 Oct.
Article En | MEDLINE | ID: mdl-19857698

OBJECTIVE: Urinary tract infection (UTI) is among the common infection in simultaneous pancreas-kidney transplantation (SPKT). PATIENTS AND METHODS: The study included 26 adult patients undergoing SPKT between September 2001 and December 2006. All the patients were followed prospectively for UTI during the first 4 weeks after surgery. Urine samples were investigated for bacteriologic cultures. The micro-organisms were identified in accordance with standard bacteriologic procedures. Susceptibility testing was carried out using Clinical and Laboratory Standards Institute (CLSI) procedures. RESULTS: Among 77 urine specimens obtained from all recipients during the first month, there were 30 isolated bacterial strains. The most common were Gram-positive bacteria (53.3%) with predominance of enterococci (75%) associated with high levels of aminoglycoside resistant strains (HLAR; 58.3%) and vancomycin-resistant strains (VRE; 25%). Gram-negative bacteria were detected in 46.7% of positive cultures. CONCLUSIONS: In our study, enterococci predominated as 75% of Gram-positive isolates. The increased proportion of multi-drug-resistant bacteria, which can caused severe UTI in patients after SPKT, may be due to the frequent use of prophylaxis of bacterial infections in patients.


Kidney Transplantation/adverse effects , Pancreas Transplantation/adverse effects , Urinary Tract Infections/epidemiology , Adult , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Cadaver , Drug Resistance, Bacterial , Female , Gram-Positive Bacteria/isolation & purification , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Male , Microbial Sensitivity Tests , Middle Aged , Pancreas Transplantation/immunology , Tissue Donors
13.
Transplant Proc ; 41(8): 3151-3, 2009 Oct.
Article En | MEDLINE | ID: mdl-19857699

BACKGROUND: Bacteremia is among the known complications in simultaneous pancreas-kidney transplantation (SPKT). This study evaluated the frequency of microbial isolates and their susceptibility profiles among cultures of clinical samples obtained from blood and from the tips of blood vessel catheters of 26 SPKT recipients suspected of bacteremia in the early posttransplant period. PATIENTS AND METHODS: Data on microbiologic blood cultures of 26 adult patients undergoing SPKT were collected prospectively from 2001 to the end of 2006. The isolation and identification of cultured microorganisms were performed according to standard microbiological procedures and commercially available tests. The susceptibility of the strains to antibacterial agents was established by the Clinical and Laboratory Standards Institute guidelines. RESULTS: All patients were followed prospectively for the first 4 weeks after surgery. Among 66 clinical samples, there were 23 microbial isolates from blood samples of 17 recipients and catheter tips of 12 recipients. The most common isolates were Gram-positive bacteria (73.9%) with domination of staphylococci (64.7%) and MRCNS strains (81.8%). Gram-negative bacteria comprised 17.4% of positive cultures, whereas yeast-like fungi, 8.7% with a predominance of Candida glabrata. CONCLUSION: Our study showed predominately Gram-positive bacteria in 73.9% of isolates. The increased proportion of multi-drug-resistant bacteria and fungi to antimicrobial agents may be due to the frequent use of these agents for prophylaxis of bacterial infections in patients.


Anti-Bacterial Agents/therapeutic use , Bacteremia/epidemiology , Kidney Transplantation/adverse effects , Pancreas Transplantation/adverse effects , Adult , Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , Bacteremia/etiology , Female , Gram-Positive Bacteria/isolation & purification , Humans , Immunosuppressive Agents/therapeutic use , Male , Methicillin-Resistant Staphylococcus aureus , Middle Aged , Mycophenolic Acid/therapeutic use , Postoperative Period , Retrospective Studies , Staphylococcus/drug effects
14.
Xenobiotica ; 39(6): 476-85, 2009 Jun.
Article En | MEDLINE | ID: mdl-19480553

The pharmacokinetics of ibuprofen enantiomers and its chiral metabolites, namely (R,S)-29-hydroxyibuprofen and (RR,RS,SR,SS)-29-carboxyibuprofen, was studied in healthy volunteers carrying different alleles coding cytochrome P450 (CYP) 4502C isoenzymes. Following administration of 400 mg of racemic ibuprofen, enantiomers of the parent compound and their metabolites were isolated from plasma and urine samples using solid-phase extraction and were quantified by the validated capillary zone electrophoresis method. The levels of the analytes in biological fluids were used to calculate their pharmacokinetic parameters in subjects with different variants of CYP2C8 and CYP2C9 isoenzymes. The analysis of each subject's genotype was carried out using polymerase chain reaction-restriction fragment length polymorphism. Impaired metabolism of ibuprofen enantiomers was associated with the presence of CYP2C8*3, CYP2C9*2 and CYP2C9*3 alleles. The greatest effect of mutated alleles on pharmacokinetics was observed in a subject with a CYP2C8*1/*3, CYP2C9*1/*2 genotype. This subject appeared to have lower value of clearance, greater area under the curve (AUC) and longer time t(0.5) in comparison with the wild-type.


Aryl Hydrocarbon Hydroxylases/genetics , Genetic Variation , Ibuprofen/chemistry , Ibuprofen/pharmacokinetics , Adolescent , Adult , Alleles , Cytochrome P-450 CYP2C8 , Cytochrome P-450 CYP2C9 , Electrophoresis, Capillary , Female , Genotype , Humans , Ibuprofen/blood , Ibuprofen/urine , Isoenzymes/genetics , Male , Middle Aged , Reproducibility of Results , Solid Phase Extraction , Stereoisomerism
15.
Biomed Pharmacother ; 63(4): 262-6, 2009 May.
Article En | MEDLINE | ID: mdl-18602794

Epidemiological and experimental evidence implicates estrogens in the etiology and progression of breast cancer. The biosynthesis of estrogens from androgens is catalyzed by an enzymatic complex designated as aromatase (CYP19). Using quantitative real-time PCR and Western blot analysis, we demonstrated that trichostatin A (TSA) histone deacetylase inhibitor significantly reduced CYP19 transcript and protein contents in MCF-7 breast cancer cells. We also found that TSA lowered CYP19 transcript stability and significantly decreased the transcript's half-life from approximately 6h to 3.5h. Our results from experiments with a protein biosynthesis inhibitor suggest the involvement of an RNase and/or mRNA stabilization protein in CYP19 transcript stabilization. Since malignant tissue aromatase is a significant estrogen producer involved in breast tumor progression, our findings may have clinical implication.


Adenocarcinoma/pathology , Antineoplastic Agents, Hormonal/pharmacology , Aromatase Inhibitors/pharmacology , Aromatase/biosynthesis , Breast Neoplasms/pathology , Gene Expression Regulation, Neoplastic/drug effects , Hydroxamic Acids/pharmacology , Neoplasm Proteins/biosynthesis , Adenocarcinoma/metabolism , Aromatase/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor/drug effects , Down-Regulation/drug effects , Female , Half-Life , Histone Deacetylase Inhibitors , Humans , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/genetics , RNA Stability/drug effects , RNA, Messenger/drug effects , RNA, Neoplasm/drug effects
16.
Mycoses ; 52(3): 263-5, 2009 May.
Article En | MEDLINE | ID: mdl-18705664

Trichosporon spp. is not an important factor of mycotic infections in immunocompetent patients. It may be a cause of invasive mycoses with a high mortality rate in patients undergoing solid organ transplantation. We have analysed the antifungal agents' susceptibility of Trichosporon asahii and its frequency of occurrence as a prospective etiological agent of infections in liver, kidney and simultaneous pancreas-kidney transplant recipients. Clinical specimens (urine, blood, peritoneal fluid and swabs) were obtained from patients hospitalised in the Institute of Transplantation Medicine, Department of General and Transplantation Surgery, Medical University of Warsaw in 2005 and 2006. Microbiological tests were performed in Mycological Laboratory, Department of Microbiology, Medical University of Warsaw. A total of 475 strains of yeast-like fungi were isolated from clinical specimens taken from 263 liver, kidney and simultaneous pancreas-kidney transplant recipients and from 26 organ donors. Trichosporon asahii was found in 26 clinical samples taken from 18 patients and one organ donor. Positive cultures were obtained from 22 urine samples, one stoma fluid, one wound swab, one tracheal aspirate and one ejaculate. Isolates of Trichosporon asahii were found in 6% of total positive mycological cultures in the solid organ transplant recipients. Among cultured strains, 11 isolates were resistant to fluconazole, four to itraconazole and three of them demonstrated resistance to amphotericin B.


Kidney Transplantation , Liver Transplantation , Mycoses/microbiology , Mycoses/transmission , Pancreas Transplantation , Postoperative Complications/microbiology , Transplants/microbiology , Trichosporon/isolation & purification , Antifungal Agents/pharmacology , Drug Resistance, Fungal , Humans , Trichosporon/drug effects
17.
Transplant Proc ; 39(9): 2800-6, 2007 Nov.
Article En | MEDLINE | ID: mdl-18021991

OBJECTIVE: This study evaluated the frequency of microbial isolates and their susceptibility profiles from cultures at the surgical site of 83 liver recipients in the early posttransplantation period. PATIENTS AND METHODS: We prospectively collected microbiologic culture data on 83 adult patients undergoing orthotopic liver transplantation (OLT) using standard procedures and commercially available tests. Susceptibility of the strains to antibacterial agents was performed by the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: All patients were followed prospectively for the first 4 weeks after surgery. Among 284 microbial isolates from clinical surgical site samples in 80 liver recipients, cultures were positive in 110 samples. The most commonly isolated species were: Gram-positive cocci (n = 222 isolates, 78%) with dominance of methicillin-resistant coagulase-negative staphylococci (MRCNS; 42%) and high-level aminoglycoside-resistant enterococci (HLAR strains; 24.3%). Gram-negative bacteria were identified in 21.5% of positive cultures, including 30 strains (24%) from the Enterobacteriaceae family, with 13.3% of extended spectrum beta-lactamase producers [ESBL(+)]. Significant differences (P = .0012) were observed during the analysis of changes in the occurrence of Gram-positive bacteria isolated from the surgical site in the first week versus the second to the end of the fourth week. CONCLUSION: Gram-positive bacteria predominated as 78% of isolates.


Liver Transplantation/adverse effects , Surgical Wound Infection/epidemiology , Adolescent , Adult , Aged , Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Negative Bacterial Infections/epidemiology , Gram-Positive Bacteria/drug effects , Gram-Positive Bacterial Infections/epidemiology , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Postoperative Period , Retrospective Studies , Staphylococcal Infections/drug therapy , Staphylococcal Infections/epidemiology , Staphylococcus/drug effects , Surgical Wound Infection/etiology
18.
Transplant Proc ; 39(9): 2807-11, 2007 Nov.
Article En | MEDLINE | ID: mdl-18021992

OBJECTIVE: We estimated the frequency and susceptibility to antibacterial agents of bacterial isolates from bile samples obtained from 83 liver recipients in the early period after transplantation. PATIENTS AND METHODS: We prospectively collected data on 83 adult patients undergoing orthotopic liver transplantation (OLT), including bile samples taken during the first 30 days after OLT from adult liver recipients suspected to have bile infections. The isolation/identification of cultured bacteria was performed according to standard microbiological procedures and commercially available tests. Susceptibility of the strains to antibacterial agents was determined according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: Among 210 bile samples obtained from 79 liver recipients, bacterial cultures were positive in 110 samples from 59 (75%) recipients yielding 156 bacterial strains. The most commonly isolated species were as follows: gram-positive cocci (109 isolates) with dominance of coagulase-negative staphylococci (52%) and enterococci (36%); and gram-negative bacteria, 21 strains from the Enterobacteriaceae family and 14 of non-fermenting rods. We identified some multidrug-resistant (MDR) bacterial strains. In the first week after OLT, we investigated samples from 59 patients, yielding 36 bacterial strains. From the second to the end of the fourth week after OLT, 120 bacterial strains were isolated from 65 recipients. CONCLUSION: Gram-positive bacteria comprised 68.5%. The dominance of MDR gram-positive bacteria may be related to selection by perioperative antibiotic prophylaxis.


Bacteria/isolation & purification , Bacterial Infections/epidemiology , Bile/microbiology , Liver Transplantation/adverse effects , Adolescent , Adult , Aged , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Female , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Postoperative Period
19.
Transplant Proc ; 39(9): 2812-5, 2007 Nov.
Article En | MEDLINE | ID: mdl-18021993

OBJECTIVE: We examined the frequency of detection of Clostridium difficile (CD) toxins compared with the recovery of C. difficile in stool specimen cultures among orthotopic liver transplant (OLT) patients with nosocomial diarrhea in the early period. MATERIALS AND METHODS: The study included stool samples obtained during the first 30 days after OLT in adults who were suspected of CD-associated diseases. The identification of cultured CD strains was performed by standard microbiological methods. The presence of CD toxins was assayed using a commercial immunoassay. RESULTS: All patients were followed prospectively for CD infections from the date of OLT for the first 4 weeks after surgery. Among 54 samples, 16.7% were culture-positive for CD. CD toxins were tested on 54 samples, yielding 63% toxin-positive samples and 30% toxin- and culture-negative results. In the first week after OLT, samples from 19 patients were subjected to CD investigation. Among 19 samples positive for toxin, 52.6% of all samples were culture-negative. We analyzed 35 samples from the second to the fourth week after OLT in 31 recipients. Among 35 samples, 68.6% and 25.7% were positive for CD toxin and for culture, while 20% of samples were negative for toxin and culture. CONCLUSION: In our study, 63% of samples were toxin-positive with 16.7% yielding growth of CD and 30% being negative for toxins and cultures.


Clostridioides difficile/isolation & purification , Enterocolitis, Pseudomembranous/epidemiology , Feces/microbiology , Liver Transplantation/adverse effects , Postoperative Complications/microbiology , Adult , Aged , Bacterial Toxins/analysis , Cross Infection/epidemiology , Cross Infection/microbiology , Enterotoxins/analysis , Female , Humans , Male , Middle Aged , Postoperative Period , Retrospective Studies
20.
Transplant Proc ; 39(9): 2816-21, 2007 Nov.
Article En | MEDLINE | ID: mdl-18021994

Bacteremia is one of the major infections in orthotopic liver transplantation (OLT). The study of 83 adults who underwent OLT from 2001 to 2004, included patients followed prospectively from the day of transplantation to 4 weeks after the procedure by bacteriological cultures. The microorganisms were investigated according to standard National Committee for Clinical Laboratory Standards (NCCLS) procedures. Blood samples were examined in 59 recipients (71.1%) before and in 76 patients (91.6%) during the month after transplantation. Among 249 investigated samples, 96 were positive, as cultured from 19 recipients before OLT and 48 patients afterward. The most common were Gram-positive cocci (n = 71) and coagulase-negative staphylococci (n = 52), including methicillin-resistant coagulase-negative staphylococci (MRCNS). Enterococcus spp. occurred in 9 isolates (high-level aminoglycoside-resistant enterococci [HLAR] strains were cultured). We cultured the Enterobacteriaceae family (n = 16 isolates) and (n = 15 isolates), Gram-negative nonfermenting rods some of which were extended spectrum beta-lactamase producing [ESBL(+)] strains. The predominance of Gram-positive cocci was caused by CNS, and the use of prophylaxis to reduce Gram-negative bacteria. The increased rate of isolation of bacteria with multidrug resistance (MDR) to antimicrobial agents may be due to their frequent use for prophylaxis of bacterial infections in OLT. These MDR bacterial strains caused severe BSI after OLT.


Bacteremia/etiology , Liver Transplantation/adverse effects , Adolescent , Adult , Aged , Bacteremia/epidemiology , Bacteria/classification , Bacteria/isolation & purification , Cadaver , Enterobacter/classification , Enterobacter/isolation & purification , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/epidemiology , Gram-Positive Bacteria/isolation & purification , Gram-Positive Bacterial Infections/epidemiology , Humans , Middle Aged , Mycoses/epidemiology , Postoperative Period , Retrospective Studies , Tissue Donors
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