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2.
Anaesthesiol Intensive Ther ; 55(5): 319-325, 2023.
Article in English | MEDLINE | ID: mdl-38282497

ABSTRACT

INTRODUCTION: Patients after major surgery are at high risk of developing sepsis, which is accompanied by elevated serum levels of C-reactive protein (CRP) and procalcitonin (PCT). This study aimed to examine the differences in serum biomarker levels concerning the causative agent of sepsis in surgical patients. MATERIAL AND METHODS: A retrospective study was carried out in the surgical intensive care unit (ICU) and included 81 septic patients admitted from January 2019 to May 2022, who had positive blood cultures (BC). Serum levels of PCT, CRP, white blood cells (WBC) and platelet counts were recorded on the day of the positive BC and over the following 3 days. RESULTS: Patients with gram(-) sepsis had significantly higher PCT levels, and lower platelet count compared to patients with gram(+) sepsis. High PCT and low platelets levels in all measurements were a significant predictor of gram(-) isolate with the highest predictive value on the third day after BC sampling, with AUROC 0.821 (95% CI: 0.692-0.950), P = 0.001, and AUROC 0.676 (95% CI: 0.541-0.811), P = 0.02, respectively. In multivariate logistic regression, platelets the day after BC sampling and PCT on the third day made a significant contribution in distinguishing gam(+) from gram(-) BC. Age and high serum CRP levels were significant predictors of poor outcomes. CONCLUSIONS: PCT and platelets may be useful biomarkers for predicting the causative agent of sepsis in surgical patients.


Subject(s)
Bacteremia , Gram-Negative Bacterial Infections , Sepsis , Humans , Retrospective Studies , Calcitonin , Biomarkers , Sepsis/diagnosis , C-Reactive Protein/analysis , Gram-Negative Bacterial Infections/diagnosis , Procalcitonin , ROC Curve
3.
Diagnostics (Basel) ; 12(11)2022 Nov 04.
Article in English | MEDLINE | ID: mdl-36359529

ABSTRACT

Streptococcus constellatus (SC) is a species of Streptococcus belonging to the Streptococcus anginosus group, along with Streptococcus anginosus and Streptococcus intermedius. Despite its commensal nature, underlying risk factors and medical conditions might lead to various anatomic site infections caused by this opportunistic pathogen. Although SC infections have mostly been associated with bacteremia, some case reports of abscess and empyema formation have been documented. Herein, we report a case of a middle-aged female patient who initially presented with radiculopathy symptoms. Subsequent neurologic imaging revealed a pyogenic abscess along paravertebral muscles, which was found to be caused by SC. The patient was successfully treated with abscess drainage from the lumbar zone and antibiotics, and the symptoms of radiculopathy have completely resolved.

4.
BMJ Case Rep ; 14(9)2021 Sep 21.
Article in English | MEDLINE | ID: mdl-34548297

ABSTRACT

Genital warts (also known as condylomata acuminata) caused by the human papillomavirus (HPV) represent one of the most common sexually transmitted infections. Although they are usually found in the outer genital region, a small proportion of men can present with (often unrecognised) intraurethral warts, generally limited to the distal urethra and urethral meatus. This poses a treatment challenge not adequately addressed by the current guidelines. Here, we present two cases of low-risk HPV-positive patients with protruding and non-protruding condylomata acuminata of the distal urethra, which were treated successfully by using two different topical regimens (ie, a combination of policresulen and imiquimod for one patient and 5-fluorouracil monotherapy for the other). Although this type of management results in lower rates of tissue destruction and complications and may be given preference as an initial therapeutic option, additional prospective comparative clinical studies are needed to elucidate its potential in similar cases.


Subject(s)
Condylomata Acuminata , Sexually Transmitted Diseases , Condylomata Acuminata/drug therapy , Humans , Male , Papillomaviridae , Prospective Studies , Urethra
5.
Future Med Chem ; 13(21): 1865-1884, 2021 11.
Article in English | MEDLINE | ID: mdl-34533068

ABSTRACT

Aim: The aim of this study was to synthesize new coumarin-based compounds and evaluate their antibacterial and antitumor potential. Results: Using transition metal-catalyzed reactions, a series of 7-hydroxycoumarin derivatives were synthesized with aliphatic and aryl moiety attached directly at C-3 of the coumarin ring and through the ethynyl or 1,2,3-triazole linker. The 3-substituted coumarin derivative bearing bistrifluoromethylphenyl at the C-4 position of 1,2,3-triazole (33) showed strong and selective antiproliferative activity against cervical carcinoma cells. The 7-hydroxy-4-methylcoumarin with a phenyl ring directly attached to coumarin at C-3 (10) showed good potency against the methicillin-resistant Staphylococcus aureus and vancomycin-resistant strains. Conclusion: The most active coumarin derivatives owe their antiproliferative potential to the 3,5-ditrifluoromethylphenyl substituent (in 33) and antibacterial activity to the aromatic moiety (in 10); their structure can be optimized further for improved effect.


Subject(s)
Anti-Bacterial Agents/pharmacology , Coumarins/pharmacology , Cytostatic Agents/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Transition Elements/chemistry , Vancomycin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Catalysis , Coumarins/chemical synthesis , Coumarins/chemistry , Cytostatic Agents/chemical synthesis , Cytostatic Agents/chemistry , Humans , Microbial Sensitivity Tests , Molecular Structure
6.
Clin Lab ; 66(12)2020 Dec 01.
Article in English | MEDLINE | ID: mdl-33337847

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) is a major risk factor for cervical dysplasia and invasive cervical cancer; therefore, regular screening by cervical smear cytology or HPV testing is recommended. We aimed to determine the overall and risk group-specific HPV prevalence, age distribution, and temporal trends and to appraise the correlation of HPV positivity with abnormal cervical cytological findings. METHODS: This retrospective, single-center study involved a total of 751 women (aged 18 - 67) concurrently subjected to HPV DNA testing and cervical cytology evaluation over a 10-year period in Zagreb, Croatia. Digene HC2 HPV DNA test (Qiagen Corporation, USA) was employed in screening specimens for both low-risk and high-risk HPV risk groups. The cytology was reported using the Bethesda system and in accordance with uniform classification of uterine cervix cytological findings in Croatia "Zagreb 2002". Statistical significance was set at p < 0.05. RESULTS: The overall HPV prevalence in our study population was 48.6%, and the 18 - 30 age group presented with the highest infection burden (p = 0.046). A decrease in low-risk and high-risk mono-positivity has been observed over the 10-year period; conversely, there was a significant increase in low-risk/high-risk co-positivity (p = 0.007). Low-risk/high-risk HPV co-infection resulted in a compounding effect which increased the occurrence of abnormal cells, HPV-associated changes and low grade squamous intraepithelial lesions (LSIL/cervical intraepithelial neoplasia grade I) in cervical cytology when compared to mono-infection with either low-risk or high-risk HPV. On the other hand, such effect has not been demonstrated for high grade squamous intraepithelial lesions (HSIL/ cervical intraepithelial neoplasia grades II and III). CONCLUSIONS: The overall HPV prevalence in female outpatients was high, underscored with rising co-positivity rates. Such co-infection with both low-risk and high-risk HPV (predominantly seen in women younger than 30) can exhibit a compounding effect in the occurrence of cytological abnormalities and low grade squamous intra-epithelial lesions (LSIL), which has to be considered in future diagnostic and screening algorithms.


Subject(s)
Alphapapillomavirus , Coinfection , Papillomaviridae , Papillomavirus Infections , Uterine Cervical Neoplasms , Adolescent , Adult , Aged , Coinfection/epidemiology , Croatia/epidemiology , Female , Humans , Middle Aged , Papillomaviridae/genetics , Papillomavirus Infections/diagnosis , Papillomavirus Infections/epidemiology , Prevalence , Retrospective Studies , Uterine Cervical Neoplasms/epidemiology , Young Adult
7.
Acta Clin Croat ; 59(1): 126-134, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32724283

ABSTRACT

Recently an increase has been reported in the number of HBV transmissions from anti-HBc positive blood donors that were repeatedly negative in HBsAg and nucleic acid testing using the most sensitive tests available. The aim of the study was to show the effect of anti-HBc antibody testing performed in 2006 on permanent deferral of voluntary blood donors (VBDs), and to estimate occult hepatitis B infection (OBI) rate in this population after the introduction of mandatory molecular testing in the 2013-2016 period. More than 30,000 blood donations collected during the 2005-2007 period and more than 14,000 VBDs having donated blood during the 2013-2016 period after the introduction of molecular testing from eastern Croatia were included in the study. Serologic testing was performed with HBsAg assay throughout the study period, and anti-HBc assay was only performed in 2006. As part of the confirmatory algorithm testing, all HBsAg positive and unclear results were tested with molecular tests. Anti-HBc prevalence among VBDs in 2006 was 1.5%, with a rate of 1:197, whereas HBsAg prevalence was stable from 2005 to 2007 (0.04%, 0.1% and 0.1%, respectively). The calculated OBI rate from 2013 to 2016 was 1:30,250. Ten of 161 (12.4%) VBDs had serologic anti-HBc-only pattern. Anti-HBc testing in 2006 resulted in statistically more deferrals of VBDs compared to 2005 and 2007, and to the rest of Republic of Croatia. The strategy of universal anti-HBc testing of VBDs in addition to the existing HBsAg and molecular screening could be an additional measure to prevent HBV transmission by blood and blood components.


Subject(s)
Blood Donors , Hepatitis B virus , Hepatitis B , Croatia/epidemiology , DNA, Viral , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Hepatitis B virus/genetics , Humans
8.
Med Hypotheses ; 126: 38-41, 2019 May.
Article in English | MEDLINE | ID: mdl-31010496

ABSTRACT

The predominance of the genus Corynebacterium in the healthy male urogenital system contributes to the resident microbiome of not only the distal urethra, but potentially the proximal urethra and urinary bladder as well. However, for certain species in this genus, pathogenic potential was described, and the salient representative is Corynebacterium glucuronolyticum (C. glucuronolyticum) implicated in cases of urethritis and prostatitis in men. Nonetheless, some still question whether C. glucuronolyticum can actually be considered pathogenic or rather just a commensal species fortuitously isolated in patients with urogenital symptoms and/or syndromes. Although pathogen/commensal dichotomy is not always clear-cut, we hypothesize that specific genetic markers may expose C. glucuronolyticum as a convincingly pathogenic Corynebacterium. More specifically, characteristic pathogenic gene constellation inherent to this species (most notably the presence of specific sortase/SpaA-type pili gene clusters, but also the augmentative role of type VII secretion system) may significantly facilitate host tissue adhesion, with subsequent suppression/evasion of the immune response and acquisition of vitally important nutrients. Consequently, these genetic markers differentiate C. glucuronolyticum from its commensal counterparts, and give this species a pathogenic facet, which can be even further influenced by the Allee effect. In this paper we also propose a specific methodological approach on how to analyze C. glucuronolyticum epithelial colonization capacity and explore inceptive host cell-pathogen interactions that manipulate host environment and immune responses. This entails moving from approaches based primarily on overall homology of primary sequences towards specific structure-function studies to precisely evaluate all stakeholders involved in pili assemblage, cell adhesion and the expression of other virulence traits. In the era of high precision medicine, the hypothesized roles of C. glucuronolyticum adhesion systems in both virulence and nutrient acquisition may also reveal promising targets for future drug developments.


Subject(s)
Corynebacterium/genetics , Prostatitis/microbiology , Urethra/microbiology , Urethritis/microbiology , Urinary Bladder/microbiology , Virulence , Corynebacterium/pathogenicity , Genitalia, Male/microbiology , Genome, Bacterial , Host-Pathogen Interactions , Humans , Male , Microbiota , Models, Biological , Phenotype
9.
Microb Drug Resist ; 25(5): 696-702, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30614759

ABSTRACT

The purpose of this study was to report the identification OXA-48 carbapenemase in seven extended-spectrum ß-lactamase (ESBL)-positive Escherichia coli clinical isolates, fully susceptible to all carbapenems by disk diffusion and E-test methods, but with borderline minimal inhibitory concentration (MIC) values of ertapenem. This report points to the necessity for determination of carbapenem MICs in ESBL-positive E. coli isolates and additional phenotypic testing for carbapenemases in all isolates with borderline ertapenem MIC defined by EUCAST. The isolates showed a high level of resistance to expanded-spectrum cephalosporins because of the production of an additional ESBL belonging to CTX-M family. All isolates and their respective tranconjugants were found to possess L plasmid. Pulsed-field gel electrophoresis analysis revealed two clusters containing highly related isolates. The global spread of multidrug-resistant E. coli should be monitored closely because of the ability of isolates to rapidly obtain additional antibiotic resistance traits such as plasmid-mediated OXA-48 genes.


Subject(s)
Drug Resistance, Multiple, Bacterial/genetics , Escherichia coli Infections/epidemiology , Escherichia coli Proteins/genetics , Escherichia coli/genetics , Genes, Bacterial , beta-Lactam Resistance/genetics , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Cephalosporins/pharmacology , Conjugation, Genetic , Croatia/epidemiology , Electrophoresis, Gel, Pulsed-Field , Epidemiological Monitoring , Escherichia coli/classification , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Escherichia coli Infections/drug therapy , Escherichia coli Infections/microbiology , Escherichia coli Proteins/metabolism , Gene Expression , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing , Plasmids/chemistry , Plasmids/metabolism , beta-Lactamases/metabolism
10.
J Enzyme Inhib Med Chem ; 33(1): 1323-1334, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30165753

ABSTRACT

Amidinobenzimidazole derivatives connected to 1-aryl-substituted 1,2,3-triazole through phenoxymethylene linkers 7a-7e, 8a-8e, and 9a-9e were designed and synthesised with the aim of evaluating their anti-bacterial and anti-trypanosomal activities and DNA/RNA binding affinity. Results from anti-bacterial evaluations of antibiotic-resistant pathogenic bacteria revealed that both o-chlorophenyl-1,2,3-triazole and N-isopropylamidine moieties in 8c led to strong inhibitory activity against resistant Gram-positive bacteria, particularly the MRSA strain. Furthermore, the non-substituted amidine and phenyl ring in 7a induced a marked anti-bacterial effect, with potency against ESBL-producing Gram-negative E. coli better than those of the antibiotics ceftazidime and ciprofloxacin. UV-Vis and CD spectroscopy, as well as thermal denaturation assays, indicated that compounds 7a and 8c showed also binding affinities towards ctDNA. Anti-trypanosomal evaluations showed that the p-methoxyphenyl-1,2,3-triazole moiety in 7b and 9b enhanced inhibitory activity against T. brucei, with 8b being more potent than nifurtimox, and having minimal toxicity towards mammalian cells.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/pharmacology , Benzimidazoles/metabolism , Benzimidazoles/pharmacology , DNA/metabolism , RNA/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/metabolism , Benzimidazoles/chemical synthesis , Benzimidazoles/chemistry , Dose-Response Relationship, Drug , Escherichia coli/drug effects , Microbial Sensitivity Tests , Molecular Structure , Parasitic Sensitivity Tests , Structure-Activity Relationship , Trypanosoma brucei brucei/drug effects
11.
J Med Microbiol ; 67(8): 1031-1041, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29927373

ABSTRACT

PURPOSE: A dramatic increase in OXA-48 ß-lactamase was observed recently not only in large hospital centres, but also in smaller suburban hospital centres in geographic areas bordering Croatia. The aim of the study was to analyse the epidemiology, the mechanisms of antibiotic resistance and the routes of spread of OXA-48 carbapenemase in Croatia. METHODS: Carbapenemase and other ß-lactamase and fluoroquinolone resistance genes were detected by PCR and sequencing. Whole-genome sequencing (WGS) was performed on five representative isolates. The isolates were genotyped by PFGE. RESULTS: Forty-eight isolates positive for OXA-48, collected from seven hospital centres in Croatia from May 2016 to May 2017, were analysed (40 Klebsiella pneumoniae, 5 Enterobacter cloacae, 2 Escherichia coli and one Citrobacter freundii). Thirty-three isolates were ESBL positive and harboured group 1 CTX-M 1 ß-lactamases. In addition to the ß-lactam resistance genes detected by PCR (blaSHV-1, blaOXA-48 and blaOXA-1), WGS of five representative isolates revealed the presence of genes encoding aminoglycoside resistance, aadA2 and aph3-Ia, fluoroquinolone resistance determinants aac(6)Ib-c, oqxA and oqxB, the sulfonamide resistance gene sul1, and fosA (fosfomycin resistance). IncL plasmid was found in all isolates. Two K. pneumoniae isolates belonged to ST16, two E. cloacae to ST66 and E. coli to ST354. K. pneumoniae isolates were allocated to five clusters by PFGE which occured in different hospitals, indicating epidemic spread. CONCLUSIONS: The OXA-48-positive organisms found in this study showed wide variability in antibiotic susceptibility, ß-lactamase content and PFGE banding patterns. This study revealed a switch from the predominance of VIM-1 in 2012-2013 to that of OXA-48 in the 2015 to 2017.


Subject(s)
Drug Resistance, Bacterial/genetics , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae/enzymology , Plasmids/genetics , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Croatia/epidemiology , Electrophoresis, Gel, Pulsed-Field , Enterobacteriaceae/genetics , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/microbiology , Escherichia coli Proteins/genetics , Genotype , Hospitals , Humans , Microbial Sensitivity Tests , Whole Genome Sequencing , beta-Lactam Resistance/genetics
12.
J Chemother ; 30(1): 16-24, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28956494

ABSTRACT

The ability of A cinetobacter baumannii strains to form biofilm is one of the most important virulence factor which enables bacterial survival in a harsh environment and decreases antibiotic concentration as well. Subminimal inhibitory concentrations (subMICs) of antibiotics may change bacterial ultrastructure or have an influence on some different molecular mechanisms resulting in morphological or physiological changes in bacteria itself. The aim of this study was to determine effects of 1/2, 1/4, 1/8 and 1/16 minimal inhibitory concentrationsof imipenem, ampicillin-sulbactam, azithromycin, rifampicin and colistin on biofilm formation ability of 22 biofilm non-producing and 46 biofilm producing A. baumannii strains (30 weak producing strains and 16 moderate producing strains). Results of this study indicate that 1/2-1/16 MICs of imipenem, azithromycin, and rifampicin can reduce bacterial biofilm formation ability in moderate producing strains (p < 0.05), whereas 1/16 MIC of imipenem and 1/4-1/8 MICs of rifampicin reduce the biofilm formation in weak producing strains (p < 0.05). Statisticaly significant effect was detected among biofilm non-producing strains after their exposure to 1/16 MIC of azithromycin (p = 0.039). SubMICs of ampicillin-sulbactam and colistin did not have any significant effect on biofilm formation among tested A. baumannii strains.


Subject(s)
Acinetobacter baumannii/physiology , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Ampicillin/pharmacology , Azithromycin/pharmacology , Colistin/pharmacology , Imipenem/pharmacology , Microbial Sensitivity Tests , Rifampin/pharmacology , Sulbactam/pharmacology
13.
Acta Clin Croat ; 57(3): 473-479, 2018 Sep.
Article in English | MEDLINE | ID: mdl-31168180

ABSTRACT

- This study aimed to investigate the impact of posture and anesthesia techniques on blood pressure changes, heart rate and regional cerebral oxygen saturation during shoulder arthroscopy in the beach chair position (BCP). Sixty patients were included in this prospective cohort study: 30 patients mechanically ventilated and subjected to general anesthesia (GA) and 30 patients subjected to interscalene block (ISB) without mechanical ventilation. Noninvasive blood pressure, heart rate (HR), peripheral blood oxygen saturation and regional oxygen saturation of the brain were measured in twelve predefined points during perioperative period. The GA group patients had significantly lower mean arterial pressure and heart rate values compared to patients in ISB group during BCP (p<0.001). There was a significant difference in regional cerebral saturation between the groups measured only in points of induction and emergence from anesthesia in favor of GA group when receiving 100% oxygen (p<0.001). Changes in the mean arterial pressure and regional cerebral oxygen saturation for both brain hemispheres correlated only at the 10th minute after setting up BCP in GA patients (right, p=0.004 and left, p=0.003). This correlation did not exist in the ISB group patients at any of the points measured. Cerebral desaturation events recorded in both groups were not statistically significantly different. Results of this study demonstrated that GA preserved regional cerebral oxygenation in a safe range during BCP despite changes in the arterial blood pressure and heart rate in comparison to ISB.


Subject(s)
Anesthesia, General , Heart Rate , Nerve Block , Oxygen Consumption , Patient Positioning/methods , Shoulder/diagnostic imaging , Adult , Aged , Anesthesia, General/adverse effects , Anesthesia, General/methods , Arthroscopy/methods , Blood Pressure Determination/methods , Brain/metabolism , Female , Humans , Male , Middle Aged , Nerve Block/adverse effects , Nerve Block/methods , Outcome Assessment, Health Care , Prospective Studies
14.
Med Glas (Zenica) ; 14(1): 85-90, 2017 Feb 01.
Article in English | MEDLINE | ID: mdl-27917855

ABSTRACT

Aim To identify and investigate a difference between microorganisms present on intensive care unit (ICU) health care workers' (HCW, doctors, nurses or medical technicians) and medical students' mobile phones as well as to investigate a difference between the frequency and the way of cleaning mobile phones. Methods Fifty swabs were collected from HCWs who work in the ICU (University Hospital Centre Osijek) and 60 swabs from medical students (School of Medicine, University of Osijek). Microorganisms were identified according to standard microbiological methods and biochemical tests to the genus/species level. Results Out of 110 processed mobile phones, mobile phones microorganisms were not detected on 25 (22.7%), 15 (25%) students' and 10 (20%) HCW's mobile phones. No statistically significant difference was found between the number of isolated bacteria between the HCW' and students' mobile phones (p>0.05). Statistically significant difference was found between both HCW and students and frequency of cleaning their mobile phones (p<0.001). A significant difference was also obtained with the way of cleaning mobile phones between HCWs and students (p<0.001). Conclusion The most common isolated microorganisms in both groups were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus. Most HCWs cleaned their mobile phones at least once a week, 35 (52.0%), and most medical students several times per year, 20 (33.3%). HCW clean their mobile phones with alcohol disinfectant in 26 (40.0%) and medical students with dry cloth in 20 (33.3%) cases.


Subject(s)
Bacteria/isolation & purification , Decontamination/methods , Fomites/microbiology , Fomites/statistics & numerical data , Adult , Bacteria/classification , Cell Phone , Community-Acquired Infections/microbiology , Community-Acquired Infections/prevention & control , Equipment Contamination/statistics & numerical data , Female , Health Personnel , Humans , Intensive Care Units , Male , Middle Aged , Students, Medical , Tertiary Care Centers , Young Adult
15.
Eur J Med Chem ; 124: 794-808, 2016 Nov 29.
Article in English | MEDLINE | ID: mdl-27639370

ABSTRACT

The 4-substituted 1,2,3-triazole core in designed coumarin hybrids (4-35) with diverse physicochemical properties was introduced by eco-friendly copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition under microwave irradiation. Coumarin-1,2,3-triazole-benzofused heterocycle hybrids emerged as the class of compounds exhibiting the highest antiproliferative activity. The strong relationship between lipophilicity and antiproliferative activities was observed indicating that lipophilic 1,2,3-triazole-coumarin hybrids containing phenylethyl (13), 3,5-difluorophenyl (14), 5-iodoindole (30) and benzimidazole (33 and 35) subunits showed the most potent cytostatic effects. The 7-methylcoumarin-1,2,3-triazole-2-methylbenzimidazole hybrid 33 can be highlighted as a lead that exerted the highest cytotoxicity against hepatocellular carcinoma HepG2 cells with IC50 value of 0.9 µM and high selectivity (SI = 50). This compound induced cell death, mainly due to early apoptosis. Strong antiproliferative effect of 33 could be associated with its inhibition of 5-lipoxygenase (5-LO) activity and perturbation of sphingolipid signaling by interfering with intracellular acid ceramidase (ASAH) activity. Outlined considerable effect of lipophilicity on antiproliferative activity was not observed for antibacterial activity. The compounds with p-pentylphenyl (17), 2-chloro-4-fluorobenzenesulfonamide (23) and dithiocarbamate (27) moiety were endowed with high selectivity against Enterococcus species. Moreover, these compounds were found to be superior in inhibiting the growth of clinically isolated vancomycin-resistant Enterococcus faecium, while the reference antibiotics exhibited the lack of activity. Our findings indicate that coumarin-1,2,3-triazole could be used as the scaffold for structural optimization to develop more potent and selective anticancer agents and encourage further development of novel structurally related analogs of 33 as more effective 5-LO inhibitors.


Subject(s)
Computer Simulation , Coumarins/chemical synthesis , Coumarins/pharmacology , Drug Design , Triazoles/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Bacteria/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , Coumarins/chemistry , Drug Screening Assays, Antitumor , Humans , Microbial Sensitivity Tests , Structure-Activity Relationship
16.
J Matern Fetal Neonatal Med ; 29(2): 264-9, 2016.
Article in English | MEDLINE | ID: mdl-25586317

ABSTRACT

OBJECTIVES: To investigate the genetic and acquired thrombophilic risk factors in pregnancy-associated complications and venous thromboembolism (VTE) and evaluate the association between particular thrombophilic risk factors and thromboembolic complications. METHODS: In this study, pregnant women with pregnancy complications and VTE (N = 101) were the study group, and the control group were women with normal pregnancy (N = 102). All women underwent testing for factor V Leiden mutation (FVL), mutation of the coagulation factors II (FII20210), methylenetetrahydrofolate reductase (MTHFR), plasminogen activator inhibitor-1, antithrombin III (ATIII), protein C (PC) and protein S, lupus anticoagulant (LAC) antibodies, anticardiolipin antibodies and anti-beta-2-glycoprotein-1. RESULTS: In this study group, mutations of the FVL was 15.8% (16/101), FII20210 5.9% (6/101) and the MTHFR at locus 677 was TT in 19.8% (20/101). Deficiency of ATIII and PC were rare: 3.0% and 1.0%, respectively. LAC were significantly higher in the study group than in the control group: 32.7% versus 3.9%; p < 0.0005. Pregnant women with VTE have been more frequent for FVL (41.7%; p < 0.005), PC deficiency (25.0%; p < 0.005) and LAC (33.3%; p < 0.005). Combination of FVL and MTHFR mutation was related to the risk of recurrent fetal death and habitual abortion. CONCLUSION: The inherited and the acquired thrombophilic risk factors were found to be up to 10 times more common in the study group than in the control group.


Subject(s)
Blood Coagulation Factor Inhibitors/genetics , Blood Coagulation Factors/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Pregnancy Complications, Cardiovascular/genetics , Venous Thromboembolism/genetics , Adult , Antibodies, Anticardiolipin/genetics , Case-Control Studies , Female , Humans , Pregnancy , Risk Factors , Young Adult
17.
Coll Antropol ; 37(1): 195-201, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23697273

ABSTRACT

Postoperative increase in inflammation biologic markers is associated with a nonspecific inflammatory response to a surgical injury. We investigated the kinetics of changes in serum concentrations of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6) after abdominal surgeries and we focused on the behaviour of those markers in the case of development of the systemic inflammatory response syndrome (SIRS). In the single centre we conducted a prospective observational study and we included patients admitted to the ICU after elective abdominal surgery. A total of 41 patients were included and 8 (19.5%) of them had clinical and laboratory signs of SIRS. Sepsis was confirmed in one of the patients, a 72-year old patient operated due to having an abdominal aortic aneurysm. Plasma concentrations of PCT, CRP and IL-6 were measured in all the patients before surgery and at the postoperative day 1 (POD1), postoperative day 2 (POD2) and postoperative day 3 (POD3). Systemic release of PCT, CRP and IL-6 was present in all the measured time points after the abdominal surgery. Median concentrations of IL-6 (100.4 pg/mL) and PCT (1, 17 pg/mL) production were measured highest at POD1 and the median of CRP (147 mg/L) was measured at highest POD2. A larger increase of all three measured markers was found in patients with SIRS compared to those without. IL-6 at POD1 and POD2 was a good predictor of SIRS (areas under curves were 0.71 and 0.765, respectively), showing the highest accuracy among investigated markers at those time points. CRP at POD3 was a good predictor of SIRS (AUC was 0.76). A cut-off of 95 mg/mL in the level of CRP at POD3 yielded a sensitivity of 87.5% and specificity of 66.7% in detecting SIRS. IL-6 and CRP were the best in detecting postoperative SIRS after abdominal surgery with the highest area under ROC curve. This study is showing that PCT is not a good marker of SIRS caused only by surgical injury without sepsis.


Subject(s)
Abdomen/surgery , C-Reactive Protein/metabolism , Calcitonin/blood , Elective Surgical Procedures/adverse effects , Interleukin-6/blood , Postoperative Complications/diagnosis , Protein Precursors/blood , Aged , Calcitonin Gene-Related Peptide , Female , Humans , Inflammation , Kinetics , Male , Middle Aged , Prospective Studies , ROC Curve , Sensitivity and Specificity , Systemic Inflammatory Response Syndrome , Time Factors
18.
Med Glas (Zenica) ; 8(2): 301-4, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21849960

ABSTRACT

This case report describes a case of venous thrombosis in a young woman who had undergone tympanoplasty due to chronic otitis media. Other than that she was healthy. According to the anamnesis she stopped taking oral contraceptive pills (OCP) a month before the surgery. She did not receive thromboprophylaxis before the surgery because it was estimated that there was a low risk for a thromboembolic incident. Several hours after the surgery she was still not responding properly to external stimulus and there was no verbal contact. An urgent computed tomography (CT) scan of head and neck revealed thrombosis of the left internal jugular vein. She was admitted to the Intensive Care Unit (ICU) and heparin therapy started. After a few days she was fully recovered. Later it was confirmed that the patient had an inherited fibrinolysis disorder caused by plasminogen activator inhibitor 1 (PAI-1) gene polymorphism. Our opinion is that the unexpected thrombotic incident was a result of interaction of multiple factors, including the venous stasis at the surgery site, decreased fibrinolysis ability, and the prothrombotic effect of OCP.


Subject(s)
Blood Coagulation Disorders, Inherited/complications , Contraceptives, Oral/adverse effects , Fibrinolysis , Jugular Veins , Plasminogen Activator Inhibitor 1/genetics , Postoperative Complications , Tympanoplasty , Venous Thrombosis/etiology , Blood Coagulation Disorders, Inherited/genetics , Female , Humans , Plasminogen Activator Inhibitor 1/blood , Polymorphism, Genetic , Risk Factors , Young Adult
19.
Wien Klin Wochenschr ; 120(15-16): 504-6, 2008.
Article in English | MEDLINE | ID: mdl-18820856

ABSTRACT

Pasteurella multocida infections in humans can present as localized infections of soft tissues surrounding the lesions, as respiratory tract infections or as systemic infections with slow or fulminant development. Over 90% of human infections are cases of wound infections or abscesses related to a bite, scratch, or licking of skin lesions by a cat or dog. Severe systemic diseases such as pneumonia, lung abscess, peritonitis, endocarditis, meningitis and sepsis are also well known, especially in patients with underlying medical conditions. In this paper we report on an immunocompromised patient who was bitten by an unknown cat and very quickly developed fulminant sepsis, dying 70 hours after the cat bite, despite all the intensive care, therapy and reanimation he was given. Unfortunately, he asked for medical help too late. We emphasize the need for primary healthcare to provide more information to patients at risk of infections from contact with animals and to warn them about the possible consequences of injuries, even when the animals are pets.


Subject(s)
Bites and Stings/complications , Bites and Stings/immunology , Cats/immunology , Immunocompromised Host/immunology , Pasteurella Infections/etiology , Pasteurella Infections/immunology , Pasteurella multocida , Animals , Fatal Outcome , Humans , Male , Middle Aged , Pasteurella Infections/microbiology
20.
Coll Antropol ; 31(1): 221-5, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17598405

ABSTRACT

The aim of this study was to determine the effect of subminimal inhibitory concentrations (subMICs) of ceftazidime, meropenem and gentamicin on the in vitro serum sensitivity of Pseudomonas aeruginosa strains isolated from a variety of isolation sites at two medical wards and an intensive care unit in a government university hospital in Croatia. A total of 20 serum-resistant P aeruginosa strains isolated from different clinical specimens were selected. Bacteria were exposed to 1/2, 1/4, 1/8, 1/16, and 1/32 x MIC of each antibiotic tested. Sensitivity of P. aeruginosa strains to bactericidal activity of normal human serum before and after bacterial exposure to subMICs was determined. Significant difference in serum sensitivity of the strains was observed after the bacteria were exposed to subMICs of ceftazidime and meropenem (p < 0.01), while the exposure to subMICs of gentamicin did not affect significantly the resistance of tested strains to the serum bactericidal activity. Comparing the number of serum-resistant strains before and after exposure to subMICs of antibiotics, statistically significant differences were determined (p < 0.01) after exposure of the strains to 1/2, 1/4, 1/8 and 1/16 x MIC of meropenem, and after exposure to 1/2, 1/4 and 1/8 x MIC of ceftazidime. SubMICs of ceftazidime and meropenem affected not only the resistance to serum bactericidal activity of bacteria, but also their morphology. The alterations in bacterial morphology caused by subMICs of ceftazidime and meropenem could be connected with consecutive bacterial serum sensitivity.


Subject(s)
Anti-Bacterial Agents/pharmacology , Blood Bactericidal Activity , Ceftazidime/pharmacology , Pseudomonas aeruginosa/drug effects , Thienamycins/pharmacology , Gentamicins/pharmacology , Humans , Meropenem , Microbial Sensitivity Tests
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