Biomedical subjects

M Petrovic

Publications and source records attributed to M Petrovic.

At least 19 recordsLinked to original sources

PubMed2007

Recently developed GC/MS and LC/MS methods for determining NSAIDs in water samples.

Pharmaceuticals have become major targets in environmental chemistry due to their presence in aquatic environments (following incomplete removal in wastewater treatment or point-source contaminations), threat to drinking water sources and concern about their possible effects to wildlife and humans. Recently several methods have been developed for the determination of drugs and their metabolites in the lower nanogram per litre range, most of them using solid-phase extraction (SPE) or solid-phase microextraction (SPME), derivatisation and finally gas chromatography mass spectrometry (GC-MS), gas chromatography tandem mass spectrometry (GC-MS/MS) and liquid chromatography electrospray tandem mass spectrometry (LC-ES/MS/MS). Due to the elevated polarity of non-steroidal anti-inflamatory drugs (NSAIDs), analytical techniques based on either liquid chromatography coupled to mass spectrometry (LC-MS) and gas chromatography coupled to mass spectrometry (GC-MS) after a previous derivatisation step are essential. The most advanced aspects of current GC-MS, GC-MS/MS and LC-MS/MS methodologies for NSAID analysis are presented.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Radiolytic decomposition of multi-class surfactants and their biotransformation products in sewage treatment plant effluents.

Electron beam irradiation (EBI), as one of the most efficient advanced oxidation processes, was applied to the treatment of sewage treatment plant (STP) effluent, with the objective of evaluating the effectiveness of radiolytic decomposition of multi-class surfactants. Target compounds, included several high-volume surfactant groups, such as alkylphenol ethoxylates (APEOs) and their biotransformation products, linear alkylbenzene sulfonates (LAS), alkyl sulfates (AS), alkylether sulfates (AES), coconut diethanol amides (CDEA), alcohol ethoxylates (AEO) and polyethylene glycols (PEGs). EBI treatment of STP effluent (total concentration of APEO-derived compounds 265mugl(-1), being APE(2)C the most abundant by-degradation products) resulted in efficient decomposition of all alkylphenolic compounds; elimination of 94% longer ethoxy chain nonylphenol ethoxylates (NPEO, n(EO)=3-15) was obtained when 3kGy were applied. Slightly less efficient decomposition of short ethoxy chain oligomers (NPEO(1) and NPEO(2)) was observed, resulting in disappearance of about 80% of the initially present compounds. LC-MS analysis of treated wastewater suggested that the mechanism of EBI degradation of APEOs is a combination of two parallel pathways: a progressive shortening and oxidation of the ethoxy chain, which resulted in a formation of short ethoxy chain oligomers and APECs and central fission that resulted in formation of PEGs. Decomposition of APECs at 1kGy initially yielded APs, which were subsequently eliminated applying higher radiation doses. With a radiation dose of 2kGy about 95% of NPE(1)C and 97% of NPE(2)C were decomposed. Similar elimination rates were obtained for octylphenolic compounds. Radiolytic treatment applied was also very effective in removing PEGs formed as by-products from APEO degradation, as well as in decomposing other surfactants, such as linear LAS, AS and AES.

Alkanesulfonic Acids↗

PubMed2006

Trace-level determination of pharmaceutical residues by LC-MS/MS in natural and treated waters. A pilot-survey study.

A pilot-survey study was performed by collecting samples (influent and effluent wastewaters, rivers and tap waters) from different locations in Europe (Spain, Belgium, Germany and Slovenia). A solid-phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry method was applied for the determination of pharmaceuticals (ibuprofen, naproxen, ketoprofen, diclofenac and clofibric acid). Method detection limits and method quantification limits were at the parts-per-trillion level (7.5-75 ng/L). The recovery rates of the SPE from deionized water and effluent wastewater samples spiked at 100- and 1,000-ng/L levels ranged from 87 to 95%. Identification criteria in compliance with the EU regulation for confirmatory methods of organic residues were applied. A detailed study of signal suppression evaluation for analysis of pharmaceutical residues in effluent wastewaters is presented.

Chromatography, Liquid↗

PubMed2006

Presence of surfactants and their degradation intermediates in sediment cores and grabs from the Cadiz Bay area.

The occurrence and distribution of the major surfactants--LAS, AES, APEOs and AEOs--and their degradation intermediates--SPCs, AP and APECs--in a marine-estuarine environment at Spain are presented. Results show that their concentration in surface sediments is clearly correlated with their usage and the existence of wastewater discharges. The degradation processes appear to lead to the formation of SPCs in the case of LAS, and to the shortening of the average ethoxylated chain length in the case of NPEOs, AEOs and AES. Vertical profiles for AEOs and AES are reported for the first time and present the highest values nearest the surface, followed by a sharp decrease with depth for all surfactants, as well as the appearance of degradation intermediates in deeper sedimentary layers. Shorter LAS homologues and SPCs tend to be present in pore water while strongly non-polar intermediates like NP are firmly attached to the sediments.

Biodegradation, Environmental↗

PubMed2006

Application of liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-QqTOF-MS) in the environmental analysis.

This paper gives an overview of the potentials of liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QqTOF) in the environmental analysis. Examples of applications of QqTOF instruments for target analysis of pharmaceuticals and pesticides are presented and discussed, as well as applications aimed on the identification of unknown compounds present in environmental waters or on the elucidation of structures of biodegradation and photodegradation products. Specific issues such as uncertainty of mass measurement and quantitative performances are discussed in details.

Chromatography, Liquid↗

PubMed2006

A characterization of selected endocrine disruptor compounds in a Portuguese wastewater treatment plant.

Anthropogenic compounds that are able to disrupt the endocrine system of wildlife species are a major cause for concern and have led to a demand for new screening methods. The identification and quantification of endocrine disruptor compounds at wastewater treatment plant is of major interest to assess the endocrine activity of wastewater treatment plant discharges into the environment. This study consists of a preliminary survey of concentrations of previously selected endocrine disruptor compounds, undertaken to establish environmental concentrations and to support a biological program assay exposing freshwater fish to them. Selected endocrine disrupting chemicals (APEs, bisphenol A and 17 beta-estradiol) were measured in samples from a wastewater treatment plant located in Lisbon (Portugal), using recent commercial enzyme-linked immunosorbent assay kits and also LC-MS/MS. The results show that the wastewater treatment plant treatment process is efficient on the removal of target endocrine disruptor compounds. However, environmentally significant concentrations are still present in the treated effluent. The results also show that enzyme-linked immunosorbent assay kit is suitable for routine analysis of the selected compounds. The results are also useful since the wastewater treatment plant is located in a Mediterranean region, which results in an effluent with its own characteristics.

Benzhydryl Compounds↗

PubMed2006

Visceral and testicular calcifications as part of the phenotype in pseudoxanthoma elasticum: ultrasound findings in Belgian patients and healthy carriers.

Occasionally calcifications in abdominal organs, breasts and testicles have been reported in pseudoxanthoma elasticum (PXE) patients. In the present study, an ultrasound evaluation was performed of the abdomen and--in male patients--of the testicles in 17 PXE patients and 17 heterozygous carriers. Blood samples were taken to evaluate calcium load, liver and kidney function. Calcifications in liver, kidneys and spleen were detected in 59% of the patients and in 23.5% of healthy carriers. Parameters of kidney and liver function were normal in both groups, suggesting that the calcifications have no direct effect on organ function. Testicular ultrasound revealed parenchymous calcifications in all males investigated. Widespread, small hyperechogenic foci resembling testicular microlithiasis were seen. In some carriers, focal calcifications were identified. The current data suggest that visceral and testicular calcifications are part of the phenotype of PXE patients. Their presence in some of the healthy carriers are suggestive of subclinical manifestations in these relatives. The natural history and long-term effects of the parenchymal calcifications remain to be elucidated. As testicular microlithiasis may be associated with a higher risk for malignancy, regular clinical and ultrasound follow-up seems indicated in these patients.

Adolescent↗

PubMed2006

Radioimmunoscintigraphy of colorectal carcinomas with three different radiopharmaceuticals.

The aim of the study was evaluation of the clinical reliability of the immunoscintigraphy for the detection of metastases and recurrences of colorectal carcinomas using three different radiopharmaceutical substances. With IMACIS 1, the number of true negative findings (TN) was 4/7 and true positive (TP) 3/7, while in one patient, the results of immunoscintigraphy significantly influenced the therapeutical management. With INDIMACIS 19-9, there were 2/8 TN and 6/8 TP. In three patients, immunoscintigraphy results influenced patient further management. With ONCOSCINT in 2 patients findings were TN, in one FN and in one FP. In 3 patients, immunoscintigraphy influenced the management of the patient. Other imaging methods (CT, US, MRI) have advantage in detection of liver metastases, while immunoscintigraphy is more specific for the assessment of reccurences of the abdominal tumors. Thus immunoscintigraphy should be applied in patients with suggested recurrences and inconclusive outcome of routine diagnostic workup.

Adenocarcinoma↗

PubMed2006

Investigation of a tuberculosis cluster at a job centre in Manchester, United Kingdom.

During the summer of 2005, four cases of active tuberculosis from the same occupational setting were investigated in Manchester, UK. The index case had been diagnosed in December of the previous year. At that stage the closest occupational contacts had been screened, all of whom were assessed as being free from active disease, and none had met nationally recommended criteria for chemoprophylaxis for latent tuberculosis infection (LTBI). In June 2005, two work contacts developed progressive primary extrapulmonary (pleural) TB. Following a detailed risk assessment, the screening programme was widened to include 137 staff who worked at the job centre (employment agency) where the first four cases had been found. This screening programme was based on tuberculin Mantoux testing, CXR and gamma-interferon testing. Of these 137 contacts screened, one additional person was found to have active disease and six others were offered chemoprophylaxis for LTBI. The isolates from the index case and the first two secondary cases were indistinguishable on VNTR-MIRU (variable number tandem repeat--mycobacterial interspersed repetitive unit) typing at 15 loci. No samples were available for testing from the fourth case of active disease. Management of this incident has benefited from the evolving fields of both genotyping and diagnostic testing for LTBI. However, further research into the epidemiological inferences made through genotyping, as well as the significance of a positive gamma-interferon test in assessing the risk of development of active disease, is still required.

Cluster Analysis↗

PubMed2005

Radical retropubic prostatectomy--results in 127 surgically treated patients.

Radical prostatectomy represents an optimal therapeutic method in treatment of the localized prostatic carcinoma. It may be performed using retropubic, perineal, transcoccygeal or laparoscopic approach. In a multicenter study, the authors have analyzed 127 patients surgically treated in the period 1992 - 2003. All the patients were preoperatively diagnosed with the localized prostatic carcinoma. The patients were operated at the Clinic of Urology in Belgrade (92 patients) and other departments of urology in Serbia (35 patients). The youngest patient was 49 while the oldest one was 75 (mean age 64 years). The surgical procedure duration ranged between 60 and 120 minutes. Over the last five years, the need for blood transfusion was below 50%. All the patients underwent retropubic radical prostatectomy.

Adenocarcinoma↗

PubMed2004

Analysis by liquid chromatography-electrospray ionization tandem mass spectrometry and acute toxicity evaluation for beta-blockers and lipid-regulating agents in wastewater samples.

This paper describes a multiresidue method for the extraction and determination of two therapeutic groups of pharmaceuticals, lipid-regulating agents (clofibric acid, bezafibrate, gemfibrocil, fenofibrate) and beta-blockers (atenolol, sotalol, metoprolol, betaxolol) in waters by solid-phase extraction followed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS). Recoveries obtained from spiked HPLC water, as well as, from spiked real samples (sewage treatment plants influent and effluents, river and tap water) were all above 60%, with the exception of betaxolol with a 52% recovery. The quantitative MS analysis was performed using a multiple reaction monitoring. The LC-MS-MS method gave detection limits ranging from 0.017 to 1.25 microg/l in spiked effluent. Precision of the method, calculated as relative standard deviation, ranged from 3.7 to 18.5%. Individual and combined effects on Daphnia magna were evaluated for both therapeutic groups. Individual effects in culture medium showed these compounds as not harmful and not toxic, an exception is fenofibrate that was found to be harmful, but at high, in the environment unrealistic concentrations (EC50 of 50 mg/l). Combined effect in wastewater showed synergistic toxic effects at low concentration level (2 microg/l).

Adrenergic beta-Antagonists↗

PubMed2004

Intracellular spermine decreases open probability of N-methyl-D-aspartate receptor channels.

Spermine and related polyamines have been shown to be endogenous regulators of several ion channel types including ionotropic glutamate receptors. The effect of spermine on N-methyl-d-aspartate (NMDA) receptors in cultured rat hippocampal neurons was studied using single-channel and whole-cell patch clamp recordings. Intracellular spermine resulted in the dose-dependent inhibition of NMDA-induced responses. Spermine reversibly inhibited the single NMDA receptor channel activity in inside-out patches suggesting a membrane-delimited mechanism of action. Open probability of NMDA receptor channels was decreased in a dose-dependent manner. Mechanism of spermine-induced inhibition of NMDA receptor was different from that of intracellular Ca(2+)-induced NMDA receptor inactivation. Both pharmacological studies and single channel analysis indicate that in contrast to the effect of extracellular spermine the intracellular spermine effect is not dependent on the NMDA receptor subunit composition. We propose that intracellular spermine has a direct inhibitory effect on NMDA receptors that is different from calcium-induced NMDA receptor inactivation and spermine-induced voltage-dependent inhibition of AMPA/kainate receptors. Spermine-induced tonic change in the open probability of NMDA receptor channels may play a role in mechanisms underlying short-term changes in the synaptic efficacy.

Animals↗

PubMed2004

Activation and modulation of ligand-gated ion channels.

Ligand-gated ionic channels are integral membrane proteins that enable rapid and selective ion fluxes across biological membranes. In excitable cells, their role is crucial for generation and propagation of electrical signals. This survey describes recent results from studies performed in the Department of Cellular Neurophysiology, Institute of Physiology ASCR, aimed at exploring the conformational dynamics of the acetylcholine, glutamate and vanilloid receptors during their activation, inactivation and desensitization. Distinct families of ion channels were selected to illustrate a rich complexity of the functional states and conformational transitions these proteins undergo. Particular attention is focused on structure-function studies and allosteric modulation of their activity. Comprehension of the fundamental principles of mechanisms involved in the operation of ligand-gated ion channels at the cellular and molecular level is an essential prerequisite for gaining an insight into the pathogenesis of many psychiatric and neurological disorders and for efficient development of novel specifically targeted drugs.

Allosteric Regulation↗

PubMed2004

LC-MS-(MS) determination of oxidative degradation products of nonylphenol ethoxylates, carboxylates and nonylphenols in water.

A commercial blend of nonylphenol ethoxylates (NPEOs) was chosen as representative for non-ionic polyethoxylated surfactants to study the oxidative degradation of this class of surfactants in water using ozonation as well as electron beam irradiation with and without the addition of ozone as treatment processes. The electron beam irradiation processes applied represent so-called Advanced Oxidation Processes (AOPs); the combined ozone/electron beam irradiation is, moreover, the most powerful AOP which can be applied in aqueous systems. It was found that both ozonation and the two AOPs applied were able to decompose not only the NPEOs but also the polyethyleneglycoles (PEGs) formed as by-products from NPEO degradation to residual concentrations below the limit of detection. Moreover, the treatment processes were also used to study the oxidative degradation of nonylphenoxy acetic acid (NPEC) and of nonylphenol (NP) which are formed as by-products from biodegradation of NPEOs.

Biodegradation, Environmental↗

PubMed2003

Endocrine disrupting compounds and other emerging contaminants in the environment: a survey on new monitoring strategies and occurrence data.

An overview of Toxicity Identification and Evaluation (TIE) procedures, used for the effect-based analysis of endocrine disrupting compounds (EDCs) in environmental samples, is presented. Future trends in advanced chemical analysis of EDCs and some emerging contaminants are outlined. The review also gives an overview of concentration levels found in environmental samples and discusses the correlation of calculated estrogenicity (based on chemical analysis of target EDCs) with that measured by various bioassays.

Animals↗

PubMed2003

Low nanogram per liter determination of halogenated nonylphenols, nonylphenol carboxylates, and their non-halogenated precursors in water and sludge by liquid chromatography electrospray tandem mass spectrometry.

A new LC-MS-MS method for quantitative analysis of nonylphenol (NP), nonylphenol carboxylates (NPECs), and their halogenated derivatives: brominated and chlorinated nonylphenols (BrNP, ClNP), brominated and chlorinated nonylphenol carboxylates (BrNPE(1)C and ClNPE(1)C) and ethoxycarboxylates (BrNPE(2)C and ClNPE(2)C) in water and sludge has been developed. Electrospray negative ionization MS-MS was applied for the identification of above mentioned compounds. Upon collision-induced dissociation, their deprotonated molecules gave different fragments formed by the cleavage of the alkyl moiety and/or (ethoxy)carboxylic moiety. For halogenated compounds a highly diagnostic characteristic pattern of isotopic doublet signals was obtained and fragmentation yielded, in addition to above mentioned ions, [Br](-) and [Cl](-), respectively. Quantitative analysis was done in the multiple reaction monitoring (MRM) mode, using two specific combinations of a precursor-product ion transitions for each compound. Additionally, for halogenated compounds two specific channels for each transition reaction, corresponding to two isotopes, were monitored and the ratio of their abundances used as an identification criterion. The method has been validated in terms of sensitivity, selectivity, accuracy, and precision and was applied to the analysis of water and sludge samples from drinking water treatment plant (DWTP) of Barcelona (Catalonia, NE Spain). Halogenated NP and NPECs were detected in prechlorinated water in concentrations up to 315 ng/L, BrNPE(2)C being the most abundant compound. In the DWTP effluent non-halogenated compounds were detected at trace levels (85, 12 and 10 ng/L for NP, NPE(1)C, and NPE(2)C, respectively), whereas concentration of halogenated derivatives never exceeded 10 ng/L. Nonylphenol, brominated and chlorinated NPs were found in flocculation sludge in concentrations of 150, 105, and 145 microg/kg, respectively. Acidic polar metabolites were found in lower concentrations up to 20 microg/kg.

Carboxylic Acids↗

PubMed2003

Parents' attitude towards the second dose of measles, mumps and rubella vaccine: a case-control study.

In response to media scares and subsequent falls in measles, mumps and rubella (MMR) vaccine uptake, a case-control study was conducted to identify factors associated with non-uptake of the second dose of the vaccine in children resident in North Wales. Subjects were selected from parents of children scheduled for the second dose between October and December 1997. Postal questionnaires were used to compare knowledge, attitudes and practice of non-acceptors (cases) and acceptors (controls). Of non-acceptors, 92.1% (95% CI 82.2-97.5%) stated that they would allow another child to have at least one dose of MMR, and 39.2% (95% CI 25.8-53.9%) both doses of MMR vaccine. Non-acceptors were more likely to report having obtained information from newspapers/television (OR 2.04, 95% CI 1.03-4.02) or from the general practitioner (OR 2.02, 95% CI 1.07-3.86) and to report having 'a lot' or 'some' influence from newspapers/television (OR 3.52, 95% CI 1.57-7.86). The 'combination of three vaccines in one jab' was identified as a worry by 55.1% (95% CI 40.2-69.3%) of non-acceptors and 38.5% (95% CI 30.6-46.9%) of acceptors. On this evidence, catch-up campaigns would be an effective way of increasing coverage; also health professionals need tools to enable them to communicate effectively in the face of ongoing scares.

Attitude to Health↗

PubMed2002

Fast withdrawal from benzodiazepines in geriatric inpatients: a randomised double-blind, placebo-controlled trial.

OBJECTIVE: We have previously demonstrated that temporary substitution with a low-dose hypnosedative drug may lead to successful withdrawal from chronic benzodiazepine (BZD) use in the majority of patients admitted to a geriatric ward. In the present study, a withdrawal programme was evaluated in which the habitual treatment with BZDs was replaced by either 1 mg lormetazepam or placebo, defining withdrawal success rate, sleep quality and withdrawal symptoms as main outcomes. METHODS: The target population was geriatric inpatients who had been taking BZDs for at least 3 months. Subjects suffering from mental disorders were excluded. Lormetazepam or placebo were randomly assigned and given in a double-blind fashion. After 1 week, the replacement therapy was discontinued. Subjective estimations of sleep quality and withdrawal symptoms were registered at predefined intervals, four times in a period of 30 days, using standard questionnaires (the Pittsburgh Sleep Quality Index and the Benzodiazepine Withdrawal Symptom Questionnaire, respectively). RESULTS: The success rate was significantly higher in the lormetazepam substitution group (80% vs 50% in the placebo group, P < 0.05). Both the subjective quality of sleep and withdrawal symptoms were significantly better in the lormetazepam substitution group. Important withdrawal effects were observed in the control group in two patients with a history of chronic alcohol abuse. CONCLUSIONS: Initial replacement therapy with a low-dose BZD is preferred over placebo, since the latter alternative is associated with worse sleep quality and a lower success rate. Placebo must only be used under medical scrutiny, given the potential for unmasking delirious symptoms, especially in patients with concomitant alcoholism.

Aged↗