A New Solid-Phase Extraction Method for Determination of Pantoprazole in Human Plasma Using High-Performance Liquid Chromatography

BACKGROUND: A new simple, selective and accurate high-performance liquid chromatographic (HPLC) method utilising solid-phase extraction for the determination of pantoprazole in human plasma samples has been developed. AIM: The purpose of this paper was developing a new HPLC method suitable for the determination of pantoprazole in plasma samples, which enables simple and rapid isolation and concentration of the analysed drug.METHODS: The chromatographic separation was accomplished on a LiChroCart LiChrospher 60 RP select B column using a mobile phase composed of 0.2 % (V/V) water solution of triethylamine (pH 7) and acetonitrile (58:42, V/V) followed by UV detection was at 280 nm. The solid-phase extraction method using LiChrolut RP-18 (200 mg, 3 ml) was applied to the obtained good separation of investigated drug from endogenous plasma components. Best results were achieved when plasma samples were buffered with 0.1 mol/L KH2PO4 (pH 9) before extraction, eluted and reconstituted with acetonitrile and 0.001 mol/L NaOH after extraction, respectively. RESULTS: The standard calibration curves showed good linearity within the range of 25.0-4000.0 ng/mL with a correlation coefficient greater than 0.996. Retention times of pantoprazole and internal standard, lansoprazole was 4.1 and 6.0 min respectively. The limit of quantification was 25.0 ng/mL. For intra- and inter-day precision relative standard deviations ranged from 4.2 to 9.3%. The relative errors for stability investigations were ranged from 0.12 to -10.5%. CONCLUSION: This method has good precision and accuracy and was successfully applied to the pharmacokinetic and bioequivalence study of 40 mg pantoprazole in healthy volunteers

Distribution of CYP2C9 and VKORC1 Gene Polymorphisms in Healthy Macedonian Male Population

Background: Distribution of CYP2C9 and VKORC1 gene polymorphisms may vary significantly among different ethnic groups, and eventually influence the variation in drug metabolism or even failure.Objective: The aim of this study was to evaluate the prevalence of CYP2C9 and VKORC1 alleles in the healthy population of Republic of Macedonia compared to the global geographic data reported from different ethnic populations. Also, to genotype CYP2C9 and VKORC1 genes and eventually to divide individuals in poor, extensive, or intermediate metabolizer.Material and Methods: Blood samples were collected after signing written consent, DNA was isolated from peripheral blood, and CYP2C9 and VKORC1 genes were typed (n=124). Genotyping was performed by commercially available kits (GeneID GmbH, Strassberg, Germany, AID Diagnostica), based on the method of polymerase chain reaction with a subsequent hybridization. The population genetics analysis package, PyPop ver. 0.6.0, was used for analysis of the data.Results: The frequency of alleles varies from 0.931 for CYP2C9*3 to 0.109 for CYP2C9*2 indicating common “wild type†allele in those genes. The frequency ranges spanned ~50% for each allele of VKORC1 gene, indicating no common “wild type†allele in this gene. Test of neutrality showed significant negative value for VKORC1 polymorphism that indicates balancing selection operating on the alleles at that locus. All polymorphisms of CYP2C9*2, CYP2C9*3 and VKORC1 showed a good fit with Hardy-Weinberg expectations.Conclusion: The results of polymorphic alleles of CYP2C9 and VKORC1 genes in Macedonian population can be used for the variation in drug metabolism studies as well for adapting dosage regimes for oral anticoagulant therapies

Combining prostate health index and mpMRI data (MRI Spectroscopy) to manage PI-RADS lesions and reduce excessive biopsy, a single center study

To evaluate the values of PHI and PI-RADS findings in the early detection and prediction of prostate cancer, as well as their application in clinical trials, especially when values of PSA are in the „ grey zone„ with negative DRE. The 100 patients, men aged 50 years or older with prostate-specific antigen 4 to 10 ng/ml („gray zone„) and normal digital rectal examination with suspected prostate cancer were examined, who had undergone biopsy and were divided in two groups. A group with no evidence of PCa (non PCa) and the group with PCa. The performance of PHI and mpMRI PI-RADS score was compared to predict biopsy results and, specifically, the presence of clinically significant prostate cancer (csPCa) using multiple criteria. Among 100 subjects, 21 (21.0%) were diagnosed with PC, including 13 (61.95%) with csPC (Gleason≥7). By the threshold of PHI≥36, the sensitivity, specificity, PPV, and NPV to predict PCa were 100%, 68.35%, 45.65%, and 100%, respectively. The best cut-off (PHI) was 42.8% with sensitivity 85.7% and specificity 86.1%. The area under the receiver operator characteristic curve (AUC) of combining PHI and mpMRI was greater than that of PHI alone (0.993 vs. 0.954, p=0.002) and mpMRI alone (0.993 vs. 0.976, p=0.025). Comparing the performance in the identification of clinically significant prostate cancer (csPCa), we found that PHI ≥ 73.04 and PI-RADS score ≥ 4 were able to identify csPCa (Gleason score ≥ 7 (3 + 4)) both alone and added to a base model including age, PSA, fPSA-to-tPSA ratio and prostate volume. If biopsy was restricted to patients with PI-RADS 5 as well as PI-RADS 3 or 4 and PHI≥36.0, 50% of biopsy could be avoided with one csPCa patient being missed. The analyzed correlation between PHI and PI-RADS score was statistically significant (p<0.0001). According to the value of Spearman's coefficient, R=0.748, the correlation is positive, i.e. direct, and they showed that with an increase in the value of the prostatic health index, (PHI) the PI-RADS score increases, and vice versa. The combination of PHI and mpMRI had higher accuracy for detection of csPC compared with PHI or mpMRI alone. Keywords: Prostate health index, mpMRI PI-RADS, detection of prostate cance

Efektite na prostaciklin vo tretmanot na dijabeticnata nefropatija kaj staorci

Mikrovaskularnite komplikacii, a pred se dijabeticnata nefropatija, se edni od najteskite komplikacii na dijabetot, od koi vo golema mera zavisi i prognozata na dijabetot kaj ovie pacienti. Etiopatogenezata na ovaa komplikacija e multifaktorijalna i za sega se uste ne kompletno rasvetlena, a vklucuva morfoloski, patolosko-anatomski i biohemiski metabolni narusuvanja. Se smeta deka narusuvanjeto na modularnata funkcija na endoteliumot moze da bide kriticen i inicijalen faktor vo razvojot na dijabeticnite vaskularni komplikacii. Vrz osnova na farmakodinamskite efekti koi sto gi poseduva prostaciklinot (PGI2) i negovite analozi, se smeta deka istite moze da bidat korisni vo tretmanot na dijabeti~nata nefropatija. Osnovna cel na ovaa studija be{e da se procenat efektite na prostaciklin (PGI2) vo tretmanot na dijabeticnata nefropatija, eksperimentalno predizvikana so streptozocin. Kaj normotenzivni staorci od sojot Wistar, eksperimentalno bese induciran najprvin dijabet so ednokratna i.p. administracija na streptozocin (STZ), a kako komplikacija na dijabetot i jasni znaci i simptomi na dijabeticna nefropatija (proteinurija, zgolemeno serumsko nivo na urea i kreatinin, poliurija, zgolemena aktivnost na NAG vo mockata). Tretman so prostaciklin (p.o.) vo doza od 0.1 mg/kg /t.t./den, vo tekot na 4 nedeli, dovede do signifikantno namaluvanje na simptomite i znacite na bubreznite ostetuvanja, vo odnos na grupata zivotni koi ne primaa prostaciklin. Vrz osnova na dobienite rezultati moze da se zakluci deka prostaciklinot moze da ima znacajna uloga vo tretmanot na dijabeticnata nefropatija, eksperimentalno inducirana so streptozocin

Efekti na amifostin vo prevencija na nefrotoksicnost inducirana so cisplatin kaj staorci

Amifostin e relativno nov organski citoprotektiven lek, koj vsusnost pretstavuva prolek, namenet za namaluvanje na kumulativnata renalna toksicnost inducirana od povtoruvana administracija na cisplatin. Mehanizmot na nefroprotektivnoto dejstvo na amifostin ne e kompletno razjasnet, no se smeta deka lekot poseduva direktno citoprotektivno dejstvo na bubreznite tubuli. Osnovnata cel na ovaa studija bese da se utvrdi efektot na amifostin vo prevencijata na nefrotoksicnost eksperimentalno inducirana so dolgotrajna administracija na cisplatin vo doza od 2 mg/kg/t.t./nedela vo tek na 8 nedeli. Dobienite rezultati od ovaa studija pokazuvaat deka amifostin, iako ne kompletno, vo golema mera ja reducira nefrotoksicnosta inducirana so dolgotrajna administracija na cisplatin

Ulogata na endoetelin-1 vo razvojot na dijabeticna nefropatija inducirana so streptozocin

Dijabeticnata nefropatija pretstavuva edna od hronicnite mikrovaskularni komplikacii na dijabetot, so multifaktorijalna i ne do kraj rasvetlena etiopatogeneza. So ogled na toa sto kaj pacientite so dijabet, osobeno kaj onie so dijabeticna nefropatija, se najdeni zgolemeni vrednosti na endotelin-1, se pretpostavuva deka istiot moze da ima znacajna uloga vo razvojot na dijabeticnata nefropatija. Osnovna cel na nasata studija bese da se detektiraat promenite vo plazmatskoto nivo na endotelin-1 po eksperimentalno induciran dijabet, i dijabeticna nefropatija kaj staorci so streptozocin. So ogled na dobro poznatite efekti na AKE-inhibitorite, vo ovaa studija go ispituvavme i vlijanieto na enalapril (AKE inhibitor) na plazmatskite koncentracii na endotelin-1, kako i negovite efekti vo tretmanot na dijabeti~na nefropatija. Ednokratnata i.p. administracija na streptozocin (STZ) predizvika signifikantno zgolemuvanje na plazmatskite koncentracii na endotelin-1, proprateni so jasno izrazeni simptomi i znaci na dijabeticna nefropatija (mikroalbuminurija, zgolemeni urinarni vrednosti na N-acetyl-fl-D-glucosamidase, zgolemeni serumski koncentracii na urea, poliurija). Cetiri nedelniot tretman so enalapril dovede do signifikantno namaluvanje na plazmatskite koncentracii na endotelin-1 i do podobruvanje na simtomite i znacite na dijabeticnata nefropatija. Dobienite rezultati potvrduvaat deka endotelin-1 moze da ima znacajna uloga vo razvojot i progresijata na dijabeticnata nefropatija, a AKE inhibitorite, odnosno enalapril, mozat da ja ublazat i usporat progresijata na dijabeticnata nefropatij

Epoetin alfa ja namaluva nefrotoksicnosta inducirana so cisplatin kaj staorci

Klinickata efikasnost na cisplatin kako antitumorski lek e nesomnena, no dozno-limitiracki faktor za negova upotreba pretstavuva izrazitata nefrotoksicnost. Najnovite istrazuvawa pokazuvaat deka epoetin alfa moze da ima znacajna uloga ne samo vo terapiski celi za korekcija na razni vidovi na anemii, tuku istiot moze da bide efikasen i kako nevroprotektiv, hepatoprotektiv, kardioprotektiv i osobeno znacajno kako nefroprotektiv kaj nefrotoksicnost inducirana od preparati na baza na platina. Glavna cel na ovaa studija bese da se utvrdi efektot na epoetin alfa vo prevencijata na nefrotoksicnost eksperimentalno inducirana so dolgotrajna administracija na cisplatin vo doza od 2 mg/kg/t.t./nedela vo tek na 8 nedeli, kaj Wistar staorci. Dobienite rezultati od ovaa studija pokazuvaat deka epoetin alfa signifikantno gi ublazuva funkcionalnite bubrezni poremetuvawa inducirani so dolgotrajna administracija na cisplatin, ja podobruva opstata sostojba i go namaluva mortalitetot kaj ispituvanite zivotni

Serum Matrix Metalloproteinase-2, -7 and -9 (MMP-2, MMP-7, MMP-9) levels as Prognostic Markers in Patients with Colorectal Cancer

<p><strong>Introduction:</strong> Matrix metalloproteinases are produced by tumour cells, hence, they may be associated with tumour progression including invasion, migration, angiogenesis and metastasis. Finding prognostic markers to better identify patients with higher risk for poor survival would be valuable in order to customize pre- and postoperative treatment as well as to enable closer follow-up of these patients. Aim of our study was to examine<br />MMP-2, MMP-7 and MMP-9 serum levels and correlated them with pathological data such as stage of the colorectal cancer (CRC) and outcome.</p><p><strong>Methods: </strong>The investigation included 82 patients with operable CRC without distant metastases, who had underwent blood tests in order to determine the MMP-2, MMP-7 and MMP-9 serum levels in the following time periods: preoperatively, 3, 6, 9 and 12 months postoperatively.</p><p><br /><strong>Results</strong>: The values of the investigated MMPs decrease postoperatively and start to increase 6 month later in patients of all stages of the disease, reaching the highest value 12 month postoperatively with statistically important differences of MMP-2, MMP-7 and MMP-7 serum levels in terms of disease staging and defined points of time. Analysis of the results showed that the MMP-2 serum levels obtained 3 and 12 months postoperatively,<br />than MMP-7 serum levels 12 months postoperatively and the MMP-9 serum levels in all analyzed points in time were in significant association with the CRC patients’outcome.</p><p><br /><strong>Conclusion: </strong>The MMP-2, MMP-7 and especially MMP-9 serum values could be important indicators for diagnosis of the patients with CRC and for monitoring of disease progression.</p