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54th ERA-EDTA Congress, Madrid, Spain 3-6 June 2017

Purpose: Advanced lung carcinoma is charasterized with fast disease progression. Interleukin (IL)10 and transforming growth factor (TGF)b1 are immunosuppressive mediators and their role in lung carcinoma pathogenesis and in the antitumor response has not yet been elucidated. The purpose of this study was to correlate IL10 and TGFb1 levels in the serum and lung tumor microcirculation with clinical stage, disease extent, histological features and TNM stage. Methods: The study included 41 lung cancer patients in clinical stage III and IV. Histological type was determined immunohistochemically, while tumor size, localization and dissemination were determined radiologically by multislice computerized tomography (MSCT). IL10 and TGFb1 levels were quantified with commercial flow cytometric test in serum and lung tumor microcirculation samples. Results: Non small cell lung cancer (NSCLC) patients had significantly elevated TGFb1 while small cell lung cancer (SCLC) patients had significantly increased IL10 in tumor microcirculation. IL10 was significantly elevated in patients with the largest tumors, as well as in patients with III clinical stage and without metastases, both in the serum and tumor microcirculation. TGFb1 was significantly increased in serum and tumor microcirculation in patients with larger tumors. We found significant correlation between these two immunosuppressive cytokines, IL10 and TGFbl, in tumor microcirculation but not in patient serum samples. Conclusion: IL10 and TGFb1 in systemic and tumor microcirculation are significantly associated with particular histological type of lung cancer, tumor size and degree of disease extent.

Alcohol biomarkers play a significant role in the early diagnosis of alcohol intoxication/abuse, alcohol-related organ damages, assessment of alcoholism therapy outcomes, and in forensic medicine. Laboratory detection of excessive alcohol consumption can be carried out by direct measuring of the ethanol and/or metabolites in biological samples which is of particular importance in the cases of acute ethanol intoxication/controlling and/or monitoring of alcohol consumption, or indirectly, by using biomarkers. Preferred diagnostic characteristics of alcohol biomarkers, specificity and sensitivity dependent on the particular demands such as: prevention and treatment of alcoholism in primary and social care, criminal justice, workplace health and safety screening, trafficking control, etc. Alcohol biomarkers traditionally used in clinical practice [blood alcohol concentration (BAC), gamma-glutamyl transferase (GGT), carbohydrate-deficient transferrin (CDT), the ratio GGT/CDT, alanine aminotransferase (ALT), aspartate aminotransferase (AST), the ratio AST/ALT, mean corpuscular volume (MCV), phosphatidylethanol (PEth)] are well validated. They are used as screening/monitoring markers of acute/chronic excessive alcohol intake, alcoholism in pregnancy, and other disorders/conditions related to alcohol abuse. Numerous potential alcohol biomarkers have been discovered, but few are validated. Potential alcohol biomarkers (ethanol and serotonin metabolites, sialic acids, etc.) have good diagnostic characteristics, but their application in clinical practice is limited due to the costly equipment necessary for their measurement. Significant progress has been made in the development of sensitive and practical alcohol transdermal devices that can instantly/continuously measure BAC through human skin. Transdermal sensing of alcohol may become a valuable method for monitoring abstinence. A special aspect of alcoholism is genetic predisposition to alcohol abuse and alcoholism, or alcohol-related organ damage. Recent genome-wide association studies (GWASs) have proposed several susceptibility loci for alcohol dependence.

Abuse of psychoactive substances (PAS) is a major health and social problems, worldwide. The overall population is in direct daily contact with the PAS and thus, at risk of PAS abuse. Pharmacists have a unique and comprehensive knowledge about drugs and PAS, as well as, about the adverse effects of their inappropriate use (abuse). So far, regarding this problematic, the role of pharmacists, as health promoters, is mostly recognized in the field of pharmacotherapy and clinico-toxicological laboratory analysis. However, the role of pharmacists should be recognized more widely in the society, in the sense of prevention, advisory and educational role. According to the American model, in this area of work, pharmacists are responsible for prevention, education and assistance in overall health and social care system of addicts. Also, this paper gives an overview of the importance of institutional harmonization in the PAS domain abuse, at the city, region and state level. Inadequate cooperation at this level is a immense threat to society, and in the same time, an indicator of irresponsibility and neglect of the community regarding addiction related problems. Zloupotreba psihoaktivnih supstanci (PAS) je veliki zdravstveno-društveni problem kod nas i u svetu. Sveukupna populacija je u neposrednom svakodnevnom kontaktu sa PAS i izložena je stalnom riziku od PAS. Farmaceuti imaju jedinstveno i sveobuhvatno znanje o bezbednoj i efikasnoj primeni lekova i PAS, kao i o neželjenim efektima do kojih dovodi njihova neadekvatna upotreba (zloupotreba). Uloga farmaceuta, za sada je uglavnom prepoznata u domenu farmakoterapije i kliničko-toksikoloških laboratorijskih analiza. Međutim, uloga farmaceuta kao promotera zdravlja bi trebalo da se prepozna šire u društvu, kada je reč o zloupotrebi i tretmanu zavisnika od PAS, kako u domenu prevencije, tako i tokom lečenja i kasnijoj fazi reintegracije lečenog pacijenta u društvenu zajednicu. Takođe, savetodavna i edukativna uloga farmaceuta u društvu, kod nas je oblast koja je u začetku, kada je reč o zloupotrebi PAS. Prema američkom modelu, odgovornosti farmaceuta u ovom domenu rada podeljene su u tri grupe: prevencija, edukacija i angažman u sveukupnom zdravstveno-socijalnom sistemu zbrinjavanja zavisnika. Takođe, u radu je dat osvrt na značaj institucionalne harmonizacije u domenu zloupotrebe PAS, na nivou grada, regiona i države. Neadekvatna saradnja na ovom nivou je velika pretnja društvu, a i u isto vreme, pokazatelj neodgovornosti i nebrige cele zajednice o problemu zavisnosti kod nas.

Contact herbicide paraquat (DQ) is bipyridylium compound, which undergoes redox metabolism; hence enlarged in humans radical production mediated its toxicity. Target organs of systemic effect of PQ poisoning are lung and kidney. The mechanism of PQ-induced neurotoxicity is not elucidated till now. The objective of our study was to examine the role of nitric oxide (NOx) in PQ-induced neurotoxicity, primarily focusing on glutathione cycles [total glutathione content (GSH) and glutathione peroxidase (GPx) activity]. In order to investigate the role of NOx in oxidative stress (OS) and/or nitrosative stress (NS) response to PQ neurotoxicity, we used NG-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of nitric oxide synthase (NOS) in the pretreatment of PQ administration. Study was conducted on Wistar rats randomly divided in groups (n=8 for controls and n=24 for experimental groups) depending on the applied treatments. The tested compounds were intrastriatally (i.s.) administered. Measuring of GSH content and GPx activity was performed at 30 min, 24 hours and 7 days after treatments. Parkinsonism’s like symptoms were observed only in the group of rats treated with PQ. The L-NAME protected animals from PQ-induced neurotoxicity, which could be concluded from the absence of Parkinsonism’s like symptoms and reduced OS/NS response in the striatum of rats pretreated with L-NAME. Kontaktni herbicid parakvat (PK) je dipiridinsko jedinjenje, koje podleže redoks metabolizmu i svoju toksičnost ispoljava posredstvom povećanog stvaranja slobodnih radikala. Ciljni organi sistemskog toksičnog efekta PK kod čoveka su pluća i bubrezi. Mehanizam PKindukovane neurotoksičnosti do sada još uvek nije u potpunosti rasvetljen. Cilj našeg rada bio je da se ispita uloga azot oksida (NOx) u neurotoksičnosti PK, sa posebnim osvrtom na glutationski ciklus [glutation (GSH) i enzim glutation peroksidazu (GPx)]. U cilju da se istraži uloga NOx u oksidativnom stresu (OS) i / ili nitrosativnom stresu (NS), kao odgovoru na neurotoksičnost PK. U predtretmanu parakvatom koristili smo NG-nitro- L-arginin metil estar (L-NAME), neselektivni inhibitor azot oksid sintetaze (NOS), aplikovan je pre davanja PQ . Studija je sprovedena na pacovima Wistar soja nasumice podeljenim u grupe (n = 8 za kontrolnu grupu i n = 24 za eksperimentalne grupe) u zavisnosti od tretmana. Testirana jedinjenja su intrastrijatalno (i.s.) aplikovana. Merenje sadržaja GSH i aktivnosti GPx izvršena su 30 min, 24 sata i 7 dana posle tretmana. Parkinsonizam je kao simptom primećen samo u grupi pacova tretiranih PK - om. L-NAME je ispoljio zaštitni efekat kod životinja kod kojih je i.s. davan PK, što bi se moglo zaključiti na osnovu odsustva simptoma parkinsonizma i smanjenog OS/NS odgovora u strijatumu u grupi pretretiranoj sa L-NAME.

Oxidative stress development in different brain structures and the influence of nitric oxide (NO) overproduction during sepsis was investigated using male Wistar rats. Rats were subjected to cecal ligation and puncture (CLP) or were sham-operated. To evaluate the source of NO production, 30 min before the operation septic and control animals were treated with single intraperitoneal doses of NO synthase (NOS) inhibitors: L-NAME and aminoguanidine (AG) (10, 30 or 90 mg/kg) and 7-nitroindazole (7-NI) (30 mg/kg). The concentration of GSH in the cortex, brain stem, cerebellum, striatum and hippocampus significantly decreased post CLP at both early and late stage sepsis. Lipid peroxidation also occurred in the cortex and cerebellum in late stage sepsis. Pre-treatment with a non-selective NOS inhibitor (L-NAME) and with selective inducible and neuronal NOS inhibitors (AG and 7-NI) revealed benefit effects on the GSH concentrations. Unexpectedly, NOS inhibition resulted in diverse effects on TBARS concentrations, suggesting the importance of specific quantities of NO in specific brain structures during sepsis.

IV Kongres farmaceuta Srbije sa međunarodnim učešćem, 29. novembar – 2. decembar 2006 godine, Beograd

IV Kongres farmaceuta Srbije sa međunarodnim učešćem, 29. novembar – 2. decembar 2006 godine, Beograd

IV Kongres farmaceuta Srbije sa međunarodnim učešćem, 29. novembar – 2. decembar 2006 godine, Beograd

Considering free radicals (FR) involvement in mechanisms of numerous xenobiotics' adverse effects (UV radiation, poisonings, some drugs, smoking, environmental pollutions, etc.), the goal of this paper is to elucidate principles of oxidative stress (OS), modes of antioxidanase (AO) actions, as well as, to pont at numerous brand new AO pharmaceutical products/drugs, their rationale usage and to emphasize expansion of activities regarding this subject. Free radicals (FR) produced in high concentration initiate development of OS. Partly, FR are involved in numerous pathologies (degenerative, malignant, cardiovascular diseases, diabetes mellitus, poisonings, etc.), aging, as well in physical exercises. Fundamental scientific studies in this field trigger complex machinery of pharmaceutical-management activities, such as: conferences, congresses, work shops, educative programs and projects, publishing of the science-popular books and brochures. Moreover, strategic program leads to the manufacture of the new product, what implies innovative and modern technology processing, and its realization on the market. Usually, wide range of human population consumes AO. ICT marketing (information-communication-technology) and concept of social marketing (rational usage of the recent AO products/drugs, prevention of diseases, cost benefit effect, etc.) are very well recognized. Marketing survey has shown increased consumption of AO. Importantly, diagnostic kits for determination of OS in presymptomatic phase of diseases are also available on the market, but yet unattractive for daily routine in our country, unlike in developed countries. Imajući u vidu uključenost slobodnih radikala (SR) u mehanizme štetnog delovanja brojnih ksenobiotika (UV zračenje, trovanja, neki lekovi, pušenje, zagađenje čovekove okoline itd.) cilj ovog rada je da približimo i objasnimo osnovne principe nastanka oksidativnog stresa (OS) i način delovanja antioksidanasa (AO), kao i da ukažemo na racionalno korišćenje preparata sa AO delovanjem koji su na tržištu i na porast aktivnosti koji se tiču ove problematike. Nastali u prekomernoj količini, SR iniciraju nastanak i razvoj OS. Jednim delom su uključeni u brojna patološka zbivanja (degenerativne bolesti, maligne bolesti, šećerne bolesti, kardiovaskularne bolesti, trovanja, starenje i td.), starenju, kao i pri fizičkoj aktivnosti. Fundamentalna naučna istraživanja u ovoj oblasti su pokrenula kompleksnu mrežu farmaceutsko-menadžerskih aktivnosti, usmerenih na organizovanje konferencija, kongresa, radionica, edukativnih programa i publikovanje naučnopopularne literature. Takođe, strateška planiranja idu ka proizvodnji novog proizvoda, što podrazumeva primenu inovativnih tehnoloških postupaka/procesa kod razvoja i proizvodnje, kao i njegovu realizaciju na tržištu. Preparati sa antioksidantnim dejstvom su najčešće namenjeni širokoj populaciji. U promotivnim akcijama ICT marketinga (information-communicatontehnology) prepoznajemo koncept socijalnog marketinga (pravilna i racionalna upotreba novog proizvoda/leka, preventiva bolesti, cena leka, itd.). Istraživanje tržišta proizvoda sa AO dejstvom ukazuje na porast prodaje ovih proizvoda. Značajno je napomenuti da ovo tržište obuhvata i niz proizvoda za laboratorijsku dijagnostiku OS u presimptomatskoj fazi bolesti, što je nedovoljno prepoznato i prihvaćeno na domaćem tržištu.

A high-performance liquid chromatographic (HPLC) assay was developed to determine HI-6 and trimedoxime concentrations in small volumes of plasma. The HPLC system comprised a high-pressure pump (model 2150), a multiwavelenght detector (model 2140) set at 284 nm and 295 nm for detection of trimedoxime and HI-6, respectively, and a sample injector (Rheodyne, model 7125) with a 20 μL sample loop. A Superpac starter kit 5 μm ODS 2; 4 x 250 mm (Pharmacia LKB) stainless steel column was used. To plasma sample, 10 μL of 20% trichlorocetic acid, was added. From the supernatant, 20 μL was injected directly into HPLC. The solvent was 25% acetonitrile in 0.08 mol/L acetic acid (pH 3) containing 0.01 mol/L heptane-1-sulfonic acid (sodium salt) and 0.0025 mol/L tetramethylammonium chloride. The flow rate was 0.8 mL/min HI-6, and trimedoxime eluted at about 6.0 min and 8.0 min, respectively. The limit of sensitivity was 1.4 μmol/L of trimedoxime and 2.5 μmol/L of HI-6. Recovery rates were 99.02% in determination of HI-6 and 100.6% in determination of trimedoxime. Coefficients of variation for HI-6 and trimedoxime ranged from 1.4% to 8.2% and 0.9% to 3.4%, respectively. Our results indicate that the method is sensitive, accurate and precise.