Goran M. Babić

Oxidative stress and changes in antioxidative defense system in erythrocytes of preeclampsia in women.

The present study was designed to investigate whether oxidative stress occurred to erythrocytes in preeclampsia and was related to disease. Indicative markers of oxidative stress and changes in antioxidant defense system were assayed in the erythrocytes of 22 healthy pregnant and 20 women with preeclampsia. Results of our work indicated high concentration of hydrogen peroxide, nitrite, peroxynitrite and lipid peroxides in preeclampsia compared to healthy pregnant women. Concentration of superoxide anion was lower in preeclamptic women. There were no differences in concentrations of vitamin E, reduced glutathione and oxidized glutathione. Activity of glutathione-S-transferase (GST) was higher while activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were lower in preeclamptic women. There were no differences in glutathione peroxidase (GSH-Px) activity between the two investigated groups. These results suggest that preeclampsia was characterized by oxidative stress and alteration of antioxidative defense system by disbalance in oxidative/antioxidative status of erythrocytes.

The antioxidative effect of estradiol therapy on erythrocytes in women with preeclampsia.

In the present study, we evaluated changes of both oxidative stress marker concentrations in erythrocytes and values of blood pressure, as well as their relation during short-term estradiol therapy in preeclampsia. Serum estradiol concentrations were also recorded. The results of this study showed significant decrease of mean arterial pressure (MAP) values during estradiol therapy, whereas there was no significant change in serum estradiol concentrations. Decreased concentrations of superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)), nitrite (NO(2)(-)), peroxynitrite (ONOO(-)) and lipid peroxide (LPO) were found during estradiol therapy in erythrocytes. No changes were found in the activity of gluthatione-S-transferase (GST). The decrease of MAP values was positively correlated with the reduction of concentrations of O(2)(-), H(2)O(2), NO(2)(-) and ONOO(-) in erythrocytes during estradiol therapy. The obtained results suggest that short-term intramuscular administration of estradiol shows antioxidative effects in erythrocytes and reduces blood pressure in preeclampsia.

Risk factors for potential drug-drug interactions in intensive care unit patients

Purpose: To determine risk factors for each severity‐based category of potential drug‐drug interactions (DDIs) encountered at intensive care unit (ICU) patients. Methods: This was a retrospective cohort analysis of patients treated at the ICU of the Clinical Center Kragujevac, a public tertiary care hospital in Kragujevac, Serbia. Three interaction checkers were used to reveal drug‐drug interactions: Medscape, Epocrates and Micromedex. Results: The study included 201 patients, 66.19 ± 16.11 years of age. Average number of DDIs per patient ranged from 10.49 ± 8.80 (Micromedex) to 29.43 ± 21.51 (Medscape). Antiarrhythmic or anticonvulsant drug prescription, Charlson Comorbidity Index, male sex, length of hospitalization, number of drugs or therapeutic groups prescribed and surgery increased the risk of DDIs in ICU patients, while presence of delirium or dementia and transfer from emergency department to ICU protected against. Conclusions: The rate of the DDIs in ICU patients at a tertiary care hospital is high, and adversely influenced by number of drugs or drug groups prescribed per patient, antiarrhythmic or anticonvulsant drug prescription, comorbidities, length of hospitalization and surgery. On the other hand, presence of cognitive deficit and transfer from emergency department to ICU protect ICU patients from the DDIs. Highlights:The rate of the DDIs in ICU patients at a tertiary care hospital is high.Drug related risk factors for DDIs: antiarrhythmics, anticonvulsants, number of prescribed drugs and therapeutic groups.Patient related risk factors for DDIs: higher Charlson Comorbidity Index, male sex, length of hospitalization and surgery.Presence of delirium or dementia and transfer from emergency department to ICU seem to protect against DDIs.The most frequently detected DDI was between midazolam and tramadol.

Investigational cannabinoids in seizure disorders, what have we learned thus far?

ABSTRACT Introduction:The anticonvulsant activity of cannabinoids attracted much attention in the last decade. Cannabinoids that are currently investigated with the intention of making them drugs for the treatment of epilepsy are cannabidiol, cannabidivarin, Δ9-tetrahydrocannabivarin, and Δ9-tetrahydrocannabinolic acid. Areas covered:In this review, the authors look at the results of preclinical and clinical studies with investigational cannabinoids. Relevant literature was searched for in MEDLINE, SCOPUS, EBSCO, GOOGLE SCHOLAR, and SCINDEX databases. Expert opinion: Preclinical studies confirmed anticonvulsant activity of cannabidiol and cannabidivarin in a variety of epilepsy models. While the results of clinical trials with cannabidivarin are still awaited, cannabidiol showed clear therapeutic benefit and good safety in patients with therapy-resistant seizures associated with Dravet syndrome and in patients with Lennox–Gastaut syndrome who have drop seizures. However, the full therapeutic potential of cannabinoids in treatment-resistant epilepsy needs to be investigated in the near future.

Estradiol decreases blood pressure in association with redox regulation in preeclampsia

ABSTRACT In this study, we tested a hypothesis that a short-term estradiol therapy may reduce blood pressure in preeclampsia by modulating plasma oxidative stress. The intramuscular injections of 10 mg 17-beta-estradiol were prescribed to preeclamptic pregnant women during the 3-day therapy before a labor induction. The analyses of mean arterial pressure (MAP), serum estradiol concentrations, plasma superoxide anion (O2.), hydrogen peroxide (H2O2), nitrites (NO2−), and peroxynitrite (ONOO−) were conducted before and during the therapy. We found that the plasma concentrations of oxidative stress markers, such as O2– and H2O2, are higher in preeclampsia and positively correlated with the MAP value. Moreover, it was shown that the plasma concentration of NO2– as an indicator of NO levels is higher in preeclampsia. A short-term intramuscular application of estradiol decreases the MAP value and the plasma concentration of O.–, H2O2, NO2−, and ONOO– in preeclampsia. A positive correlation between the decrease of MAP values and the decrease of plasma concentrations of O2–, H2O2, and ONOO– was found in preeclampsia during a short-term estradiol therapy. We conclude that the short-term estradiol therapy decreases the MAP value in preeclampsia by modulating the plasma oxidative stress. We speculate that the estradiol metabolism in preeclampsia is an important mechanism that contributes to vascular dysfunction.

Correlation Between Cervical Cytology and Histopathological Cervical Biopsy Findings According to the Bethesda System / Stepen Korelacije Cervikalne Citologije Po Bethesda Klasifikaciji Sa Patohistološkim Nalazima Cervikalne Biopsije

ABSTRACT The Pap test (Pap smear) is a morphological cytodiagnostic test that reveals premorbid and early stages of cervical cancer through the use of cervicovaginal cytology. The present study was conducted at the Department of Gynecology and Obstetrics, Clinical Center Kragujevac, from January 01, 2013, to December 1, 2013, with patients who were part of the national screening program and who used a secondary cytological examination (Pap test) performed using a conventional method. The patients were grouped according to the results of a Pap smear and histopathological findings. The classification of cytological smears was performed in accordance with the Bethesda system. The hypotheses established in this study were statistically tested. The greatest number of cytological findings was NILM. However, the most frequent abnormal cytological findings in terms of percentage were ASC-US. After secondary cervical findings of 8.1% of the total number of women, biopsies were performed. In 68.57% of the biopsies performed, CIN was present in all of them, with the most frequent ones being LSIL (50.6%), HSIL (10.4%) and CA Invasiva (0.5%). This study, using the X2 test, confirmed that cervical cytology and biopsy results are dependent features (sig. = 0.036), between which there is a medium association (Cramer’s V = 0.176). In the ASC-US cytological findings, small percentages of CIN1 and CIN2 were detected. Cervical cytology in this study presented high sensitivity, specificity, positive and negative predictive value. As a relatively inexpensive, painless and easily approachable method, cervical cytology fully substantiates its implementation in diagnostic procedures as well as in organized screening programs. SAŽETAK Papa test je morfološki citodijagnostički test kojim se pomoću analize cervikovagnalne citologije otkrivaju predstadijumi i rani stadijumi karcinoma grlića materice. Studija je sprovedena na Klinici za ginekologiju i akušerstvo, KC Kragujevac u periodu od 01. 01. 2013. god. do 01. 12. 2013. god. na pacijentkinjama kojima je u okviru Nacionalnog skrining programa odrađen sekundarni citološki pregled (PAP test) konvencionalnom metodom. Pacijentkinje su grupisane prema rezultatima PAP testa i patohistološkim rezultatima. Klasifikacija citoloških briseva je vršena prema Bethesda klasifikaciji. Statističkim testovima su testirane hipoteze postavljene u ovoj studiji. Najveći broj citoloških nalaza bio je NILM. Procentualno najzastupljeniji abnormalni citološki nalazi su bili ASCUS. Nakon sekundarnog cervikalnog nalaza kod 8,1% od ukupnog broja žena je odrađena biopsija. U 68,57% urađenih biopsija je bio prisutan CIN od kojih je najzastupljeniji bio nalaz LSIL (50,6%), zatim HSIL (10,4%), i CA INVASIVA (0,5%). Ovom studijom, uz primenu Xi2 testa, potvrđeno je da su cervikalna citologija i rezultati biopsije zavisna obeležja (Sig.=0,036), između kojih postoji veza srednje jačine (Cramer’s V=0,176). U citološkom nalazu ASCUS detektovano je mali procenat CIN1 i CIN2. Cervikalna citologija u ovoj studiji pokazuje visoku senzitivnost, specifičnost, pozitivnu i negativnu prediktivnu vrednost. Kao relativno jeftina, bezbolna i lako dostupna metoda u potpunosti potvrđuje svoju primenu, kako u dijagnostičkim procedurama, tako i u organizovanim skrining programima.