Inter-Specialty Controversies on the Treatment of Cardiovascular Diseases during Pregnancy: A Questionnaire Study.

Background and Objectives: Management of cardiovascular disease (CVD) during pregnancy is challenging and usually requires eminence-based decisions due to limited strong-evidence data in this field. The purpose of our study was to compare the attitudes of anaesthesiologists, cardiologists, and gynaecologists towards the diagnosis and treatment of potentially life-threatening CVDs during pregnancy. Materials and Methods: A cross-sectional, questionnaire-based study was performed among 111 doctors (55 anaesthesiologists, 36 cardiologists, 20 gynaecologists). Personal opinions on the recommendations (n = 19) regarding rare, potentially life-threatening CVDs during pregnancy were recorded using a five-item Likert scale. Results: Opinions regarding eight statements (42%) varied substantially between specialties (p < 0.05). The most distinctive differences between physicians concerned the following recommendations: "thrombolysis should only be used in pulmonary embolism with cardiogenic shock" (agree: 52.7% of anaesthesiologists, 80.4% of cardiologists, 25.0% of gynaecologists; p < 0.001); "women with the antiphospholipid syndrome should restart treatment with vitamin K antagonists from the second trimester of pregnancy" (agree: 12.7% of anaesthesiologists, 69.4% of cardiologists, 20.0% of gynaecologists; p < 0.001); "women with symptomatic pulmonary hypertension should have a Swan-Ganz catheter inserted for labour" (agree: 20.0% of anaesthesiologists, 11.1% of cardiologists, 55.0% of gynaecologists; p = 0.001). Conclusions: Physicians' opinions regarding diagnostics and treatment of CVDs in pregnancy remain controversial. A multidisciplinary approach is recommended to ensure the safety and effectiveness of management in these unique medical conditions.

Assessment of Immunomodulatory Activities and in vitro Toxicity of New Quinolone 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate.

Our previous studies on leukemia cells L1210 and cervical cancer HeLa cells revealed cytotoxic effects of the 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate (E2h), a new synthetically prepared quinolone derivative, toward selected cancer cell lines. The aim of the present study was to examine the cytotoxicity of E2h toward next cell lines and tissues; that is, human cancer HL-60 and A549 cells, human non-cancer fibroblast BHNF-1 cells, and reconstructed human epidermis tissues. Further we investigated the immunomodulatory activity of E2h on murine macrophage RAW 264.7 cells. Selenadiazoloquinolone E2h induced specific antiproliferative/cytotoxic activity against leukemia HL-60 cells and is the potent inducer of apoptotic cell death. Quinolone derivative demonstrated the immunomodulatory activities on RAW 264.7 cell line murine macrophages. The immunobiological studies revealed time- and concentration-dependent effective immunomodulation of pro- and anti-inflammatory cytokines' release and antiproliferative/cytotoxic effect following exposure of RAW 264.7 cells to E2h. ABBREVIATIONS: DMEM, Dulbecco's modified eagle medium; DMSO, Dimethylsulfoxide; EtBr, Ethidium bromide; PI, Propidium iodide; E2h, 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate.

Hydrogen peroxide generation by the Weissberger biogenic oxidative system during hyaluronan degradation.

By applying the enzyme catalase, our study on hyaluronan degradation confirms the generation of hydrogen peroxide using the Weissberger biogenic oxidative system (WBOS), which is composed of ascorbate and cupric ions. Dynamic viscosities of hyaluronan (HA) solutions influenced by WBOS in the absence and presence of catalase were analysed by rotational viscometry. Molar masses of HAs were determined by size-exclusion chromatography with multi-angle laser-light scattering. Our results show that catalase dose-dependently inhibited the degradation of HA macromolecules, which presumably confirms the generation of H2O2 in the reaction system. This has implications in range of biomedical applications such as arthritic joint treatment, tissue engineering, ocular and cosmetic surgery.

Kinetics of ABTS derived radical cation scavenging by bucillamine, cysteine, and glutathione. Catalytic effect of Cu(2+) ions.

Kinetics of reduction of the stable radical cation derived from 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) in reaction with the anti-rheumatic drug bucillamine (BUC) and two reference thiols - cysteine (Cys) and glutathione (GSH) was followed spectrophotometrically in acidic medium with 10-fold molar excess of the reductant. Decay of the radical is governed by pseudo-first order kinetics with small deviation in the case of GSH. H(+) ions displayed second order inhibition of the reaction with all the studied compounds. The reaction of BUC exhibits zero order kinetics to the radical at lower acidities with a moderate acceleration of the reaction rate by H(+) ions. A significant catalytic effect of Cu(2+) ions on the reactions with all the reductants was observed. The most sensitive to Cu(2+)-catalysis was the reaction of BUC with the radical cation, while Cu(2+) ions showed much lower effect on the reaction with GSH. The presence of EDTA strongly inhibited the reactions and equalized the reaction rates for all the reductants. A Cu(I) selective chelator bathocuproine disulfonate reduced the reaction rate with Cys, but accelerated the reaction with BUC at the lower acidities. The experimental results were rationalized in the framework of the mechanism of reductive chelation. The conclusions may have important consequences for interpretation of antioxidant capacity assays, such as TEAC, utilizing the ABTS derived radical cation.

Study of the cytotoxic/toxic potential of the novel anticancer selenodiazoloquinolone on fibroblast cells and 3D skin model.

The new synthetically prepared quinolone derivative 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo [3,4-h]quinoline-7-carboxylate (E2h) showed in our previous study cytotoxic effects towards tumor cells and immunomodulatory activities on RAW 264.7 cell line murine macrophages. E2h may have a potential use as a novel chemotherapeutic agent with immunomodulatory properties and the ability to induce apoptotic death of cancer cells. The aim of the present study was to examine the antiproliferative/cytotoxic activities of E2h on human non-cancer fibroblast BHNF-1 cells and reconstructed human epidermis EpiDerm™. Further the effects of E2h on tissue structure and morphology were examined. Cytotoxic/toxic studies showed that selenadiazoloquinolone is not toxic on normal human fibroblast cells BHNF-1 and dimensional skin constructs EpiDerm™. Evaluation of morphological changes in EpiDerm™ showed no change in the construction and morphology of skin tissue treated by E2h compared to control.

Influence of tiopronin, captopril and levamisole therapeutics on the oxidative degradation of hyaluronan.

The ability to protect hyaluronic acid (HA) from oxidative degradation by cupric ions and ascorbate (production of (•)OH and peroxy-type radicals) during acute phase joint inflammation has been investigated using the following drugs: tiopronin, captopril, and levamisole. Radical scavenging activity, i.e. the propensity for donation of electrons was assessed for the drugs by ABTS and DPPH assays. The kinetics of HA degradation have been measured in the presence of each drug using rotational viscometry. The results of ABTS and DPPH assays show the highest radical scavenging activity for captopril, followed by tiopronin. For levamisole, no effect was observed. Captopril and tiopronin prevented HA degradation induced by (•)OH radicals in a similar manner, while tiopronin was more effective in scavenging peroxy-type radicals. On the other hand, levamisole was shown to be a pro-oxidant. Recovered HA fragments were characterized using FT-IR analysis, the incorporation of a sulphur atom from captopril and tiopronin but not from levamisole into the HA molecule was demonstrated.

Determination of antioxidative properties of herbal extracts: Agrimonia herba, Cynare folium, and Ligustri folium.

OBJECTIVES: Hyaluronan (HA) molecules were exposed to free radical-mediated degradation performed by the reaction mixture Cu(II) and ascorbate, the so-called Weissberger biogenic oxidative system, which mimics the situation of acute inflammation. To achieve protection of HA from degradation, herbal extracts such as Agrimonia herba, Cynare folium, and Ligustri folium were selected. METHODS: Time- and dose-dependent changes of dynamic viscosity of the HA solutions in the presence and absence of the herbal extracts were recorded by rotational viscometry (RV). Radical scavenging capacity of the extracts was investigated by the spectrocolorimetric ABTS and DPPH assays. RESULTS: The results of RV revealed that the extracts of Agrimonia herba and Cynare folium were effective in inhibiting the degradation of HA. On the other hand, the extract of Ligustri folium increased the rate of HA degradation. The highest radical scavenging capacity of ABTS(*+) and DPPH(*) was observed in Agrimonia herba extract followed by the extracts of Ligustri folium and Cynare folium.