Search

In the treatment of cutaneous leishmaniasis (CL), developing drug resistance, existing toxic effects of drugs and failure respond to treatment cause the need to try different treatment methods. We investigated the effect of gold-conjugated macrophage-specific antibody on amastigotes under infra-red light for the treatment of CL. Female BALB/c (4–8 weeks old, 20 ± 5 g weight) mice were used in the study. The L. major strain was inoculated on the soles of mice in amastigote form and subpassed. Nanogold (Au), Au + macrophage-specific antibody (MSA) modification and near infra-red (NIR) (5 seconds) were applied to mice groups that developed cutaneous leishmaniasis on their soles. On the 5th and 10th days of the treatment, the lesions were examined clinically and pathologically. When the erythema values were examined, the highest decrease was calculated in the Au + MSA + NIR group in the measurements made on the 10th day (p < 0.014). The best improvement in 10th day measurements is in the NIR and Au + MSA + NIR groups when area values were examined (p = 0.011, p = 0.001). There was a statistically significant difference between the groups in terms of parasite load (PL) (p < 0.005) in pathological evaluation. According to PL grouping, the best result is NIR (p = 0.002). When both main titles (clinical and pathological) are examined, the Au + MSA + NIR group is thought to have an optimal therapeutical feature. Au + MSA + NIR combination could be a new treatment approach for CL treatment. [ABSTRACT FROM AUTHOR]

Background: Although there have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV) titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ in CCHF patients. Methods: In total, 31 CCHF cases (11 fatal) were studied. Serum samples were obtained daily from all patients from the time of admission and continued for a 7-day hospitalization period for serologic (ELISA), virologic (real-time PCR), and cytokine (ELISA) analysis. Results: The mean serum CCHFV titer at admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6 and TNF-α at admission were found to be significantly increased in fatal cases. The serum levels of IL-6, TNF-α and serum CCHFV titer at admission were significantly and positively correlated with disseminated intravascular coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r = 0.625, p = 0.003, respectively). When the data obtained from the sequential determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-α, IL-10 and IFN-γ were grouped according to the days of illness, the initial serum CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09 (copies/mL) in a survivor on the 2 day of illness. While significant alterations were observed in all cytokines during the monitoring period, IL-6 levels remained consistently higher in fatal cases and TNF-α levels increased in both in fatal and non-fatal CCHF cases. Conclusions: The increased CCHFV load and higher concentrations of IL-6 and TNF-α, the presence of DIC, and the absence of CCHFV specific immunity are strongly associated with death in CCHF. [ABSTRACT FROM AUTHOR]

Poly(maleic anhydride-co-styrene) (MAST) was synthesized by a free-radical polymeriza-tion reaction. A bioactive molecule, procainamide hydrochloride (PH), was then conjugated to MAST. The conjugation product was named as MAST/PH. Structural characterization of MAST and MAST/PH was carried out by Fourier Transform Infrared and Nuclear Mag-netic Resonance spectroscopy. Their molecular weights were determined by size-exclusion chromatography. A mechanism was then suggested for the conjugation reaction. The results of the cytotoxicity assay, employing a mouse fibroblast cell line (L929), indicated that MAST/PH had no cytotoxicity at concentrations <62pgmL~' (p > 0.05). Antiproliferative activities of MAST/PH and PH were determined by the BrdU cell proliferation ELISA assay, using C6 and HeLa cell lines. In the experiment, two anticancer chemotherapy drugs, cisplatin and 5-fluorouracil, were included as positive control. Antiproliferative activity results demonstrated that MAST/PH yielded the highest suppression profile (approximately 42%) at 20p.g/ml, while free PH exerted the same activity at 100pg/ml. Interestingly, both MAST/PH and PH suppressed the proliferation of only one of the cell lines, C6 cells. Both cisplatin and 5-fluorouracil yielded approximately 60% antiproliferative activity on C6 cells at 20 and 100pg/ml concentrations. Antiangiogenic capacity of both MAST and MAST/PH was also investigated by using the chicken chorioallantoic membrane assay. Results obtained indicated that while MAST/PH could be included into the category of good antiangiogenic substances, the activity score of MAST was within the weak category. [ABSTRACT FROM AUTHOR]

Poly[(maleic anhydride)- co-(vinyl acetate)] (MAVA) copolymer was synthesized by free radical polymerization reaction, in methyl ethyl ketone at 80 °C, using benzoyl peroxide as the initiator. The copolymer was then modified with a biomolecule, noradrenaline (NA). The modification reaction was performed at 70 °C in dimethylformamide containing triethylamine as the catalyst. The modified polymer was named MAVA/NA. Structural characterization of the copolymer and the modified product was carried out by Fourier transform infrared (FTIR) and 1H NMR and 13C NMR spectroscopy. The FTIR, 1H NMR and 13C NMR spectra confirmed that NA was successfully covalently bound to the MAVA copolymer backbone. Surface morphology was visualized by atomic force microscopy. The cumulative release of NA from MAVA/NA was determined in phosphate buffered saline solution for 7 days at 37 °C and compared with MAVA. Cytotoxicity of the MAVA/NA was evaluated by using a mouse fibroblast cell line (L929). Results obtained indicated that MAVA/NA had almost no toxicity and no negative effect on cell viability at 250 µg mL−1 concentration. © 2012 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Maleic anhydride copolymer was modified with another biologically active agent, noradrenaline (NA), using both chemical and enzymatic methods. The modification and synthesized products were named as follows: chemical modification, MASTNAc; enzymatic modification, MASTNAe; enzymatically synthesized MASTNA from individual monomers, MASTNAem. Chemical and enzymatic reactions were performed at 70°C and 38°C, respectively. In the chemical reactions azobisisobutyronitrile was used as the initiator. In the enzymatic reactions, an extracellular extract, including an enzyme with peroxidase-like activity, was used. All the reactions were performed in an organic medium, methyl ethyl ketone. Structural characterization of the copolymer and modified copolymer were carried out by Fourier transform infrared (FTIR) and nuclear magnetic resonance (1H NMR). FTIR and 1H NMR spectra confirmed that NA was successfully covalently bound onto the MAST copolymer backbone by both chemical and enzymatic methods. Surface morphology of the samples was studied by scanning electron microscopy. Results obtained indicated that chemical and enzymatic addition of NA to MAST backbone yielded products having quite similar physical and chemical properties. On the other hand, MASTNA-modified copolymer synthesized by individual monomers appeared to be different in its chemical structure. Furthermore, enzymatic modification and synthesis appeared to provide a good alternative method because it required much milder conditions such as low temperature, and better product qualities: higher solubility in water, higher yield and purity. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

Acanthamoeba is a free-living amoeba causing a potentially blinding infection of the cornea. Acanthamoeba keratitis is difficult to treat, without total efficacy in some patients because of cysts that are less susceptible than trophozoites to the usual treatments. Contact lens wearers are most at risk and account for some 95% of cases. Cationic steroid antibiotic (CSA)-13 is a small molecule aminosterol that has been shown to mimic the activity of endogenous antimicrobial peptides and has bactericidal activity based on membrane disruption. We investigated here the in vitro effectiveness of CSA-13 with a concentration of 100, 75, 50, and 25 mg/mL on proliferation of Acanthamoeba castellanii trophozoites and cysts and cytotoxic potential. CSA-13 was evaluated for its amoebicidal activity using an inverted light microscope at 1, 2, 4, 8, 12, and 24 h. For the determination of cytotoxicity of the CSA-13 on L929 cells, agar diffusion tests were performed. CSA-13 inhibited trophozoite growth in dose- and time-dependent ways. At 1 h, no viable trophozoites were observed in the presence of CSA-13 solution in a concentration 100 mg/mL in phosphate-buffered saline. Results of cytotoxicity experiments demonstrated that CSA-13 solution had mild toxicity at 100 mg/mL concentration on cells, whereas it had no toxicity at 75 mg/mL concentration. The findings of this experiment as in vitro ameboebicidal activity for Acanthamoeba suggest that CSA-13 has a potential to be used as a new agent in lens solutions to prevent Acanthamoeba growth and infections. [ABSTRACT FROM AUTHOR]

Background/Aims: Amoebic keratitis is difficult to treat with total efficacy in some patients because of cysts, which are less susceptible than trophozoites to the usual treatments. We investigated the in vitro effectiveness of methanolic extract of Salvia staminea and Salvia caespitosa against Acanthamoeba castellanii, as well as their cytotoxicity on corneal cells in vitro. Methods: Extracts were evaluated for their amoebicidal activities using an inverted light microscope. The effect of Savia species, with concentrations ranging between 1.0 and 32.0 mg/mL, on the proliferation of A. castellanii trophozoites and cysts were examined in vitro. For determining the cytotoxicity of Salvia species on corneal cells, agar diffusion tests were performed. Results: According to the results obtained from these tests, S. staminea showed remarkable amoebicidal effect on A. castellanii. In the case of the cytotoxic activity, methanolic extract of S. staminea showed no cytotoxicity on corneal cells with a concentration of 16 mg/mL. Conclusions: Methanolic extract of S. staminea could be considered a new natural agent against Acanthamoeba. However, further evaluation by in vivo testing is needed to confirm the efficiency of its biological effect. [ABSTRACT FROM AUTHOR]

Free-living protozoa of the genus Acanthamoeba can cause one of the most severe, potentially sight-threatening infections of the eye, the so-called A. keratitis. A. keratitis is difficult to treat because, under adverse conditions, the amoeba encyst and medical therapy is often less effective against cysts than against trophozoites. The aim of this study was to investigate evaluate the in vitro effect of the nonpolar subfraction of the methanol extract of garlic ( Allium sativum) on the growth of A. castellanii trophozoites and cysts and also its cytotoxicity on corneal cells in vitro. Extract was evaluated for its amoebicidal activity, using an inverted light microscope. The effect of the nonpolar extract with the concentrations, ranging from 0.78 to 62.5 mg/mL on the proliferation of A. castellanii trophozoites and cysts, were examined in vitro. For the determination of cytotoxicity of the extract on corneal cells, agar diffusion tests were performed. The present study demonstrates the in vitro effectiveness of the garlic against the A. castellanii growth curve. Evaluations revealed that garlic inhibits trophozoite growth in dose- and time-dependent ways. In the case of the cyctotoxic acitivities, it showed no cytotoxicity for the cornea cells in the concentration of 3.90 mg/mL. These findings indicate that nonpolar subfraction of the methanol extracts of garlic has amoebicidal, as well as its cysticidal, properties on Acanthamoeba trophozoites and cysts. Garlic alone, and in combination with other amoebicidal agents, may be used in clinical practices after further investigations. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the in vitro effects of an ethanolic extract of propolis on the growth and adherence of Acanthamoeba castellanii trophozoites and cysts. Methods: The effect of propolis with concentrations of 8.0, 6.0, 5.0, 4.0, 3.0, and 2.0 mg/mL on the proliferation of A. castellanii trophozoites, and with a concentration of 62.25, 31.25, 15.62, 7.81, 3.90, 1.95, and 0.97 mg/mL on the proliferation of A. castellanii cysts, at 1, 3, 6, 12, 24, 48, and 72 h were examined in vitro. Results: After 1–72 h, incubation in concentrations between 2.0 and 6.0 mg/mL, its effect was amoebistatic; at concentrations of 8.0 mg/mL and higher, its effect was amoebicidal. After 48 h or longer incubation times at 15.62 mg/mL and at higher concentrations, the propolis extract was cysticidal. At concentrations of 1.97 mg/mL or lower, there was no observable effect at any time point. Conclusions: These findings indicate that ethanolic extract of propolis has amoebicidal, as well as cysticidal, properties for Acanthamoeba trophozoites and cysts. Propolis alone, or in combination with other amoebicidal agents, may be used in clinical practice after further investigations. [ABSTRACT FROM AUTHOR]

Abstract: Background: There is a physiological balance between the stimulatory and inhibitory signals for blood vessel growth. In many symptomatic patients with peripheral artery disease, coronary artery disease, and ischemic chronic wounds, there is a pathological insufficiency of angiogenesis. Therefore, determining the angiogenic or antiangiogenic effects of molecules currently used in cardiovascular treatment is crucial. Although levosimendan is the most well studied calcium sensitizer in preclinical and clinical practice, to the best of our knowledge, there are no previous studies investigating its angiogenic or antiangiogenic effects. In the present study, we aimed to investigate the effects of levosimendan on angiogenesis. Methods: The antiangiogenic efficacy of levosimendan was examined in vivo in the chick chorioallantoic membrane (CAM) model by using 20 fertilized eggs and drug solutions of 1 and 10μmol/L concentrations. Decreases in the density of the capillaries were assessed and scored. Results: Significant antiangiogenic effects were observed at 1 and 10μmol/L concentrations of levosimendan. The antiangiogenic scores of levosimendan at 1 and 10μmol/L concentrations were 0.6 and 1.10, respectively. The antiangiogenic score of bevacizumab, used as a positive control, was 0.95 at 1.0μmol/L concentration. No significant difference was found between the antiangiogenic scores of levosimendan and bevacizumab (p=0.54). Conclusions: Our results indicate that levosimendan has antiangiogenic effects on the chorioallantoic membrane. However, these findings must be confirmed in future studies on humans. [Copyright &y& Elsevier]