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WOS: 000319496400007, PubMed ID: 23713427, Poly(maleic anhydride-co-styrene) (MAST) was synthesized by a free-radical polymerization 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 Magnetic 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 62gmL(1) (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 20g/ml, while free PH exerted the same activity at 100g/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 100g/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., Sciences Research Projects Foundation of Cumhuriyet University [F258], This work was supported by Sciences Research Projects Foundation of Cumhuriyet University (Project No: F258). The structural characterizations were carried out at Technology Research and Developing Centre, Erciyes University, Kayseri, Turkey.

WOS: 000374972400021, PubMed ID: 27078662, Trichomonosis, caused by the protozoan parasite Trichomonas vaginalis, is a curable sexually transmitted disease that is most commonly encountered worldwide. Increasing importance of trichomoniasis and emerging of resistance against metronidazole lead to search for alternative drugs with different mode of activity. The purpose of this study was to determine in vitro activity of ceragenins (CSA-13, CSA-44, CSA-13, and CSA-138) against the metronidazole-susceptible (ATCC 30001) and metronidazole-resistant (ATCC 50138) strains of T. vaginalis. The effective concentrations were evaluated using two strains of T. vaginalis with different metronidazole susceptibilities (ATCC 30001 and ATCC 50138) in the presence of dilution series of ceragenins in 24-well microtitre assays. Overall, all the ceragenins killed the metronidazole-susceptible (ATCC 30001) and metronidazole-resistant (ATCC 50138) strains of T. vaginalis (p > 0.05). With regard to the their effects against the studied strains of T. vaginalis, in order of effectiveness, overall, the ceragenins ordered as CSA-13 (the most effective), CSA-131 and CSA-138 (effective similarly), and CSA-44 (the least effective) (p < 0.05). All of the ceragenins reduced the trophozoite numbers of both of studied strains of T. vaginalis with a time-and dose-dependent manner (p < 0.05). Although all of the study ceragenins, CSA-13, CSA-44, CSA-13, and CSA-138, killed the studied strains of T. vaginalis. CSA-13 is the leading ceragenin as the most effective anti-trichomonas compound, followed by CSA-131 and CSA-138. They have a potential to have a place in the armemantarium of gynecologic and urologic practice for the management of sexually transmitted diseases.

WOS: 000302264600008, PubMed ID: 22343683, Unfractionated heparin (UFH) and low molecular weight heparins have been used as anticoagulation agents in cardiovascular clinics for decades. However, these molecules also have potent antiangiogenic effects. Whereas, angiogenesis may be the most crucial determinant of the prognosis of cardiovascular diseases, and except some special situation, antiangiogenic effect is not desirable in the most of the cardiovascular disease. In this study, we aimed to compare the antiangiogenic potency of UFH, enoxaparin, and tinzaparin. The antiangiogenic efficacies of UFH, enoxaparin, and tinzaparin were examined in vivo by using the chick chorioallantoic membrane (CAM) model. Twenty fertilized eggs were used for each studied drug. Drug solutions were prepared in 10 and 1 IU/10 mu l concentrations. Decreases in the density of the capillaries were assessed and scored. All three drugs showed antiangiogenic effects on the chick CAM at the 10 IU/10 mu l concentration. However, the antiangiogenic score of the UFH was significantly higher than that of enoxaparin and tinzaparin at 1 and 10 IU/10 mu l concentrations. UFH had stronger and antiangiogenic potential than enoxaparin and tinzaparin. However, tinzaparin showed dose-dependent antiangiogenic effects. We think that an anticoagulant molecule with a less and dose-dependent antiangiogenic effect, as in the case of tinzaparin, may be more desirable in case of cardiovascular disease related with insufficient angiogenesis. Blood Coagul Fibrinolysis 23: 218-221 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

WOS: 000299519800004, PubMed ID: 21748351, Acanthamoeba keratitis is a painful corneal infection and difficult to treat because no sufficiently efficient drug has yet been available. The aim of the study therefore was to assess the therapeutic potential of miltefosine on Acanthamoeba keratitis-infected hamster eyes. The cornea of hamsters were infected with Acanthamoeba hatchetti, a human corneal isolate. On the fifth day, all the cornea were microscopically examined in order to determine the degree of infections (G, from 0 to 3). Four groups were then prepared: miltefosine (160 mu M); 0.1% propamidine isetionate plus 0.02% polyhexnide; infected control (0.05% ethanol in PBS) and a non-infected control (0.05% ethanol in PBS) groups. The treatment was continued for 28 days. After the treatment, the cornea were excised and used for Acanthamoeba culture to investigate the presence of Acanthamoeba growth. Miltefosine treatment yielded much higher cure scores than propamidine isetionate plus polyhexanide. On the last day of treatment, 85% of the miltefosine-treated eyes were graded as G0; no changes were observed in the uninfected control group eyes; G3 eyes showed only a partial improvement. Furthermore, no Acanthamoeba cells could be recovered from the miltefosine-treated eye samples. Miltefosine appeared to hold necessary therapeutic properties for the treatment of Acanthamoeba keratitis., Orphanidis Pharma Research GmbH, Vienna, Austria, This work was supported by Orphanidis Pharma Research GmbH, Wilhelminenstr. 91/IIf, 1160 Vienna, Austria. The authors also thank Prof. Ali Fazil Yenidunya for his invaluable contribution in the preparation of the manuscript.

WOS: 000294772400076, 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 degrees C and 38 degrees 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 ((1)H NMR). FTIR and (1)H 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. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 122: 2821-2828, 2011

WOS: 000268629800001, PubMed ID: 19450152, 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.

WOS: 000313517300006, PubMed ID: 22987257, The aim of this study was to investigate the effects of bemiparin, nadroparin, enoxaparin, and heparin on viability of human umbilical vein endothelial cells (HUVEC). Cultivation of HUVEC was performed in an incubator having 5 % CO2 at 37 A degrees C and with predefined supplemented medium, until cell monolayers attained confluence which occurred after 7 days. The assays were performed in the exponential growth phase of the cells. The cell viability was assessed using the cleavage of tetrazolium salts added to the culture medium. Heparin sodium, enoxaparin sodium, bemiparin sodium, and nadroparin calcium with concentrations of 100, 10, and 1 IU/100 mu L were used for the proliferation assay in which cells were incubated for 24, 48, and 72 h with these drugs. The experiments were conducted in four replicates. Among the study drugs with maximal concentration used in the experiments (100 IU/100 mu L), heparin was found to be associated with the lowest viability score in 24 and 48 h, while bemiparin showed the lowest at 72 h. Bemiparin 100 IU/100 mu L was significantly associated with lower viability score than that of bemiparin 10 IU/100 mu L and bemiparin 1 IU/100 mu L at every time interval. Among gradual concentrations of enoxaparin, however, concentration of 1 IU/100 mu L was associated with the lowest viability scores at every time point. Heparin 1 IU/100 mu L, nadroparin 100 IU/100 mu L, and enoxaparin 100 IU/100 mu L groups had the highest viability score after 72 h of incubation. Among low molecular weight heparins (LMWHs), 100 IU/100 mu L concentration of bemiparin was associated with a more pronounced effect on reducing viability of HUVEC after 72 h of incubation, while nadroparin 100 IU/100 mu L and enoxaparin 100 IU/100 mu L showed the least effects. LMWHs differ both from each other and heparin with respect to their effects on cellular viability of HUVEC in dose- and time-dependent manner.

WOS: 000303690800001, PubMed ID: 22285653, 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 10 mu mol/L. concentrations. Decreases in the density of the capillaries were assessed and scored. Results: Significant antiangiogenic effects were observed at 1 and 10 mu mol/L concentrations of levosimendan. The antiangiogenic scores of levosimendan at 1 and 10 mu mol/L concentrations were 0.6 and 1.10, respectively. The antiangiogenic score of bevacizumab, used as a positive control, was 0.95 at 1.0 mu mol/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. (C) 2012 Elsevier Inc. All rights reserved.

WOS: 000302814700043, PubMed ID: 22160252, Acanthamoeba keratitis (AK) is a painful, sight-threatening, and difficult-to-treat corneal infection caused by the ubiquitous free-living amoebae Acanthamoeba species. The aim of the present study was to compare the severity of keratitis, caused by Acanthamoeba hatchetii and Acanthamoeba castellanii infections, and to assess the therapeutic effects of combined chlorhexidine (CHX) and NeosporinA (R) treatment in rats. The rats were first divided into two groups, in which the eyes of the animals were infected with A. hatchetii or A. castellanii trophozoites. On day 5, all corneas were examined in order to determine the degree of infection (grade 0 to 3), and animals were divided into two new groups, treatment and infected control groups. The treatment was continued for 28 days, followed by excision and histological evaluation of the corneas. In conclusion, the clinical picture progressed more rapidly and severely in eyes infected by A. castellanii, while it was non-invasive and slower to progress with A. hatchetii. Moreover, eyes infected by A. hatchetii responded quicker and more positively to therapy, consistent with its clinical course, while a longer recovery was seen with A. castellanii. Histological examinations revealed the presence of A. castellanii and A. hatchetii trophozoites in the stroma of eyes of the treatment and control groups. As a result, our findings suggest that a combination of Neosporin with lower doses of CHX may be beneficial to treat patients with early diagnosis of AK.

WOS: 000287482000001, PubMed ID: 21142940, 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 25mg/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 100mg/mL in phosphate-buffered saline. Results of cytotoxicity experiments demonstrated that CSA-13 solution had mild toxicity at 100mg/mL concentration on cells, whereas it had no toxicity at 75mg/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.

WOS: 000295212200006, PubMed ID: 21605890, Introduction: The low-molecular-weight heparins have been demonstrated to have antiangiogenic effects in various assays. We aimed to demonstrate and compare the antiangiogenic effects of four types of commercially available low-molecular weight heparins in the chick embryo chorioallantoic membrane model. Materials and methods: The antiangiogenic efficacies of bemiparin, enoxaparin, nadroparin, and tinzaparin were examined in vivo in the chick chorioallantoic membrane model. Drug solutions are prepared in three different concentrations (100 IU, 10 IU, or 1 IU/10 mu l). For each set of experiment twenty fertilized eggs were used. The decrease of vessel formation is examined and scored according to previous literature. Results: Bemiparin, enoxaparin, nadroparin, and tinzaparin sodium all have antiangiogenic effects on chick chorioallantoic membrane at the concentration of 100 IU/10 mu l. This effect was also observed in 10 IU/10 mu l concentrations of nadroparin and tinzaparin. Conclusions: The low molecular weight heparins studied have obvious antiangiogenic effects. There may be a difference in the potency of the drugs that could have a significant implication for further clinical research. (C) 2011 Elsevier Ltd. All rights reserved.

WOS: 000252814200002, PubMed ID: 18370873, 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.