Papers by Zacharias Suntres
Journal of Liposome Research, Mar 9, 2012
Journal of Drug Targeting, May 26, 2011
Journal of Drug Targeting, 1995
... the accumula-tion of paraquat in tissues and include procedures such as induced emesis or dia... more ... the accumula-tion of paraquat in tissues and include procedures such as induced emesis or diarrhoea, gastric lavage, administration of oral absorbents, hemodialysis, and hemoperfusion (Bateman, 1987; Meredith and Vale, 1987; Proudfoot ... 494 ZE SUNTRES AND PN SHEK ...
Biochemical Pharmacology, Mar 1, 1992
ABSTRACT
Microbial Pathogenesis, 2002
Pseudomonas aeruginosa is a Gram-negative pathogen that can cause lung injury in immunocompromise... more Pseudomonas aeruginosa is a Gram-negative pathogen that can cause lung injury in immunocompromised patients, primarily by inducing a release of host-derived mediators responsible for the influx of phagocytes to the lung. These phagocytes exert their antimicrobial actions by releasing toxic metabolites, including reactive oxygen species and proteases, which can also cause cell injury. This study was carried out to assess the pulmonary oxidant-antioxidant status of male adult Sprague-Dawley rats infected with different numbers of P. aeruginosa (10(4)-10(7)cfu/animal). Intratracheal instillation of P. aeruginosa resulted in lung injury, as evidenced by increases in wet lung weight and decreases in the lung activities of angiotensin converting enzyme and alkaline phosphatase, enzymes localized primarily in pulmonary endothelial and alveolar type II epithelial cells, respectively. The P. aeruginosa -induced lung injury was directly related to the infiltration of neutrophils, as indicated by increases in myeloperoxidase activity. The challenge of animals with P. aeruginosa resulted in increases in lipid peroxidation and decreases in glutathione content, which were associated with the indices of lung injury and neutrophil infiltration. Such a challenge also resulted in weakening the antioxidant defence system, as evidenced by decreases in superoxide dismutase, catalase and glutathione peroxidase activities. These data suggest that changes in the pulmonary oxidant-antioxidant status may play an important role in the P. aeruginosa -induced lung injury.
Chemico-Biological Interactions, Dec 1, 2010
Paraquat (PQ), a commonly used herbicide, is highly toxic to humans and animals. The primary inju... more Paraquat (PQ), a commonly used herbicide, is highly toxic to humans and animals. The primary injury occurs in the lung, where PQ is actively taken up by alveolar epithelial cells and consequently produces damaging reactive oxygen species (ROS) via redox cycling. ROS have also been shown to induce expression of several early response genes and to activate transcription factors, which may contribute to the inflammatory response associated with PQ injury. In order to further elucidate the mechanism(s) of PQ injury, we investigated its effects on the cellular status and gene expression profile of immortalized human alveolar epithelial A549 cells in vitro. Incubation of cells with PQ resulted in concentration-and time-dependent PQ uptake, which correlated with increases in intracellular ROS levels and decreases in intracellular glutathione content, mitochondrial membrane potential, and cell viability. Gene array analysis showed differential expression in response to PQ exposure over time, particularly increases in: (i) the expression of growth arrest and cell cycle-related genes (e.g. CDKN1A, DDIT3 GADD45A, GDF15, MDM2, EGR1, CASP10, CASP8) and (ii) the expression of pro-inflammatory genes (e.g. IL1A, IL6, IL18, NFKB1, SER-PINE1), which correlated with increases in the secretion of pro-inflammatory cytokines (e.g. IL-8, IL-6). These data suggest that uptake of PQ by A549 cells altered the cellular redox status and the expression of several early response genes, including the inflammatory response, all of which might contribute to the overall cytotoxicity of PQ.
International Journal of Antimicrobial Agents, Jul 1, 2009
and had an MIC of 2 mg/L. S. hominis novobiosepticus, S. lugdunensis, and S. simulans were most s... more and had an MIC of 2 mg/L. S. hominis novobiosepticus, S. lugdunensis, and S. simulans were most susceptible, all having an MIC of 0.25 mg/L or less. A correlation between degree of vancomycin susceptibility and relative daptomycin susceptibility was observed, with isolates with higher MICs to vancomycin showing a decreased susceptibility to daptomycin. The presence or absence of the MecA gene did not appear to influence daptomycin MICs. The correlation between Etest and the agar dilution method was good. Despite a tendency towards higher MICs by agar dilution, 95.4% and 93.4% of results of agar dilution were within one dilution of the Etest MIC. Reproducibility of the agar dilution method was excellent. Conclusions: Daptomycin has excellent activity against all species of CoNS and non susceptible strains are rare. Our results also demonstrate that the agar dilution method produces acceptable susceptibility results and is a convenient alternative for in-vitro studies of daptomycin.
Free Radical Biology and Medicine, 1990
Free Radical Biology and Medicine, 1990
Free Radical Biology and Medicine, 1990
Springer eBooks, 2006
Oxidative stress has been characterized by an elevation in the steady- state concentration of rea... more Oxidative stress has been characterized by an elevation in the steady- state concentration of reactive oxygen species including superoxide anion, hydrogen peroxide, and hydroxyl radical. There is increasing evidence connecting oxidative stress with a variety of pathological conditions including cancer, cardiovascular diseases, chronic inflammatory disease, post-ischaemic organ injury, diabetes mellitus, xenobiotic/drug toxicity, and rheumatoid arthritis. A pharmacological strategy in preventing
Expert Opinion on Drug Discovery, Mar 10, 2020
Introduction: To date, over 1,000 lichen secondary metabolites have been identified. Despite thei... more Introduction: To date, over 1,000 lichen secondary metabolites have been identified. Despite their promising cytotoxic properties, the number of literature reports on anticancer evaluation of lichenochemicals is limited. As cancer prevalence among the human population increases, there is growing interest in lichens as a natural source of secondary metabolites for anti-cancer drug discovery and development. Areas covered: The lack of significant progress in lichen anticancer research is due to the low levels of cytotoxic compounds contained in lichens, the technical difficulties associated with their isolation and characterization, and the insufficient understanding of their mechanism of action on different cancer cell lines. In this review, the authors discuss these challenges and provide systematically organized information on the limitations and advantages of commonly used and newly developed methods for lichen exploration and screening of lichen secondary metabolites for their anticancer potential. Expert opinion: Recent research activities have demonstrated that lichen secondary metabolites possess chemotherapeutic properties. A systematic and multidisciplinary approach is required to advance lichen research and improve our understanding of the mechanisms responsible for the potent cytotoxic properties of lichenochemicals. More efforts need to focus on screening and discovery of new lichen-derived compounds with unique anticancer properties.
Journal of the Science of Food and Agriculture, May 29, 2017
BACKGROUND: Lichens provide a large array of compounds with the potential for pharmaceutical deve... more BACKGROUND: Lichens provide a large array of compounds with the potential for pharmaceutical development. In the present study, extracts from three previously undescribed North American lichen species were examined for antioxidant, antibacterial and anticancer activities. RESULTS: The results from this study demonstrated the following: 1) Acarospora socialis ethanol extract exhibited significant DPPH antioxidant scavenging activities which were concentration-dependent; 2) the acetone and ethyl acetate extracts of Xanthoparmelia mexicana inhibited Gram-positive bacteria but had no effect on Gram-negative bacteria; the X. mexicana acetone extract yielded a minimum inhibitory concentration (MIC) of 20.9 ug mL-1 against Staphylococcus aureus, and 41.9 ug mL-1 against Enterococcus faecalis; 3) the acetone extract of Lobothallia alphoplaca inhibited growth of cultured breast cancer MCF-7 cells at with an effective concentration (EC 50) of 87 µg mL-1 ; the MCF-7 cell cycle appears arrested in the G2 phase whereas the DNA synthesis cell cycle (S) may be inhibited. CONCLUSION: New lichen species that possess strong biological activities have been identified. These lichens comprise secondary metabolites that possess antioxidant, antibacterial and anticancer properties.
Exosomes and microvesicles, 2013
Exosomes are membrane vesicles with a diameter of 40-100 nm that are secreted by many cell types ... more Exosomes are membrane vesicles with a diameter of 40-100 nm that are secreted by many cell types into the extracellular milieu. Exosomes are found in cell culture supernatants and in different biological fluids and are known to be secreted by most cell types under normal and pathological conditions. Considerable research is focusing on the exploitation of exosomes in biological fluids for biomarkers in the diagnosis of disease. More recently, exosomes are being exploited for their therapeutic potential. Exosomes derived from dendritic cells, tumor cells, and malignant effusions demonstrate immunomodulatory functions and are able to present antigens to T-cells and stimulate antigenspecific T-cell responses. Exosomes have also been examined for their therapeutic potential in the treatment of infections such as toxoplasmosis, diphtheria, tuberculosis and atypical severe acute respiratory syndrome as well as autoimmune diseases. Attempts to find practical applications for exosomes continue to expand with the role of exosomes as a drug delivery system for the treatment of autoimmune/inflammatory diseases and cancers.
Biochemical Pharmacology, Mar 1, 1990
To elucidate the mechanism underlying the protective effect of metallothionein (MT) against carbo... more To elucidate the mechanism underlying the protective effect of metallothionein (MT) against carbon tetrachloride (CCL) toxicity, in uitro experiments were carried out to study the interaction of metallothionein and CCL,. Results from this study showed that incubation of Cd,Zn-MT with CCI, in the presence of hepatic microsomes and NADPH resulted in a time-dependent depletion of MT thiols with a concurrent reduction in the metal-binding sites of the protein. Moreover, this reaction also released Zn and Cd from MT. Results from experiments conducted to determine whether or not the CC&-induced decrease in MT-thiol content was due to the scavenging of Ccl, metabohte(s) showed that the trichloromethyl radical, chloroform and phosgene as well as the products of CCL-induced microsomal lipid peroxidation were not directly involved. Although covalent binding of r4CC1, to MT was detected following incubation in the presence of a microsomal bioactivation system. it did not account for the CC&-induced loss of MT thiol groups for the following reasons: (i) prior oxidation of sulfhydryl groups of MT by hydrogen peroxide did not alter the binding; and (ii) anaerobiosis did not alter the extent of covalent binding but obliterated the inhibitory effect of CC& on MT thiol content. Measurement of the thiol content of C&-treated MT after treatment with 1,4-dithiothreitol revealed that all the thiol groups that were lost subsequent to CC& treatment could be regenerated. These data suggest that CCL,-linked oxidation of MT, rather than the covalent binding of 14CC14 metabolite(s), may be responsible for the CC&-induced loss of metal binding sites of MT with the concurrent release of Zn and Cd. However. the orecise role of the metal released during the oxidation of MT in CC& toxicity remains to be defined. L
Fitoterapia, Nov 1, 2018
Paraquat dichloride, a herbicide used for weed and grass control, is extremely toxic to humans an... more Paraquat dichloride, a herbicide used for weed and grass control, is extremely toxic to humans and animals. The mechanisms of toxicity involve the redox cycling of paraquat resulting in the generation of reactive oxygen species and the depletion of the cellular NADPH. The major cause of death in paraquat poisoning is respiratory failure due to its specific uptake by and oxidative insult to the alveolar epithelial cells and inflammation with subsequent obliterating fibrosis. Paraquat also causes selective degeneration of dopaminergic neurons in the substantia nigra pars compacta, reproducing an important pathological feature of Parkinson disease. Currently, there are no antidotes for the treatment of paraquat poisoning and therapeutic management is mostly supportive and directed towards changing the disposition of the poison. The lack of effective treatments against paraquat poisoning has led to the exploration of novel compounds with antioxidant and/or anti-inflammatory properties. Recently, there is an interest in plant compounds, particularly those used in traditional medicine. Phytochemicals have been highlighted as a possible therapeutic modality for a variety of diseases due to their putative efficacies and safety. In this review, the status of plant extracts and traditional medicines in ameliorating the toxicity of paraquat is discussed.
Biochemical Pharmacology, Nov 1, 1992
The present study was undertaken to investigate whether cu-tocopherol, entrapped in hposomes and ... more The present study was undertaken to investigate whether cu-tocopherol, entrapped in hposomes and delivered directly to the lung, could protect against paraquat-induced lung damage in the rat. Plain Iiposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or DPPC/o-tocopherol liposomes were administered intratracheally to animals 24 hr prior to an intraperitoneal injection of paraquat (20 mg/kg); rats were killed 24 or 48 hr after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were damaged extensively as evidenced by an increase in lung weight and a significant reduction in lung angiotensin~nverting enzyme (ACE) activity and cytochrome P450 concentration. Furthermore, paraquat treatment resulted in a significant decrease in reduced glutathione (GSH) concentrations and a marked elevation in microsomal lipid peroxidation levels as measured by the formation of diene conjugates. Pretreatment of rats with DPPC liposomes alone did not alter significantly the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with DPPC/cu-tocopherol liposomes 24 hr prior to paraquat challenge resulted in a significant increase in pulmonary ru-tocopherol ~ncentrations and antagonized paraquat-induced changes in lipid peroxidation, GSH/GSSG ratio, lung ACE activity and cytochrome P45Oconcentrations. Results of this study suggested that a-tocopherol, delivered directly to the lung in a liposomal formulation 24 hr prior to paraquat administration, confers protection against paraquat-induced lung
Journal of Antimicrobial Chemotherapy, May 22, 2009
This study evaluated the potential of DNase, alginate lyase (AlgL) and N-acetylcysteine (NAC) in ... more This study evaluated the potential of DNase, alginate lyase (AlgL) and N-acetylcysteine (NAC) in enhancing the in vitro bactericidal activity of conventional (free) and vesicle-entrapped (liposomal) gentamicin, amikacin and tobramycin. Methods: The MICs and biofilm eradication for two clinical isolates of Pseudomonas aeruginosa (a mucoid strain and a non-mucoid strain) were determined in the presence and absence of AlgL. The co-activity of aminoglycosides with DNase and/or AlgL against endogenous P. aeruginosa in cystic fibrosis (CF) sputum was also measured. The inhibitory effects of mucin in the presence and absence of the mucolytic agent NAC on aminoglycosidic activity were also examined. Results: The MIC values of the liposomal aminoglycosides were similar to or lower than those of free aminoglycosides. Biofilm formation increased the bactericidal concentrations of these drugs by 8-to 256-fold and treatment with AlgL improved killing of the mucoid strain. The activity of some aminoglycosides against the sputum was increased by the addition of DNase or AlgL (P <0.05), and was increasingly evident with concurrent DNase and AlgL administration. Addition of mucin inhibited liposomal aminoglycosidic activity (up to 32-fold) evidently more than the free aminoglycosides (up to 8-fold). The addition of NAC did not improve activity significantly (P > 0.05). Tobramycin was the most effective aminoglycoside to reduce biofilms and sputum. Conclusions: Liposomal aminoglycosides do not fare better than conventional forms. The coadministration of DNase and AlgL is essential for enhanced activity in reducing biofilm growth and sputum bacterial counts. While mucin retards bactericidal activity, NAC does not improve aminoglycosidic activity.
Journal of Cystic Fibrosis, Jun 1, 2009
We reviewed the patients attending the "Cystic Fibrosis National Center" in Tbilisi, Georgia from... more We reviewed the patients attending the "Cystic Fibrosis National Center" in Tbilisi, Georgia from November, 2006 until October, 2008. All strains isolated from the patients' specimens were subjected to taxonomic analysis. For the genus-and species-level identification of the bacterial strains PCR analysis was used. Genetic relatedness of bacterial strains was determined by PFGE. Antibiotic susceptibility of the strains was determined by the disc diffusion method. 30 strains of P. aeruginosa and 76 strains of S. aureus have been identified. Phage sensitivity in vitro was determined using Pyophage. Four patients who were diagnosed to have cystic fibrosis were selected for Pyophage application (by nebulizer administration). According to the bacteriological testing, in two out of four patients S. aureus and P. aeruginosa were the main causative agents of the secondary infections. The other two were infected only by S. aureus. All patients were treated by the standard scheme of therapy, including antibiotics, anti-mucus medications and vitamins. We studied the bacterial cultures before, after and during the treatment, including checking antibiotic-and phage-resistance and PFGE. The existence of phage-neutralizing antibodies was checked in all patients' blood sera. The treatment continued for 6−10 days (several times); titter of bacterial cells isolated has been drastically decreased and the general state of the patients was clearly improved: expectoration was facilitated, and no crepitating was observed. Bacteriophage treatment provided long infection-free periods between colonization episodes Supported by: PhageBiotics Foundation. 112 A gift of Nature for the treatment of Pseudomonas aeruginosa, Burkholderia cepacia and MRSA in Cystic Fibrosis cases
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Papers by Zacharias Suntres