Pub Date : 2018-02-01DOI: 10.1515/pteridines-2018-0015
A. Wadhawan, D. Hill, Aline Dagdag, Hira Mohyuddin, P. Donnelly, Jeffrey L. Jones, T. Postolache
Abstract Background: Toxoplasma gondii (T. gondii) has been associated with acute food-borne illness, chronic low-grade inflammation, neuropsychiatric conditions and reactivation of chronic latent infection in immunocompetent hosts. Primary infection with T. gondii in pregnant women can lead to congenital toxoplasmosis. In addition to well-known oral tissue-cyst or oocyst ingestion, we hypothesized that the very high prevalence of T. gondii in certain populations exposed to agricultural dust could be, in part, a consequence of airborne infection with oocysts. Methods: We collected environmental dust samples from an area with a reportedly high T. gondii seroprevalence in the Old Order Amish population, in Lancaster, Pennsylvania. Samples included: a) air filters from air-conditioning units; b) swabs of settled dust; and c) vacuum filters containing airborne field dust. Pools of the swabs and shredded sub-samples of the air filters were fed to pigs, with inoculation into mice of heart tissue from seroconverted pigs. We also investigated the presence of T. gondii DNA using PCR amplification. Results: Only one pig seroconverted. However, bioassay of pig heart tissue further inoculated into mice showed no evidence of T. gondii infection. Consistently, no evidence of T. gondii DNA was revealed in any sample. Conclusions: No evidence of airborne transmission was found in the environmental samples that were examined.
{"title":"No evidence for airborne transmission of Toxoplasma gondii in a very high prevalence area in Lancaster County","authors":"A. Wadhawan, D. Hill, Aline Dagdag, Hira Mohyuddin, P. Donnelly, Jeffrey L. Jones, T. Postolache","doi":"10.1515/pteridines-2018-0015","DOIUrl":"https://doi.org/10.1515/pteridines-2018-0015","url":null,"abstract":"Abstract Background: Toxoplasma gondii (T. gondii) has been associated with acute food-borne illness, chronic low-grade inflammation, neuropsychiatric conditions and reactivation of chronic latent infection in immunocompetent hosts. Primary infection with T. gondii in pregnant women can lead to congenital toxoplasmosis. In addition to well-known oral tissue-cyst or oocyst ingestion, we hypothesized that the very high prevalence of T. gondii in certain populations exposed to agricultural dust could be, in part, a consequence of airborne infection with oocysts. Methods: We collected environmental dust samples from an area with a reportedly high T. gondii seroprevalence in the Old Order Amish population, in Lancaster, Pennsylvania. Samples included: a) air filters from air-conditioning units; b) swabs of settled dust; and c) vacuum filters containing airborne field dust. Pools of the swabs and shredded sub-samples of the air filters were fed to pigs, with inoculation into mice of heart tissue from seroconverted pigs. We also investigated the presence of T. gondii DNA using PCR amplification. Results: Only one pig seroconverted. However, bioassay of pig heart tissue further inoculated into mice showed no evidence of T. gondii infection. Consistently, no evidence of T. gondii DNA was revealed in any sample. Conclusions: No evidence of airborne transmission was found in the environmental samples that were examined.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"29 1","pages":"172 - 178"},"PeriodicalIF":0.4,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pteridines-2018-0015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43449805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.1515/pterid-2017-0016
B. Melichar, K. Hruzová, L. Krčmová, L. Javorská, Eliška Pešková, D. Solichová, R. Hyšpler, E. Malířová, M. Vošmik, M. Bartoušková, D. Klos, H. Študentová
Abstract The aim of the present study was to investigate the association of peripheral-blood cell count (PBC)-derived ratios, other biomarkers of inflammation and biomarkers of tumor growth with outcome in a cohort of patients presenting for the next line of therapy after the failure of prior systemic treatment. The data of 51 patients with advanced/metastatic colorectal carcinoma treated with cetuximab in the second or higher line of therapy were retrospectively analyzed. The median duration of cetuximab therapy and the median survival were 5.1 and 12.1 months, respectively. C-reactive protein (CRP), but not urinary neopterin correlated significantly with PBC-derived ratios. Both CRP and urinary neopterin correlated positively with carcinoembryonic antigen (CEA) concentrations and biomarkers of liver dysfunction. Although a number of parameters predicted overall survival in univariate analysis, only hemoglobin, CEA change and serum bilirubin were independent predictors of survival. In conclusion, in patients with metastatic colorectal carcinoma and predominantly liver metastases, the outcome of therapy in the advanced line setting was associated with initial hemoglobin level, a decrease of CEA concentration and initial presence of liver dysfunction. Urinary neopterin did not correlate with PBC-derived ratios, in contrast to CRP, but both urinary neopterin and serum CRP concentrations correlated with laboratory parameters of liver dysfunction.
{"title":"Association of peripheral blood cell count-derived ratios, biomarkers of inflammatory response and tumor growth with outcome in previously treated metastatic colorectal carcinoma patients receiving cetuximab","authors":"B. Melichar, K. Hruzová, L. Krčmová, L. Javorská, Eliška Pešková, D. Solichová, R. Hyšpler, E. Malířová, M. Vošmik, M. Bartoušková, D. Klos, H. Študentová","doi":"10.1515/pterid-2017-0016","DOIUrl":"https://doi.org/10.1515/pterid-2017-0016","url":null,"abstract":"Abstract The aim of the present study was to investigate the association of peripheral-blood cell count (PBC)-derived ratios, other biomarkers of inflammation and biomarkers of tumor growth with outcome in a cohort of patients presenting for the next line of therapy after the failure of prior systemic treatment. The data of 51 patients with advanced/metastatic colorectal carcinoma treated with cetuximab in the second or higher line of therapy were retrospectively analyzed. The median duration of cetuximab therapy and the median survival were 5.1 and 12.1 months, respectively. C-reactive protein (CRP), but not urinary neopterin correlated significantly with PBC-derived ratios. Both CRP and urinary neopterin correlated positively with carcinoembryonic antigen (CEA) concentrations and biomarkers of liver dysfunction. Although a number of parameters predicted overall survival in univariate analysis, only hemoglobin, CEA change and serum bilirubin were independent predictors of survival. In conclusion, in patients with metastatic colorectal carcinoma and predominantly liver metastases, the outcome of therapy in the advanced line setting was associated with initial hemoglobin level, a decrease of CEA concentration and initial presence of liver dysfunction. Urinary neopterin did not correlate with PBC-derived ratios, in contrast to CRP, but both urinary neopterin and serum CRP concentrations correlated with laboratory parameters of liver dysfunction.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"28 1","pages":"221 - 232"},"PeriodicalIF":0.4,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pterid-2017-0016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48860896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.1515/pterid-2017-0018
J. Mergancová, L. Javorská, J. Šiller, L. Sákra, J. Mergancová, D. Solichová, L. Krčmová, B. Melichar, B. Mohelníková-Duchoňová, H. Študentová, D. Klos
Abstract The aim of the present pilot study was to investigate the concentrations of neopterin, kynurenine and tryptophan in wound secretion in patients undergoing surgery for breast cancer or malignant melanoma. Twenty-two patients, 16 females and 6 males, undergoing surgery for breast cancer (n=15) or malignant melanoma (n=7) were evaluated. Neopterin, kynurenine and tryptophan were determined using a high-performance liquid chromatography method. When the concentrations in wound secretions from the primary breast tumor and the axilla were compared, the neopterin/tryptophan ratio was significantly higher in the tumor wound secretions (0.92±0.41 vs. 0.61±0.14 mmol/mol; p=0.049), but no significant differences were observed in neopterin (49.2±28.6 vs. 31.5±11.1 nmol/L), tryptophan (52.9±13.0 vs. 51.2±13.3 μmol/L) and kynurenine concentrations (5.97±7.49 vs. 5.34±6.25 μmol/L) and kynurenine/tryptophan ratio (108.1±107.7 vs. 103.5±106.7 mmol/mol). No marked differences were noted in neopterin, tryptophan and kynurenine concentrations and kynurenine/tryptophan and neopterin/tryptophan ratios in sequential samples from the axilla of breast cancer patients obtained on days 1 and 2. In conclusion, present data demonstrate that the measurement of neopterin, kynurenine and tryptophan can be used to monitor local immune response after cancer surgery.
摘要本初步研究的目的是研究乳腺癌或恶性黑色素瘤手术患者伤口分泌物中新蝶呤、犬尿氨酸和色氨酸的浓度。22例因乳腺癌(n=15)或恶性黑色素瘤(n=7)接受手术的患者，其中女性16例，男性6例。采用高效液相色谱法测定新蝶呤、犬尿氨酸和色氨酸。比较原发乳腺肿瘤和腋窝创面分泌物中新蝶呤/色氨酸的浓度，肿瘤创面分泌物中新蝶呤/色氨酸的比值(0.92±0.41∶0.61±0.14 mmol/mol)显著高于腋窝创面分泌物(0.61±0.14 mmol/mol);p=0.049)，但新蝶呤(49.2±28.6 vs. 31.5±11.1 nmol/L)、色氨酸(52.9±13.0 vs. 51.2±13.3 μmol/L)、犬尿氨酸浓度(5.97±7.49 vs. 5.34±6.25 μmol/L)和犬尿氨酸/色氨酸比值(108.1±107.7 vs. 103.5±106.7 mmol/mol)差异无统计学意义。在第1天和第2天获得的乳腺癌患者腋窝连续样品中，新蝶呤、色氨酸和犬尿氨酸浓度以及犬尿氨酸/色氨酸和新蝶呤/色氨酸比率没有明显差异。总之，目前的数据表明，测量新蝶呤、犬尿氨酸和色氨酸可用于监测肿瘤手术后局部免疫反应。
{"title":"Concentrations of neopterin, kynurenine and tryptophan in wound secretions of patients with breast cancer and malignant melanoma: a pilot study","authors":"J. Mergancová, L. Javorská, J. Šiller, L. Sákra, J. Mergancová, D. Solichová, L. Krčmová, B. Melichar, B. Mohelníková-Duchoňová, H. Študentová, D. Klos","doi":"10.1515/pterid-2017-0018","DOIUrl":"https://doi.org/10.1515/pterid-2017-0018","url":null,"abstract":"Abstract The aim of the present pilot study was to investigate the concentrations of neopterin, kynurenine and tryptophan in wound secretion in patients undergoing surgery for breast cancer or malignant melanoma. Twenty-two patients, 16 females and 6 males, undergoing surgery for breast cancer (n=15) or malignant melanoma (n=7) were evaluated. Neopterin, kynurenine and tryptophan were determined using a high-performance liquid chromatography method. When the concentrations in wound secretions from the primary breast tumor and the axilla were compared, the neopterin/tryptophan ratio was significantly higher in the tumor wound secretions (0.92±0.41 vs. 0.61±0.14 mmol/mol; p=0.049), but no significant differences were observed in neopterin (49.2±28.6 vs. 31.5±11.1 nmol/L), tryptophan (52.9±13.0 vs. 51.2±13.3 μmol/L) and kynurenine concentrations (5.97±7.49 vs. 5.34±6.25 μmol/L) and kynurenine/tryptophan ratio (108.1±107.7 vs. 103.5±106.7 mmol/mol). No marked differences were noted in neopterin, tryptophan and kynurenine concentrations and kynurenine/tryptophan and neopterin/tryptophan ratios in sequential samples from the axilla of breast cancer patients obtained on days 1 and 2. In conclusion, present data demonstrate that the measurement of neopterin, kynurenine and tryptophan can be used to monitor local immune response after cancer surgery.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"28 1","pages":"205 - 211"},"PeriodicalIF":0.4,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pterid-2017-0018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47644922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.1515/pterid-2017-0015
Hye-Lim Kim, H. Ryu, Young Shik Park
Abstract We have developed a fluorescence assay system to monitor the protein levels of human phenylalanine hydroxylase (hPAH). Wild-type (WT) and three mutant hPAHs (I65T, L255V, and S349L) were expressed as green fluorescent protein (GFP)-tagged forms in a PAH knockout mutant (pah−) of Dictyostelium discoideum Ax2. The fluorescence-activated cell sorting (FACS) analysis showed that the GFP positive cells were the most frequent in WT but were rare in pah−, demonstrating the successful expression of GFP-tagged hPAHs in Dictyostelium. The fluorescence levels of mutants relative to WT were higher than expected from the protein amounts determined from the non-tagged forms, probably due to the presence of the N-terminal GFP. However, treatment of the cells with cumene hydroperoxide, which is known to accelerate protein degradation, decreased fluorescence levels, suggesting that protein stability changes in individual mutations can be monitored by FACS analysis. For an evaluation study, a putative pharmacological chaperone effect of yeast extract on S349L was examined by Western blot and FACS analysis. Both the protein amount and the fluorescence levels were increased by yeast extract, supporting that the FACS analysis could replace the time- and labor-consuming procedures such as the Western blot and cell culture. The fluorescence-based cell assay system may be valuable for the high-throughput screening of pharmacological chaperones for phenylketonuria mutations.
{"title":"Quantitative analysis by flow cytometry of green fluorescent protein-tagged human phenylalanine hydroxylase expressed in Dictyostelium","authors":"Hye-Lim Kim, H. Ryu, Young Shik Park","doi":"10.1515/pterid-2017-0015","DOIUrl":"https://doi.org/10.1515/pterid-2017-0015","url":null,"abstract":"Abstract We have developed a fluorescence assay system to monitor the protein levels of human phenylalanine hydroxylase (hPAH). Wild-type (WT) and three mutant hPAHs (I65T, L255V, and S349L) were expressed as green fluorescent protein (GFP)-tagged forms in a PAH knockout mutant (pah−) of Dictyostelium discoideum Ax2. The fluorescence-activated cell sorting (FACS) analysis showed that the GFP positive cells were the most frequent in WT but were rare in pah−, demonstrating the successful expression of GFP-tagged hPAHs in Dictyostelium. The fluorescence levels of mutants relative to WT were higher than expected from the protein amounts determined from the non-tagged forms, probably due to the presence of the N-terminal GFP. However, treatment of the cells with cumene hydroperoxide, which is known to accelerate protein degradation, decreased fluorescence levels, suggesting that protein stability changes in individual mutations can be monitored by FACS analysis. For an evaluation study, a putative pharmacological chaperone effect of yeast extract on S349L was examined by Western blot and FACS analysis. Both the protein amount and the fluorescence levels were increased by yeast extract, supporting that the FACS analysis could replace the time- and labor-consuming procedures such as the Western blot and cell culture. The fluorescence-based cell assay system may be valuable for the high-throughput screening of pharmacological chaperones for phenylketonuria mutations.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"28 1","pages":"153 - 156"},"PeriodicalIF":0.4,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pterid-2017-0015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49369013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.1515/pterid-2017-0012
G. Bjelaković, I. Stojanovic, T. Stoimenov, D. Pavlović, G. Kocić, G. Bjelakovic, D. Sokolović, J. Bašić
Abstract Clinical practice and experimental studies have shown the necessity of sufficient quantities of folic acid intake for normal embryogenesis and fetal development in the prevention of neural tube defects (NTDs) and neurological malformations. So, women of childbearing age must be sure to have an adequate folate intake periconceptionally, prior to and during pregnancy. Folic acid fortification of all enriched cereal grain product flour has been implemented in many countries. Thus, hundreds of thousands of people have been exposed to an increased intake of folic acid. Folate plays an essential role in the biosynthesis of methionine. Methionine is the principal aminopropyl donor required for polyamine biosynthesis, which is up-regulated in actively growing cells, including cancer cells. Folates are important in RNA and DNA synthesis, DNA stability and integrity. Clinical and epidemiological evidence links folate deficiency to DNA damage and cancer. On the other hand, long-term folate oversupplementation leads to adverse toxic effects, resulting in the appearance of malignancy. Considering the relationship of polyamines and rapidly proliferating tissues (especially cancers), there is a need for better investigation of the relationship between the ingestion of high amounts of folic acid in food supplementation and polyamine metabolism, related to malignant processes in the human body.
{"title":"Polyamines, folic acid supplementation and cancerogenesis","authors":"G. Bjelaković, I. Stojanovic, T. Stoimenov, D. Pavlović, G. Kocić, G. Bjelakovic, D. Sokolović, J. Bašić","doi":"10.1515/pterid-2017-0012","DOIUrl":"https://doi.org/10.1515/pterid-2017-0012","url":null,"abstract":"Abstract Clinical practice and experimental studies have shown the necessity of sufficient quantities of folic acid intake for normal embryogenesis and fetal development in the prevention of neural tube defects (NTDs) and neurological malformations. So, women of childbearing age must be sure to have an adequate folate intake periconceptionally, prior to and during pregnancy. Folic acid fortification of all enriched cereal grain product flour has been implemented in many countries. Thus, hundreds of thousands of people have been exposed to an increased intake of folic acid. Folate plays an essential role in the biosynthesis of methionine. Methionine is the principal aminopropyl donor required for polyamine biosynthesis, which is up-regulated in actively growing cells, including cancer cells. Folates are important in RNA and DNA synthesis, DNA stability and integrity. Clinical and epidemiological evidence links folate deficiency to DNA damage and cancer. On the other hand, long-term folate oversupplementation leads to adverse toxic effects, resulting in the appearance of malignancy. Considering the relationship of polyamines and rapidly proliferating tissues (especially cancers), there is a need for better investigation of the relationship between the ingestion of high amounts of folic acid in food supplementation and polyamine metabolism, related to malignant processes in the human body.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"28 1","pages":"115 - 131"},"PeriodicalIF":0.4,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pterid-2017-0012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42925690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.1515/pterid-2017-0009
H. Edalat, M. Akhoundi, H. Basseri
Abstract Determining the accurate age of malaria vectors is crucial to measure the risk of malaria transmission. A group of fluorescent chemicals derived from a pyrimidine-pyrazine ring structure known as pteridines from the head, thorax and whole body of adult female Anopheles stephensi were identified and evaluated as a tool for chronological and physiological age determination of malaria vectors. The female mosquitoes were collected from an insectary colony at an interval of every 5 days, up to 30 days, and the pteridines of head, thorax and whole body were detected fluorometrically by high-pressure liquid chromatography (HPLC) using excitation and emission wavelengths of 365 and 455 nm, respectively. In addition, alteration of the pteridines compounds was compared between blood and sugar fed mosquito groups. Although four pteridines including pterin-6-carboxylic acid, biopterin, xanthopterin and isoxanthopterin were detected, some of them were absent in the head or thorax of mosquitoes. Levels of all four pteridines were similarly decreased in a linear manner throughout 30 days. No significant difference in alteration of pteridine compounds was observed between the two groups of blood or sugar fed mosquitoes. This result indicates that diet has a little effect on pteridines alteration. Age determination based on pteridines, as an age-grading technique, could be used for field collected mosquitoes, which have either sugar or blood meal. In addition, analyzing total pteridine fluorescence from only whole body could be a convenient method to estimate the age.
{"title":"Age-dependance of pteridines in the malaria vector, Anopheles stephensi","authors":"H. Edalat, M. Akhoundi, H. Basseri","doi":"10.1515/pterid-2017-0009","DOIUrl":"https://doi.org/10.1515/pterid-2017-0009","url":null,"abstract":"Abstract Determining the accurate age of malaria vectors is crucial to measure the risk of malaria transmission. A group of fluorescent chemicals derived from a pyrimidine-pyrazine ring structure known as pteridines from the head, thorax and whole body of adult female Anopheles stephensi were identified and evaluated as a tool for chronological and physiological age determination of malaria vectors. The female mosquitoes were collected from an insectary colony at an interval of every 5 days, up to 30 days, and the pteridines of head, thorax and whole body were detected fluorometrically by high-pressure liquid chromatography (HPLC) using excitation and emission wavelengths of 365 and 455 nm, respectively. In addition, alteration of the pteridines compounds was compared between blood and sugar fed mosquito groups. Although four pteridines including pterin-6-carboxylic acid, biopterin, xanthopterin and isoxanthopterin were detected, some of them were absent in the head or thorax of mosquitoes. Levels of all four pteridines were similarly decreased in a linear manner throughout 30 days. No significant difference in alteration of pteridine compounds was observed between the two groups of blood or sugar fed mosquitoes. This result indicates that diet has a little effect on pteridines alteration. Age determination based on pteridines, as an age-grading technique, could be used for field collected mosquitoes, which have either sugar or blood meal. In addition, analyzing total pteridine fluorescence from only whole body could be a convenient method to estimate the age.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"28 1","pages":"157 - 161"},"PeriodicalIF":0.4,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pterid-2017-0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41453307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.1515/pterid-2017-0011
Thandeeswaran Murugesan, Karuppuswamy Velliayadevar, Murugesh Easwaran, Kiran kG, A. Ka, M. Ramasamy, Palaniswamy Muthusamy, A. Jayaraman
Abstract As early as 1974, reports have confirmed the anticancer activity of pterin deaminase isolated from fungi. The enzyme has also been reported in bacteria, fungi and slime mold genera, but the enzyme characterization was effetely done. The present study attempted to purify and characterize pterin deaminase enzyme from Saccharomyces cerevisiae NCIM 3458. The protein was extracted from the extracellular extract by using the ethanol precipitation method. Partial purification of pterin deaminase enzyme was achieved by ion exchange chromatography (Hi-Trap QFF) by fast protein liquid chromatography (AKTA purifier). The molecular weight of the protein was apparently determined by SDS-PAGE, and the presence of pterin deaminase was confirmed by activity staining. The purified enzyme was further biochemically characterized. Molecular docking studies showed higher binding affinity towards folic acid interaction. The structural characterization of this protein may open the windows for new drug targets for cancer therapy.
{"title":"Molecular architecture of pterin deaminase from Saccharomyces cerevisiae NCIM 3458","authors":"Thandeeswaran Murugesan, Karuppuswamy Velliayadevar, Murugesh Easwaran, Kiran kG, A. Ka, M. Ramasamy, Palaniswamy Muthusamy, A. Jayaraman","doi":"10.1515/pterid-2017-0011","DOIUrl":"https://doi.org/10.1515/pterid-2017-0011","url":null,"abstract":"Abstract As early as 1974, reports have confirmed the anticancer activity of pterin deaminase isolated from fungi. The enzyme has also been reported in bacteria, fungi and slime mold genera, but the enzyme characterization was effetely done. The present study attempted to purify and characterize pterin deaminase enzyme from Saccharomyces cerevisiae NCIM 3458. The protein was extracted from the extracellular extract by using the ethanol precipitation method. Partial purification of pterin deaminase enzyme was achieved by ion exchange chromatography (Hi-Trap QFF) by fast protein liquid chromatography (AKTA purifier). The molecular weight of the protein was apparently determined by SDS-PAGE, and the presence of pterin deaminase was confirmed by activity staining. The purified enzyme was further biochemically characterized. Molecular docking studies showed higher binding affinity towards folic acid interaction. The structural characterization of this protein may open the windows for new drug targets for cancer therapy.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"28 1","pages":"141 - 151"},"PeriodicalIF":0.4,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pterid-2017-0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46289884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.1515/pterid-2017-0021
E. Zvetkova, D. Fuchs
Abstract In our individual and collaborative studies, we have played a part in pioneering investigations on the usefulness of biomarkers – red blood cell distribution width (RDW) and neopterin. This mini review includes historical data on the topic and is related to the first contributions in this field, as well as to the possibilities for further improvement and simultaneous application of RDW and neopterin measurements in the prevention, prognosis and treatment of a great number of socially important disease conditions (arterial, cardiovascular, brain vascular, peripheral artery diseases, inflammations, autoimmune states, cancers and leukemias, addictions, etc.). When comparing the results obtained with the immunobiochemical biomarker neopterin with RDW, they are reported to be very similar as independent predictors of the same pathological states in the human body although their biomedical origins are very different. Both the parameters were until now successfully, but only separately used in medical practice. The combined use of these two biomarkers can shed some more light on their interrelationships and provide some clues as to how the interaction between immune system activation and red blood cells biology are intertwined.
{"title":"Medical significance of simultaneous application of red blood cell distribution width (RDW) and neopterin as diagnostic/prognostic biomarkers in clinical practice","authors":"E. Zvetkova, D. Fuchs","doi":"10.1515/pterid-2017-0021","DOIUrl":"https://doi.org/10.1515/pterid-2017-0021","url":null,"abstract":"Abstract In our individual and collaborative studies, we have played a part in pioneering investigations on the usefulness of biomarkers – red blood cell distribution width (RDW) and neopterin. This mini review includes historical data on the topic and is related to the first contributions in this field, as well as to the possibilities for further improvement and simultaneous application of RDW and neopterin measurements in the prevention, prognosis and treatment of a great number of socially important disease conditions (arterial, cardiovascular, brain vascular, peripheral artery diseases, inflammations, autoimmune states, cancers and leukemias, addictions, etc.). When comparing the results obtained with the immunobiochemical biomarker neopterin with RDW, they are reported to be very similar as independent predictors of the same pathological states in the human body although their biomedical origins are very different. Both the parameters were until now successfully, but only separately used in medical practice. The combined use of these two biomarkers can shed some more light on their interrelationships and provide some clues as to how the interaction between immune system activation and red blood cells biology are intertwined.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"28 1","pages":"133 - 140"},"PeriodicalIF":0.4,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pterid-2017-0021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48411388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.1515/pterid-2017-0007
Angel Fenol, V. Swetha, Sajitha Krishnan, Jayachandran Perayil, Rajesh Vyloppillil, Anuradha Bhaskar, M. Shereef, Biju Balakrishnan, Lakshmi Puzhankara
Abstract Neopterin is a novel predictor for coronary events especially in diabetic patients and also an indicator for the effectiveness of the periodontal treatment. In this study, we assessed whether salivary neopterin can be used as a potential biomarker in evaluating the risk of cardiovascular disease in type 2 diabetic patients with chronic periodontitis. Forty subjects between 25 and 75 years of age and who matched the criteria were selected and divided into four groups. Their periodontal status was evaluated. Stimulated whole saliva and blood were collected for analysis of salivary neopterin and fibrinogen and HbA1c levels, respectively. Nonsurgical periodontal therapy was carried out. Patients were recalled after 3 months, and the same procedure was repeated. A reduction in all the parameters was seen after treatment in all the four groups. Salivary neopterin levels showed significant difference (p<0.001) in the values between the study groups and the control group before treatment. After 3 months of treatment, salivary neopterin levels showed a statistical significant reduction (p<0.001) in all the study groups. Neopterin could serve as an effective tool to assess the inflammatory process related to periodontitis and diabetes mellitus and also predict future cardiovascular events in diabetic patients.
{"title":"Correlation of salivary neopterin and plasma fibrinogen levels in patients with chronic periodontitis and/or type 2 diabetes mellitus","authors":"Angel Fenol, V. Swetha, Sajitha Krishnan, Jayachandran Perayil, Rajesh Vyloppillil, Anuradha Bhaskar, M. Shereef, Biju Balakrishnan, Lakshmi Puzhankara","doi":"10.1515/pterid-2017-0007","DOIUrl":"https://doi.org/10.1515/pterid-2017-0007","url":null,"abstract":"Abstract Neopterin is a novel predictor for coronary events especially in diabetic patients and also an indicator for the effectiveness of the periodontal treatment. In this study, we assessed whether salivary neopterin can be used as a potential biomarker in evaluating the risk of cardiovascular disease in type 2 diabetic patients with chronic periodontitis. Forty subjects between 25 and 75 years of age and who matched the criteria were selected and divided into four groups. Their periodontal status was evaluated. Stimulated whole saliva and blood were collected for analysis of salivary neopterin and fibrinogen and HbA1c levels, respectively. Nonsurgical periodontal therapy was carried out. Patients were recalled after 3 months, and the same procedure was repeated. A reduction in all the parameters was seen after treatment in all the four groups. Salivary neopterin levels showed significant difference (p<0.001) in the values between the study groups and the control group before treatment. After 3 months of treatment, salivary neopterin levels showed a statistical significant reduction (p<0.001) in all the study groups. Neopterin could serve as an effective tool to assess the inflammatory process related to periodontitis and diabetes mellitus and also predict future cardiovascular events in diabetic patients.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"28 1","pages":"177 - 183"},"PeriodicalIF":0.4,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pterid-2017-0007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46414179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.1515/pterid-2017-0005
B. Melichar, D. Vitásková, M. Bartoušková, L. Javorská, L. Kujovská Krčmová, Eliška Pešková, R. Hyšpler, D. Solichová, K. Hruzová, H. Študentová
Abstract In the present study, we determined complex indices of inflammatory activity and compared the performance of these indices as prognostic biomarkers in a cohort of breast cancer patients. All proposed composite biomarkers could be evaluated in 418 out of 474 patients in the cohort with complete data on peripheral blood cell count, urinary neopterin, albumin and C-reactive protein. Neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory index, Glasgow prognostic index, modified Glasgow prognostic index, prognostic nutritional index and C-reactive protein/albumin ratio were calculated and further complex indices were proposed. Although a number of the investigated indices were significantly associated with survival in the univariate analysis, only age and stage, but none of the laboratory biomarkers or composite biomarkers, were significant predictors of survival in the whole group in the multivariate analysis. In patients evaluated before the start of the treatment, age, stage and urinary neopterin were significant predictors of survival. These results underscore the importance of neopterin as a prognostic biomarker in breast cancer.
{"title":"Comparison of performance of composite biomarkers of inflammatory response in determining the prognosis of breast cancer patients","authors":"B. Melichar, D. Vitásková, M. Bartoušková, L. Javorská, L. Kujovská Krčmová, Eliška Pešková, R. Hyšpler, D. Solichová, K. Hruzová, H. Študentová","doi":"10.1515/pterid-2017-0005","DOIUrl":"https://doi.org/10.1515/pterid-2017-0005","url":null,"abstract":"Abstract In the present study, we determined complex indices of inflammatory activity and compared the performance of these indices as prognostic biomarkers in a cohort of breast cancer patients. All proposed composite biomarkers could be evaluated in 418 out of 474 patients in the cohort with complete data on peripheral blood cell count, urinary neopterin, albumin and C-reactive protein. Neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory index, Glasgow prognostic index, modified Glasgow prognostic index, prognostic nutritional index and C-reactive protein/albumin ratio were calculated and further complex indices were proposed. Although a number of the investigated indices were significantly associated with survival in the univariate analysis, only age and stage, but none of the laboratory biomarkers or composite biomarkers, were significant predictors of survival in the whole group in the multivariate analysis. In patients evaluated before the start of the treatment, age, stage and urinary neopterin were significant predictors of survival. These results underscore the importance of neopterin as a prognostic biomarker in breast cancer.","PeriodicalId":20792,"journal":{"name":"Pteridines","volume":"28 1","pages":"213 - 220"},"PeriodicalIF":0.4,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pterid-2017-0005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43854400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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