Pub Date : 2017-01-03DOI: 10.1080/15257770.2016.1257807
G. Elgemeie, N. Fathy, W. Zaghary, A. Farag
ABSTRACT A one-pot reaction of a sodium 2-cyanoethylene-1-thiolate salt with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galactopyranosyl bromides affords a new class of cyanoethylene thioglycosides. The conversion to the corresponding 5-aminopyrazoles confirms the E-configuration of these cyanoethylene thioglycosides.
摘要:2-氰乙基-1-硫代酸钠盐与2,3,4,6-四- o-乙酰-α- d -葡萄糖-和半乳糖吡喃酰溴一锅反应得到了一类新的氰乙基硫代苷。转化为相应的5-氨基吡唑证实了这些氰乙烯硫甙的e -构型。
{"title":"S-glycosides in medicinal chemistry: Novel synthesis of cyanoethylene thioglycosides and their pyrazole derivatives","authors":"G. Elgemeie, N. Fathy, W. Zaghary, A. Farag","doi":"10.1080/15257770.2016.1257807","DOIUrl":"https://doi.org/10.1080/15257770.2016.1257807","url":null,"abstract":"ABSTRACT A one-pot reaction of a sodium 2-cyanoethylene-1-thiolate salt with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galactopyranosyl bromides affords a new class of cyanoethylene thioglycosides. The conversion to the corresponding 5-aminopyrazoles confirms the E-configuration of these cyanoethylene thioglycosides.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"17 1","pages":"198 - 212"},"PeriodicalIF":0.0,"publicationDate":"2017-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79246724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-03DOI: 10.1080/15257770.2016.1231319
K. Nguyen, R. Naviaux, W. Nyhan
ABSTRACT Lesch–Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The authors report three novel independent mutations in the coding region of the HPRT1 gene from genomic DNA of (a) a carrier sister of two male patients with LND: c.569G>C, p.G190A in exon 8; and (b) two LND affected male patients unrelated to her who had two mutations: c.648delC, p.Y216X, and c.653C>G, p.A218G in exon 9. Molecular analysis reveals the heterogeneity of genetic mutation of the HPRT1 gene responsible for the HGprt deficiency. It allows fast, accurate detection of carriers and genetic counseling.
Lesch-Nyhan病(LND)是一种罕见的嘌呤代谢的x连锁遗传神经遗传性疾病，其中，次黄嘌呤-鸟嘌呤磷酸核糖基转移酶(HGprt)存在缺陷。作者报告了来自(a)两名LND男性患者的携带者姐妹的基因组DNA中HPRT1基因编码区三个新的独立突变:C .569 g >C, p.G190A外显子8;(b)两名与她无关的LND男性患者，他们在第9外显子中有两个突变:c.648delC, p.Y216X和c.653C>G, p.A218G。分子分析揭示了导致HGprt缺乏的HPRT1基因突变的异质性。它允许快速，准确地检测携带者和遗传咨询。
{"title":"Human HPRT1 gene and the Lesch–Nyhan disease: Substitution of alanine for glycine and inversely in the HGprt enzyme protein","authors":"K. Nguyen, R. Naviaux, W. Nyhan","doi":"10.1080/15257770.2016.1231319","DOIUrl":"https://doi.org/10.1080/15257770.2016.1231319","url":null,"abstract":"ABSTRACT Lesch–Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The authors report three novel independent mutations in the coding region of the HPRT1 gene from genomic DNA of (a) a carrier sister of two male patients with LND: c.569G>C, p.G190A in exon 8; and (b) two LND affected male patients unrelated to her who had two mutations: c.648delC, p.Y216X, and c.653C>G, p.A218G in exon 9. Molecular analysis reveals the heterogeneity of genetic mutation of the HPRT1 gene responsible for the HGprt deficiency. It allows fast, accurate detection of carriers and genetic counseling.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"107 1","pages":"151 - 157"},"PeriodicalIF":0.0,"publicationDate":"2017-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80945823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-03DOI: 10.1080/15257770.2016.1243716
E. Eskandari‐Nasab, M. Hashemi, Seyed-Shahab-adin Hasani, M. Naderi, S. Sadeghi-bojd, M. Taheri
ABSTRACT We examined the possible relationship between three RAGE polymorphisms, −429C/T, −374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE −374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.
{"title":"Evaluation of functional RAGE gene polymorphisms in childhood acute lymphoblastic leukemia—A case-control study from Iran","authors":"E. Eskandari‐Nasab, M. Hashemi, Seyed-Shahab-adin Hasani, M. Naderi, S. Sadeghi-bojd, M. Taheri","doi":"10.1080/15257770.2016.1243716","DOIUrl":"https://doi.org/10.1080/15257770.2016.1243716","url":null,"abstract":"ABSTRACT We examined the possible relationship between three RAGE polymorphisms, −429C/T, −374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE −374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"813 1","pages":"170 - 180"},"PeriodicalIF":0.0,"publicationDate":"2017-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77540587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-02DOI: 10.1080/15257770.2016.1163381
S. Baba, Takashi Saito, Yasukazu Yamada, E. Takeshita, N. Nomura, Kenichiro Yamada, N. Wakamatsu, M. Sasaki
ABSTRACT Lesch-Nyhan disease (LND) is a rare X-linked recessive disorder caused by deficiency of the purine salvage enzyme hypoxanthine–guanine phosphoribosyltransferase (HPRT), encoded by the HPRT1. To date, nearly all types of mutations have been reported in the whole gene; however, duplication mutations are rare. We here report the case of a 9-month-old boy with LND. He showed developmental delay, athetosis, and dystonic posture from early infancy, but no self-injurious behaviors. Hyperuricemia was detected, and his HPRT enzyme activity in erythrocytes was completely deficient. A novel duplication mutation (c.372dupT, c.372_374 TTT > c.372_375 TTTT) was identified in exon 4 of the HPRT1, which causes aberrant splicing. This is the third case of a duplication mutation in the HPRT1 that causes splicing error.
{"title":"Novel mutation in HPRT1 causing a splicing error with multiple variations","authors":"S. Baba, Takashi Saito, Yasukazu Yamada, E. Takeshita, N. Nomura, Kenichiro Yamada, N. Wakamatsu, M. Sasaki","doi":"10.1080/15257770.2016.1163381","DOIUrl":"https://doi.org/10.1080/15257770.2016.1163381","url":null,"abstract":"ABSTRACT Lesch-Nyhan disease (LND) is a rare X-linked recessive disorder caused by deficiency of the purine salvage enzyme hypoxanthine–guanine phosphoribosyltransferase (HPRT), encoded by the HPRT1. To date, nearly all types of mutations have been reported in the whole gene; however, duplication mutations are rare. We here report the case of a 9-month-old boy with LND. He showed developmental delay, athetosis, and dystonic posture from early infancy, but no self-injurious behaviors. Hyperuricemia was detected, and his HPRT enzyme activity in erythrocytes was completely deficient. A novel duplication mutation (c.372dupT, c.372_374 TTT > c.372_375 TTTT) was identified in exon 4 of the HPRT1, which causes aberrant splicing. This is the third case of a duplication mutation in the HPRT1 that causes splicing error.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"22 1","pages":"1 - 6"},"PeriodicalIF":0.0,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82229919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-02DOI: 10.1080/15257770.2016.1218023
S. Mahmoud, Hao Li, Tamara R. Mcbrayer, L. Bassit, S. Hammad, S. Coats, F. Amblard, R. Schinazi
ABSTRACT A novel series of tetrafluoro and hexafluoro acyclic nucleosides and their phosphoramidates were successfully prepared from commercially available 2,2,3,3-tetrafluoro-1,4-butanediol and 2,2,3,3,4,4-hexafluoro-1,5-pentanediol in four to six steps. Their ability to block HIV, HCV, HSV-1, and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM, and Vero cells was assessed.
{"title":"Synthesis and antiviral evaluation of fluorinated acyclo-nucleosides and their phosphoramidates","authors":"S. Mahmoud, Hao Li, Tamara R. Mcbrayer, L. Bassit, S. Hammad, S. Coats, F. Amblard, R. Schinazi","doi":"10.1080/15257770.2016.1218023","DOIUrl":"https://doi.org/10.1080/15257770.2016.1218023","url":null,"abstract":"ABSTRACT A novel series of tetrafluoro and hexafluoro acyclic nucleosides and their phosphoramidates were successfully prepared from commercially available 2,2,3,3-tetrafluoro-1,4-butanediol and 2,2,3,3,4,4-hexafluoro-1,5-pentanediol in four to six steps. Their ability to block HIV, HCV, HSV-1, and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM, and Vero cells was assessed.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"23 1","pages":"66 - 82"},"PeriodicalIF":0.0,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75042950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-02DOI: 10.1080/15257770.2016.1218019
N. Shahabadi, Mehdi Pourfoulad, Neda Hosseinpour Moghadam
ABSTRACT DNA-binding properties of an antiviral drug, valganciclovir (valcyte) was studied by using emission, absorption, circular dichroism, viscosity, differential pulse voltammetry, fluorescence techniques, and computational studies. The drug bound to calf thymus DNA (ct-DNA) in a groove-binding mode. The calculated binding constant of UV-vis, Ka, is comparable to groove-binding drugs. Competitive fluorimetric studies with Hoechst 33258 showed that valcyte could displace the DNA-bound Hoechst 33258. The drug could not displace intercalated methylene blue from DNA double helix. Furthermore, the induced detectable changes in the CD spectrum of ct-DNA as well as changes in its viscosity confirm the groove-binding mode. In addition, an integrated molecular docking was employed to further investigate the binding interactions between valcyte and calf thymus DNA.
{"title":"Experimental and computational studies on the effects of valganciclovir as an antiviral drug on calf thymus DNA","authors":"N. Shahabadi, Mehdi Pourfoulad, Neda Hosseinpour Moghadam","doi":"10.1080/15257770.2016.1218019","DOIUrl":"https://doi.org/10.1080/15257770.2016.1218019","url":null,"abstract":"ABSTRACT DNA-binding properties of an antiviral drug, valganciclovir (valcyte) was studied by using emission, absorption, circular dichroism, viscosity, differential pulse voltammetry, fluorescence techniques, and computational studies. The drug bound to calf thymus DNA (ct-DNA) in a groove-binding mode. The calculated binding constant of UV-vis, Ka, is comparable to groove-binding drugs. Competitive fluorimetric studies with Hoechst 33258 showed that valcyte could displace the DNA-bound Hoechst 33258. The drug could not displace intercalated methylene blue from DNA double helix. Furthermore, the induced detectable changes in the CD spectrum of ct-DNA as well as changes in its viscosity confirm the groove-binding mode. In addition, an integrated molecular docking was employed to further investigate the binding interactions between valcyte and calf thymus DNA.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"160 38 1","pages":"31 - 48"},"PeriodicalIF":0.0,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87771425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-02DOI: 10.1080/15257770.2016.1210805
Rebba C. Boswell-Casteel, F. Hays
ABSTRACT Equilibrative nucleoside transporters (ENTs) are polytopic integral membrane proteins that mediate the transport of nucleosides, nucleobases, and therapeutic analogs. The best-characterized ENTs are the human transporters hENT1 and hENT2. However, non-mammalian eukaryotic ENTs have also been studied (e.g., yeast, parasitic protozoa). ENTs are major pharmaceutical targets responsible for modulating the efficacy of more than 30 approved drugs. However, the molecular mechanisms and chemical determinants of ENT-mediated substrate recognition, binding, inhibition, and transport are poorly understood. This review highlights findings on the characterization of ENTs by surveying studies on genetics, permeant and inhibitor interactions, mutagenesis, and structural models of ENT function.
{"title":"Equilibrative nucleoside transporters—A review","authors":"Rebba C. Boswell-Casteel, F. Hays","doi":"10.1080/15257770.2016.1210805","DOIUrl":"https://doi.org/10.1080/15257770.2016.1210805","url":null,"abstract":"ABSTRACT Equilibrative nucleoside transporters (ENTs) are polytopic integral membrane proteins that mediate the transport of nucleosides, nucleobases, and therapeutic analogs. The best-characterized ENTs are the human transporters hENT1 and hENT2. However, non-mammalian eukaryotic ENTs have also been studied (e.g., yeast, parasitic protozoa). ENTs are major pharmaceutical targets responsible for modulating the efficacy of more than 30 approved drugs. However, the molecular mechanisms and chemical determinants of ENT-mediated substrate recognition, binding, inhibition, and transport are poorly understood. This review highlights findings on the characterization of ENTs by surveying studies on genetics, permeant and inhibitor interactions, mutagenesis, and structural models of ENT function.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"28 1","pages":"30 - 7"},"PeriodicalIF":0.0,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73021158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-02DOI: 10.1080/15257770.2016.1218021
N. Shahabadi, M. Falsafi, M. Maghsudi
ABSTRACT The interaction of anticancer drug cytarabine with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multispectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove-binding mode, while the binding constant of UV-vis and the number of binding sites were 4.0 ± 0.2 × 104 L mol−1 and 1.39, respectively. The fluorimetric studies showed that the reaction between the drugs with CT-DNA is exothermic. Circular dichroism spectroscopy was employed to measure the conformational change of DNA in the presence of cytarabine. Furthermore, the drug induces detectable changes in its viscosity for DNA interaction. The molecular modeling results illustrated that cytarabine strongly binds to groove of DNA by relative binding energy of docked structure −20.61 KJ mol−1. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the interaction of small molecular pollutants and drugs with biomacromolecules for clarifying the molecular mechanism of toxicity or side effect in vivo.
{"title":"DNA-binding study of anticancer drug cytarabine by spectroscopic and molecular docking techniques","authors":"N. Shahabadi, M. Falsafi, M. Maghsudi","doi":"10.1080/15257770.2016.1218021","DOIUrl":"https://doi.org/10.1080/15257770.2016.1218021","url":null,"abstract":"ABSTRACT The interaction of anticancer drug cytarabine with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multispectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove-binding mode, while the binding constant of UV-vis and the number of binding sites were 4.0 ± 0.2 × 104 L mol−1 and 1.39, respectively. The fluorimetric studies showed that the reaction between the drugs with CT-DNA is exothermic. Circular dichroism spectroscopy was employed to measure the conformational change of DNA in the presence of cytarabine. Furthermore, the drug induces detectable changes in its viscosity for DNA interaction. The molecular modeling results illustrated that cytarabine strongly binds to groove of DNA by relative binding energy of docked structure −20.61 KJ mol−1. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the interaction of small molecular pollutants and drugs with biomacromolecules for clarifying the molecular mechanism of toxicity or side effect in vivo.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"31 3 1","pages":"49 - 65"},"PeriodicalIF":0.0,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82751673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-01DOI: 10.1080/15257770.2016.1149193
E. Giovannetti, L. Leon, V. Gómez, P. Zucali, F. Minutolo, G. Peters
ABSTRACT Malignant pleural mesothelioma (MPM) is a very hypoxic malignancy, and hypoxia has been associated with resistance towards gemcitabine. The muscle-isoform of lactate dehydrogenase (LDH-A) constitutes a major checkpoint for the switch to anaerobic glycolysis. Therefore we investigated the combination of a new LDH-A inhibitor (NHI-1) with gemcitabine in MPM cell lines. Under hypoxia (O2 tension of 1%) the cell growth inhibitory effects of gemcitabine, were reduced, as demonstrated by a 5- to 10-fold increase in IC50s. However, the simultaneous addition of NHI-1 was synergistic (combination index < 1). Flow cytometry demonstrated that hypoxia caused a G1 arrest, whereas the combination of NHI-1 significantly increased gemcitabine-induced cell death. Finally, the mRNA expression levels of the human equilibrative transporter-1 (hENT1) were significantly down-regulated under hypoxia, but treatment with NHI-1 was associated with a recovery of hENT1 expression. In conclusion, our data show that hypoxia increased MPM resistance to gemcitabine. However, cell death induction and modulation of the key transporter in gemcitabine uptake may contribute to the synergistic interaction of gemcitabine with the LDH-A inhibitor NHI-1 and support further studies for the rational development of this combination.
{"title":"A specific inhibitor of lactate dehydrogenase overcame the resistance toward gemcitabine in hypoxic mesothelioma cells, and modulated the expression of the human equilibrative transporter-1","authors":"E. Giovannetti, L. Leon, V. Gómez, P. Zucali, F. Minutolo, G. Peters","doi":"10.1080/15257770.2016.1149193","DOIUrl":"https://doi.org/10.1080/15257770.2016.1149193","url":null,"abstract":"ABSTRACT Malignant pleural mesothelioma (MPM) is a very hypoxic malignancy, and hypoxia has been associated with resistance towards gemcitabine. The muscle-isoform of lactate dehydrogenase (LDH-A) constitutes a major checkpoint for the switch to anaerobic glycolysis. Therefore we investigated the combination of a new LDH-A inhibitor (NHI-1) with gemcitabine in MPM cell lines. Under hypoxia (O2 tension of 1%) the cell growth inhibitory effects of gemcitabine, were reduced, as demonstrated by a 5- to 10-fold increase in IC50s. However, the simultaneous addition of NHI-1 was synergistic (combination index < 1). Flow cytometry demonstrated that hypoxia caused a G1 arrest, whereas the combination of NHI-1 significantly increased gemcitabine-induced cell death. Finally, the mRNA expression levels of the human equilibrative transporter-1 (hENT1) were significantly down-regulated under hypoxia, but treatment with NHI-1 was associated with a recovery of hENT1 expression. In conclusion, our data show that hypoxia increased MPM resistance to gemcitabine. However, cell death induction and modulation of the key transporter in gemcitabine uptake may contribute to the synergistic interaction of gemcitabine with the LDH-A inhibitor NHI-1 and support further studies for the rational development of this combination.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"37 1","pages":"643 - 651"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84438014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-01DOI: 10.1080/15257770.2016.1184276
L. Gisbert de la Cuadra, R. Torres, L. Beltrán, Arantxa Sánchez, J. Puig
ABSTRACT We report two Lesch–Nyhan Disease (LND) patients who developed new forms of self-injurious behavior following total dental extraction. Patients 1 and 2 were submitted to total teeth extraction at the age of 13 and 8 years, respectively, due to continuous self-biting, not prevented by mouth guards. Severity of dystonia was markedly reduced and quality of life improved. After 12 and 17 months, respectively, patient 1 started rubbing one foot against other and scratching toenails with his hands, and patient 2 stuck his legs and feet against hard objects. These forms of self-injury behavior could be easily prevented with protective materials, according to the mothers.
{"title":"Development of new forms of self-injurious behavior following total dental extraction in Lesch–Nyhan disease","authors":"L. Gisbert de la Cuadra, R. Torres, L. Beltrán, Arantxa Sánchez, J. Puig","doi":"10.1080/15257770.2016.1184276","DOIUrl":"https://doi.org/10.1080/15257770.2016.1184276","url":null,"abstract":"ABSTRACT We report two Lesch–Nyhan Disease (LND) patients who developed new forms of self-injurious behavior following total dental extraction. Patients 1 and 2 were submitted to total teeth extraction at the age of 13 and 8 years, respectively, due to continuous self-biting, not prevented by mouth guards. Severity of dystonia was markedly reduced and quality of life improved. After 12 and 17 months, respectively, patient 1 started rubbing one foot against other and scratching toenails with his hands, and patient 2 stuck his legs and feet against hard objects. These forms of self-injury behavior could be easily prevented with protective materials, according to the mothers.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"28 1","pages":"524 - 528"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81978620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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