Deoxyribonucleotides (dNTPs) are important for the efficient growth of DNA viruses. Therefore, many DNA viruses have strategies for the upregulation of cellular dNTP levels. Both α- and γ-herpesviruses encode functional homologs of cellular dNTP anabolic enzymes, including the class I ribonucleotide reductase (RNR) large (R1) and small (R2) subunits, whereas β-herpesviruses modulate host cells to induce genes that increase dNTP levels. Interestingly, β-herpesviruses still express the nonfunctional RNR R1 subunit. However, it is not clear why β-herpesviruses still carry inactive R1 homologs. Recently, the R1 homologs of herpesviruses have been shown to inhibit innate immune signaling pathways. In particular, both functional and nonfunctional R1 homologs target receptor-interacting protein kinase 1 (RIP1) and inhibit RIP1-mediated signaling pathways to promote viral replication. Here, we summarize recent findings on the activity of herpesviral R1 homologs and discuss their roles in the regulation of innate immune signaling pathways.
Deoxyribonucleotides ; DNA Viruses ; Herpesviridae ; Protein Kinases ; Ribonucleotide Reductases* ; Up-Regulation

Hydroxyurea is an antitumor agent that has attained an important role in the management of myeloproliferative syndromes. Its mechanism of action is not fully understood, but it appears to affect DNA synthesis and genetic control of cell replication by inhibiting the conversion of ribonucleotides in deoxyribonucleotides. Cutaneous side effects such as xerosis, hyperpigmentation, nail changes, skin ulceration, alopecia, and palmoplantar keratoderma may occur, especially with long-term treatment. We report a case of 65-year-old chronic myelogenous leukemia(CML) patient showing various cutaneous manifestations after receiving long-term hydroxyurea therapy.
Aged ; Alopecia ; Deoxyribonucleotides ; DNA ; Humans ; Hydroxyurea* ; Hyperpigmentation ; Keratoderma, Palmoplantar ; Ribonucleotides ; Skin Ulcer

OBJECTIVETo evaluate the therapeutic efficacy of deoxyribonucleotidum in treatment of acute viral myocarditis.

METHODSEighty-eight patients with acute viral myocarditis were randomized equally into therapeutic group and control group. Patients in the control group were treated with routine treatment and those in the therapeutic group were given deoxyribonucleotidum in addition to routine treatment. After 4 weeks, the total efficacy rate and median time of symptom disappearance were compared between the two groups.

RESULTSThe total efficacy rate in the control and therapeutic groups was 79.54% and 95.45% (P=0.049), and the median time of symptom disappearance was 9.5 days and 6.5 days, respectively (P=0.035). Hypotension and mild dizziness were found in 2 patients in the therapeutic group without other severe side effects.

CONCLUSIONDeoxyribonucleotidum can improve the therapeutic effect for acute viral myocarditis.

Adolescent ; Adult ; Deoxyribonucleotides ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Myocarditis ; drug therapy ; Treatment Outcome ; Virus Diseases ; drug therapy

OBJECTIVETo detect the structure and chemical characteristics of the adduct from the reaction of p-benzoquinone (BQ) with deoxyguanoside (dGMP).

METHODSdGMP and calf thymus DNA were reacted with BQ in buffered solutions with neutral pH, the reaction products were separated and purified by high performance liquid chromatograph (HPLC), and then characterized by UV spectroscopy and mass spectrometry.

RESULTSThe reaction of BQ with dGMP yielded two adduct products (Ad(1) and Ad(2) respectively). The characterized results of Ad(1) suggested that BQ reacted at the N-1 and N(2) position of dGMP by losing one H(2)O molecule, the molecular weight of Ad(1) was 437, and the molecular formula was C(16)H(16)O(8)N(5)P. Ad(1) could also be detected from calf thymus DNA reacted with BQ in vitro, which possessed the same elution profile by HPLC analysis. Meanwhile, Ad(2) was detected in the experimental condition. It was proposed that Ad(2) was formed by BQ reacted at the N-9 position of dGMP by losing one molecule of deoxyribose, the molecular weight was 241, and the molecular formula was C(11)H(7)O(2)N(5).

CONCLUSIONThe structure of one major adduct from reaction of BQ with DNA is (3'-OH)-1, N(2)-C(6)H(5)CH-2'-deoxyguanosine-5'-monophosphate.

Benzoquinones ; metabolism ; DNA Adducts ; chemistry ; Deoxyguanine Nucleotides ; metabolism ; Hydrogen-Ion Concentration ; Mass Spectrometry ; Molecular Weight ; Spectrophotometry, Ultraviolet

OBJECTIVETo evaluate of therapeutic efficacy of deoxyribouncleotidum on pulmonary tuberculosis.

METHODSEighty patients with pulmonary tuberculosis sustaining hepatic lesion after treatment with antituberculosis drugs were randomized into therapeutic group and control group. Patients in the control group received regular treatment and those in the therapeutic group had additional deoxyribouncleotidum injection.

RESULTSALT, AST, ALP and TBIL levels were significantly higher in the therapeutic group than in the control group 4 weeks after treatment. IgG, IgA, IgM levels, and CD3(+) and CD8(+) lymphocytes were significantly increased in the therapeutic group after treatment (P<0.05).

CONCLUSIONdeoxyribouncleotidum can improve hepatic function and immunity in patients with pulmonary tuberculosis.

Adjuvants, Immunologic ; administration & dosage ; therapeutic use ; Adult ; Alanine Transaminase ; metabolism ; Antitubercular Agents ; adverse effects ; therapeutic use ; Aspartate Aminotransferases ; metabolism ; CD3 Complex ; immunology ; CD8-Positive T-Lymphocytes ; cytology ; drug effects ; immunology ; Chemical and Drug Induced Liver Injury ; Deoxyribonucleotides ; administration & dosage ; therapeutic use ; Female ; Humans ; Immunoglobulin A ; blood ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Injections ; Liver Diseases ; blood ; drug therapy ; Male ; Middle Aged ; Treatment Outcome ; Tuberculosis, Pulmonary ; blood ; drug therapy

Unusual dTDP-sugars are key intermediate in many pathogenic bacteria. In this study, negative-ion electrospray tandem mass spectrometry (ESI-MS-MS) with collision-induced dissociation (CID) was used to study the fragmentation characteristics of six unusual nucleotide diphosphate sugars. The results indicated the major fragment of the six unusual nucleoside sugars observed in the ESI-MS-MS spectra resulted from cleavage of diphosphate moiety and their characteristic fragment ions at m/z 401, 383, and 321, correspond to [TDP-H] together with fragment ions resulting from the loss of water and phosphate moiety, respectively. Furthermore, 4-position substituted change of unusual sugar rings affected the stability of two important characteristic fragment ions of [glycosyl-1"-PO3](-) and [glycosyl-1"-P2O6](-).
Molecular Structure ; Nucleoside Diphosphate Sugars ; chemical synthesis ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; methods ; Tandem Mass Spectrometry ; methods

Topical photochemotherapy is effective for the treatment of vitiligo, However the effectiveness of photosensitizer, 4,5', 8-trimethyl-psoralen is not well known. For thesie reasons, we evaluated the pigment producing effect of various concentrations of TMP in fifty-six male black mice doing photochemotherapy. 1) The number of melanocytes according to the concentrations of TMP: The melanocytes were not increased in the control group. However, melanocytes were increased, in three TMP applied groups in the order of 0.1% 0.3% and 0.5% group at 1,2,3 weeks, respectively but the difference of melanocyte counts in the TMP applied groups was not remarkable at 4 weeks. 2) The area of melanocytes in relation to the concentrations of TMP: The area significantly increased from the second week of UVA exposure in the control group. There was marked increase in the area of the melanocytes in the TMP applied groups compared with those of control group in the order of 0. l%, 0, 3% and 0. 5% respectively. 3) The circumference of the melanocytes in relation to the Concentrations of TMP: Circumference of the control groups increased in proportion to the frequency of UVA exposure. TMP applied groups showed significant increase of the circumference compared that of the control group and generally increased in proportion to the increase in the concentration of TMP.
Animals ; Humans ; Male ; Melanocytes ; Mice ; Photochemotherapy* ; Thymidine Monophosphate ; Trioxsalen* ; Vitiligo

BACKGROUND: Continuous venovenous hemodiafiltration (CVVHDF) is advantageous in ARF patients with the unstable emodynamics and multiorgan failure. However, use of anticoagulation is sometimes hampered by their concurrent bleeding tendency. We performed the retrospective analysis to investigate the factors that could influence on the filter life. METHODS: The patients on CVVHDF without anticoagulation who required exchange of filter 8 times or more due to clotting were included. We measured filter life, clotting time, hemoglobin, platelet count, blood flow rate, dialysate flow rate, replacement fluid flow rate and blood pressure just before the initiation of every filter. We also measured mechanical pressures relevant to the filter, such as access pressures, filter pressure, return pressure and transmembrane pressure (TMP) within the last 6 hours before termination of every filter. RESULTS: Twenty-three patients (age 57+/-16, M: F=19: 4) showed the median filter life of 9 hours 20 minutes. The filter life was not influenced by the included variables. TMP significantly increased every hour during the last 6 hours before the end of filter life (p<0.01). When TMP was greater than 120 mmHg, TMP significantly increased every hour thereafter and CVVHDF was terminated within 4 hours. CONCLUSION: This study suggested that the possibility of filter clotting should be suspected when TMP is greater than 120 mmHg in the setting of CVVHDF without anticoagulation.
Blood Pressure ; Hemodiafiltration* ; Hemorrhage ; Humans ; Platelet Count ; Retrospective Studies ; Thymidine Monophosphate

One hundred sixteen C57 BL mice were painted with either 8-MOP, 5-MOP or TMP solution in concentrations of 0.02%, 0.1%, and 0.5% each and UVA irradiated. Skin biopsies were performed at 1, 3, 5 and 7 weeks after LJVA irradiation. The results measuring the number, area, and perimeter of the melanocytes after topical PLJVA were higher in the TMP-painted group than in the 8-MOP or 5-MOP painted groups. In all groups, the weekly changes showed an increasing value through five weeks. In comparing the drug concentrations used, 0.1% of chemicals produced the same or higher values than 0.5%. There have been few studies on the effects of 5-MOP in photochemotherapy. In tho study 5-MOP produced a pigment-producing effect similar to 8-MOP. Therefore, if topical PIJVA with 5-MOP is used in clinical practice, we could expect a significant therapeutic effect in vitiligo.
Animals ; Biopsy ; Melanocytes* ; Methoxsalen ; Mice* ; Paint ; Photochemotherapy ; Skin ; Thymidine Monophosphate ; Vitiligo

BACKGROUND AND OBJECTIVES: Aspiration thrombectomy (AT) during primary percutaneous coronary intervention (PCI) is an effective adjunctive therapy for ST-segment elevation myocardial infarction (STEMI). An elevated neutrophil count in STEMI is associated with microvascular dysfunction and adverse outcomes. We evaluated whether AT can improve microvascular dysfunction in patients with STEMI and an elevated neutrophil count. SUBJECTS AND METHODS: Seventy patients with STEMI undergoing primary PCI from August 2007 to February 2009 in our institution were classified by tertiles of neutrophil count on admission (<5,300/mm3, 5,300-7,600/mm3, and >7,600/mm3). The angiographic outcome was post-procedural thrombolysis in myocardial infarction (TIMI) flow grade. Microvascular dysfunction was assessed by TIMI myocardial perfusion (TMP) grade and ST-segment resolution on electrocardiography 90 minutes after PCI. The clinical outcome was major adverse cardiac event (MACE), defined as cardiac death, re-infarction, and target lesion revascularization at 9 months. RESULTS: There were no significant differences in the clinical characteristics and pre- and post-procedural TIMI flow grades between the neutrophil tertiles. As the neutrophil count increased, a lower tendency toward TMP grade 3 (83% vs. 52% vs. 54%, p=0.06) and more persistent residual ST-segment elevation (>4 mm: 13% vs. 26% vs. 58%, p=0.005) was observed. The 9-month MACE rate was similar between the groups. On subgroup analysis of AT patients (n=52) classified by neutrophil tertiles, the same tendency toward less frequent TMP grade 3 (77% vs. 56% vs. 47%, p=0.06) and persistent residual ST-segment elevation (>4 mm: 12% vs. 28% vs. 53%, p=0.05) was observed as neutrophil count increased. CONCLUSION: A higher neutrophil count at presentation in STEMI is associated with more severe microvascular dysfunction after primary PCI, which is not improved with AT.
Death ; Electrocardiography ; Humans ; Myocardial Infarction ; Neutrophils ; Percutaneous Coronary Intervention ; Perfusion ; Thrombectomy ; Thymidine Monophosphate