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Chemical Compound Review

Carbovir     2-amino-9-[(1R,4R)-4- (hydroxymethyl)-1...

Synonyms: Carbovir, (-)-, CHEMBL372283, SureCN180360, AG-D-44624, SureCN3026963, ...
 
 
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Disease relevance of Carbovir

 

Psychiatry related information on Carbovir

 

High impact information on Carbovir

  • Changes in cerebral oxygen consumption (DeltaCMR(O2)/CMR(O2)) were derived from the BOLD signal (at 7T) by independent determinations in cerebral blood flow (DeltaCBF/CBF) and volume (DeltaCBV/CBV) [6].
  • Under the same conditions localized changes in brain energy metabolism (DeltaCMR(O2)/CMR(O2)) were obtained from BOLD fMRI data in conjunction with measured changes in cerebral blood flow (DeltaCBF/CBF), cerebral blood volume (DeltaCBV/CBV), and transverse relaxation rates of tissue water (T(2)(*) and T(2)) by MRI methods at 7T [7].
  • Inhalation of oxygen induced a significant decrease of both the total (delta LDF, -307%, p less than 0.02) and nutritional (delta CBV, -17%, p less 0.002) skin microcirculation in normal legs compared with baseline values [8].
  • We performed a retrospective analysis of 35 patients with primary diffuse large B-cell lymphoma of the mediastinum treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) plus autologous hematopoietic cell transplantation to determine outcome and prognostic features for progression-free survival (PFS) [9].
  • CBV and PSCT for patients with relapsed Hodgkin's diseases who have marrow hypocellularity in traditional harvest sites or histopathologic evidence of BM metastases can result in long-term event-free survival [10].
 

Chemical compound and disease context of Carbovir

 

Biological context of Carbovir

  • In this heavily pretreated patient population, most of whom had high volume residual disease, complete responses (CRs) to CBV and ABMT occurred in 25% of assessable patients with NHL and 43% of patients with HD [16].
  • Phosphorylation of carbovir enantiomers by cellular enzymes determines the stereoselectivity of antiviral activity [14].
  • A fetal infection with CBV similar to rubella virus may initiate autoimmunity or cause persistent infection that may lead to progressive beta-cell destruction [17].
  • The significant effect of ACZ on CBF and CBV suggests that cerebral perfusion might be increased using pharmacological vasodilation in CADASIL [18].
  • It was achieved in anesthetized rats by determining total cerebral blood volume (TCBV), parenchymal blood (CBV), plasma (CPV), erythrocyte (CEV) volumes and cerebral hematocrit (CHct) as well as CBF at about 40, 60, and 80 mm Hg PaCO2 [19].
 

Anatomical context of Carbovir

  • PATIENTS AND METHODS: Patients with relapsed, refractory, or poor-risk intermediate- and high-grade non-Hodgkin's lymphoma were treated with CBV with autologous marrow or peripheral-blood progenitor cell support [20].
  • We conclude that both CBV enantiomers enter human erythrocytes by two transporters that are enantiomerically selective [15].
  • CBV was measured in capillaries of the dorsal middle phalangeal area of the finger in six subjects using a recently developed capillary anemometer [21].
  • Using human lymphoid cells severely deficient in nucleoside kinases, we were able to identify the route of activation of CBV metabolism [22].
  • Its hydrolytic stability and its ability to inhibit the infectivity and replication of HIV in T-cells at concentrations of approximately 200-400-fold below toxic concentrations make carbovir an excellent candidate for development as a potential antiretroviral agent [23].
 

Associations of Carbovir with other chemical compounds

 

Gene context of Carbovir

  • All siblings with antibodies against GAD 65 had significant titre increase against any of the CBV strains [27].
  • Evidence was obtained that neither deoxycytidine kinase, adenosine kinase, or mitochondrial deoxyguanosine kinase is primarily involved in the initial step of phosphorylation of CBV in CCRF-CEM cells [22].
  • In the capsid coding region five clusters were seen: PVs, CAV21 and CAV24 formed one cluster (PV-like); ENV70 formed a cluster of its own; all CBVs, CAV9, EV11, EV12 and SVDV formed the third cluster (CBV-like); CAV16, CAV2 and ENV71 belonged to the fourth cluster (CAV16-like) and BEVs formed their own cluster (BEV-like) [28].
  • Perfusion weighted MRI has proven very useful for deriving hemodynamic parameters such as CBF, CBV and MTT [29].
  • In conclusion, this study indicates that children of mothers who expressed CBV IgM at delivery are at increased risk for developing childhood onset IDDM [17].
 

Analytical, diagnostic and therapeutic context of Carbovir

  • High-dose CBV chemotherapy induced complete responses in 15 patients and partial responses in 10 patients [2].
  • Transcutaneous oxygen tension (tc PO2) was measured on the dorsal skin of the foot, and the nailfold microcirculation was investigated by a combination of laser Doppler flowmetry (LDF) and dynamic capillaroscopy (CBV) in the great toes of 17 legs of 11 patients, with 13 legs of eight normal subjects as a control group [8].
  • The actuarial event-free survival for these 56 patients at 3 years was 37% and was at least as good as that reported for relapsed Hodgkin's disease patients treated with CBV and ABMT [10].
  • However, formal restaging was not performed after these conventional therapies; ie, the therapies were not used to select responding patients for transplantation, and all who received such therapy subsequently received CBV and autologous marrow grafts [30].
  • Thirty-four eligible patients received short-course conventional chemotherapy and/or involved-field radiotherapy before CBV [30].

References

  1. Orthotopic reimplantation of cryopreserved ovarian cortical strips after high-dose chemotherapy for Hodgkin's lymphoma. Radford, J.A., Lieberman, B.A., Brison, D.R., Smith, A.R., Critchlow, J.D., Russell, S.A., Watson, A.J., Clayton, J.A., Harris, M., Gosden, R.G., Shalet, S.M. Lancet (2001) [Pubmed]
  2. High-dose cyclophosphamide, carmustine, and etoposide and autologous bone marrow transplantation for relapsed Hodgkin's disease. Jagannath, S., Dicke, K.A., Armitage, J.O., Cabanillas, F.F., Horwitz, L.J., Vellekoop, L., Zander, A.R., Spitzer, G. Ann. Intern. Med. (1986) [Pubmed]
  3. Antiviral treatment with WIN 54 954 reduces mortality in murine coxsackievirus B3 myocarditis. Fohlman, J., Pauksen, K., Hyypiä, T., Eggertsen, G., Ehrnst, A., Ilbäck, N.G., Friman, G. Circulation (1996) [Pubmed]
  4. Catheter balloon valvuloplasty of aortic and mitral stenosis in adults: 1987. Rahimtoola, S.H. Circulation (1987) [Pubmed]
  5. Association of depression with Alzheimer's disease and vascular dementia in an elderly Arab population of Wadi-Ara, Israel. Bowirrat, A., Oscar-Berman, M., Logroscino, G. International journal of geriatric psychiatry. (2006) [Pubmed]
  6. Total neuroenergetics support localized brain activity: implications for the interpretation of fMRI. Hyder, F., Rothman, D.L., Shulman, R.G. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Cerebral energetics and spiking frequency: the neurophysiological basis of fMRI. Smith, A.J., Blumenfeld, H., Behar, K.L., Rothman, D.L., Shulman, R.G., Hyder, F. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. Effects of oxygen inhalation on skin microcirculation in patients with peripheral arterial occlusive disease. Bongard, O., Bounameaux, H., Fagrell, B. Circulation (1992) [Pubmed]
  9. Primary diffuse large B-cell lymphoma of the mediastinum: outcome following high-dose chemotherapy and autologous hematopoietic cell transplantation. Sehn, L.H., Antin, J.H., Shulman, L.N., Mauch, P., Elias, A., Kadin, M.E., Wheeler, C. Blood (1998) [Pubmed]
  10. High-dose cyclophosphamide, carmustine, and etoposide followed by autologous peripheral stem cell transplantation for patients with relapsed Hodgkin's disease. Kessinger, A., Bierman, P.J., Vose, J.M., Armitage, J.O. Blood (1991) [Pubmed]
  11. High-dose cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation in patients with lymphoid malignancies who have received dose-limiting radiation therapy. Weaver, C.H., Appelbaum, F.R., Petersen, F.B., Clift, R., Singer, J., Press, O., Bensinger, W., Bianco, J., Martin, P., Anasetti, C. J. Clin. Oncol. (1993) [Pubmed]
  12. Phase I trial of dacarbazine with cyclophosphamide, carmustine, etoposide, and autologous stem-cell transplantation in patients with lymphoma and multiple myeloma. Adkins, D.R., Salzman, D., Boldt, D., Kuhn, J., Irvin, R., Roodman, G.D., Lyons, R., Smith, L., Freytes, C.O., LeMaistre, C.F. J. Clin. Oncol. (1994) [Pubmed]
  13. Escalating dose of mitoxantrone with high-dose cyclophosphamide, carmustine, and etoposide in patients with refractory lymphoma undergoing autologous bone marrow transplantation. Attal, M., Canal, P., Schlaifer, D., Chatelut, E., Dezeuze, A., Huguet, F., Payen, C., Pris, J., Laurent, G. J. Clin. Oncol. (1994) [Pubmed]
  14. Phosphorylation of carbovir enantiomers by cellular enzymes determines the stereoselectivity of antiviral activity. Miller, W.H., Daluge, S.M., Garvey, E.P., Hopkins, S., Reardon, J.E., Boyd, F.L., Miller, R.L. J. Biol. Chem. (1992) [Pubmed]
  15. Enantiomeric selectivity of carbovir transport. Mahony, W.B., Domin, B.A., Daluge, S.M., Miller, W.H., Zimmerman, T.P. J. Biol. Chem. (1992) [Pubmed]
  16. Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study. Wheeler, C., Antin, J.H., Churchill, W.H., Come, S.E., Smith, B.R., Bubley, G.J., Rosenthal, D.S., Rappaport, J.M., Ault, K.A., Schnipper, L.E. J. Clin. Oncol. (1990) [Pubmed]
  17. Indications that maternal coxsackie B virus infection during pregnancy is a risk factor for childhood-onset IDDM. Dahlquist, G., Frisk, G., Ivarsson, S.A., Svanberg, L., Forsgren, M., Diderholm, H. Diabetologia (1995) [Pubmed]
  18. Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking. Chabriat, H., Pappata, S., Ostergaard, L., Clark, C.A., Pachot-Clouard, M., Vahedi, K., Jobert, A., Le Bihan, D., Bousser, M.G. Stroke (2000) [Pubmed]
  19. Induced response to hypercapnia in the two-compartment total cerebral blood volume: influence on brain vascular reserve and flow efficiency. Keyeux, A., Ochrymowicz-Bemelmans, D., Charlier, A.A. J. Cereb. Blood Flow Metab. (1995) [Pubmed]
  20. Prognostic factors for treatment outcome in autotransplantation of intermediate-grade and high-grade non-Hodgkin's lymphoma with cyclophosphamide, carmustine, and etoposide. Wheeler, C., Strawderman, M., Ayash, L., Churchill, W.H., Bierer, B.E., Elias, A., Gilliland, D.G., Antman, K., Guinan, E.C., Eder, J.P. J. Clin. Oncol. (1993) [Pubmed]
  21. The effect of acetylcholine on finger capillary pressure and capillary flow in healthy volunteers. Morris, S.J., Kunzek, S., Shore, A.C. J. Physiol. (Lond.) (1996) [Pubmed]
  22. Metabolism of the carbocyclic nucleoside analogue carbovir, an inhibitor of human immunodeficiency virus, in human lymphoid cells. Bondoc, L.L., Shannon, W.M., Secrist, J.A., Vince, R., Fridland, A. Biochemistry (1990) [Pubmed]
  23. Synthesis and anti-HIV activity of carbocyclic 2',3'-didehydro-2',3'-dideoxy 2,6-disubstituted purine nucleosides. Vince, R., Hua, M. J. Med. Chem. (1990) [Pubmed]
  24. Cerebral hemodynamics evaluation by near-infrared time-resolved spectroscopy: correlation with simultaneous positron emission tomography measurements. Ohmae, E., Ouchi, Y., Oda, M., Suzuki, T., Nobesawa, S., Kanno, T., Yoshikawa, E., Futatsubashi, M., Ueda, Y., Okada, H., Yamashita, Y. Neuroimage (2006) [Pubmed]
  25. High microvascular blood volume is associated with high glucose uptake and tumor angiogenesis in human gliomas. Aronen, H.J., Pardo, F.S., Kennedy, D.N., Belliveau, J.W., Packard, S.D., Hsu, D.W., Hochberg, F.H., Fischman, A.J., Rosen, B.R. Clin. Cancer Res. (2000) [Pubmed]
  26. Capillary electrophoresis-ion trap mass spectrometry analysis of Ziagen and its phosphorylated metabolites. Cai, Z., Fung, E.N., Sinhababu, A.K. Electrophoresis (2003) [Pubmed]
  27. Enterovirus infections with beta-cell tropic strains are frequent in siblings of children diagnosed with type 1 diabetes children and in association with elevated levels of GAD65 antibodies. Frisk, G., Tuvemo, T. J. Med. Virol. (2004) [Pubmed]
  28. Genetic and phylogenetic clustering of enteroviruses. Pöyry, T., Kinnunen, L., Hyypiä, T., Brown, B., Horsnell, C., Hovi, T., Stanway, G. J. Gen. Virol. (1996) [Pubmed]
  29. Bayesian estimation of cerebral perfusion using a physiological model of microvasculature. Mouridsen, K., Friston, K., Hjort, N., Gyldensted, L., Ostergaard, L., Kiebel, S. Neuroimage (2006) [Pubmed]
  30. Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease. Reece, D.E., Barnett, M.J., Connors, J.M., Fairey, R.N., Fay, J.W., Greer, J.P., Herzig, G.P., Herzig, R.H., Klingemann, H.G., LeMaistre, C.F. J. Clin. Oncol. (1991) [Pubmed]
 
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