Herpes virus hepatitis

The synthesis of a number of phosphonate derivatives of methylenecyclo-propane nucleoside analogues (86a-l) has been reported by Zemlicka. Most were obtained by an alkylation-elimination approach. Starting from a meth-anesulfonate, methylenecyclopropane phosphonates were obtained by Michaelis-Becker reaction with alkyl phosphites and converted to vicinal dibromides, subsequently used for alkylation-elimination of nucleic acid type bases. All compounds were evaluated against herpes viruses, hepatitis B and HIV and were found to be inactive except for (86b), which was found to inhibit VZV proliferation. 

Fig. 23.2 Acute herpes virus hepatitis with intranuclear bodies (Cowdry type A) (- )...

Since the pioneering work of Kleymann et al. (2002), Betz et al. (2002), Baumeister et al. (2007), and Crute et al. (2002), who showed that compounds identified as inhibitors of the helicase-primase enzyme complex could alleviate herpesvirus-induced disease in animal models, the attention of researchers developing antiviral compounds has been drawn more and more towards the virus-encoded helicases, particularly those of Herpes viruses and of RNA viruses such as Hepatitis C Virus (HCV) and SAKS coronavirus (SARS-CoV). Enzyme activity is usually assayed by measuring NTPase activity in the presence of an appropriate nucleic acid co-substrate although, more recently, novel fiuorimetric and luminescence principles have been applied to the measurement of strand unwinding and/or translocation of the protein along the nucleic acid (Frick 2003, 2006). 

In this chapter, we have described the spectrum of antiviral activities that have been discovered beyond the world of nucleoside analogues, protease and fusion inhibitors. The compounds and mechanisms described here may one day add significantly to the armamentarium of antiviral agents, not only against Herpes Simplex, Hepatitis B and Human Immunodeficiency Virus, but also against Hepatitis C and Human Cytomegalovirus. 

In advanced AIDS, MM is usually associated with opportunistic infections such as CMV (Said et al. 1991 RouUet et al. 1994 Kolson and Gonzalez-Scarano 2001) or is secondary to lymphoma (Fuller et al. 1993). Despite a role for other herpes viruses in AIDS-associated myelitis, no substantive evidence has been published in support of a role for other vimses in the development of HIV-associated MM, including herpes simplex 1 or 2, varicella zoster, or Epstein Barr vims (Kolson and Gonzalez-Scarano 2001). MM can occur secondary to hepatitis B and C viruses, which are common co-infections of HIV-infected patients, particularly when there is an associated cryoglobulinemia (Taillan et al. 1993 Caniatti et al. 1996). Rarely... 

Hepatitis C virus NS3/NS4A protease inhibitors, 44 (2006) 65 Herpes virus, chemotherapy, 23 (1985) 67 Heterocyclic analogues of GABA,... 

CP coat protein CtxB cholera toxin B subunit scFv single chain Fv antibody fragment TMOF trypsin modulating oostatic factor MAB monoclonal antibody GFP green fluorescent protein CPV Canine parvovirus BHV Bovine herpes virus FMDV Foot and mouth disease virus HCV Hepatitis C virus HRV Human rhino Virus MEV Mink enteritis virus MHV Murine hepatitis virus MV Measles virus RSV Respiratory syncytial virus... 

Over the past years, synthetic base-modified nucleosides and nucleotides have displayed important impact in diverse fields. Their biological properties have found application as antiviral tools against hepatitis virus (HBV), herpes virus (VZV) and human immunodeficiency (HIV).94,95,136 Many of those compounds exhibit antiproliferative, antibiotic and antifungal activities and some have been used as probes for DNA damages96,97,137 as well as in the anti-sense approach and DNA-probe technology with fluorescence properties.99... 

Tinea pedis is a fungal infection commonly known as athlete s foot. Chickenpox is a childhood infection caused by the herpes zoster virus. Hepatitis is a viral infection of the liver. Mumps is a viral infection characterised by bilateral or unilateral inflammation of the salivary glands. Rubella (German measles) is caused by the rubella virus. 

Interferons (IFN) are glycoproteins that, among other products, are released from virus-infected cells. In neighboring cells, interferon stimulates the production of "antiviral proteins." These inhibit the synthesis of viral proteins by (preferential) destruction of viral DNA or by suppressing its translation. Interferons are not directed against a specific virus, but have a broad spectrum of antiviral action that is, however, species-specific. Thus, interferon for use in humans must be obtained from cells of human origin, such as leukocytes (IFN-a), fibroblasts (IFN-P), or lymphocytes (IFN-y). Interferons are also used to treat certain malignancies and autoimmune disorders (e.g., IFN-a for chronic hepatitis C and hairy cell leukemia IFN-p for severe herpes virus infections and multiple sclerosis). 

Pharmacology Ganciclovir, a synthetic guanine derivative active against CMV, is an acyclic nucleoside analog of 2 -deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo. Sensitive human viruses include CMV, herpes simplex virus (HSV)-I and -2, herpes virus type 6, Epstein-Barr virus, varicella-zoster virus, and hepatitis B virus. 

Their DNA is also integrated into the host genome. Some viruses that usually produce lysis of cells, e.g., SV40, adenoviruses, herpes viruses, and hepatitis B virus, can occasionally be integrated into the DNA of the host. If such integration occurs in the middle of a gene, that gene will be mutated. This is one way in which such viruses may induce cancers. 

Viruses other than HIV may be treated by blocking the action of nucleotide polymerases. Acyclovir (Zovirax, 6.56) and famciclovir (Famvir, 6.57) are used against various herpes viruses (Figure 6.22). Cidofovir (Vistide, 6.58) is active against cytomegaloviral retinitis in patients who are infected with HIV. Ribavirin (Rebetol, 6.59) is approved for use against hepatitis C virus. 

Viruses Hepatitis, Herpes simplex, polio, rabies... 

In histomorphological terms, hepatitis means inflammation of the liver . The factor causing the disease may spread from the initially or predominantly affected mesenchyma to the liver cells (such as in kala-azar and malaria), or the primarily or mainly affected Hver cells may subsequently incorporate the mesen-ch)mia into the damaging process (as for example in yellow fever). In leptospirosis and herpes virus infection, the morphological finding is determined almost exclusively by changes in the parenchyma, while mesench)mial reactions are hardly or not at all present. 

Fagan, E.A., Partridge, M., Sowray, J.H., Williams, R. Review of the herpes-viruses and hepatitis A the potential hazards in dental care. Oral Surg. Oral Med. Oral Pathol. 1987 64 693-696... 

Dienes, H.P., Schirmacher, P., Weise, K., Falke, D. Herpes simplex virus hepatitis and related problems. Int. Rev. Exper. Path. 1994 35 2-38... 

Kaufman, B., Gandhi, S.A., Louie, E., Rlzzi, R., Blei, P. Herpes simplex virus hepatitis case report and review. Chn. Infect. Dis. 1997 24 334-338... 

Klein, N.A., Mabie, W.C., Shaver, D.C., Latham, P.S., Adamec, T.A., Pinstein, M.L., Riely, C.A. Herpes simplex virus hepatitis in pregnancy. Two patients successfully treated with acyclovir. Gastroenterology 1991 100 239 - 244... 

Hepatitis transmitted by blood or blood products can be caused by several viruses. Hepatitis B virus (HBV) and hepatitis C virus (HCY), together with serologically unidentified hepatitis viruses that cause non-A, non-B, non-C hepatitis are leading pathological agents. Less important are hepatitis A virus (153,154), cytomegalovirus, Epstein-Barr virus. Herpes simplex virus, and other vimses that may cause liver damage. 

Viral, parasitic, and bacterial infections have been linked to cancer (Table 9). DNA viruses such as Epstein-Barr, hepatitis B, hepatitis C, papillomaviruses, and Kaposi sarcoma herpes virus and RNA viruses such as human T-cell leukemia virus type I and human immunodeficiency virus have been implicated in causing cancer in humans and are listed as known-to-cause-cancer in humans by the International Agency for Research on Cancer (lARC). In man, the liver fluke, Opisthorchis viverrini, is associated with the development of cholangiocarcinomas of the liver and the blood fluke. Schistosoma haematobium, with carcinoma of the urinary bladder. There is evidence that chronic Helicobacter pylori infection of the stomach in man is not only related to... 

Kaufman B, Gandhi S, Louie E, Rizzi R, Illei P. Herpes simplex virus hepatitis Case report and review. Clin Infect Dis 1997 24 334-8. 

Antigenically altered T lymphocytes also found in cytomegalovirus infection, drug reactions, herpes virus, malaria, mumps, mycoplasma, rubella, rubeola, serum sickness, toxoplasmosis, tuberculosis, typhoid, viral hepatitis... 

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