HERP values

HERP value is the lifetime daily exposure rate experienced by humans (in milligrams per kilogram of body weight) that lowers, by one-half, the percent of tumor-free animals in a bioassay experiment over a standard lifetime of the animal. Asterisks imply that the substance acts as a promoter of cancer and is not genotoxic itself. 

Overall, our analyses have shown that HERP values for some historically high exposures in the workplace—to butadiene and tetrachloroethylene—and to some pharmaceuticals—clolibrate —rank high, and that there is an enormous background of naturally occurring rodent carcinogens in typical portions of common foods. The background of natural exposures casts doubt on the relative importance of low-dose exposures to residues of synthetic chemicals such as pesticides. (A committee of the National Research Council of the National Academy of Sciences reached similar conclusions about natural vs. synthetic chemicals in the diet, and called for further research on natural chemicals.) 16... 

Aciclovir (acyclovir) was one of the first effective selective antiviral agents. It is a guanine derivative of value in treating herpes viruses, though it does not eradicate them, and is only useful if drug treatment is started at the onset of infection. 

The tubingensins A (379) and B (380) showed activity against the widespread crop pest Heliothis zea, and display in vitro anti-viral activity against herpes simplex virus type 1 with IC50 values of 8 and 9 pg/mL, respectively (346) (see Scheme 2.100). Some bis-basic ethers of carbazoles are anti-viral. When tested against Encephala myocarditis viral infection, several N-ethyl substituted bis-basic carbazoles of the general formula 490 were shown to be active (448) (Scheme 4.9). 

A series of macrolides bearing a thiazole moiety have been isolated from tunicates and sponges. The tunicate Lissoclinum patella has afforded the patellazoles A-C (428-430), which were found to be potent cytotoxins in the NCI human cell line protocol with mean IC50 values of 10-3—10-6 pg/ml as well as exhibiting antifungal activity [334, 335]. Furthermore, patellazole B (429) exhibited very potent antiviral activity against Herpes symplex viruses [334],... 

The 7-azabenzisoselenazol-3(27/)-ones (169) (Fig. 12), substituted at the 2-position with phenyl or alkyl groups, and the methiodides (170) were found in the antiviral assay to be strong inhibitors of cytopathic activity of herpes simplex type 1 virus (HSV-1) and encephalomyocarditis virus (EMCV), more potent than ebselen. The minimal inhibitory concentration (MIC) values were in the range 0.4-6.0 pg mL 1, substantially lower than those when toxicity was observed. The vesicular stomatis virus (VSV) remained resistant toward tested compounds, except moderately active methiodide (171) [51, 271],... 

Azetidine 25 has shown promising anti-human cytomegalovirus (HCMV) activity. Human cytomegalovirus is a ubiquitous member of the herpes virus family. The EGso value obtained for this compound has been found to be similar to that of the standard reference compound ganciclovir and slightly better than that of cidofovir... 

Although oral corticosteroids have had an established use in herpes zoster treatment, their value has become controversial.They are clearly contraindicated in HIV and while the virus is still present in immunocompetent patients. Some authors report increased quality of life and decreased acute pain with oral steroid use in the elderly, but this value is offset by potential risk. Significant relief may be obtained with early antiviral therapy so that oral steroids are an unnecessary risk. Oral steroids are of no value in preventing PHN as was previously believed. The duration of PHN, however, is significantly shortened by early and aggressive use of oral antiviral agents in the acute phase of herpes zoster. Tricyclic antidepressants may also be useful when prescribed at the time of acute... 

EC50 values are the concentrations of compound in mg/ml which inhibited by 50% the production of gp 120 of HIV or SIV, or herpes simplex virus type 1 surface antigens. 

Dimethylsulphoxide is a universal solvent but can cause itching erythema and uticaria when applied to skin. However, it has been used medicinally in bladder instillations (at 50% in water) for interstitial cystitis, and is a vehicle for idoxuridine for herpes infections (though is of little value). Together with acetone, DMSO is a class 3 solvent under the FDA guidance, not known as a human health hazard at levels normally expected in pharmaceuticals and which can thus be limited by appropriate GMP practices. 

Torvanol A and torvoside H isolated from Solanum torvum (76) showed antiviral activity (herpes simplex virus type 1) in vitro. The IC50 values were threefold less compared with the reference compound, acyclovir. 

Results in ocular herpes keratitis are usually more positive and there is no doubt of the value of the drug in this form of infection [191, 192]. Some patients have been found to be resistant to treatment but in only 2 out of 12 such patients in one trial was the isolated virus found to be actually more drug-resistant than the normal wild-type virus. In this paper [192] the value of IDUR in herpes keratitis of man was critically assessed from the information available in mid-1969. 

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