Separate administration of polyribocytidylic acid [poly(rC)] and polyriboinosinic acid [poly(rI)] to cell cultures in vitro resulted in an antiviral activity identical to or greater than that resulting from addition of the poly(rI) * poly(rC) complex. Priming of cells with poly(rI), followed by treatment with poly(rC), gave a consistently greater antiviral activity than poly(rI) * poly(rC) itself. This priming effect was obtained in several cell cultures challenged with different viruses. In vivo, the antiviral activity of poly(rI) * poly(rC) was only partially restored if poly(rI) and poly(rC) were injected separately; prior injection of poly(rI) proved superior in restoring this antiviral activity as compared to prior injection of poly(rC).
Thirteen established anti-herpes compounds have been directly compared in a single assay system for their effects on the development of herpetic skin lesions, and mortality associated therewith, in athymic nude (nu/nu) mice inoculated intracutaneously with herpes simplex virus type 1 (KOS). When applied topically (at 1% in a water-soluble ointment), phosphonoacetic acid, E-5-(2-bromovinyl)-2'-deoxyuridine, acycloguanosine, and trisodium phosphonoformate emerged as the most active agents.
Poxviruses continue to pose a major threat to human health. Monkeypox is endemic in central Africa, and the discontinuation of the vaccination (with vaccinia virus) has rendered most humans vulnerable to variola virus, the etiologic agent of smallpox, should this virus be used in biological warfare or terrorism. However, a large variety of compounds have been described that are potent inhibitors of vaccinia virus replication and could be expected to be active against other poxviruses as well. These compounds could be grouped in different classes: (i) IMP dehydrogenase inhibitors (e.g., EICAR); (ii) SAH hydrolase inhibitors (e.g., 5'-noraristeromycin, 3-deazaneplanocin A, and various neplanocin A derivatives); (iii) OMP decarboxylase inhibitors (e.g., pyrazofurin) and CTP synthetase inhibitors (e.g., cyclopentenyl cytosine); (iv) thymidylate synthase inhibitors (e.g., 5-substituted 2'-deoxyuridines); (v) nucleoside analogues that are targeted at viral DNA synthesis (e.g., Ara-A); (vi) acyclic nucleoside phosphonates [e.g., (S)-HPMPA and (S)-HPMPC (cidofovir)]; and (vii) polyanionic substances (e.g., polyacrylic acid). All these compounds could be considered potential candidate drugs for the therapy and prophylaxis of poxvirus infections at large. Some of these compounds, in particular polyacrylic acid and cidofovir, were found to generate, on single-dose administration, a long-lasting protective efficacy against vaccinia virus infection in vivo. Cidofovir, which has been approved for the treatment of cytomegalovirus retinitis in immunocompromised patients, was also found to protect mice, again when given as a single dose, against a lethal aerosolized or intranasal cowpox virus challenge. In a biological warfare scenario, it would be advantageous to be able to use a single treatment for an individual exposed to an aerosolized poxvirus. Cidofovir thus holds great promise for treating human smallpox, monkeypox, and other poxvirus infections. Anecdotal experience points to the efficacy of cidofovir in the treatment of the poxvirus infections molluscum contagiosum and orf (ecthyma contagiosum) in immunosuppressed patients.
No abstract is provided for this article.
No abstract is provided for this article.
The Belgian National Health Insurance Institute (NHII) and other Healthcare Authorities intend to improve the quality of care through promoting clinical pathway driven care and by optimising cooperation between the responsible primary care physician and the diabetologist. Patients and healthcare professionals are granted some (financial) benefits when meeting the conditions defined in a mutual agreement.This article describes the conditions and the functional requirements to be met by an EHR to enable and to maximise the benefits of a clinical pathway driven patient care to a specific group of diabetic type 2 patients, based on a mandate issued by the NHII.The generic and specific functional requirements are then translated in test criteria for certification and prioritised in an implementation plan.
Reaction of 3',5'-di-O-benzoyl-6-methyl-2'-deoxyuridine ( IIa ) with elementary bromine or iodine afforded 5-halogeno derivatives IIc and IId which on methanolysis gave 5-bromo-6-methyl-2'-deoxyurine ( Ic ) and 5-iodo-6-methyl-2'-deoxyurine ( Id ), respectively. The CD spectra of Ic, Id and 6-methyl-2'-deoxyuridine ( Ia ) are compared and discussed with regard to determination of the nucleoside conformation. Unlike 5-bromo- and 5-iodo-2'-deoxyuridine, the 6-methyl derivatives Ic and Id exhibit neither antibacterial nor antiviral activity. Nor do they exert any antimetabolic effect on the de novo DNA synthesis in primary rabbit kidney cells.
