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The anti-herpesvirus activity of (1′S,2′R)-9-[[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl] guanine is markedly potentiated by the immunosuppressive agent mycophenolate mofetil

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ANTIVIRAL RESEARCH 2001年第2期49卷 121-127页

作者： Neyts, J De Clercq, E Katholieke Univ Leuven Rega Inst Med Res B-3000 Louvain Belgium

Mycophenolic acid (MPA), the active form of the immunosuppressive agent mycophenolate mofetil (MMF), was found to markedly potentiate the anti-herpesvirus activity of the novel anti-herpesvirus agent A-5021, (1 'S,2 'R)-9-[[1 ' ,2 ' -bis(hydroxymethyl)cycloprop-1 '- yl]methyl]guanine. For example, at a concentration of 1 mug/m (l) over tilde MPA, the activity of A-5021 against HSV-1, HSV-2 and TK- HSV-1 increased by a factor of 130, 14 and greater than or equal to 189, respectively. Exogenously added guanosine reversed this potentiating effect, suggesting that a depletion of the endogenous dGTP pools enhanced the inhibitory effect of the 5 ' -triphosphate metabolite of A-5021 on the viral DNA polymerase. The combined effect of A-5021 and MPA on the growth of uninfected Vero cells was additive rather than synergistic. The combination of topically applied MMF (5%) with 0.05% A-5021 (a subactive concentration) completely protected against HSV-1-induced cutaneous lesions in hairless mice, whereas therapy with either compound used alone had no protective effect. These findings may have implications for those transplant recipients that receive MMF as (part of) their immunosuppressive therapy and that develop intercurrent herpesvirus infections for which they need treatment. (C) 2001 Elsevier Science B.V. All rights reserved.

关键词：抗病毒药/药理学抗病毒药/治疗应用细胞系长尾猴黑巨细胞病毒/药物作用巨细胞病毒感染/病毒学药物协同作用药物疗法联合鸟嘌呤/类似物和衍生物鸟嘌呤/药理学鸟嘌呤/治疗应用疱疹单纯/药物疗法疱疹单纯/病毒学疱疹病毒1型人/药物作用微生物敏感性试验霉酚酸/类似物和衍生物霉酚酸/药理学霉酚酸/治疗应用 Vero细胞动物人类小鼠

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Intravitreal antiviral injections as adjunctive therapy in the management of immunocompetent patients with necrotizing herpetic retinopathy

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AMERICAN JOURNAL OF OPHTHALMOLOGY 2000年第6期129卷 811-813页

作者： Luu, KKM Scott, IU Chaudhry, NA Verm, A Davis, JL Bascom Palmer Eye Inst Miami FL 33136 USA

PURPOSE: To report the use of intravitreal antiviral injections as adjunctive therapy in the management of three immunocompetent patients with necrotizing herpetic retinopathy. METHOD: Case series. RESULTS: Three patients with necrotizing herpetic retinopathy received intravitreal antiviral injections for treatment of progressive retinitis, despite standard intravenous acyclovir therapy. The retinitis resolved and visual acuity improved after a minimum of 6 months of follow up in each case. CONCLUSION: Intravitreal antiviral injections may be a safe and efficacious adjunctive therapy in the management of patients with necrotizing herpetic retinopathy. (C) 2000 by Elsevier Science Inc. All rights reserved.

关键词：阿昔洛韦/治疗应用抗病毒药/治疗应用化学疗法辅助药物疗法联合眼感染病毒性/药物疗法眼感染病毒性/免疫学眼感染病毒性/病毒学更昔洛韦/治疗应用疱疹单纯/药物疗法疱疹单纯/免疫学疱疹单纯/病毒学免疫活性注射视网膜坏死综合征急性/药物疗法视网膜坏死综合征急性/免疫学视网膜坏死综合征急性/病毒学视敏度玻璃体成年人女(雌)性人类男(雄)性中年人

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Herpes simplex virus dermatitis in patients using latanoprost

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AMERICAN JOURNAL OF OPHTHALMOLOGY 2001年第1期132卷 114-116页

作者： Morales, J Shihab, ZM Brown, SM Hodges, MR Texas Tech Univ Hlth Sci Ctr Dept Ophthalmol & Visual Sci Lubbock TX 79430 USA

PURPOSE: To describe the possible association of latanoprost with herpetic dermatitis of the periocular skin, METHOD: Interventional case reports. A 79-year-old woman with open-angle glaucoma developed a vesicular dermatitis of the left lower eyelid 14 months after starting latanoprost. therapy, An 84-year-old man with pigmentary glaucoma developed a vesicular dermatitis of the right upper lid after 2 months of treatment with latanoprost: and 8 days of treatment with tobramycin/ dexamethasone for presumed bacterial conjunctivitis. Ln both cases, the dermatitis was characteristic of a herpetic infection. RESULTS: Latanoprost was discontinued in both cases. The woman was treated with vidarabine 3% ointment,. and the man was not treated with antiviral agents. In both patients, the dermatitis healed uneventfully. The lesions of the man were cultured, and a biopsy was performed;herpes simplex virus type I was recovered from the culture and confirmed by immunofluorescence testing. CONCLUSION: Latanoprost, which has been associated with reactivation of herpetic keratitis, may also cause reactivation of herpetic dermatitis of the periocular skin. (Am J Ophthalmol 2001;132:114-116 (C) 2001 by Elsevier Science Inc. All rights reserved.).

关键词：抗病毒药/治疗应用皮炎/诊断皮炎/药物疗法皮炎/病毒学眼睑/病毒学青光眼开角型/药物疗法疱疹单纯/诊断疱疹单纯/药物疗法疱疹单纯/病毒学疱疹病毒1型人/生长和发育疱疹病毒1型人/分离和提纯阿糖腺苷/治疗应用病毒激活/药物作用老年人老年人 80以上女(雌)性人类男(雄)性

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Erythema multiforme due to herpes simplex virus - Recurring target lesions are the clue to diagnosis

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POSTGRADUATE MEDICINE 1999年第5期106卷 151-+页

作者： Singla, R Brodell, RT Christ Hosp Cincinnati OH USA NE Ohio Univ Coll Med Rootstown OH 44272 USA Case Western Reserve Univ Sch Med Cleveland OH USA

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关键词：阿昔洛韦/治疗应用抗病毒药/治疗应用红斑多形/诊断红斑多形/药物疗法红斑多形/病理学红斑多形/病毒学疱疹单纯/并发症疱疹单纯/药物疗法复发皮肤/病理学老年人人类男(雄)性

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Influence of the treatment protocol upon the in vivo efficacy of cidofovir (HPMPC) and of acyclovir (ACV) formulations in topical treatment of cutaneous HSV-1 infection in hairless mice

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JOURNAL OF PHARMACEUTICAL SCIENCES 1999年第5期88卷 530-534页

作者： Afouna, MI Mehta, SC Ghanem, AH Higuchi, WI Kern, ER DeClercq, E El-Shattaway, HH Univ Alabama Dept Pediat Birmingham AL 35294 USA Univ Utah Dept Pharmaceut Salt Lake City UT 84112 USA Univ Utah Dept Pharmaceut Chem Salt Lake City UT 84112 USA Glaxo Wellcome Inc Res Triangle Pk NC 27709 USA Katholieke Univ Leuven Rega Inst Med Res B-3000 Louvain Belgium Al Azhar Univ Dept Pharmaceut Nasr City Cairo Egypt

In recent studies we found that the topical effectiveness of acyclovir (ACV) formulations was a single-valued function of C*-the target site free drug concentration. The topical efficacy was the same when the therapy was initiated 0, 1, or 2 days after intracutaneous herpes simplex virus type-1 (HSV-1) inoculation in hairless mice. The purpose of the present study was to examine the hypothesis that the topical effectiveness of cidofovir (HPMPC) would not be a single valued function of C* and that it would be dependent upon when the therapy was initiated relative to the time of viral infection. Formulations of HPMPC and AGV in 95% DMSO as a vehicle were used. Hairless mice intracutaneously infected with HSV-1 were used, and 20 mu L of the test formulation was topically applied twice a day. In protocol A, the treatment was continued until the fourth day after virus inoculation, whereas in protocol B the treatment was terminated on the day of virus inoculation. Treatment was initiated on various days ranging from day -6 to day 4, and the lesions were scored on day 5. Treatment of ACV according to protocol A proved efficacious whether started as early as 6 days before virus inoculation or later, whereas the efficacy of ACV was annihilated if applied following protocol B. For HPMPC, on the other hand, the in vivo efficacies were found to be strongly dependent on how early the therapy was initiated, and significant efficacy was observed even when the treatment was terminated on the day of virus inoculation. This difference was attributed to the virus-independent intracellular phosphorylation of HPMPC and slow clearance of its metabolites from the cell. It was also noted that, similar to ACV, for HPMPC the topical efficacy is likely to be a function of C* for a fixed protocol. However, unlike for ACV, for HPMPC the efficacy was not a single-valued function of C*.

关键词：阿昔洛韦/投药和剂量投药局部抗病毒药/投药和剂量胞嘧啶/投药和剂量胞嘧啶/类似物和衍生物疱疹单纯/药物疗法有机磷化合物/投药和剂量皮肤疾病病毒性/药物疗法动物女(雌)性小鼠

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Atypical herpes simplex encephalitis presenting as operculum syndrome

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PEDIATRIC RADIOLOGY 1999年第3期29卷 191-193页

作者： Wolf, RW Schultz, D Fretz, C Weissert, M Waibel, P Kantonsspital Inst Radiol CH-9007 St Gallen Switzerland Ostschweizer Kinderspital Abt Padiatr Neurol CH-9007 St Gallen Switzerland Ostschweizer Kinderspital Abt Radiol CH-9007 St Gallen Switzerland Inst Klin Microbiol & Immunol CH-9007 St Gallen Switzerland

This case report demonstrates the course of herpes simplex virus cerebritis in a patient aged 7 years 2 months who presented with non-specific symptoms followed by an epileptic attack. Subcortical, bilateral opercular and bilateral thalamic lesions were detected, but the temporal and inferior frontal lobes were spared. The patient developed anarthria, impairment of mastication and swallowing consistent with operculum syndrome. Diagnosis was made by magnetic resonance imaging and elevation of oligoclonal antibodies specific to herpes simplex virus in cerebrospinal fluid after an unexpectedly negative polymerase chain reaction test.

关键词：抗体病毒/分析抗病毒药/治疗应用失用症/诊断失用症/病因学脑/病理学吞咽障碍/诊断吞咽障碍/病因学诊断鉴别药物疗法联合构音困难/诊断构音困难/病因学脑炎病毒性/并发症脑炎病毒性/诊断脑炎病毒性/药物疗法癫痫/诊断癫痫/病因学随访研究疱疹单纯/并发症疱疹单纯/诊断疱疹单纯/药物疗法磁共振成像单纯疱疹病毒属/免疫学综合征儿童人类男(雄)性

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Herpes simplex virus esophagitis in the immunocompetent host: An overview

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AMERICAN JOURNAL OF GASTROENTEROLOGY 2000年第9期95卷 2171-2176页

作者： Ramanathan, J Rammouni, M Baran, J Khatib, R St John Hosp & Med Ctr Dept Med Detroit MI 48236 USA

OBJECTIVE: The aim of this study was to delineate the characteristics of herpes simplex virus esophagitis (HSVE) in the immunocompetent host. METHODS: The study entailed a case report and a review of relevant literature through a MEDLINE search back to 1966. All cases with documented HSVE in patients without immunosuppression were selected and their characteristics defined. RESULTS: A total of 38 cases were identified. The age range was 1-76 yr and the male/female ratio 3.2/1. Antecedent exposure to HSV disease was described in eight cases (21.1%). A prodrome of systemic manifestations preceded the onset of esophageal symptoms in nine subjects (23.6%). Manifestations included acute odynophagia (76.3%), heartburn (50%), and fever (44.7%). Concurrent oropharyngeal lesions were uncommon (n = 8, 21.1%). Endoscopically, extensive involvement was common, showing friable mucosa (84.2%), numerous ulcers (86.8%), and whitish-exudates (39.5%). The distal esophagus was most commonly affected (63.8%). Microscopic examination showed characteristic viral cytopathology in 26 (68.4%) cases. Virus was recovered from esophageal-brushes or biopsies in 23 of 24 (95.8%) patients and immunocytochemistry was positive in seven of eight (87.5%) cases. Immune status was consistent with primary HSV infection in eight (21.1%) cases. The disease was self-limiting, although esophageal perforation and upper GI bleeding were reported in one case each. CONCLUSIONS: HSVE in the immunocompetent host is a rare but distinct entity, and is significantly more common in male subjects. It represents either primary infection or reactivation, and is characterized by acute onset, systemic manifestations, and extensive erosive-ulcerative involvement of the mid-distal esophagus. Histopathological examination alone may miss the diagnosis;adding tissue-viral culture optimizes the diagnostic sensitivity. It is usually self-limiting;whether antiviral therapy is beneficial remains unknown. (Am J Gastroenterol 2000;9

关键词：阿昔洛韦/治疗应用抗体病毒/分析抗病毒药/治疗应用活组织检查 CD4-CD8比值诊断鉴别食管炎/药物疗法食管炎/免疫学食管炎/病毒学食管镜检查食管/病毒学疱疹单纯/药物疗法疱疹单纯/免疫学疱疹单纯/病毒学疱疹病毒1型人/免疫学疱疹病毒1型人/分离和提纯免疫减弱宿主/免疫学免疫球蛋白G/免疫学免疫球蛋白M/免疫学回顾性研究人类男(雄)性中年人

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Anti-herpesvirus activity of (1′S,2′R)-9-[[1′,2′-bis(hydroxymethyl)-cycloprop-1′-yl]methyl] x guanine (A-5021) in vitro and in vivo

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ANTIVIRAL RESEARCH 2001年第2期49卷 115-120页

作者： Neyts, J Naesens, L Ying, CX De Bolle, L De Clercq, E Katholieke Univ Leuven Rega Inst Med Res B-3000 Louvain Belgium

The novel nucleoside analog (1S ' ,2R ')-9-[[1 ' ,2 '- bis(hydroxymethyl)cycloprop-1-yl]methyl]guanine (A-5021) was previously shown to be a potent inhibitor of the replication of herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) and varicella tester virus (VZV), both in vitro and in vivo (J. Med. Chem. 41, 1284-1298;Antimicrob. Agents Chemother. 42, 1666-1670). Here we demonstrate that A-5021 is also a potent inhibitor of Epstein-Barr virus (EBV) and human herpes virus 6 (HHV-6A and HHV-6B), but that the compound lacks activity against HHV-8. A-5021, in comparison to acyclovir, was also assessed for protective activity against HSV-l-induced mortality in SCID mice. The compounds were administered at 50 mg/kg per day by subcutaneous injection for four consecutive days and treatment was initiated at either 2 h, 1 or 2 days post infection (p.i.). When administered from day 0 to 4 p.i., A-5021 conferred complete protection against the infection las assessed at 22 days p.i.), whereas acyclovir delayed virus induced mortality by only 5 days. When treatment was begun on day 1 or 2, A-5021 still afforded marked protection against the infection, whereas acyclovir was virtually devoid of any activity under these conditions. Our data underline that A-5021 may offer great promise for the treatment of herpesvirus infections. (C) 2001 Elsevier Science B.V. All rights reserved.

关键词：阿昔洛韦/药理学抗病毒药/药理学抗病毒药/治疗应用细胞系鸟嘌呤/类似物和衍生物鸟嘌呤/药理学鸟嘌呤/治疗应用疱疹单纯/药物疗法疱疹单纯/病毒学疱疹病毒科/药物作用疱疹病毒科感染/病毒学疱疹病毒1型人/药物作用小鼠 SCID 动物人类小鼠

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Herpes simplex virus infections - New treatment approaches make early diagnosis even more important

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POSTGRADUATE MEDICINE 2000年第3期107卷 189-+页

作者： Nadelman, CM Newcomer, VD Univ So Calif Los Angeles Cty Med Ctr Div Dermatol Dept Med Los Angeles CA 90033 USA Univ Calif Los Angeles Sch Med Los Angeles CA USA

The herpes simplex viruses HSV-1 and HSV-2 cause problems for millions of people worldwide. Infections range from simple cold sores and fever blisters to severe central nervous system disorders. Development of effective antiviral medications has made prompt recognition important in primary care practice. Appropriate therapy can significantly reduce both medical and psychosocial ramifications of herpes infections and can greatly improve the duality of life for many patients.

关键词：抗病毒药/治疗应用疱疹生殖器/诊断疱疹生殖器/药物疗法疱疹单纯/诊断疱疹单纯/药物疗法疱疹单纯/预防和控制疱疹单纯/病毒学复发人类

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