Apoptosis mediated by Fas but not tumor necrosis factor receptor 1 prevents chronic disease in mice infected with murine cytomegalovirus.

The role of Fas- and TNF-receptor 1 (TNF-R1)-mediated apoptosis in the clearance of virally infected cells and in the regulation of the immune response was analyzed after murine cytomegalovirus (MCMV) infection of C57BL/6 (B6)-+/+ mice, Fas-mutant B6-lpr/lpr mice, TNF-R1 knockout B6-tnfr0/0 mice, and double-deficient B6-tnfr0/0 lpr/lpr mice. There was approximately equivalent clearance of MCMV in B6-+/+, B6-tnfr0/0, and B6-lpr/lpr mice, and by day 28 no infectious virus could be detected in the liver, kidney, lung, or peritoneal exudate. However, delayed virus clearance was observed in B6-tnfr0/0 lpr/lpr mice.

Assessment of correlation between skin target site free drug concentration and the in vivo topical antiviral efficacy in hairless mice for (E)-5-(2-bromovinyl)-2'-deoxyuridine and acyclovir formulations.

Recently, we reported that the in vivo efficacy of acyclovir (ACV) formulations was a single valued function of skin target site free drug concentration (C) irrespective of the formulation compositions. A long-term objective of this research has been to generalize the C concept using model drugs which are similar to as well as different from ACV in their mechanism of actions. (Bromovinyl)deoxyuridine (BVDU) was selected as a model drug based on the reported similarity in its mechanism of action with ACV.

The versatile autogenous rib graft in septorhinoplasty.

In the graft depleted revision rhinoplasty patient and the patient with major tissue needs, alternatives to septal and conchal cartilage grafts are needed. The costal cartilage graft and rib bone/costal cartilage combination graft are excellent alternatives. In this study 14 patients received 40 grafts from 20 autogenous ribs harvested during septorhinoplasty.

Evaluation of a live attenuated recombinant virus RAV 9395 as a herpes simplex virus type 2 vaccine in guinea pigs.

Recombinant virus RAV 9395 was constructed by deleting both copies of the gamma(1)34.5 gene, and the UL55 and UL56 open reading frames from herpes simplex virus type 2 (HSV-2) strain G. The potential use of RAV 9395 as an HSV-2 vaccine was investigated by evaluating the ability of RAV 9395 to protect guinea pigs from severe disease by HSV-2(G) challenge.

Sluder's sphenopalatine ganglion neuralgia--treatment with 88% phenol.

Patients who experience chronic recurring head and face pain present a diagnostic and therapeutic challenge. Treatment options for Sluder's neuralgia, an uncommon cause for recurring head and face pain, are controversial. We reviewed the outcomes of patients who underwent intranasal phenolization of the sphenopalatine ganglion for the treatment of Sluder's neuralgia.

The role of outfracture in correcting post-rhinoplasty nasal obstruction.

Post-rhinoplasty nasal osbtruction is often related to narrowing in the region of the nasal valve. Correction of this obstruction can include inferior turbinectomy, septoplasty spreader grafts and nasal valvuloplasty. The authors have seen cases of severe valve stenosis related to infracture after osteotomy which did not respond to any of the aforementioned procedures.

Chronic vulvar ulceration in an immunocompetent woman due to acyclovir-resistant, thymidine kinase-deficient herpes simplex virus.

A 34-year-old healthy woman presented with a 15-month history of persistent, nonhealing vulvar ulcerations due to herpes simplex virus (HSV) type 2. Extensive dermatologic workup and serial skin biopsies failed to reveal an underlying vulvar dermatosis or autoimmune bullous disorder. Virologic studies revealed resistance to acyclovir in vitro due to deficiency in thymidine kinase activity.

Evaluation of antioxidant healing formulations in topical therapy of experimental cutaneous and genital herpes simplex virus infections.

A genital HSV-2 infection of guinea pigs and a cutaneous HSV-1 infection in mice were used to examine the ability of antioxidant components CRT1 to reduce lesion development, duration, and severity. CRT is a patented antioxidant formulation developed by Warner-Lambert Worldwide Consumer Healthcare R. and D.

(Z)- and (E)-2-((hydroxymethyl)cyclopropylidene)methyladenine and -guanine. New nucleoside analogues with a broad-spectrum antiviral activity.

New nucleoside analogues 14-17 based on a methylenecyclopropane structure were synthesized and evaluated for antiviral activity. Reaction of 2,3-dibromopropene (19) with adenine (18) led to bromoalkene 20, which was benzoylated to give N6,N6-dibenzoyl derivative 23. Attempts to convert 20 or 23 to bromocyclopropanes 21 and 22 by reaction with ethyl diazoacetate catalyzed by Rh2(OAc)4 were futile.

Effects of Aspergillus fumigatus and Alternaria alternata on human ciliated epithelium in vitro.

Fungi represent the etiologic agent in a large number of patients with chronic sinusitis. Despite this, no study has examined the effects of fungi on ciliated epithelium. This study evaluates the effects of cultures and filtrates of Aspergillus fumigatus and Alternaria alternata on ciliary beat frequency (CBF) in vitro.

Relationship of skin target site free drug concentration (C*) to the in vivo efficacy: an extensive evaluation of the predictive value of the C* concept using acyclovir as a model drug.

For the past few years, our laboratory has been involved in the development of a novel approach for predicting topical in vivo efficacy based on the estimation of skin target site free drug concentration (C*) from in vitro flux data. We have used acyclovir (ACV) as a model drug in the treatment of cutaneous herpes simplex virus type 1 infections in hairless mice. The goal of this study was to rigorously evaluate the applicability of this approach over the entire range of topical efficacy (i.

The synthesis and immunogenicity of varicella-zoster virus glycoprotein E and immediate-early protein (IE62) expressed in recombinant herpes simplex virus-1.

In order to evaluate the conditions for optimal expression and immunogenicity of varicella-zoster virus (VZV) proteins in a herpes simplex virus-1 (HSV-1) vector, we selected the VZV glycoprotein E (gE), encoded by ORF 68 and the VZV product of ORF 62, an immediate-early major tegument protein (IE62). Three HSV/VZV recombinants were generated: (1) VZV gE protein coding sequences along with the promoter region were inserted into the thymidine kinase (TK) gene of HSV-1 strain KOS; (2) VZV gE expressed from the HSV-1 ICP4 promoter was inserted into the glycoprotein C (gC) gene of HSV-1 strain F; and (3) VZV IE62 protein coding sequences under the control of the HSV-1 ICP4 promoter were inserted into the gC gene of HSV-1 strain F. Immunoblot analysis and immunoperoxidase staining of infected cell monolayers demonstrated vector expression of VZV proteins.

Differential effect of recombinant human and mouse interferons on replication of herpes simplex virus type 1 in mouse cells.

Pretreatment of murine (BALB/3T3) cells with either murine or recombinant hybrid human B/D interferon (IFN) blocked the release of infectious herpes simplex virus type 1 (HSV-1) from treated cells. The block in replication was not due to an effect on attachment of HSV-1 to the target cells or to toxic effects of IFN. Immunoblot analyses showed that murine IFN significantly reduced the expression of virus-specific proteins in IFN-treated cells.

Nasofrontal duct reconstruction with silicone rubber sheeting for inflammatory frontal sinus disease: analysis of 164 cases.

The authors reviewed their experience in reconstructing the nasofrontal duct with thin silicone rubber sheeting in patients who had chronic inflammatory frontal sinus disease. The 164 patients were divided into four groups. The patients in group 1 had the traditional modified Lynch procedure, while those in group 2 had certain technical variations of the modified Lynch operation.

Correlation of in vivo topical efficacies with in vitro predictions using acyclovir formulations in the treatment of cutaneous HSV-1 infections in hairless mice: an evaluation of the predictive value of the C* concept.

The purpose of this study was to carry out an extensive examination of the C* concept for prediction of the topical antiviral efficacies of acyclovir (ACV) formulations in a hairless mouse model for the treatment of cutaneous herpes simplex virus type-1 (HSV-1) infections. This method is based on estimation of the free drug concentration at the target site (C*), which is presumed to be the basal cell layer of the epidermis. Five different formulations (containing 5% ACV) were examined in a finite dose multiple dosing regimen (twice a day application) to simulate the clinical situation.

Role of animal models in selecting antiviral combinations for clinical studies.

Although experimental viral infections in animals have been used extensively in the development of antiviral drugs used as monotherapy, they have not been utilized widely for evaluation of combination chemotherapy. One of the major reasons for the lack of use of animal models is that for the diseases that are the main target for combination therapy, AIDS and hepatitis B and C infections, there is a lack of suitable models for these diseases. In contrast, most combination studies in animal models have been directed against herpes simplex virus infections but there are relatively few patients available who would benefit from combination therapy over single agent therapy.

Reconstruction of caudal end of septum. A case for transplantation.

Objective: To examine the results of complete removal and reconstruction of the caudal end of the septum with emphasis on long term success.

Design: A case series reviewing the surgical outcome of 45 consecutive cases of transplantations for severely deformed of absent caudal ends of the septum. After at least 18 months, all 45 patients were given a postoperative evaluation.

Synthesis and antiproliferative and antiviral activity of 2'-deoxy-2'-fluoroarabinofuranosyl analogs of the nucleoside antibiotics toyocamycin and sangivamycin.

The glycosylation of 3,4-dicyano-2-[(ethoxymethylene)amino]pyrrole (7) with 2-deoxy-2-fluoro-alpha-D-erythro-pentofuranosyl bromide (2) furnished an anomeric mixture of nucleosides (8a,b). This mixture was separated, and the individual anomers were treated with methanolic ammonia to effect a concomitant deblocking and ring closure. This furnished both anomers of 2'-deoxy-2'-fluoro-ara-toyocamycin (9a,b).

Estimation of skin target site acyclovir concentrations following controlled (trans)dermal drug delivery in topical and systemic treatment of cutaneous HSV-1 infections in hairless mice.

The use of controlled transdermal delivery of acyclovir (ACV) in the treatment of cutaneous herpes simplex virus type 1 infections in hairless mice was investigated. Using an in vivo animal model (A. Gonsho, et al.

Efficacy of A-73209, a potent orally active agent against VZV and HSV infections.

A-73209 is a novel oxetanocin derivative with potent in vitro and in vivo activity against VZV, HSV-1, and HSV-2. A-73209 was two logs more potent than acyclovir against five thymidine kinase positive (TK+) strains of VZV in vitro (mean EC50 0.01 vs.