A5035195952- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Virus-based gene therapy research
- Head and Neck Cancer Studies
- Viral-associated cancers and disorders
- HIV/AIDS drug development and treatment
- Synthetic Organic Chemistry Methods
- Viral Infections and Outbreaks Research
- Phosphorus compounds and reactions
- Viral Infections and Vectors
- Natural product bioactivities and synthesis
- Advanced Chemical Sensor Technologies
- Chemical Synthesis and Reactions
- Organophosphorus compounds synthesis
- Tracheal and airway disorders
- Dysphagia Assessment and Management
- RNA and protein synthesis mechanisms
- Salivary Gland Tumors Diagnosis and Treatment
- CAR-T cell therapy research
- Nutrition and Health in Aging
- DNA and Nucleic Acid Chemistry
- Voice and Speech Disorders
- Glycosylation and Glycoproteins Research
Canon (United Kingdom)
2024
Sarepta Therapeutics (United States)
2024
Royal Brisbane and Women's Hospital
2006-2023
Novartis (United States)
2021
New Frontier
1992-1993
Massey University
1990
AgriBio
1989
The metabolism and mode of action penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; BRL 39123] were studied compared with those acyclovir. In uninfected MRC-5 cells, low concentrations the triphosphates acyclovir occasionally just detectable, limit detection being about 1 pmol/10(6) cells. contrast, in cells infected either herpes simplex virus type 2 (HSV-2) or varicella-zoster (VZV), was phosphorylated quickly to give high triphosphate ester. Following removal from culture medium,...
The limited oral absorption in rodents of the antiherpesvirus agent 9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine (BRL 39123 [penciclovir; British approved name]) prompted a search for prodrugs. 6-deoxy derivative penciclovir 42359) and corresponding diacetyl dipropionyl derivatives 42810 [famciclovir; name] BRL 43599) were tested as vivo (dose, 0.2 mmol/kg) conversion to active compound, penciclovir, determined rats. Compared with sodium salt given intravenously, bioavailabilities from...
Famciclovir is the oral form of penciclovir, a highly selective antiherpesvirus agent. Both famciclovir and penciclovir are being evaluated in clinical studies. This review covers conversion to formation stability penciclovir-triphosphate, its effect on herpesvirus DNA polymerases inhibition viral synthesis cell cultures. The into described, emphasising work with human tissues including elucidation structures chiral monoacetylated derivatives. To reflect metabolism during absorption, was...
The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity mouse non-human primates following single injection confers complete from challenge macaques. Peak neutralizing antibody...
The metabolism and mode of action 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) were studied in herpes simplex virus type 1 (HSV-1)-infected uninfected MRC-5 cells compared with those acyclovir. In incubated 10 microM acyclonucleoside for 4 h, no phosphorylation either BRL 39123 or acyclovir was detected. contrast, HSV-1-infected cells, both phosphorylated up to the triphosphate esters. Phosphorylation occurred much more rapidly proceeded a greater extent than did that...
This review describes the studies that have been carried out to date investigate mode of action penciclovir. Penciclovir is phosphorylated much more efficiently than acyclovir in herpesvirus-infected cells yet host cell kinases phosphorylate both compounds a small but comparable extent. highly preferential metabolism major factor its selective antiviral activity. ( S)-penciclovir-triphospate enantiomer produced and it has longer half-life acyclovir-triphosphate HSV-1, HSV-2, varicella-zoster...
<h3>Objective</h3> To review the experience of 2 institutions in management localized carcinoma cervical esophagus with chemoradiation therapy. <h3>Design</h3> A series 34 patients received therapy for a 5-year period. All were treated curative intent. Three different regimens used, all involving concomitant chemotherapy and high-dose radiation Data relating to toxic effects, local control disease, disease-free overall survival prospectively collected. <h3>Setting</h3> Two combined clinics...
Potential oral prodrugs of the antiherpesvirus acyclonucleoside 9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]guanine (1, BRL 39123) have been synthesized and evaluated for bioavailability 1 in blood mice. Reduction 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-amino-6-chloropurine (13) using ammonium formate 10% palladium on carbon afforded 2-aminopurine 14, which was hydrolyzed to monoacetate 15 2-amino-9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]purine (5). The 5 subsequently converted additional...
Abstract Background The purpose of this study was to evaluate combined autofluorescence (AF) and narrow band imaging (NBI) for detection mucosal lesions additional known primary head neck cancers determine impact on management. Methods Patients with cancer requiring preoperative screening or posttreatment surveillance had white light (WL), AF NBI inspection the bronchus. Known were not analyzed, only lesions. Moderate dysplasia worse considered significant. Results In all, 73 patients...
Abstract Purpose Malnutrition is an important prognostic indicator of post-operative outcomes in patients undergoing surgery for head and neck cancer, however, limited studies utilize validated nutrition assessment tools to accurately assess risk. The aim this study was determine the relationship between nutritional status on complications length stay either a laryngectomy, pharyngectomy or pharyngolaryngectomy cancer. Methods Patients with cancer at tertiary hospital Australia were eligible...
Volatile organic compound (VOC) breath testing of lung and head neck squamous cell carcinoma (SCC) has been widely studied, however little is known regarding VOC profiles in-situ SCC. A prospective study in patients with histologically proven SCC, either or advanced, controls. Breath samples were analysed using the E-nose Cyranose ®320 by gas chromatography/mass spectroscopy. Predictive models developed bootstrap forest all 32 sensors. Data from 55 participants was analysed: 42 SCC cases...
The severe and complex COVID-19 symptoms, often needing hospital care, occur suddenly, late in the virus replication stage of SARS-CoV-2 infection. Hospitalised patients have tissue damage due to micro-clots at multiple sites. Could long-covid, also clinically variable, be a milder form caused by &ldquo;nano-clots&rdquo;, too small cause detectable damage? timing suddenness onset serious disease needs an explanation. A paper reported on first 20 children urgent care. No child had any...
Abstract Background Swallowing and nutrition guidelines for patients with head neck cancer are available identification of proactive gastrostomy placement in high nutritional risk. The purpose this study was to investigate improvements the validity these guidelines. Methods A multivariate analysis fitted original dataset ( n = 501) examine variables that may predict (eg, tumor site, treatment, sex, age). Using factors, risk category modified retrospectively validated same cohort provide new...
Summary The SARS-CoV-2 pandemic has affected more than 70 million people worldwide and resulted in over 1.5 deaths. A broad deployment of effective immunization campaigns to achieve population immunity at global scale will depend on the biological logistical attributes vaccine. Here, two adeno-associated viral (AAV)-based vaccine candidates demonstrate potent immunogenicity mouse nonhuman primates following a single injection. Peak neutralizing antibody titers remain sustained 5 months are...
The 26th International Conference on Antiviral Research (ICAR) was held in San Francisco, California from May 11 to 15, 2013. This article summarizes the principal invited lectures at meeting. opening symposium legacy of late Antonín Holý included presentations his pioneering work with nucleotide analogs, which led development several antiviral drugs including tenofovir. drug has transformed treatment HIV infection and recently become first-line therapy for chronic hepatitis B. Gertrude...
Penciclovir is a potent antiherpesvirus agent which highly selective due to its phosphorylation only in virus infected cells. Phosphorylation of one the hydroxymethyl groups penciclovir (PCV) creates chiral centre leading possible formation (R)- and (S)-enantiomers. The absolute configuration stereospecificity PCV-phosphates produced cells with herpes simplex viruses types 1 2 (HSV-1 HSV-2), as well by HSV-1-encoded thymidine kinase, were determined using isotopically [4'-13C]PCV precursors...
Methyl crepenynate has been synthesised from non-3-yn-1-yl-triphenylphosphonium bromide (obtained hept-1-yne via non-3-yn-1-ol and 1-bromonon-3-yne) the C9 aldehyde-ester with butyl-lithiumin ether, it crepenynic acid was obtained by alkaline hydrolysis.
Panendoscopy is used in selected patients with head and neck cancer to detect second primary disease. We hypothesized that adding autofluorescence the bronchoscopy laryngoscopy part of this procedure could add detection clinically meaningful dysplasias carcinomas both bronchus, resultant change management.Prospective observational study on consecutive who had panendoscopy prior surgery.Teaching hospital, tertiary referral center.All white-light inspection observed by ENT surgeons, followed...
The 27th International Conference on Antiviral Research (ICAR) was held in Raleigh, North Carolina, USA from May 12 to 16, 2014. This article summarizes the principal invited lectures. John Drach (Elion Award) described early days of antiviral drugs and their novel modes action. Piet Herdewijn (Holý used evolutionary pressure select DNA polymerases that accept nucleoside analogs. Replacing thymine by 5-chlorouracil led generation a new form Escherichia coli. Adrian Ray (Prusoff demonstrated...
Isotopically chiral [13C]penciclovir (BRL 39123) has been synthesised via a stereospecific hydrolysis catalysed by the lipase from Candida cylindraceae and used to determine, 13C NMR, that triphosphate of penciclovir formed in herpes simplex type 1 infected cells (S) stereochemistry with an enantiomeric purity > 95%.